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Entamoeba histolytica, the causative agent of amebiasis, is one of the top three parasitic causes of mortality worldwide. However, no vaccine exists against amebiasis. Using a lead candidate vaccine containing the LecA fragment of Gal-lectin and GLA-3M-052 liposome adjuvant, we immunized rhesus macaques via intranasal or intramuscular routes. The vaccine elicited high-avidity functional humoral responses as seen by the inhibition of amebic attachment to mammalian target cells by plasma and stool antibodies. Importantly, antigen-specific IFN-γ-secreting peripheral blood mononuclear cells (PBMCs) and IgG/IgA memory B cells (BMEM) were detected in immunized animals. Furthermore, antigen-specific antibody and cellular responses were maintained for at least 8 months after the final immunization as observed by robust LecA-specific BMEM as well as IFN-γ+ PBMC responses. Overall, both intranasal and intramuscular immunizations elicited a durable and functional response in systemic and mucosal compartments, which supports advancing the LecA+GLA-3M-052 liposome vaccine candidate to clinical testing.
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Administración Intranasal , Anticuerpos Antiprotozoarios , Entamoeba histolytica , Entamebiasis , Interferón gamma , Leucocitos Mononucleares , Liposomas , Macaca mulatta , Vacunas Antiprotozoos , Animales , Entamoeba histolytica/inmunología , Liposomas/inmunología , Liposomas/administración & dosificación , Vacunas Antiprotozoos/inmunología , Vacunas Antiprotozoos/administración & dosificación , Anticuerpos Antiprotozoarios/sangre , Anticuerpos Antiprotozoarios/inmunología , Leucocitos Mononucleares/inmunología , Entamebiasis/prevención & control , Entamebiasis/inmunología , Interferón gamma/inmunología , Interferón gamma/metabolismo , Inyecciones Intramusculares , Inmunogenicidad Vacunal , Adyuvantes de Vacunas/administración & dosificación , Adyuvantes Inmunológicos/administración & dosificación , Linfocitos B/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Inmunoglobulina A/inmunología , Inmunoglobulina A/sangre , Antígenos de Protozoos/inmunología , Inmunidad Humoral , Memoria Inmunológica , Proteínas Protozoarias/inmunologíaRESUMEN
Globally, streptococcal disease caused by Streptococcus agalactiae is known for its high mortality rate, which severely limits the development of the tilapia breeding industry. As a third-generation vaccine, DNA vaccines have shown great application prospects in the prevention and control of aquatic diseases, but their low immunogenicity limits their development. The combination of DNA vaccines and molecular adjuvants proved to be an effective method for inducing protective immunity. This study constructed recombinant plasmids encoding tilapia HSP70 and IL-1ß genes (pcHSP70 and pcIL-1ß) to verify their effectiveness as molecular adjuvants for S. agalactiae DNA vaccine (pcSIP) in the immunized tilapia model. The results revealed that serum-specific IgM production, enzyme activities, and immune-related gene expression in tilapia immunized with pcSIP plus pcHSP70 or pcIL-1ß were significantly higher than those in tilapia immunized with pcSIP alone. It is worth noting that combination with molecular adjuvants improved the immune protection of DNA vaccines, with a relative percentage survival (RPS) of 51.72% (pcSIP plus pcHSP70) and 44.83% (pcSIP plus pcIL-1ß), respectively, compared with that of pcSIP alone (24.14%). Thus, our study indicated that HSP70 and IL-1ß in tilapia are promising molecular adjuvants of the DNA vaccine in controlling S. agalactiae infection.
