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The development of sensors for detection of biomarkers exhibits an exciting potential in diagnosis of diseases. Herein, we propose a novel electrochemical sensing strategy for label-free dual-biomarker detection, which is based on the combination of stimulus-responsive molecularly imprinted polymer (MIP)-modified nanopores and a polymeric membrane chronopotentiometric sensor. The ion fluxes galvanostatically imposed on the sensing membrane surface can be blocked by the recognition reaction between the target biomarker in the sample solution and the stimulus-responsive MIP receptor in the nanopores, thus causing a potential change. By using two external stimuli (i.e., pH and temperature), the recognition abilities of the stimulus-responsive MIP receptor can be effectively modulated so that dual-biomarker label-free chronopotentiometric detection can be achieved. Using alpha fetoprotein (AFP) and prostate-specific antigen (PSA) as model biomarkers, the proposed sensor offers detection limits of 0.17 and 0.42 ng/mL for AFP and PSA, respectively.
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Biomarcadores , Polímeros Impresos Molecularmente , Nanoporos , Antígeno Prostático Específico , alfa-Fetoproteínas , Antígeno Prostático Específico/análisis , Polímeros Impresos Molecularmente/química , alfa-Fetoproteínas/análisis , Humanos , Biomarcadores/análisis , Límite de Detección , Técnicas Electroquímicas/métodos , Concentración de Iones de Hidrógeno , Técnicas Biosensibles/métodos , Potenciometría/métodos , Polímeros/química , Impresión Molecular , TemperaturaRESUMEN
Gossypol, a naturally occurring compound found in cottonseed meal, shows promising therapeutic potential for human diseases. However, within the aquaculture industry, it is considered an antinutritional factor. The incorporation of cottonseed meal into fish feed introduces gossypol, which induces intracellular stresses and hinders overall health of farmed fish. The aim of this study is to determine the role of General control nonderepressible 2 (gcn2), a sensor for intracellular stresses in gossypol-induced stress responses in fish. In the present study, we established two gcn2 knockout zebrafish lines. A feeding trial was conducted to assess the growth-inhibitory effect of gossypol in both wild type and gcn2 knockout zebrafish. The results showed that in the absence of gcn2, zebrafish exhibited increased oxidative stress and apoptosis when exposed to gossypol, resulting in higher mortality rates. In feeding trial, dietary gossypol intensified liver inflammation in gcn2-/- zebrafish, diminishing their growth and feed conversion. Remarkably, administering the antioxidant N-acetylcysteine (NAC) was effective in reversing the gossypol induced oxidative stress and apoptosis, thereby increasing the gossypol tolerance of gcn2-/- zebrafish. Exposure to gossypol induces more severe mitochondrial stress in gcn2-/- zebrafish, thereby inducing metabolic disorders. These results reveal that gcn2 plays a protective role in reducing gossypol-induced oxidative stress and apoptosis, attenuating inflammation responses, and enhancing the survivability of zebrafish in gossypol-challenged conditions. Therefore, maintaining appropriate activation of Gcn2 may be beneficial for fish fed diets containing gossypol.
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Apoptosis , Gosipol , Inflamación , Estrés Oxidativo , Pez Cebra , Animales , Gosipol/toxicidad , Gosipol/farmacología , Gosipol/administración & dosificación , Estrés Oxidativo/efectos de los fármacos , Apoptosis/efectos de los fármacos , Inflamación/inducido químicamente , Alimentación Animal/análisis , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo , Dieta/veterinaria , Enfermedades de los Peces/inducido químicamente , Enfermedades de los Peces/inmunología , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismoRESUMEN
Waterborne pathogens invariably present considerable threats to public health. The quorum sensing (QS) system is instrumental in coordinating bacterial growth and metabolisms. However, the responses and regulatory mechanisms of bacteria to various disinfection technologies through quorum sensing are still unclear. This study examines the inactivation effect of chlorination and ozonation on biofilms and planktonic cells of QS signaling-deficient mutants of Pseudomonas aeruginosa. Cell counting and viability assessment revealed that the combined disinfection of chlorine and ozone was the most effective for inactivating planktonic P. aeruginosa within 10 min of exposure. Additionally, microfluidic chip culture demonstrated that the secretion of quinolone signals escalated biofilms' disinfection resistance. Disinfection exposure significantly altered the gene expression of wild-type strains and QS signaling-deficient mutants. Moreover, the QS system triggered multilayered gene expression programs as a responsive protection to disinfectant exposure, including oxidative stress, ribosome synthesis, and the nutrient absorption of bacteria. These insights broaden our understanding of bacterial QS in response to disinfection, promising potential strategies toward efficient disinfection processes.
