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Inflammations have been linked to tumours, suggesting a potential association between NLRP1 and cancer. Nevertheless, a systematic assessment of NLRP1's role across various cancer types currently absent. A comprehensive bioinformatic analysis was conducted to determine whether NLRP1 exhibits prognostic relevance linked to immune metabolism across various cancers. The study leveraged data from the TCGA and GTEx databases to explore the clinical significance, metabolic features, and immunological characteristics of NLRP1, employing various tools such as R, GEPIA, STRING and TISIDB. NLRP1 exhibited differential expression patterns across various cancers, with elevated expression correlating with a more favourable prognosis in lung adenocarcinoma (LUAD) and pancreatic adenocarcinoma (PAAD). Downregulation of NLRP1 reduced tumour metabolic activity in LUAD. Moreover, the mutational signature of NLRP1 was linked to a favourable prognosis. Interestingly, high NLRP1 expression inversely correlated with tumour stemness while positively correlating with tumour immune infiltration in various cancers including LUAD and PAAD. Through extensive big data analysis, we delved into the role of NLRP1 across various tumour types, constructing a comprehensive role map of its involvement in pan-cancer scenarios. Our findings highlight the potential of NLRP1 as a promising therapeutic target specifically in LUAD and PAAD.
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Regulación Neoplásica de la Expresión Génica , Proteínas NLR , Humanos , Proteínas NLR/metabolismo , Proteínas NLR/genética , Pronóstico , Neoplasias/metabolismo , Neoplasias/inmunología , Neoplasias/genética , Neoplasias/patología , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Biología Computacional/métodos , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Mutación , Adenocarcinoma del Pulmón/inmunología , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/patología , Proteínas Reguladoras de la Apoptosis/metabolismo , Proteínas Reguladoras de la Apoptosis/genéticaRESUMEN
Tumor immune microenvironment (TIME) consists of intra-tumor immunological components and plays a significant role in tumor initiation, progression, metastasis, and response to therapy. Chimeric antigen receptor (CAR)-T cell immunotherapy has revolutionized the cancer treatment paradigm. Although CAR-T cell immunotherapy has emerged as a successful treatment for hematologic malignancies, it remains a conundrum for solid tumors. The heterogeneity of TIME is responsible for poor outcomes in CAR-T cell immunotherapy against solid tumors. The advancement of highly sophisticated technology enhances our exploration in TIME from a multi-omics perspective. In the era of machine learning, multi-omics studies could reveal the characteristics of TIME and its immune resistance mechanism. Therefore, the clinical efficacy of CAR-T cell immunotherapy in solid tumors could be further improved with strategies that target unfavorable conditions in TIME. Herein, this review seeks to investigate the factors influencing TIME formation and propose strategies for improving the effectiveness of CAR-T cell immunotherapy through a multi-omics perspective, with the ultimate goal of developing personalized therapeutic approaches.
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Inmunoterapia Adoptiva , Neoplasias , Receptores Quiméricos de Antígenos , Microambiente Tumoral , Humanos , Microambiente Tumoral/inmunología , Neoplasias/terapia , Neoplasias/inmunología , Inmunoterapia Adoptiva/métodos , Receptores Quiméricos de Antígenos/inmunología , Receptores Quiméricos de Antígenos/metabolismo , Receptores Quiméricos de Antígenos/genética , Animales , Genómica/métodos , Linfocitos T/inmunología , Linfocitos T/metabolismoRESUMEN
Recent research has uncovered a surprisingly high occurrence of aberrant expression and mutations in the genes that encode subunits of the SWI/SNF chromatin-remodeling complexes (SCRC). Nevertheless, the carcinogenic effects of aberrant expression and mutations in SWI/SNF genes have only been acknowledged in recent times, resulting in a comparatively limited understanding of these modifications. In this study, we comprehensively analyzed the expression difference, somatic mutation, potential biological pathways, stromal or immune cell infiltration, and drug sensitivity of SCRC-related genes (SCRGs) in pan-cancer. Furthermore, the evolutionary trend, prognostic signature, and immunotherapy response of SCRGs in kidney renal clear cell carcinoma (KIRC) were also evaluated. The expression of SCRGs was changed in 13 out of 14 tumor types, strongly linked to prognosis, and mutated in 30.9% of tumor patients. SCRGs were also closely associated with immune-related pathways and tumor metastasis pathways. The expression of SCRGs was positively associated with the immune score or stromal score but negatively correlated with Tumor purity. Three potential drugs (FK866, Ispinesib mesylate, and WZ3105) were identified to target the SCRGs. In KIRC, scRNA-seq analysis showed that the enrichment of SCRC and the communication frequency with immune cells were significantly declined during tumor cell progression. A prognostic signature was constructed in KIRC and was effective in predicting the prognosis for KIRC. Aberrant expression of eleven prognostic genes identified from the KIRC prognostic signature and the cytotoxicity of FK866 and Ispinesib mesylate to KIRC were verified by qRT-PCR and CCK-8 assay, respectively. Our study identified SCRGs as potential biomarker and therapeutic targets, providing new insights into SCRC for tumor-targeted therapy.