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OBJECTIVE: Our study aims to prospectively compare an autologous duraplasty in situ technique (IS group) with the synthetic dural graft duraplasty (SDG group) to clarify the effectiveness and superiority of the former in the treatment of patients with Chiari malformation type 1 (CM-I). METHOD: 29 patients with CM-I were randomly assigned to either IS or SDG group. In both groups, a dissection from the occipital bone was performed. All procedures were performed by the same surgeon. The two duraplasty methods were compared in terms of surgical factors and complications. Data analysis was done for the baseline material, the neurological outcome and MRI-documented syrinx size at the 6 month follow-up. RESULT: 29 patients were enrolled in this study, 14 in the IS group and 15 in the SDG group. The results showed no significant difference in operation time (P = 0.916), amount of bleeding (P = 0.120), operation complications, hospitalization time (P = 0.854) and prognosis between the two groups. The hospitalization cost of IS group was 15,125 yuan less than that of SDG group (P < 0.05). CONCLUSION: The autogenous duraplasty in situ technique is a novel, simple, effective and economical surgical management for patients with CM-I.
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Malformación de Arnold-Chiari , Duramadre , Humanos , Malformación de Arnold-Chiari/cirugía , Malformación de Arnold-Chiari/diagnóstico por imagen , Masculino , Femenino , Adulto , Duramadre/cirugía , Duramadre/diagnóstico por imagen , Estudios Prospectivos , Persona de Mediana Edad , Resultado del Tratamiento , Adulto Joven , Trasplante Autólogo/métodos , Adolescente , Procedimientos Neuroquirúrgicos/métodos , Imagen por Resonancia MagnéticaRESUMEN
Background: Neuroinflammation is a major cause of secondary brain injury in intracerebral hemorrhage (ICH). To date, the prognostic value of YKL-40 (chitinase-3-like-1 protein), a biomarker of neuroinflammation, in cerebral amyloid angiopathy-related intracerebral hemorrhage (CAA-ICH) remains undiscovered. Objective: To evaluate the relationships between serum YKL-40 and CAA-ICH recurrence. Methods: Clinical and imaging information of 68 first-onset probable CAA-ICH cases and 95 controls were collected at baseline. Serum YKL-40 was measured by Luminex assay. Cox proportional hazards model was used to analyze the associations between YKL-40 level and CAA-ICH recurrence. Results: Serum YKL-40 level was significantly higher in CAA-ICH cases than healthy controls (median [interquartile range, IQR], 46.1 [19.8, 93.4] versus 24.4 [13.9, 59.0] ng/mL, pâ=â0.004). Higher level of YKL-40 predicted increased risk of CAA-ICH recurrence adjusted for age, ICH volume and enlarged perivascular space score (ePVS) (above versus below 115.5âng/ml, adjusted hazard ratios 4.721, 95% confidence intervals 1.829-12.189, pâ=â0.001) within a median follow-up period of 2.4 years. Adding YKL-40 to a model of only MRI imaging markers including ICH volume and ePVS score improved the discriminatory power (concordance index from 0.707 to 0.772, pâ=â0.001) and the reclassification power (net reclassification improvement 28.4%; integrated discrimination index 11.0%). Conclusions: Serum YKL-40 level might be a candidate prognostic biomarker for CAA-ICH recurrence.
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Biomarcadores , Angiopatía Amiloide Cerebral , Hemorragia Cerebral , Proteína 1 Similar a Quitinasa-3 , Recurrencia , Humanos , Proteína 1 Similar a Quitinasa-3/sangre , Masculino , Femenino , Anciano , Angiopatía Amiloide Cerebral/sangre , Angiopatía Amiloide Cerebral/complicaciones , Angiopatía Amiloide Cerebral/diagnóstico por imagen , Biomarcadores/sangre , Hemorragia Cerebral/sangre , Hemorragia Cerebral/diagnóstico por imagen , Persona de Mediana Edad , Anciano de 80 o más Años , Imagen por Resonancia MagnéticaRESUMEN
Late anti-toxin-B humoral immunity acquired after treatment is important for preventing recurrent Clostridioides difficile infection. We prospectively-measured anti-toxin-B IgG and neutralization titers at diagnosis as potential early predictors of recurrence. High anti-toxin-B-IgG/neutralizing antibodies were associated with short-lasting protection within 6-weeks, however, no difference in recurrence risk was observed by 90-days post-infection.