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Iron-doped biochar has been widely used as an adsorbent to remove contaminants due to the high adsorption performance, but it still suffers from complicated preparation methods, unstable iron loading, unsatisfactory specific surface area, and uneven distribution of active sites. Here, a novel magnetic porous biochar (FeCS800) with nanostructure on surface was synthesized by one-pot pyrolysis method of corn straw with K2FeO4, and used in orange G (OG) and tetracycline (TC) adsorption. FeCS800 exhibited outstanding adsorption capacities for OG and TC after K2FeO4 activation and the adsorption data were fitted satisfactorily to Langmuir isotherm and Pseudo-second-order kinetic model. The maximum adsorption capacities of FeCS800 for OG and TC were around 303.03 mg/g and 322.58 mg/g, respectively, at 25 °C and pH 7.0, which were 16.27 and 24.61 times higher than that before modification. Thermodynamic studies showed that the adsorption of OG/TC by FeCS800 were thermodynamically favorable and highly spontaneous. And the adsorption capacity of OG and TC by FeCS800 remained 77% and 81% after 5 cycles, respectively, indicating that FeCS800 had good stability. The outstanding adsorption properties and remarkable reusability of FeCS800 show its great potential to be an economic and environmental adsorbent in contaminants removal.
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Carbón Orgánico , Tetraciclina , Contaminantes Químicos del Agua , Adsorción , Tetraciclina/química , Carbón Orgánico/química , Contaminantes Químicos del Agua/química , Porosidad , Compuestos Azo/química , Bencenosulfonatos/química , Cinética , TermodinámicaRESUMEN
Fish growth and health are predominantly governed by dietary nutrient supply. Although the beneficial effects of omega-3 polyunsaturated fatty acids supplementation have been shown in a number of fish species, the underlying mechanisms are still mostly unknown. In this study, we conducted an investigation into the effects of EPA and DHA on cell proliferation, nutrient sensing signaling, and branched-chain amino acids (BCAA) transporting in primary turbot muscle cells. The findings revealed that EPA and DHA could stimulate cell proliferation, promote protein synthesis and inhibit protein degradation through activation of target of rapamycin (TOR) signaling pathway, a pivotal nutrient-sensing signaling cascade. While downregulating the expression of myogenin and myostatin, EPA and DHA increased the level of myogenic regulatory factors, such as myoD and follistatin. Furthermore, we observed a significant increase in the concentrations of intracellular BCAAs following treatment with EPA or DHA, accompanied by an upregulation of the associated amino acid transporters. Our study providing valuable insights into the mechanisms underlying the growth-promoting effects of omega-3 fatty acids in fish.
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Proliferación Celular , Ácidos Docosahexaenoicos , Ácido Eicosapentaenoico , Peces Planos , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Serina-Treonina Quinasas TOR , Animales , Ácidos Docosahexaenoicos/farmacología , Ácido Eicosapentaenoico/farmacología , Proliferación Celular/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Células Musculares/efectos de los fármacos , Células Musculares/metabolismo , Proteínas Quinasas S6 Ribosómicas/metabolismo , Proteínas de Peces/metabolismoRESUMEN
Foveal and peripheral vision are two distinct modes of visual processing essential for navigating the world. However, it remains unclear if they engage different neural mechanisms and circuits within the visual attentional system. Here, we trained macaques to perform a free-gaze visual search task using natural face and object stimuli and recorded a large number of 14588 visually responsive neurons from a broadly distributed network of brain regions involved in visual attentional processing. Foveal and peripheral units had substantially different proportions across brain regions and exhibited systematic differences in encoding visual information and visual attention. The spike-LFP coherence of foveal units was more extensively modulated by both attention and visual selectivity, thus indicating differential engagement of the attention and visual coding network compared to peripheral units. Furthermore, we delineated the interaction and coordination between foveal and peripheral processing for spatial attention and saccade selection. Finally, the search became more efficient with increasing target-induced desynchronization, and foveal and peripheral units exhibited different correlations between neural responses and search behavior. Together, the systematic differences between foveal and peripheral processing provide valuable insights into how the brain processes and integrates visual information from different regions of the visual field. Significance Statement: This study investigates the systematic differences between foveal and peripheral vision, two crucial components of visual processing essential for navigating our surroundings. By simultaneously recording from a large number of neurons in the visual attentional neural network, we revealed substantial variations in the proportion and functional characteristics of foveal and peripheral units across different brain regions. We uncovered differential modulation of functional connectivity by attention and visual selectivity, elucidated the intricate interplay between foveal and peripheral processing in spatial attention and saccade selection, and linked neural responses to search behavior. Overall, our study contributes to a deeper understanding of how the brain processes and integrates visual information for active visual behaviors.