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Biomarcadores de Tumor , Ensamble y Desensamble de Cromatina , Regulación Neoplásica de la Expresión Génica , Neoplasias , Humanos , Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Neoplasias/genética , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/metabolismo , Pronóstico , Mutación , Proteínas Cromosómicas no Histona/genética , Proteínas Cromosómicas no Histona/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Terapia Molecular Dirigida , Perfilación de la Expresión GénicaRESUMEN
The precise mapping of collateral circulation and ischemic penumbra is crucial for diagnosing and treating acute ischemic stroke (AIS). Unfortunately, there exists a significant shortage of high-sensitivity and high-resolution in vivo imaging techniques to fulfill this requirement. Herein, a contrast enhanced susceptibility-weighted imaging (CE-SWI) using the minimalist dextran-modified Fe3O4 nanoparticles (Fe3O4@Dextran NPs) are introduced for the highly sensitive and high-resolution AIS depiction under 9.4 T for the first time. The Fe3O4@Dextran NPs are synthesized via a simple one-pot coprecipitation method using commercial reagents under room temperature. It shows merits of small size (hydrodynamic size 25.8 nm), good solubility, high transverse relaxivity (r2) of 51.3 mM-1s-1 at 9.4 T, and superior biocompatibility. The Fe3O4@Dextran NPs-enhanced SWI can highlight the cerebral vessels readily with significantly improved contrast and ultrahigh resolution of 0.1 mm under 9.4 T MR scanner, enabling the clear spatial identification of collateral circulation in the middle cerebral artery occlusion (MCAO) rat model. Furthermore, Fe3O4@Dextran NPs-enhanced SWI facilitates the precise depiction of ischemia core, collaterals, and ischemic penumbra post AIS through matching analysis with other multimodal MR sequences. The proposed Fe3O4@Dextran NPs-enhanced SWI offers a high-sensitivity and high-resolution imaging tool for individualized characterization and personally precise theranostics of stroke patients.
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Imagen por Resonancia Magnética , Accidente Cerebrovascular , Animales , Imagen por Resonancia Magnética/métodos , Accidente Cerebrovascular/diagnóstico por imagen , Dextranos/química , Ratas , Compuestos Férricos/química , Ratas Sprague-Dawley , Masculino , Nanopartículas Magnéticas de Óxido de Hierro/química , Medios de Contraste/química , Infarto de la Arteria Cerebral Media/diagnóstico por imagenRESUMEN
Vascular endothelial cells have recently been shown to be associated with osteogenic activity. However, the mechanism of vascular endothelial cells promoting osteogenesis is unclear. Here, we found that exosomes secreted from human microvascular endothelial cells (HMEC-1) promoted osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and inhibited adipogenic differentiation. Aged and ovariectomy mice treated with exosomes showed increased bone formation and decreased lipid accumulation in the bone marrow cavity. Additionally, we screened out novel exosomal miR-5p-72106_14 by miRNA-seq and confirmed that miR-5p-72106_14 promoted osteogenic differentiation and inhibited adipogenic differentiation of BMSCs by inhibiting STAT1. Our results suggest that vascular endothelial cell-derived exosomes are involved in BMSC differentiation and exosomal miR-5p-72106_14 is a major factor in regulating fate determination of BMSCs.
