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Atherosclerosis (AS) is chronic pathological process based on the inflammatory reaction associated with factors including vascular endothelial dysfunction, inflammation, and autoimmunity. Inflammasomes are known to be at the core of the inflammatory response. As a pattern recognition receptor of innate immunity, the NLRP3 inflammasome mediates the secretion of inflammatory factors by activating the Caspase-1, which is important for maintaining the immune system and regulating the gut microbiome, and participates in the occurrence and development of AS. The intestinal microecology is composed of a large number of complex structures of gut microbiota and its metabolites, which play an important role in AS. The gut microbiota and its metabolites regulate the activation of the NLRP3 inflammasome. Targeting the NLRP3 inflammasome and regulating intestinal microecology represent a new direction for the treatment of AS. This paper systematically reviews the interaction between the NLRP3 inflammasome and gut microbiome in AS, strategies for targeting the NLRP3 inflammasome and gut microbiome for the treatment of AS, and provides new ideas for the research and development of drugs for the treatment of AS.
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Aterosclerosis , Microbioma Gastrointestinal , Microbioma Gastrointestinal/fisiología , Humanos , Inflamasomas , Inflamación/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLRRESUMEN
Metastasis-associated protein 2 (MTA2) is frequently amplified in many types of cancers; however, the role and underlying molecular mechanism of MTA2 in esophageal squamous cell carcinoma (ESCC) remain unknown. Here, we reported that MTA2 is highly expressed in ESCC tissue and cells, and is closely related to the malignant characteristics and poor prognosis of patients with ESCC. Through in vitro and in vivo experiments, we demonstrated that MTA2 significantly promoted ESCC growth, metastasis, and epithelial-mesenchymal transition (EMT) progression. This integrative analysis combined with expression microarray showed that MTA2 could interact with eukaryotic initiation factor 4E (EIF4E), which positively regulates the expression of Twist, known as a master regulator of EMT. Moreover, the results of chromatin immunoprecipitation revealed that MTA2 was recruited to the E-cadherin promoter by Twist, which reduced the acetylation level of the promoter region and thus inhibited expression of E-cadherin, and subsequently promoted the aggressive progression of ESCC. Collectively, our study provided novel evidence that MTA2 plays an aggressive role in ESCC metastasis by a novel EIF4E-Twist positive feedback loop, which may provide a potential therapeutic target for the management of ESCC.
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Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas de Esófago/genética , Factor 4E Eucariótico de Iniciación/metabolismo , Histona Desacetilasas/metabolismo , Proteínas Nucleares/genética , Proteínas Represoras/metabolismo , Proteína 1 Relacionada con Twist/genética , Animales , Antígenos CD/genética , Cadherinas/genética , Línea Celular Tumoral , Transición Epitelial-Mesenquimal/genética , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/cirugía , Carcinoma de Células Escamosas de Esófago/mortalidad , Carcinoma de Células Escamosas de Esófago/secundario , Carcinoma de Células Escamosas de Esófago/cirugía , Esofagectomía , Esófago/patología , Esófago/cirugía , Factor 4E Eucariótico de Iniciación/genética , Retroalimentación Fisiológica , Femenino , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Histona Desacetilasas/genética , Humanos , Estimación de Kaplan-Meier , Masculino , Ratones , Persona de Mediana Edad , Proteínas Nucleares/metabolismo , Pronóstico , Regiones Promotoras Genéticas , Proteínas Represoras/genética , Proteína 1 Relacionada con Twist/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The production of intense isolated attosecond pulse is a major goal in ultrafast research. Recent advances in high harmonic generation from relativistic plasma mirrors under oblique incidence interactions gave rise to photon-rich attosecond pulses with circular or elliptical polarization. However, to achieve an isolated elliptical attosecond pulse via polarization gating using currently available long driving pulses remains a challenge, because polarization gating of high harmonics from relativistic plasmas is assumed only possible at normal or near-normal incidence. Here we numerically demonstrate a scheme around this problem. We show that via control of plasma dynamics by managing laser polarization, it is possible to gate an intense single attosecond pulse with high ellipticity extending to the soft X-ray regime at oblique incidence. This approach thus paves the way towards a powerful tool enabling high-time-resolution probe of dynamics of chiral systems and magnetic materials with current laser technology.