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Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer with a low 5-year survival rate. ANKRD22 is an ankyrin repeat protein capable of promoting tumor progression, and its mechanism in LUAD remains elusive. Our study aims to investigate the mechanisms underlying the involvement of ANKRD22 in the progression of LUAD. The expression of ANKRD22 in LUAD and its enriched pathway were analyzed by bioinformatics analysis. Meanwhile, the correlation between ANKRD22 and the expression of glycolysis-related genes and M2 macrophage marker genes was analyzed. qRT-PCR was used for determination of the expression of ANKRD22, IL-10 and CCL17, CCK-8 for cell viability, and western blot for expression of ANKRD22, LDHA, HK2, PGK1, and PKM2. Immunofluorescence and flow cytometry were utilized to examine the level of CD163, and kits were used to measure the contents of pyruvic acid, lactate, citrate, and malate. Seahorse XF96 analyzer was employed to determine extracellular acidification rate (ECAR) and oxygen consumption rate (OCR). Mitochondrial membrane potential was assessed using the JC-1 probe. Bioinformatics analysis, qRT-PCR, and western blot showed that ANKRD22 was highly expressed in LUAD, which had a positive connection with M2 marker genes. Knockdown of ANKRD22 considerably attenuated the expression of ANKRD22, IL-10, and CCL17 in M2. ANKRD22 overexpression demonstrated the opposite results. Bioinformatics analysis uncovered that ANKRD22 was enriched in the glycolytic pathway and positively correlated with glycolysis-related genes. The knockdown of ANKRD22 substantially attenuated pyruvic acid, lactate, citrate, malate, and ECAR levels and elevated OCR levels in cells. The knockdown of ANKRD22 also reduced mitochondrial membrane potential. Further, it was discovered that glycolysis-related genes had a positive correlation with M2 marker genes. It was revealed by rescue experiments that the usage of 2-DG, a glycolytic inhibitor, remarkably reversed the facilitating effect of overexpression of ANKRD22 on M2 polarization. This study demonstrates that ANKRD22 can facilitate LUAD M2 polarization through glycolysis, and targeting ANKRD22 to inhibit M2 polarization has the potential to be a new strategy for LUAD treatment.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Interleucina-10 , Malatos , Ácido Pirúvico , Adenocarcinoma del Pulmón/genética , Citratos , Ácido Cítrico , Lactatos , Proliferación Celular , Línea Celular TumoralRESUMEN
Deep convolutional neural networks (CNNs) are commonly used as computational models for the primate ventral stream, while deep spiking neural networks (SNNs) incorporated with both the temporal and spatial spiking information still lack investigation. We compared performances of SNN and CNN in prediction of visual responses to the naturalistic stimuli in area V4, inferior temporal (IT), and orbitofrontal cortex (OFC). The accuracies based on SNN were significantly higher than that of CNN in prediction of temporal-dynamic trajectory and averaged firing rate of visual response in V4 and IT. The temporal dynamics were captured by SNN for neurons with diverse temporal profiles and category selectivities, and most sensitively captured around the time of peak responses for each brain region. Consistently, SNN activities showed significantly stronger correlations with IT, V4 and OFC responses. In SNN, correlations with neural activities were stronger for later time-step features than early time-step features. The temporal-dynamic prediction was also significantly improved by considering preceding neural activities during the prediction. Thus, our study demonstrated SNN as a powerful temporal-dynamic model for cortical responses to complex naturalistic stimuli.