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Exosomas , Células Madre Mesenquimatosas , MicroARNs , Femenino , Humanos , Ratones , Animales , Anciano , MicroARNs/genética , Osteogénesis , Células Endoteliales , Exosomas/genética , Diferenciación CelularRESUMEN
Carborazine (B2C2N2H6) and borazine (B3N3H6) are isoelectronic analogues of benzene (C6H6). The aromatic character of borazine have basically reached a consensus after a long period of controversy, but the related properties of carborazine are even rarely reported. In this work, we systematically investigated the geometric structure, charge distribution, frontier molecular orbital characteristics, bonding, electronic delocalization, magnetic shielding effect, and induced ring current of carborazine and borazine, and compared the studied characteristics with those of benzene to determine the aromatic character of the two analogues. The combination of multiple properties shows that although they are isoelectronic, carborazine is evidently aromatic, while borazine only exhibits rather weak aromaticity. The C atom acting as a connecting bridge between B and N atoms in carborazine reduces the electronegativity difference on the molecular backbone and enhances the electronic delocalization over the conjugated path, which is the essence of the distinct disparity of aromaticity between carborazine and borazine.
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Alzheimer's disease (AD) is a neurodegenerative disease where abnormal amyloidogenic processing of amyloid-ß precursor protein (APP) occurs and has been linked to neuronal dysfunction. Hypometabolism of glucose in the brain can lead to synaptic loss and neuronal death, which in turn exacerbates energy deficiency and amyloid-ß peptide (Aß) accumulation. Lactate produced by anaerobic glycolysis serves as an energy substrate supporting neuronal function and facilitating neuronal repair. Vestigial-like family member 4 (VGLL4) has been recognized as a key regulator of the hypoxia-sensing pathway. However, the role of VGLL4 in AD remains unexplored. Here, we reported that the expression of VGLL4 protein was significantly decreased in the brain tissue of AD model mice and AD model cells. We further found that overexpression of VGLL4 reduced APP amyloidogenic processing and ameliorated neuronal synaptic damage. Notably, we identified a compromised hypoxia-sensitive capability of LDHA regulated by VGLL4 in the context of AD. Upregulation of VGLL4 increased the response of LDHA to hypoxia and enhanced the expression levels of LDHA and lactate by inhibiting the ubiquitination and degradation of LDHA. Furthermore, the inhibition of lactate production by using sodium oxamate, an inhibitor of LDHA, suppressed the neuroprotective function of VGLL4 by increasing APP amyloidogenic processing. Taken together, our findings demonstrate that VGLL4 exerts a neuroprotective effect by upregulating LDHA expression and consequently promoting lactate production. Thus, this study suggests that VGLL4 may be a novel player involved in molecular mechanisms relevant for ameliorating neurodegeneration.
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Enfermedad de Alzheimer , Enfermedades Neurodegenerativas , Ratones , Animales , Enfermedad de Alzheimer/metabolismo , Ácido Láctico , Precursor de Proteína beta-Amiloide/metabolismo , Péptidos beta-Amiloides/metabolismo , Hipoxia , Ratones Transgénicos , Factores de TranscripciónRESUMEN
From a fundamental point of view, the structure-photoluminescence relationship is vitally important for developing efficient phosphors and rationally improving their performances. In this work, Rietveld refinements on high-resolution powder X-ray diffraction (XRD) data were conducted to verify the Ce3+ distribution in K5Y(P2O7)2 (KYPO). Ce3+ ions are located at both M1 and M2 sites, with occupation factors of 0.31(2) and 0.19(2), respectively. Importantly, the crystal field strength (CFS) is stronger at the former site due to the larger bond valence sum. Correspondingly, the Ce3+ emission can be deconvoluted into four Gaussian-type bands centered at â¼353, â¼383, â¼343, and â¼369 nm, where the former two belong to Ce3+ at the M1 site and the latter two are assigned to Ce3+ at the M2 site. Ce3+ in KYPO is a highly efficient activator, with optimal internal and external quantum efficiencies of 98.9 and 74.6%, respectively, and was thus utilized to sensitize the Dy3+ emission. Indeed, energy transfer from Ce3+ to Dy3+ was confirmed by fluorescent decay curves for Ce3+/Dy3+ codoped KYPO, and the mechanism was supposed to be dominated by dipole-dipole interactions. Indeed, it can be pumped by a 310 nm LED chip and emits a bright white light. Ce3+ photoluminescence exhibits high resistance to thermal quenching, and it can be further enhanced by codoping Dy3+, i.e. the emission intensity remains 96.3% at 423 K.