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Anticuerpos Antibacterianos , Toxinas Bacterianas , Clostridioides difficile , Infecciones por Clostridium , Inmunoglobulina G , Recurrencia , Infecciones por Clostridium/inmunología , Infecciones por Clostridium/prevención & control , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Toxinas Bacterianas/inmunología , Clostridioides difficile/inmunología , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Masculino , Persona de Mediana Edad , Femenino , Anciano , Proteínas Bacterianas/inmunología , Estudios Prospectivos , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Adulto , Anciano de 80 o más AñosRESUMEN
Rhabdoviruses with rich species lead a variety of high lethality and rapid transmission diseases to plants and animals around the globe. Vaccination is one of the most effective approaches to prevent and control virus disease. However, the key antigenic epitopes of glycoprotein being used for vaccine development are unclear. In this study, fish-derived Abs are employed for a Micropterus salmoides rhabdovirus (MSRV) vaccine design by phage display and bioinformatics analysis. We constructed an anti-MSRV phage Ab library to screen Abs for glycoprotein segment 2 (G2) (G129-266). Four M13-phage-displayed Abs (Ab-5, Ab-7, Ab-8 and Ab-30) exhibited strong specificity to target Ag, and Ab-7 had the highest affinity with MSRV. Ab-7 (300 µg/ml) significantly increased grass carp ovary cell viability to 83.40% and significantly decreased the titer of MSRV. Molecular docking results showed that the key region of Ag-Ab interaction was located in 10ESQEFTTLTSH20 of G2. G2Ser11 and G2Gln12 were replaced with alanine, respectively, and molecular docking results showed that the Ag-Ab was nonbinding (ΔG > 0). Then, the peptide vaccine KLH-G210-20 was immunized to M. salmoides via i.p. injection. ELISA result showed that the serum Ab potency level increased significantly (p < 0.01). More importantly, the challenge test demonstrated that the peptide vaccine elicited robust protection against MSRV invasion, and the relative percentage survival reached 62.07%. Overall, this study proposed an approach for screening key epitope by combining phage display technology and bioinformatics tools to provide a reliable theoretical reference for the prevention and control of viral diseases.
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Lubina , Rhabdoviridae , Vacunas , Animales , Femenino , Simulación del Acoplamiento Molecular , Epítopos , Glicoproteínas , Desarrollo de VacunasRESUMEN
We proposed a "Ni sacrifice" method to fabricate Al-based highly reflective p-electrode in the ultraviolet spectral region for AlGaN-based deep-ultraviolet light-emitting diodes (DUV-LEDs). The "Ni sacrifice" p-electrode could have a high optical reflectivity of around 90% at the DUV spectral region below 300â nm. Compared to Ni/Au, indium tin oxide (ITO), and Pd p-contacts, the "Ni sacrifice" led to a higher resistivity of p-contacts and a slightly higher operated voltage of the DUV-LEDs (within 0.6â V at 20â mA). Although the electrical performance was degraded slightly, the light output power and external quantum efficiency of the DUV-LEDs could be improved by utilizing the "Ni sacrifice" p-electrode. Besides, we introduced a grid of vias in the device mesa and reduced the diameter of the vias to achieve an enhanced peak external quantum efficiency (EQE) up to 1.73%. And the wall-plug efficiency (WPE) of DUV-LEDs with a "Ni sacrifice" p-electrode was higher than that of Ni/Au p-electrode DUV-LEDs at low currents. These results highlight the great potential of the proposed "Ni sacrifice" reflective p-electrode for use in DUV-LEDs.