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For graphene/ferroelectric hybrid structures, the atomistic and electronic details of the interfaces are of crucial importance for charge doping in graphene. In this paper, we choose thermodynamically stable BiFeO3(0001) surfaces to explore the adsorption behavior and charge doping effect in a graphene/BiFeO3 system. By performing first-principles calculations, we find that both the adsorption behavior and charge doping effect show distinct characteristics for graphene adsorbed on the oppositely polarized BiFeO3(0001) surfaces. We predict that n-type doping and p-type charge doping occur in graphene on the positive and negative BiFeO3(0001) surfaces, respectively. The carrier density is estimated to be 1013 cm-2 orders of magnitude. Our results reveal that the graphene/BiFeO3 hybrid system is an intriguing candidate to make graphene-based field-effect transistors, whose p-n junctions can be made by patterning the domain structure of the BiFeO3 substrate. Moreover, the graphene/BFO hybrid structure may display an outstanding photovoltaic effect due to the combination of the bulk photovoltaic effect of the BFO substrate and the optical transparency of the graphene electrode.
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An efficient, sustainable organocatalyst, glycine betaine, was developed for the reductive functionalization of CO2 with amines and diphenylsilane. Methylamines and formamides were obtained in high yield by tuning the CO2 pressure and reaction temperature. Based on identification of the key intermediate, that is, the aminal, an alternative mechanism for methylation involving the C0 silyl acetal and aminal is proposed. Furthermore, reducing the CO2 amount afforded aminals with high yield and selectivity. Therefore, betaine catalysis affords products with a diversified energy content that is, formamides, aminals and methylamines, by hierarchical two-, four- and six-electron reduction, respectively, of CO2 coupled with C-N bond formation.
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A new scheme to generate an intense isolated few-cycle attosecond XUV pulse is demonstrated using particle-in-cell simulations. By use of unipolarlike or subcycle laser pulses irradiating a thin foil target, a strong transverse net current can be excited, which emits a few-cycle XUV pulse from the target rear side. The isolated pulse is ultrashort in the time domain with duration of several hundred attoseconds. The pulse also has a narrow bandwidth in the spectral domain compared to other XUV sources of high-order harmonics. It has most energy confined around the plasma frequency and no low-harmonic orders below the plasma frequency. It is also shown that XUV pulse of peak field strength up to 8 × 10(12) Vm(-1) can be produced. Without the need for pulse selecting and spectral filtering, such an intense few-cycle XUV pulse is better suited to a number of applications.
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This study addresses the longstanding absence of a comprehensive phylogenetic backbone for the apple tribe Maleae, a deficiency attributed to limited taxon and marker sampling. We conducted an extensive taxon sampling, incorporating 563 plastomes from a diverse range of 370 species encompassing 26 presently recognized genera. Employing a range of phylogenetic inference methods, including RAxML and IQ-TREE2 for Maximum Likelihood (ML) analyses, we established a robust phylogenetic framework for the Maleae tribe. Our phylogenomic investigations provided compelling support for three major clades within Maleae. By integrating nuclear phylogenetic data with morphological and chromosomal evidence, we propose an updated infra-tribal taxonomic system, comprising subtribe Malinae Reveal, subtribe Lindleyinae Reveal, and subtribe Vauqueliniinae B.B.Liu (subtr. nov.). Plastid phylogenetic analysis also confirmed the monophyly of most genera, except for Amelanchier, Malus, Sorbus sensu lato, and Stranvaesia. In addition, we present a comprehensive taxonomic synopsis of Photinia and its morphological allies in the Old World, recognizing 27 species and ten varieties within Photinia, three species and two varieties within Stranvaesia, and two species and three varieties within Weniomeles. Furthermore, we also lectotypified 12 names and made two new combinations, Photiniamicrophylla (J.E.Vidal) B.B.Liu and Weniomelesatropurpurea (P.L.Chiu ex Z.H.Chen & X.F.Jin) B.B.Liu.
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Diabetes, a prevalent chronic condition, significantly increases the risk of mortality from COVID-19, yet the underlying mechanisms remain elusive. Emerging evidence implicates Cathepsin L (CTSL) in diabetic complications, including nephropathy and retinopathy. Our previous research identified CTSL as a pivotal protease promoting SARS-CoV-2 infection. Here, we demonstrate elevated blood CTSL levels in individuals with diabetes, facilitating SARS-CoV-2 infection. Chronic hyperglycemia correlates positively with CTSL concentration and activity in diabetic patients, while acute hyperglycemia augments CTSL activity in healthy individuals. In vitro studies reveal high glucose, but not insulin, promotes SARS-CoV-2 infection in wild-type cells, with CTSL knockout cells displaying reduced susceptibility. Utilizing lung tissue samples from diabetic and non-diabetic patients, alongside Leprdb/dbmice and Leprdb/+mice, we illustrate increased CTSL activity in both humans and mice under diabetic conditions. Mechanistically, high glucose levels promote CTSL maturation and translocation from the endoplasmic reticulum (ER) to the lysosome via the ER-Golgi-lysosome axis. Our findings underscore the pivotal role of hyperglycemia-induced CTSL maturation in diabetic comorbidities and complications.