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Goal-directed visual attention is a fundamental cognitive process that enables animals to selectively focus on specific regions of the visual field while filtering out irrelevant information. However, given the domain specificity of social behaviors, it remains unclear whether attention to faces versus non-faces recruits different neurocognitive processes. In this study, we simultaneously recorded activity from temporal and frontal nodes of the attention network while macaques performed a goal-directed visual search task. V4 and inferotemporal (IT) visual category-selective units, selected during cue presentation, discriminated fixations on targets and distractors during the search, but were differentially engaged by face and house targets. V4 and IT category-selective units also encoded fixation transitions and search dynamics. Compared to distractors, fixations on targets reduced spike-LFP coherence within the temporal cortex. Importantly, target-induced desynchronization between the temporal and prefrontal cortices was only evident for face targets, suggesting that attention to faces differentially engaged the prefrontal cortex. We further revealed bidirectional theta influence between the temporal and prefrontal cortices using Granger causality, which was again disproportionate for faces. Finally, we showed that the search became more efficient with increasing target-induced desynchronization. Together, our results suggest domain specificity for attending to faces and an intricate interplay between visual attention and social processing neural networks.
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Inflammatory bowel diseases (IBD), with an increasing incidence, pose a significant health burden. Although there have been significant advances in the treatment of IBD, more progress is still needed. Hyperbaric oxygen therapy (HBOT) has been shown to treat a host of conditions such as carbon monoxide poisoning, decompression sickness, and gas gangrene. In the last few years, there has been an increase in research into the use of HBOT as an adjunct to conventional treatment for IBD. Related research has shown that HBOT may exert its therapeutic effects by decreasing oxidative stress, inhibiting mucosal inflammation, promoting ulcer healing, influencing gut microbes, and reducing the incidence of IBD complications. This paper aims to provide a comprehensive review of experimental and clinical trials exploring HBOT as a supplement to IBD treatment strategies.
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Visual attention and object recognition are two critical cognitive functions that significantly influence our perception of the world. While these neural processes converge on the temporal cortex, the exact nature of their interactions remains largely unclear. Here, we systematically investigated the interplay between visual attention and object feature coding by training macaques to perform a free-gaze visual search task using natural face and object stimuli. With a large number of units recorded from multiple brain areas, we discovered that units exhibiting visual feature coding displayed a distinct attentional response profile and functional connectivity compared to units not exhibiting feature coding. Attention directed towards search targets enhanced the pattern separation of stimuli across brain areas, and this enhancement was more pronounced for units encoding visual features. Our findings suggest two stages of neural processing, with the early stage primarily focused on processing visual features and the late stage dedicated to processing attention. Importantly, feature coding in the early stage could predict the attentional effect in the late stage. Together, our results suggest an intricate interplay between visual feature and attention coding in the primate brain, which can be attributed to the differential functional connectivity and neural networks engaged in these processes.
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Introduction: Spiking Neural Networks (SNNs), inspired by brain science, offer low energy consumption and high biological plausibility with their event-driven nature. However, the current SNNs are still suffering from insufficient performance. Methods: Recognizing the brain's adeptness at information processing for various scenarios with complex neuronal connections within and across regions, as well as specialized neuronal architectures for specific functions, we propose a Spiking Global-Local-Fusion Transformer (SGLFormer), that significantly improves the performance of SNNs. This novel architecture enables efficient information processing on both global and local scales, by integrating transformer and convolution structures in SNNs. In addition, we uncover the problem of inaccurate gradient backpropagation caused by Maxpooling in SNNs and address it by developing a new Maxpooling module. Furthermore, we adopt spatio-temporal block (STB) in the classification head instead of global average pooling, facilitating the aggregation of spatial and temporal features. Results: SGLFormer demonstrates its superior performance on static datasets such as CIFAR10/CIFAR100, and ImageNet, as well as dynamic vision sensor (DVS) datasets including CIFAR10-DVS and DVS128-Gesture. Notably, on ImageNet, SGLFormer achieves a top-1 accuracy of 83.73% with 64 M parameters, outperforming the current SOTA directly trained SNNs by a margin of 6.66%. Discussion: With its high performance, SGLFormer can support more computer vision tasks in the future. The codes for this study can be found in https://github.com/ZhangHanN1/SGLFormer.