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Epigenetic reader Bromodomain protein 4 (BrD4) functions as a global genomic regulator to direct hepatic stellate cell (HSC) activation (a key step in liver fibrogenesis) and liver fibrosis. The pivotal pro-fibrotic cytokine transforming growth factor-ß1 (TGFß1) signals through both Smad and Stat3 to elicit a wide array of biological effects. Stat3 is widely acknowledged as a regulator of gene transcription and is involved in fibrosis of multiple tissues. The present study focused on BrD4 function implication in the roles of TGFß1-induced Stat3 signaling in HSC activation and liver fibrosis by using heterozygous TGFß1 knockout mice and HSC culture. Results showed that Stat3 was required for TGFß1-induced BrD4 expression in HSCs. BrD4 expression paralleled Stat3 activation in activated HSCs in human cirrhotic livers. BrD4 was involved in the roles of TGFß1-induced Stat3 in HSC activation and liver fibrogenesis. Smad3 bound to phosphorylated-Stat3 and contributed to TGFß1-induced Stat3 signaling. BrD4 expression induced by Stat3 signaling required the early-immediate gene Egr1. Egr1 had a positive feedback on Stat3 activation. In conclusion, a network consisting of Stat3 signaling, Smad3 signaling, Egr1, and BrD4 was involved in the effects of TGFß1 on liver fibrosis, providing new toxicological mechanisms for TGFß1 in liver fibrogenesis.
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Proteínas Nucleares , Factor de Crecimiento Transformador beta1 , Humanos , Animales , Ratones , Citocinas , Cirrosis Hepática/inducido químicamenteRESUMEN
Graph Convolutional Network (GCN) excels at EEG recognition by capturing brain connections, but previous studies neglect the important EEG feature itself. In this study, we propose MSFR-GCN, a multi-scale feature reconstruction GCN for recognizing emotion and cognition tasks. Specifically, MSFR-GCN includes the MSFR and feature-pool characteristically, with the MSFR consisting of two sub-modules, multi-scale Squeeze-and-Excitation (MSSE) and multi-scale sample re-weighting (MSSR). MSSE assigns weights to channels and frequency bands based on their separate statistical information, while MSSR assigns sample weights based on combined channel and frequency information. The feature-pool, which pools across the feature dimension, is applied after GCN to retain EEG channel information. The MSFR-GCN achieves excellent results in emotion recognition when first tested on two public datasets, SEED and SEED-IV. Than the MSFR-GCN is tested on our self-collected Emotion and Cognition EEG dataset (ECED) for both emotion and cognition classification tasks. The results show MSFR-GCN's good performance in emotion and cognition classification tasks and reveal the implicit relationship between the two, which may provide aid in the rehabilitation of people with cognitive impairments from an emotional perspective.
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Encéfalo , Cognición , Humanos , Emociones , Reconocimiento en Psicología , ElectroencefalografíaRESUMEN
Liver fibrosis is characterized by the excessive deposition of extracellular matrix in liver. Chronic liver injury induces the activation of hepatic stellate cell (HSCs), a key step in liver fibrogenesis. The activated HSC is the primary source of ECM and contributes significantly to liver fibrosis. TGFß1 is the most potent pro-fibrotic cytokine. Bromodomain protein 4 (BrD4), an epigenetic reader of histone acetylation marks, was crucial for profibrotic gene expression in HSCs. The present study aimed to investigate the roles of BRD4 in TGFß1-dependent HSC activation and liver fibrosis, focusing on TGFß1-induced alterations of the levels of the fibrotic-related important proteins in HSCs by employing the heterozygous TGFß1 knockout mice and BrD4 knockdown in vivo and in vitro. Results revealed that BrD4 protein level was significantly upregulated by TGFß1 and BrD4 knockdown reduced TGFß1-induced HSC activation and liver fibrosis. BrD4 was required for the influences of TGFß1 on PDGFß receptor and on the pathways of Smad3, Stat3, and Akt. BrD4 also mediated TGFß1-induced increases in histone acetyltransferase p300, the pivotal pro-inflammatory NFkB p65, and tissue inhibitor of metalloproteinase 1 whereas BrD4 reduced Caspase-3 protein levels in HSCs during liver injury, independent of TGFß1. Further experiments indicated the interaction between TGFß1-induced BrD4 and NFkB p65 in HSCs and in liver of TAA-induced liver injury. Human cirrhotic livers were demonstrated a parallel increase in the protein levels of BrD4 and NFkB p65 in HSCs. This study revealed that BrD4 was a key molecular driver of TGFß1-induced HSC activation and liver fibrosis.