People with diabetes are at greater risk of developing severe COVID-19 and dying from the illness, which is caused by a virus known as SARS-CoV-2. The high blood sugar levels associated with diabetes appear to be a contributing factor to this heightened risk. However, diabetes is a complex condition encompassing a range of metabolic disorders, and it is therefore likely that other factors may contribute. Previous research identified a link between an enzyme called cathepsin L and more severe COVID-19 in people with diabetes. Elevated cathepsin L levels are known to contribute to diabetes complications, such as kidney damage and vision loss. It has also been shown that cathepsin L helps SARS-CoV-2 to enter and infect cells. This raised the question of whether elevated cathepsin L is responsible for the increased COVID-19 vulnerability in patients with diabetes. To investigate, He, Zhao et al. monitored disease severity and cathepsin L levels in patients with COVID-19. This confirmed that people with diabetes had more severe COVID-19 and that higher levels of cathepsin L are linked to more severe disease. Analysis also revealed that cathepsin L activity increases as blood glucose levels increase. In laboratory experiments, cells exposed to glucose or fluid from the blood of people with diabetes were more easily infected with SARS-CoV-2, with cells genetically modified to lack cathepsin L being more resistant to infection. Further experiments revealed this was due to glucose promoting maturation and migration of cathepsin L in the cells. The findings of He, Zhao et al. help to explain why people with diabetes are more likely to develop severe or fatal COVID-19. Therefore, controlling blood glucose levels in people with diabetes may help to prevent or reduce the severity of the disease. Additionally, therapies targeting cathepsin L could also potentially help to treat COVID-19, especially in patients with diabetes, although more research is needed to develop and test these treatments.
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COVID-19 , Catepsina L , Hiperglucemia , SARS-CoV-2 , COVID-19/mortalidad , COVID-19/metabolismo , Catepsina L/metabolismo , Catepsina L/genética , Humanos , Animales , Ratones , SARS-CoV-2/genética , Masculino , Femenino , Complicaciones de la Diabetes , Persona de Mediana Edad , Comorbilidad , Diabetes Mellitus , Retículo Endoplásmico/metabolismo , Lisosomas/metabolismo , Adulto , Anciano , Aparato de Golgi/metabolismoRESUMEN
OBJECTIVE: To observe the effect of Biantie (bian stone plaste) pretreatment on serum level of prolyl hydroxylase domain 2 (PHD2) and hypoxia-inducible factor-1α (HIF-1α) in rats with acute hypobaric hypoxia induced-brain injury, and to explore the possible mechanism of Biantie on preventing brain injury at high altitude. METHODS: Forty-five male SD rats were randomly divided into a blank group, a model group, a Biantie group, a medication group and a Biantie+inhibitor group, 9 rats in each group. The rats in the Biantie group the and the Biantie+inhibitor group were pretreated with Biantie at "Taiyuan" (LU 9), "Neiguan" (PC 6) and "Renying" (ST 9), 2 h each time, once a day; the rats in the medication group were treated with intragastric administration of rhodiola capsule solution (280 mg/kg) for 14 d; the rats in the Biantie+inhibitor group were intraperitoneally injected with the PHD inhibitor dimethyloxalyl glycine (DMOG) at a dose of 40 mg/kg 24 h before the establishment of the model. After the intervention, except for the blank group, the rats in the remaining 4 groups were placed in the oxygen chamber to simulate a high-altitude environment to establish the acute hypobaric hypoxia brain injury model. The arterial blood-gas analysis indexes [blood oxygen saturation (SaO2), lactic acid (Lac), blood sodium (Na+), blood potassium (K+)] and brain water content were detected in each group; the histomorphology of cerebral cortex was observed by HE staining; the serum levels of PHD2 and HIF-1α as well as vascular endothelial growth factor (VEGF) were detected by ELISA; the VEGF protein expression in brain tissue was detected by Western blot; the VEGF mRNA expression in brain tissue was detected by real-time fluorescent quantitative PCR. RESULTS: Compared with the blank group, the levels of SaO2 and Na+ in the model group were decreased (P<0.05), while the levels of Lac and K+ as well as the water content of brain tissue were increased (P<0.05). Compared with the model group, the level of SaO2 in the Biantie group and the medication group was increased (P<0.05), while the levels of Lac, K+ and the water content of brain tissue were decreased (P<0.05); the level of Na+ in the Biantie group was increased (P<0.05). Compared with the Biantie group, the level of SaO2 in the Biantie+inhibitor group was decreased (P<0.05), and the level of Lac and the water content of brain tissue were increased (P<0.05). In the model group, the cortical tissue cells were loose and disordered, the cortical blood vessels were dilated, and the cells were obviously swollen; the anoxic injury in the Biantie group and the medication group was lighter, and the anoxic injury in the Biantie+inhibitor group was more obvious than that in the Biantie group. Compared with the blank group, the serum PHD2 content in the model group was decreased and the HIF-1α content was increased (P<0.05), and the content of VEGF in serum and VEGF protein and mRNA expressions in brain were increased (P<0.05). Compared with the model group, the content of PHD2 in serum in the Biantie group and the medication group was increased (P<0.05), and the level of HIF-1α was decreased (P<0.05), and the content of VEGF in serum as well as VEGF protein and mRNA expressions in brain were decreased (P<0.05). Compared with the Biantie group, the serum PHD2 content in the Biantie+inhibitor group was decreased and HIF-1α level were increased (P<0.05), and the content of VEGF in serum as well as VEGF mRNA expression in brain were increased (P<0.05). CONCLUSION: Biantie at "Taiyuan" (LU 9), "Neiguan" (PC 6) and "Renying" (ST 9) could regulate serum PHD2/HIF-1α to down-regulate VEGF expression, reduce brain edema and enhance anti-hypoxia ability, so as to achieve the purpose of preventing brain injury at high altitude.
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Lesiones Encefálicas , Prolil Hidroxilasas , Animales , Ratas , Masculino , Prolil Hidroxilasas/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Ratas Sprague-Dawley , Procolágeno-Prolina Dioxigenasa/genética , Procolágeno-Prolina Dioxigenasa/metabolismo , Encéfalo/metabolismo , ARN Mensajero , AguaRESUMEN
PURPOSE: Age-related macular degeneration (AMD) is the commonest cause of permanent vision loss in the elderly. Traditional Chinese medicine (TCM) has long been used to treat AMD, although the underlying functional mechanisms are not understood. This study aims to predict the active ingredients through screening the chemical ingredients of anti-AMD decoction and to elucidate the underlying mechanisms. METHODS: We collected the prescriptions for effective AMD treatment with traditional Chinese medicine and screened several Chinese medicines that were used most frequently in order to compose "anti-AMD decoction." The pharmacologically active ingredients and corresponding targets in this anti-AMD decoction were mined using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Subsequently, the AMD-related targets were identified through the GeneCards database. Network pharmacology was performed to construct the visual network of anti-AMD decoction-AMD protein-protein interaction (PPI). Further, the Autodock software was adopted for molecular docking on the core active ingredients and core targets. The function of core ingredients against oxidative stress and inflammation in retinal pigment epithelial cells was assessed using biochemical assays. RESULTS: We screened out 268 active ingredients in anti-AMD decoction corresponding to 258 ingredient targets, combined with 2160 disease targets in AMD, and obtained 129 drug-disease common targets. The key core proteins were predominantly involved in inflammation. Furthermore, molecular docking showed that four potential active ingredients (Quercetin, luteolin, naringenin and hederagenin) had good affinity with the core proteins, IL-6, TNF, VEGFA and MAPK3. Quercetin, luteolin and naringenin demonstrated capacities against oxidative stress and inflammation in human retinal pigment epithelial cells. CONCLUSIONS: The data suggests that anti-AMD decoction has multiple functional components and targets in treating AMD, possibly mediated by suppression of oxidative stress and inflammation.