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Objective. Motor imagery-based brain-computer interaction (MI-BCI) is a novel method of achieving human and external environment interaction that can assist individuals with motor disorders to rehabilitate. However, individual differences limit the utility of the MI-BCI. In this study, a personalized MI prediction model based on the individual difference of event-related potential (ERP) is proposed to solve the MI individual difference.Approach.A novel paradigm named action observation-based multi-delayed matching posture task evokes ERP during a delayed matching posture task phase by retrieving picture stimuli and videos, and generates MI electroencephalogram through action observation and autonomous imagery in an action observation-based motor imagery phase. Based on the correlation between the ERP and MI, a logistic regression-based personalized MI prediction model is built to predict each individual's suitable MI action. 32 subjects conducted the MI task with or without the help of the prediction model to select the MI action. Then classification accuracy of the MI task is used to evaluate the proposed model and three traditional MI methods.Main results.The personalized MI prediction model successfully predicts suitable action among 3 sets of daily actions. Under suitable MI action, the individual's ERP amplitude and event-related desynchronization (ERD) intensity are the largest, which helps to improve the accuracy by 14.25%.Significance.The personalized MI prediction model that uses the temporal ERP features to predict the classification accuracy of MI is feasible for improving the individual's MI-BCI performance, providing a new personalized solution for the individual difference and practical BCI application.
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Interfaces Cerebro-Computador , Individualidad , Humanos , Imaginación , Potenciales Evocados , Electroencefalografía/métodosRESUMEN
Objectives: This study aimed to explore the value of radiomics nomogram based on computed tomography (CT) on the diagnosis of benign and malignant solitary indeterminate smoothly marginated solid pulmonary nodules (SMSPNs). Methods: This study retrospectively reviewed 205 cases with solitary indeterminate SMSPNs on CT, including 112 cases of benign nodules and 93 cases of malignant nodules. They were divided into training (n=143) and validation (n=62) cohorts based on different CT scanners. Radiomics features of the nodules were extracted from the lung window CT images. The variance threshold method, SelectKBest, and least absolute shrinkage and selection operator were used to select the key radiomics features to construct the rad-score. Through multivariate logistic regression analysis, a nomogram was built by combining rad-score, clinical factors, and CT features. The nomogram performance was evaluated by the area under the receiver operating characteristic curve (AUC). Results: A total of 19 radiomics features were selected to construct the rad-score, and the nomogram was constructed by the rad-score, one clinical factor (history of malignant tumor), and three CT features (including calcification, pleural retraction, and lobulation). The nomogram performed better than the radiomics model, clinical model, and experienced radiologists who specialized in thoracic radiology for nodule diagnosis. The AUC values of the nomogram were 0.942 in the training cohort and 0.933 in the validation cohort. The calibration curve and decision curve showed that the nomogram demonstrated good consistency and clinical applicability. Conclusion: The CT-based radiomics nomogram achieved high efficiency in the preoperative diagnosis of solitary indeterminate SMSPNs, and it is of great significance in guiding clinical decision-making.
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RATIONALE: Inflammatory bowel disease (IBD), including Crohn disease (CD) and ulcerative colitis (UC), is a chronic immune-mediated disorder characterized by inflammation of the gastrointestinal tract. Patients with IBD are susceptible to various complications, including the coexistence of Clostridioides difficile infection (CDI). The incidence of IBD combined with difficile infection is higher in patients with compromised immune function, which can lead to increased mortality. PATIENT CONCERNS: A 43-year-old male presented with recurrent episodes of mucus and bloody stools persisting for more than a month without any identifiable triggering factors. Initially, the stool consistency was normal, but it progressively shifted to a loose and watery texture, with up to 8 occurrences daily. DIAGNOSES: This case underscores the diagnosis of severe UC through colonoscopy and colonic biopsy, along with the supplementary identification of a positive result for Clostridioides difficile in the fecal sample. INTERVENTIONS: The patient initiated infliximab therapy alongside a full vancomycin course, demonstrating the potential effectiveness of this intervention in managing early-stage ulcerative colitis with concurrent Clostridioides difficile infection. OUTCOMES: Following the completion of a full vancomycin course, the patient initiated infliximab therapy. The patient was free from significant discomfort, exhibited no fever, and had no mucopurulent bloody stools. A follow-up blood test indicated reduced inflammatory markers compared to the preoperative period, and the stools were normal. LESSONS: We illustrate the potential effectiveness of this medication by presenting an in-depth case report of a patient with early-stage UC. The report outlines the patient inclusion of infliximab to better manage UC inflammation alongside an adjunct vancomycin regimen, given the ineffectiveness of mesalazine therapy and the concurrent presence of Clostridium difficile infection. This case prompts consideration of therapeutic approaches for complex UC and contributes to advancing both research and clinical practice. Nonetheless, we should remain attentive to the variations and potential risks unique to each patient in order to formulate personalized treatment strategies.