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Células Estrelladas Hepáticas , Factores de Transcripción , Humanos , Animales , Ratones , Factores de Transcripción/genética , Proteínas Nucleares/genética , Inhibidor Tisular de Metaloproteinasa-1 , Cirrosis Hepática/genética , Proteínas de Ciclo Celular/genéticaRESUMEN
Obese patients usually have hyperleptinemia and are prone to develop liver fibrosis. Leptin is intimately linked to liver fibrogenesis, a multi-receptor-driven disease. Gα-Interacting Vesicle-associated protein (GIV) functions as a multimodular signal transducer and a guanine nucleotide exchange factor for Gi controling key signalings downstream of diverse receptors. This study aimed to examine the roles of GIV in leptin-caused liver fibrosis and employed the culture-activated hepatic stellate cells (HSCs) and leptin-deficient mice, respectively. Results indicated that leptin upregulated GIV expression in HSCs. GIV was involved in leptin-induced HSC activation and liver fibrosis. GIV mediated leptin regulation of TIMP1, MMP9, PDGFß receptor and TGFß receptor and was required for leptin stimulating the pathways of Erk1/2, Akt1, and Smad3. GIV was also a mediator for leptin-regulation of Cyclin D1 and Caspase-3 activity but GIV reduced Caspase-3 level independently of leptin in vivo. Erk1/2 signaling, Egr1 and c-Jun were associated with the effect of leptin on GIV expression in HSCs. Leptin-induced Erk1/2 signaling increased Egr1 and p-c-Jun levels and promoted their binding to GIV promoter at the sites between -190 bp and -180 bp and between -382 bp and - 376 bp, respectively. Egr1 knockdown lessened leptin-upregulation of GIV in vitro and in vivo. In human cirrhotic livers, the increase in GIV protein level parallelled with the elevated p-Erk1/2 and Egr1 levels in HSCs. In summary, the unusual signal transducer GIV was identified as an important mediator in leptin-induced liver fibrosis. GIV may have significant implications in liver fibrosis progression of obese patients with hyperleptinaemia.
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Leptina , Cirrosis Hepática , Proteínas de Microfilamentos , Proteínas de Transporte Vesicular , Animales , Humanos , Ratones , Proteínas Portadoras , Caspasa 3/metabolismo , Leptina/genética , Leptina/metabolismo , Cirrosis Hepática/metabolismo , Obesidad , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/metabolismo , Proteínas de Microfilamentos/genética , Proteínas de Microfilamentos/metabolismoRESUMEN
INTRODUCTION: Sepsis is characterized by an endotoxin tolerance phenotype that occurs in the stage of infection. Persistent bacterial infection can lead to immune cell exhaustion. Triad3A, an E3 ubiquitin ligase, negatively regulates its activation by TLR4. However, the effect of Triad3A on endotoxin tolerance and bactericidal ability in the state of endotoxin tolerance remains unclear. METHODS: Using single dose LPS and repeated LPS stimulated macrophage cell lines at indicated times, we investigated miR-191, Tirad3A, TRAF3, TLR4, p-P65, TNF-α, IL-1ß, and iNOS expression, the effect of miR-191 on Triad3A and TRAF3, gene loss-of-function analyses, the effect of Triad3A on TLR4, p-P65, cytokine, and mycobactericidal activity in endotoxin tolerant cells infected with Mycobacterium marinum. RESULTS: Here we found that Triad3A is involved in regulating endotoxin tolerance. Our result also displayed that miR-191 expression is downregulated in macrophages in the state of endotoxin tolerance. miR-191 can directly bind to Triad3A and TRAF3. Additionally, knockdown of Triad3A can reverse the effect of decreasing TNF-α and IL-1ß in endotoxin tolerant macrophages. Furthermore, we demonstrated that the TLR4-NF-κB-NO pathway was associated with Triad3A and responsible for the killing of intracellular mycobacteria in a tuberculosis sepsis model. CONCLUSIONS: These results provide new insight into the mechanisms of Triad3A induced tolerogenic phenotype in macrophages, which can help the better comprehension of the pathogenesis involved in septic shock with infection of Mycobacterium tuberculosis, and suggest that Triad3A may be a potential drug target for the treatment of severe septic tuberculosis.