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Medicamentos Herbarios Chinos , Degeneración Macular , Anciano , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Inflamación/tratamiento farmacológico , Interleucina-6 , Luteolina , Degeneración Macular/tratamiento farmacológico , Medicina Tradicional China , Simulación del Acoplamiento Molecular , Quercetina , Pigmentos RetinianosRESUMEN
Although excessive salt consumption appears to hasten intestinal aging and increases susceptibility to cardiovascular disease, the molecular mechanism is unknown. In this study, mutual validation of high salt (HS) and aging fecal microbiota transplantation (FMT) in C56BL/6 mice was used to clarify the molecular mechanism by which excessive salt consumption causes intestinal aging. Firstly, we observed HS causes vascular endothelial damage and can accelerate intestinal aging associated with decreased colon and serum expression of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and increased malondialdehyde (MDA); after transplantation with HS fecal microbiota in mice, vascular endothelial damage and intestinal aging can also occur. Secondly, we also found intestinal aging and vascular endothelial damage in older mice aged 14 months; and after transplantation of the older mice fecal microbiota, the same effect was observed in mice aged 6-8 weeks. Meanwhile, HS and aging significantly changed gut microbial diversity and composition, which was transferable by FMT. Eventually, based on the core genera both in HS and the aging gut microbiota network, a machine learning model was constructed which could predict HS susceptibility to intestinal aging. Further investigation revealed that the process of HS-related intestinal aging was highly linked to the signal transduction mediated by various bacteria. In conclusion, the present study provides an experimental basis of potential microbial evidence in the process of HS related intestinal aging. Even, avoiding excessive salt consumption and actively intervening in gut microbiota alteration may assist to delay the aging state that drives HS-related intestinal aging in clinical practice.
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Trans-urocanic acid (trans-UCA) is an isomer of cis-UCA and is widely distributed in the brain, predominantly in the hippocampus and prefrontal cortex. Previous studies have investigated the role of trans-UCA in non-spatial memory; however, its influence on spatial memory remains unclear. In the present study, network pharmacology strategy and behavioral testing were used to evaluate the role of trans-UCA in spatial memory and predict its possible mechanism. The results showed that there are 40 intersecting targets between trans-UCA and spatial memory identified by several databases and Venn diagram, indicating that trans-UCA may be involved in spatial memory. Behavioral results show that trans-UCA facilitates spatial working memory in the Y-maze test as well as spatial recognition memory acquisition, consolidation and retrieval in an object location recognition (OLR) task. Furthermore, PPI (protein-protein interaction) network analysis, GO (gene ontology) and KEGG (Kyoto encyclopedia of genes and genomes) pathway enrichment analyses show that the molecular mechanisms underlying the enhancing effect of trans-UCA on spatial memory are mainly associated with the regulation of insulin, mitogen-activated protein kinase (MAPK) and nuclear factor Kappa B (NF-κB) signaling pathways, serotonergic synapse and arginine and proline metabolism. The results of this study suggest that trans-UCA facilitates spatial memory in the Y-maze test and OLR task and may offer therapeutic potential for Alzheimer's disease (AD). The underlying mechanisms predicted by network pharmacology should be further verified.
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Enfermedad de Alzheimer , Ácido Urocánico , Enfermedad de Alzheimer/tratamiento farmacológico , Hipocampo/metabolismo , Humanos , FN-kappa B/metabolismo , Memoria Espacial , Rayos Ultravioleta , Ácido Urocánico/metabolismo , Ácido Urocánico/farmacologíaRESUMEN
OBJECTIVE: To compare the clinical efficacy of total hip arthroplasty with conventional instrument OCM approach and posterolateral approach in supine position. METHODS: From February 2017 to January 2019, 67 patients underwent hip arthroplasty due to hip diseases, including 21 patients in the minimally invasive group, 12 males and 9 females;there were 10 cases of femoral neck fracture, 5 cases of aseptic necrosis of femoral head and 6 cases of hip osteoarthritis. In the traditional group, 46 cases were treated by traditional posterolateral approach, including 28 males and 18 females;there were 24 cases of femoral neck fracture, 12 cases of aseptic necrosis of femoral head and 10 cases of hip osteoarthritis. All patientsused biological ceramic artificial joint prosthesis. The operation time, intraoperative bleeding, incision length, preoperative and postoperative creatine kinase (CK-NAC), underground activity time, hospital stay, abduction angle and anteversion angle of prosthesis were observed and compared between two groups. Harris scores before operation and 12 months after operation were compared between two groups. RESULTS: All cases were followed up for 14 to 26(18.4±3.6) months. There was no significant difference in intraoperative bleeding, postoperative anteversion and abduction angle between two groups (P>0.05). There were significant differences in operation time, incision length, postoperative creatine kinase, underground time and hospital stay between two groups (P<0.05). There was no significant difference in Harris function score between two groups before operation and 12 months after operation(P>0.05). CONCLUSION: The two approaches of total hip arthroplasty can obtain satisfactory results.OCM approach has less damage and rapid postoperative recovery. It is a reliable surgical approach and can be popularized and used.