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Clostridioides difficile , Infecciones por Clostridium , Colitis Ulcerosa , Enfermedades Inflamatorias del Intestino , Masculino , Humanos , Adulto , Colitis Ulcerosa/tratamiento farmacológico , Vancomicina/uso terapéutico , Infliximab/uso terapéutico , Antibacterianos/uso terapéutico , Enfermedades Inflamatorias del Intestino/complicaciones , Infecciones por Clostridium/complicaciones , Infecciones por Clostridium/diagnóstico , Infecciones por Clostridium/tratamiento farmacológico , Inflamación/tratamiento farmacológicoRESUMEN
ABSTRACT: Patients with compensated advanced chronic liver disease (cACLD) can safely spared screening esophagogastroduodenoscopy (EGD) when they meet the Baveno VI criteria as assessed by transient elastography. Recently, the cutoff values of the Baveno VI criteria assessed by 2-dimensional shear wave elastography (2D-SWE) were proposed. We aimed to validate it to rule out high-risk varices (HRVs) in cACLD patients; combine spleen diameter (SPD) with the Baveno VI criteria and assess whether it can spare more screening EGD. A total of 173 cACLD patients with successful liver stiffness (LS) measurements and EGD examinations were included. We analyzed the risk factors that predicted HRVs and compared the performances of different models for ruling out HRVs. The platelet count, LS, and SPD were independent predictors of HRVs. The AUCs of platelet count, LS, spleen stiffness and SPD for diagnosing HRVs were 0.797, 0.757, 0.834, and 0.804, respectively. The Baveno VI criteria assessed by 2D-SWE spared 25.4% of EGD screenings and missed 2.4% of the HRV patients. Combining SPD ≤11.1 cm with the Baveno VI criteria could spare more EGD screenings than just applying the Baveno VI criteria (45.1% vs 25.4%, P < 0.001), and missed 4.9% of the HRV patients. The Baveno VI criteria assessed by 2D-SWE could be safely applied in cACLD patients to rule out HRV patients. The combined model Baveno VI/SPD could safely and significantly increase the rate of spared EGD.
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Diagnóstico por Imagen de Elasticidad , Várices Esofágicas y Gástricas , Bazo , Humanos , Diagnóstico por Imagen de Elasticidad/métodos , Bazo/diagnóstico por imagen , Femenino , Masculino , Persona de Mediana Edad , Várices Esofágicas y Gástricas/diagnóstico por imagen , Anciano , Tamaño de los Órganos , Estudios Retrospectivos , AdultoRESUMEN
Near-infrared (NIR) chromophores with analyte tunable emission and absorption properties are highly desirable for developing activatable fluorescence and photoacoustic (PA) probes for bioimaging and disease diagnosis. Here we engineer a class of new chromophores by extending the π-conjugation system of a xanthene scaffold at position 7 with different electron withdrawing groups. It is demonstrated that these chromophores exhibit pH-dependent transition from a spirocyclic "closed" form to a xanthene "open" form with remarkable changes in spectral properties. We further develop fluorescence and PA probes by caging the NIR xanthene chromophores with a dipeptidyl peptidase 4 (DPPIV) substrate. In vitro and live cell studies show that these probes allow activatable fluorescence and PA detection and imaging of DPPIV activity with high sensitivity, high specificity and fast response. Moreover, these two probes allow high-contrast and highly specific imaging of DPPIV activity in a tumour-bearing mouse model in vivo via systemic administration. This study highlights the potential of a xanthene scaffold as a versatile platform for developing high-contrast fluorescence and PA molecular probes.