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MicroARNs , Sepsis , Humanos , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Lipopolisacáridos/farmacología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Tolerancia a Endotoxinas , Factor 3 Asociado a Receptor de TNF/genética , Factor 3 Asociado a Receptor de TNF/metabolismo , Endotoxinas , MicroARNs/genéticaRESUMEN
Based on the mining of micro- and macro-relationships of genetic variation and brain imaging data, imaging genetics has been widely applied in the early diagnosis of Alzheimer's disease (AD). However, effective integration of prior knowledge remains a barrier to determining the biological mechanism of AD. This paper proposes a new connectivity-based orthogonal sparse joint non-negative matrix factorization (OSJNMF-C) method based on integrating the structural magnetic resonance image, single nucleotide polymorphism and gene expression data of AD patients; the correlation information, sparseness, orthogonal constraint and brain connectivity information between the brain image data and genetic data are designed as constraints in the proposed algorithm, which efficiently improved the accuracy and convergence through multiple iterative experiments. Compared with the competitive algorithm, OSJNMF-C has significantly smaller related errors and objective function values than the competitive algorithm, showing its good anti-noise performance. From the biological point of view, we have identified some biomarkers and statistically significant relationship pairs of AD/mild cognitive impairment (MCI), such as rs75277622 and BCL7A, which may affect the function and structure of multiple brain regions. These findings will promote the prediction of AD/MCI.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Enfermedad de Alzheimer/patología , Encéfalo/patología , Imagen por Resonancia Magnética/métodos , Algoritmos , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/patologíaRESUMEN
Human T cells and natural killer (NK) cells are major effector cells of innate immunity exerting potential immune surveillance against tuberculosis infection. CD226 is an activating receptor playing vital roles in the functions of T cells and NK cells during HIV infection and tumorigenesis. However, CD226 is a less-studied activating receptor during Mycobacterium tuberculosis (Mtb) infection. In this study, we used peripheral blood from tuberculosis patients and healthy donors to evaluate CD226 immunoregulation functions from two independent cohorts using Flow cytometry. Here, we found that a subset of T cells and NK cells that constitutively express CD226 exhibit a distinct phenotype in TB patients. In fact, the proportions of CD226+ and CD226- cell subsets differ between healthy people and tuberculosis patients, and the expression of immune checkpoint molecules (TIGIT, NKG2A) and adhesion molecules (CD2, CD11a) in CD226+ and CD226- subsets of T cells and NK cells exhibits special regulatory roles. Furthermore, CD226+ subsets produced more IFN-γ and CD107a than CD226- subsets in tuberculosis patients. Our results imply that CD226 may be a potential predictor of disease progression and clinical efficacy in tuberculosis by mediating the cytotoxic capacity of T cells and NK cells.