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Artroplastia de Reemplazo de Cadera , Fracturas del Cuello Femoral , Prótesis de Cadera , Femenino , Fracturas del Cuello Femoral/cirugía , Cabeza Femoral , Humanos , Masculino , Tempo Operativo , Estudios Retrospectivos , Posición Supina , Resultado del TratamientoRESUMEN
Repeated stress-related diarrhea is a kind of functional bowel disorders (FBDs) that are mainly stemming from dysregulation of the microbiota-gut-brain axis mediated by a complex interplay of 5-hydroxytryptophan (5-HT). Intestinal content and intestinal mucosa microbiota belong to two different community systems, and the role of the two microbiota community systems in repeated stress-related diarrhea remains largely unknown. In order to ascertain the difference in composition and the potential function between intestinal content and intestinal mucosa microbiota response on repeated stress-related diarrhea, we collected intestinal contents and mucosa of mice with repeated stress-related diarrhea for 16S rRNA PacBio SMRT gene full-length sequencing, and with the digital modeling method of bacterial species abundance, the correlations among the two microbiota community systems and serum 5-HT concentration were analyzed. We found that the microbiotal composition differences both in intestinal contents and mucosa were consistent throughout all the phylogenetic ranks, with an increasing level of resolution. Compared with intestinal content microbiota, the diversity and composition of microbiota colonized in intestinal mucosa are more sensitive to repeated stress-related diarrhea. The PICRUSt2 of metagenomic function analysis found that repeated stress-related diarrhea is more likely to perturb the intestinal mucosa microbiota metagenomic functions involved in the neural response. We further found that the mucosal microbiota-based relative abundance model was more predictive on serum 5-HT concentration with the methods of machine-learning model established and multivariate dimensionality reduction (R 2 = 0.876). These findings suggest that the intestinal mucosa microbiota might serve as a novel potential prediction model for the serum 5-HT concentration involvement in the repeated stress-related diarrhea, in addition to focusing on its mechanism in the gastrointestinal dysfunction.
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Recently, a robust least squares support vector machine (R-LSSVM) was proposed, but its computational complexity is very high compared with the traditional least squares support vector machine (LSSVM). To reduce R-LSSVM's computational complexity, an improved version, i.e., extended LSSVM (E-LSSVM), is developed in this paper. E-LSSVM and R-LSSVM are equivalent in terms of the generalization performance, but the former needs lower computational complexity than the latter. It is proved that the traditional LSSVM is a special case of E-LSSVM, and based on this fact, we know that the bias in the traditional LSSVM owns manifest physical meaning, i.e., the mean of the modeling error. To solve the mathematical model of E-LSSVM, two algorithms, DE-LSSVM (dual E-LSSVM) and PE-LSSVM (primal E-LSSVM), are proposed from dual and primal spaces, respectively. Even competing against the traditional LSSVM, DE-LSSVM takes the edge in term of the training time. In addition, the sparse problem and cross validation of DE-LSSVM are discussed as well. To verify the effectiveness and soundness of the proposed DE-LSSVM and PE-LSSVM, experiments on regression and classification problems are investigated. To be more important, DE-LSSM and PE-LSSVM are successfully applied to the fault diagnosis of aircraft engine, showing that they are eligible for potential techniques of the fault diagnosis of aircraft engine.