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Effective management of fecal sludge (FS) is essential for preventing environmental and public health risks. Developing safe and efficient FS treatment technology is crucial for reducing the health risks of onsite sanitation systems. In this study, bioelectrochemical toilets (BETs) were developed to treat FS onsite. Compared with the open-circuit BETs (OC-BETs), BETs exhibited higher removal efficiencies for total organic carbon, total nitrogen, and total phosphorus. Specifically, the enhancements in removal efficiencies were 18.82 ± 1.73 %, 7.28 ± 0.32 %, and 11.41 ± 0.05 % for urine, and 19.28 ± 4.08 %, 21.65 ± 1.23 %, and 24.68 ± 0.95 % for feces, respectively. Microbiome analysis indicated that the dominant populations were affiliated with electroactive bacteria (Desulfuromonas and Pseudomonas) in the electrode biofilm of BETs. The species co-occurrence network showed that the electrode biofilm microbiome in BETs had more complex correlations than that in OC-BETs, suggesting that a weak electrical current enhanced the microbiome stability. The relative abundance of antibiotic resistance genes in BETs and OC-BETs reduced by 59.85 ± 1.32 % and 53.01 ± 2.81 % compared with the initial FS, respectively. These findings indicate that BETs are an alternative system for enhancing onsite treatment of fecal sludge and provide a theoretical foundation for the implementation of BETs.
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Heces , Microbiota , Aguas del Alcantarillado , Aguas del Alcantarillado/microbiología , Heces/microbiología , Farmacorresistencia Microbiana/genética , Eliminación de Residuos Líquidos , Biopelículas , Bacterias/genética , Bacterias/efectos de los fármacosRESUMEN
Stain variations pose a major challenge to deep learning segmentation algorithms in histopathology images. Current unsupervised domain adaptation methods show promise in improving model generalization across diverse staining appearances but demand abundant accurately labeled source domain data. This paper assumes a novel scenario, namely, unsupervised domain adaptation based segmentation task with incompletely labeled source data. This paper propose a Stain-Adaptive Segmentation Network with Incomplete Labels (SASN-IL). Specifically, the algorithm consists of two stages. The first stage is an incomplete label correction stage, involving reliable model selection and label correction to rectify false-negative regions in incomplete labels. The second stage is the unsupervised domain adaptation stage, achieving segmentation on the target domain. In this stage, we introduce an adaptive stain transformation module, which adjusts the degree of transformation based on segmentation performance. We evaluate our method on a gastric cancer dataset, demonstrating significant improvements, with a 10.01% increase in Dice coefficient compared to the baseline and competitive performance relative to existing methods.
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Algoritmos , Neoplasias Gástricas , Humanos , Coloración y Etiquetado , Procesamiento de Imagen Asistido por ComputadorRESUMEN
Cutaneous candidiasis, caused by Candida albicans, is a severe and frustrating condition, and finding effective treatments can be challenging. Therefore, the development of farnesol-loaded nanoparticles is an exciting breakthrough. Ethosomes are a novel transdermal drug delivery carrier that incorporates a certain concentration (10-45%) of alcohols into lipid vesicles, resulting in improved permeability and encapsulation rates compared to conventional liposomes. Farnesol is a quorum-sensing molecule involved in morphogenesis regulation in C. albicans, and these ethosomes offer a promising new approach to treating this common fungal infection. This study develops the formulation of farnesol-loaded ethosomes (farnesol-ethosomes) and assesses applications in treating cutaneous candidiasis induced by C. albicans in vitro and in vivo. Farnesol-ethosomes were successfully developed by ethanol injection method. Therapeutic properties of farnesol-ethosomes, such as particle size, zeta potential, and morphology, were well characterized. According to the results, farnesol-ethosomes demonstrated an increased inhibition effect on cells' growth and biofilm formation in C. albicans. In Animal infection models, treating farnesol-ethosomes by transdermal administration effectively relieved symptoms caused by cutaneous candidiasis and reduced fungal burdens in quantity. We also observed that ethosomes significantly enhanced drug delivery efficacy in vitro and in vivo. These results indicate that farnesol-ethosomes can provide future promising roles in curing cutaneous candidiasis. IMPORTANCE: Cutaneous candidiasis attributed to Candida infection is a prevalent condition that impacts individuals of all age groups. As a type of microbial community, biofilms confer benefits to host infections and mitigate the clinical effects of antifungal treatments. In C. albicans, the yeast-to-hypha transition and biofilm formation are effectively suppressed by farnesol through its modulation of multiple signaling pathway. However, the characteristics of farnesol such as hydrophobicity, volatility, degradability, and instability in various conditions can impose limitations on its effectiveness. Nanotechnology holds the potential to enhance the efficiency and utilization of this molecule. Treatment of farnesol-ethosomes by transdermal administration demonstrated a very remarkable therapeutic effect against C. albicans in infection model of cutaneous candidiasis in mice. Many patients suffering fungal skin infection will benefit from this study.