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Antineoplásicos , Infecciones por VIH , Tuberculosis , Humanos , Antígenos de Diferenciación de Linfocitos T/metabolismo , Antineoplásicos/metabolismo , Moléculas de Adhesión Celular/metabolismo , Células Asesinas Naturales , Linfocitos T/metabolismo , Regulación hacia ArribaRESUMEN
Upon chronic damage to the liver, multiple cytokines stimulate hepatic stellate cells (HSCs), causing the alterations of gene expression profiles and thus leading to HSC activation, a key step in liver fibrogenesis. Activated HSCs are the dominant contributors to liver fibrosis. Bromodomain containing protein 4 (BrD4), an important epigenetic reader, was demonstrated to concentrate on hundreds of enhancers associated with genes involved in multiple profibrotic pathways, thereby directing HSC activation and the fibrotic responses. The present studies were designed to examine the effect of transforming growth factor beta-1 (TGFß1), the most potent pro-fibrotic cytokine, on BrD4 expression in HSCs and, if so, elucidated the underlying mechanisms in vitro and in vivo. The experiments employed the heterogeneous TGFß1 knockout (TGFß1+/- ) mice, gene knockdown in vivo, and a model of thioacetamide (TAA)-induced liver injury. The results revealed that TGFß1 enhanced BrD4 expression in HSCs, which was mediated, at least, by Smad3 signaling and early-immediate gene Egr1 (early growth response-1). TGFß1-induced Smad3 signaling increased Egr1 expression and promoted Egr1 binding to BrD4 promoter at a site around -111 bp, promoting BrD4 expression. Egr1 knockdown reduced BrD4 expression in HSCs in a mouse model of TAA-induced liver injury and lessened liver fibrosis. Double fluorescence staining demonstrated a strong increase in BrD4 expression in activated HSCs in fibrotic areas of the human livers, paralleling the upregulation of p-Smad3 and Egr1. This research suggested novel molecular events underlying the roles of the master pro-fibrotic cytokine TGFß1 in HSC activation and liver fibrogenesis.
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Enfermedad Hepática Crónica Inducida por Sustancias y Drogas , Proteína 1 de la Respuesta de Crecimiento Precoz , Células Estrelladas Hepáticas , Proteínas Nucleares , Factores de Transcripción , Animales , Humanos , Ratones , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/metabolismo , Proteína 1 de la Respuesta de Crecimiento Precoz/genética , Proteína 1 de la Respuesta de Crecimiento Precoz/metabolismo , Epigénesis Genética , Fibrosis , Células Estrelladas Hepáticas/metabolismo , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/genética , Cirrosis Hepática/metabolismo , Proteínas Nucleares/metabolismo , Proteína smad3/genética , Proteína smad3/metabolismo , Tioacetamida/efectos adversos , Factores de Transcripción/metabolismo , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
As aging deepens, early detection of mild cognitive impairment (MCI) is increasingly important to prevent Alzheimer Dementia (AD) and improve the quality of life of older adults. In recent years, a large number of studies focus on the abnormal brain cognitive function of MCI, while ignoring the quantitative evaluation of MCI's mental workload. In this study, we propose a workload index for MCI screening, named EMCI, which is a linear discriminant cumulative estimate of subjects' electroencephalography (EEG) power spectra in α and ß rhythms. Then, we design a matched prototype system to verify the effectiveness of EMCI. The results show that the EMCI is sensitive to changes of subjects' mental workload, and is significantly lower in MCI than in HC (Health control), which may be precisely caused by cognitive dysfunction. The proposed EMCI index can be used for online assessment of mental workload in older adults, which can help achieve quick screening of MCI and provide a critical window for clinical treatment interventions.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Anciano , Calidad de Vida , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/psicología , Electroencefalografía/métodos , Enfermedad de Alzheimer/diagnóstico , EncéfaloRESUMEN
The disease caused by Micropterus salmoides rhabdovirus (MSRV) has brought substantial economic losses to the largemouth bass aquaculture industry in China. Vaccination was considered as a potential way to prevent and control this disease. As a kind of sustained and controlled release system, alginate and chitosan microspheres (SA-CS) are widely used in the development of oral vaccination for fish. Here, we prepared a king of alginate-chitosan composite microsphere to encapsulate the second segment of MSRV glycoprotein (G2 protein) and then evaluated the immune effect of the microsphere vaccine on largemouth bass. Largemouth bass were vaccinated via intragastric immunization by different treatments (PBS, SA-CS, G2 and SA-CS-G2). The results showed that a stronger immune response including serum antibody levels, immune-related physiological indexes (acid phosphatase, alkaline phosphatase, superoxide dismutase and total antioxidant capacity) and the expression of immune-related gene (IgMãIL-8ãIL-1ßãCD4ãTGF-ßãTNF-α) can be induced obviously with SA-CS-G2 groups compared with G2 groups when fish were vaccinated. Furthermore, fish were injected with a lethal dose of MSRV after immunization for 28 days, and the highest relative percentage survival (54.8%) was observed in SA-CS-G2 group (40 µg per fish), which is significantly higher than that of G2 group (25.8%). This study showed that alginate-chitosan microspheres as the vaccine carrier can effectively improve the immune effect of oral vaccination and induce better immune protection effect against MSRV infection.