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OBJECTIVE: To explore the effect of Biejiajian Oral Liquid (, BOL) on CCl4-induced hepatic fibrosis in rats by detecting the changes in the levels of angiotensin II (Ang II), angiotensin-(1-7) [Ang-(1-7)], angiotensin-converting enzyme (ACE), ACE2, angiotensin II type 1 receptor (AT1R), Mas, etc. METHODS: A total of 180 Wistar rats were randomly divided into two groups by random digital table method: prevention experiment and treatment experiment. Each group was further subdivided into the following 6 subgroups: normal control group, model group, vitamin E [100 mg/(kg·d), VE] group, enalapril [10 mg/(kg·g), Ena] group, high-dosage [20 g/(kg·d)] BOL group, and low-dosage [10 g/(kg·d)] BOL group. The hepatic fibrosis rat model was established by subcutaneous injection of CCl4 for 6 weeks. Prevention experiment and treatment experiment were administered with specific drugs at different times. At the end of treatment experiment, the pathological changes of liver were observed after hematoxylin-eosin staining. The expressions of ingredients in renin-angiotensin-aldosterone system (RAAS) such as AngII, Ang-(1-7), ACE, ACE2, AT1R, Mas, renin, CYP11B2 and angen in liver were detected by enzyme linked immunosorbent assay, immunohistochemistry method or reverse transcription-polymerase chain reaction, respectively. RESULTS: The levels of AngII and Ang-(1-7) at the 6th week increased by 496.10% and 73.64%, respectively, compared with those at the 2nd week in the model group (P<0.01). With prevention or treatment with high-dosage BOL, there was an evident reduction of AngII level but an improvement of Ang-(1-7) level. Specifically, AngII level of high-dosage group decreased by 77.50% in prevention experiment (P=0.000) and by 76.93% in treatment experiment (P=0.002) compared with that in the model group. Ang-(1-7) level increased by 91.69% in prevention experiment (P=0.006) and by 70.77% in the treatment experiment (P=0.010) compared with that in the model group. The expression levels of mRNA of renin, ACE, CYP11B2, angen and AT1R decreased by 58.15%, 99.90%, 99.84%, 99.99% and 99.99% (all P<0.01), respectively. CONCLUSIONS: BOL could help resist liver fibrosis in rats by enhancing the level of each ingredient in ACE2-Ang-(1-7)-Mas axis, while decreasing the level of each ingredient in ACE-AngII-AT1R axis. To some extent, BOL could enhance the regulation of RAAS in rats with CCl4-induced hepatic fibrosis.
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Angiotensina II/fisiología , Angiotensina I/fisiología , Medicamentos Herbarios Chinos/uso terapéutico , Cirrosis Hepática Experimental/tratamiento farmacológico , Fragmentos de Péptidos/fisiología , Peptidil-Dipeptidasa A/fisiología , Receptor de Angiotensina Tipo 1/fisiología , Administración Oral , Enzima Convertidora de Angiotensina 2 , Animales , Tetracloruro de Carbono , Cirrosis Hepática Experimental/fisiopatología , Masculino , Ratas , Ratas WistarRESUMEN
Flora and mucosal immunity are considered to be the barrier, which is associated with multiple respiratory diseases, including recurrent respiratory tract infection (RRTI). Fei-Xi-Tiao-Zhi-Fang (FTF) is a traditional Chinese herbal formula used in the treatment of RRTI. However, the mechanism is little known. This study aims to identify the function of FTF in flora and mucosal immune secretory immunoglobulin A (sIgA) in the model of RRTI rats. The samples of intestine and lung were collected to detect sIgA, short chain fatty acids (SCFAS), and flora with enzyme-linked immunosorbent assay (ELISA), gas chromatography, and 16S rDNA sequencing. The body weight and viscera index were increased dynamically in RRTI rats after the administration of FTF. Furthermore, the types and proportions of aboriginal flora were significantly changed in the model group, whereas the altered flora was rescued in the FTF administration group. Desulfovibrio increased in the intestinal microflora and Ralstonia and Blautia decreased in the pulmonary microflora at the genus level, similar to that in the normal group. In addition, the expressions of sIgA in pulmonary and intestinal tissues were significantly upregulated and the level of SCFAS was increased in FTF group compared to the RRTI model group. Our study suggests that FTF can alleviate the symptoms of RRTI by increasing sIgA and SCFAS, recovering flora, and improving the immunity.
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Pristine LiNi0.5Mn1.5O4 and FePO4-coated one with Fd-3m space groups were prepared by a sol-gel method. The structure and performance were studied by X-ray diffraction (XRD) rietveld refinement, scanning electron microscopy (SEM), high resolution transmission electron microscopy (HRTEM), energy dispersive spectrometer (EDS) mapping, electrochemical impedance spectroscopy (EIS) and charge-discharge tests, respectively. The lattice parameters of all samples almost remain the same from the Rietveld refinement, revealing that the crystallographic structure has no obvious difference between pristine LiNi0.5Mn1.5O4 and FePO4-coated one. All materials show similar morphologies with uniform particle distribution with small particle size, and FePO4 coating does not affect the morphology of LiNi0.5Mn1.5O4 material. EDS mapping and HRTEM show that FePO4 may be successfully wrapped around the surfaces of LiNi0.5Mn1.5O4 particles, and provides an effective coating layer between the electrolyte and the surface of LiNi0.5Mn1.5O4 particles. FePO4 (1wt%)-coated LiNi0.5Mn1.5O4 cathode shows the highest discharge capacity at high rate (2C) among all samples. After 80 cycles, the reversible discharge capacity of FePO4 (1wt%) coated LiNi0.5Mn1.5O4 is 117mAhg-1, but the pristine one only has 50mAhg-1. FePO4 coating is an effective and controllable way to stabilize the LiNi0.5Mn1.5O4/electrolyte interface, and avoids the direct contact between LiNi0.5Mn1.5O4 powders and electrolyte, then suppresses the side reactions and enhances the electrochemical performance of the LiNi0.5Mn1.5O4.
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OBJECTIVE: To develop a new model of vascular dementia for evaluating Chinese medicine prescriptions. METHODS: Eighty-eight male Wistar rats were randomly divided into 4 groups. At d00, d42, d70, d98 (ni=20, 20, 24, 24) during fatty-feeding, rats in each group were further divided into 10 or 12 subgroups (ni=2), respectively. Lacunar stroke were replicated with the injection of thrombi which coagulated artificially from itself blood. The median lethal doses (LD50) were regressed from accumulative mortality in each geometric thrombus doses (k=0.75, 0.5, 0.85, 0.85), respectively. The degree of vascular dementia was evaluated as exploratory, learning and memorizing abilities. The median effective dose of thrombus for replicating rat model was regressed from dementia scores which were derived from the abilities. The linear correlation was regressed between the values of LD50 or effective dose (ED50) and the durations (days) of hypercholesterolemia. This model of vascular dementia was pathologically confirmed as the neural injuries from lacunar stroke in rats. RESULTS: The hypercholesterolemia was indicated as elevated total cholesterol, triglyeerides low-density lipoprotein cholesterol, and decreased high-density lipoprotein cholesterol. The values of LD50 with its 95% confidence intervals (CI) were 1525.0 (1361.0-1709.0), 584.3 (490.1-696.6), 168.7 (163.7-173.8), or 62.4 (59.5-65.4) mg/mL, at d00, d42, d70, and d98, respectively. There is a linear regression between the values of LD50 and the durations of hypercholesterolemia (y=-15.33x+1390.0, r=0.963, P<0.05). The values of ED50 with its 95% CI were 528.8 (340.5-821.4), 217.0 (20.84-2259.0), 96.3 (23.4-402.6), or 47.0 (43.7-50.6) mg/mL from dementia score, at d00, d42, d70, and d98, respectively. There is a linear regression between the values of ED50 and the durations of hypercholesterolemia (y=-4.992x+484.2, r=0.965, P<0.05). The neural injuries were demonstrated as neural degeneration and necrosis. CONCLUSIONS: For evaluating Chinese medicine, a model of vascular dementia in rats is set up with the lacunar stroke from self-thrombosis during hypercholesterolemia. This model from lacunar stroke is useful to investigate the pathogenesis and treatment of vascular dementia.
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AIM: To investigate the effect of hepatocyte nuclear factor 4α (HNF4α) on the differentiation and transformation of hepatic stellate cells (HSCs). METHODS: By constructing the recombinant adenovirus vector expressing HNF4α and HNF4α shRNA vector, and manipulating HNF4α expression in HSC-T6 cells, we explored the influence of HNF4α and its induction capacity in the differentiation of rat HSCs into hepatocytes. RESULTS: With increased expression of HNF4α mediated by AdHNF4α, the relative expression of Nanog was downregulated in HSC-T6 cells (98.33 ± 12.33 vs 41.33 ± 5.67, P < 0.001). Consequently, the expression of G-P-6 and PEPCK was upregulated (G-P-6: 14.34 ± 3.33 vs 42.53 ± 5.87, P < 0.01; PEPCK: 10.10 ± 4.67 vs 56.56 ± 5.25, P < 0.001), the expression of AFP and ALB was positive, and the expression of Nanog, Typeâ Iâ collagen, α-SMA, and TIMP-1 was significantly decreased. HNF4α also downregulated vimentin expression and enhanced E-cadherin expression. The ultrastructure of HNF4α-induced cells had more mitochondria and ribosomes compared with the parental cells. After silencing HNF4α expression, EPCK, E-cadherin, AFP, and ALB were downregulated and α-SMA and vimentin were upregulated. CONCLUSION: HNF4α can induce a tendency of differentiation of HSCs into hepatocyte-like cells. These findings may provide an effective way for the treatment of liver diseases.