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Lubina , Quitosano , Enfermedades de los Peces , Rhabdoviridae , Fosfatasa Ácida , Alginatos , Fosfatasa Alcalina , Animales , Antioxidantes , Preparaciones de Acción Retardada , Inmunoglobulina M , Interleucina-8 , Microesferas , Superóxido Dismutasa , Factor de Crecimiento Transformador beta , Factor de Necrosis Tumoral alfa , Vacunas de Subunidad , Vacunas SintéticasRESUMEN
Mass concentration is a commonly used but insufficient metric to evaluate the particulate matter (PM) exposure hazard. Recent studies have declared that small particles have more serious impacts on human health than big particles given the same mass concentration. However, state-of-the-art PM sensors cannot provide explicit information of the particle size for further analysis. In this work, we adopt Sauter mean diameter (SMD) as a key metric to reflect the particle size besides the mass concentration. To measure SMD, an effective optical sensing method and a proof-of-concept prototype sensor are proposed by using dual wavelengths technology. In the proposed method, a non-linear conversion model is developed to improve the SMD measurement accuracy for aerosol samples of different particle size distributions and reflective indices based on multiple scattering channels. In the experiment of Di-Ethyl-Hexyl-Sebacate (DEHS) aerosols, the outputs of our prototype sensor demonstrated a good agreement with existing laboratory reference instruments with maximum SMD measurement error down to 7.04%. Furthermore, the simplicity, feasibility and low-cost features of this new method present great potential for distributed PM monitoring, to support sophisticated human exposure hazard assessment.
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Contaminantes Atmosféricos , Material Particulado , Aerosoles/análisis , Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente/métodos , Humanos , Tamaño de la Partícula , Material Particulado/análisisRESUMEN
Electroencephalogram (EEG)-based tools for brain functional connectivity (FC) analysis and visualization play an important role in evaluating brain cognitive function. However, existing similar FC analysis tools are not only visualized in 2 dimensions (2D) but also are highly prone to cause visual clutter and unable to dynamically reflect brain connectivity changes over time. Therefore, we design and implement an EEG-based FC visualization framework in this study, named EEG-FCV, for brain cognitive state evaluation. EEG-FCV is composed of three parts: the Data Processing module, Connectivity Analysis module, and Visualization module. Specially, FC is visualized in 3 dimensions (3D) by introducing three existing metrics: Pearson Correlation Coefficient (PCC), Coherence, and PLV. Furthermore, a novel metric named Comprehensive is proposed to solve the problem of visual clutter. EEG-FCV can also visualize dynamically brain FC changes over time. Experimental results on two available datasets show that EEG-FCV has not only results consistent with existing related studies on brain FC but also can reflect dynamically brain FC changes over time. We believe EEG-FCV could prompt further progress in brain cognitive function evaluation.