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Chloroethylnitrosoureas (CENUs) are important chemotherapies applied in the treatment of cancer. They exert anticancer activity by inducing DNA interstrand cross-links (ICLs) via the formation of two O6-alkylguanine intermediates, O6-chloroethylguanine (O6-ClEtG) and N1,O6-ethanoguanine (N1,O6-EtG). However, O6-alkylguanine-DNA alkyltransferase (AGT), a DNA-repair enzyme, can restore the O6-alkylguanine damages and thereby obstruct the formation of ICLs (dG-dC cross-link). In this study, the inhibitory mechanism of ICL formation was investigated to elucidate the drug resistance of CENUs mediated by AGT in detail. Based on the structures of the substrate-enzyme complexes obtained from docking and MD simulations, two ONIOM (QM/MM) models with different sizes of the QM region were constructed. The model with a larger QM region, which included the substrate (O6-ClEtG or N1,O6-EtG), a water molecule, and five residues (Tyr114, Cys145, His146, Lys165, and Glu172) in the active pocket of AGT, accurately described the repairing reaction and generated the results coinciding with the experimental outcomes. The repair process consists of two sequential steps: hydrogen transfer to form a thiolate anion on Cys145 and alkyl transfer from the O6 site of guanine (the rate-limiting step). The repair of N1,O6-EtG was more favorable than that of O6-ClEtG from both kinetics and thermodynamics aspects. Moreover, the comparison of the repairing process with the formation of dG-dC cross-link and the inhibition of AGT by O6-benzylguanine (O6-BG) showed that the presence of AGT could effectively interrupt the formation of ICLs leading to drug resistance, and the inhibition of AGT by O6-BG that was energetically more favorable than the repair of O6-ClEtG could not prevent the repair of N1,O6-EtG. Therefore, it is necessary to completely eliminate AGT activity before CENUs medication to enhance the chemotherapeutic effectiveness. This work provides reasonable explanations for the supposed mechanism of AGT-mediated drug resistance of CENUs and will assist in the development of novel CENU chemotherapies and their medication strategies.
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Reparación del ADN , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , O(6)-Metilguanina-ADN Metiltransferasa , O(6)-Metilguanina-ADN Metiltransferasa/metabolismo , O(6)-Metilguanina-ADN Metiltransferasa/química , O(6)-Metilguanina-ADN Metiltransferasa/antagonistas & inhibidores , Humanos , Teoría Cuántica , Resistencia a Antineoplásicos/efectos de los fármacos , Compuestos de Nitrosourea/química , Compuestos de Nitrosourea/farmacología , Compuestos de Nitrosourea/metabolismoRESUMEN
Powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is a severe disease that affects the yield and quality of wheat. Popularization of resistant cultivars in production is the preferred strategy to control this disease. In the present study, the Chinese wheat breeding line Jimai 809 showed excellent agronomic performance and high resistance to powdery mildew at the whole growth stage. To dissect the genetic basis for this resistance, Jimai 809 was crossed with the susceptible wheat cultivar Junda 159 to produce segregation populations. Genetic analysis showed that a single dominant gene, temporarily designated PmJM809, conferred the resistance to different Bgt isolates. PmJM809 was then mapped on the chromosome arm 2BL and flanked by the markers CISSR02g-1 and CIT02g-13 with genetic distances 0.4 and 0.8 cM, respectively, corresponding to a physical interval of 704.12-708.24 Mb. PmJM809 differed from the reported Pm genes on chromosome arm 2BL in origin, resistance spectrum, physical position and/or genetic diversity of the mapping interval, also suggesting PmJM809 was located on a complex interval with multiple resistance genes. To analyze and screen the candidate gene(s) of PmJM809, six genes related to disease resistance in the candidate interval were evaluated their expression patterns using an additional set of wheat samples and time-course analysis post-inoculation of the Bgt isolate E09. As a result, four genes were speculated as the key candidate or regulatory genes. Considering its comprehensive agronomic traits and resistance findings, PmJM809 was expected to be a valuable gene resource in wheat disease resistance breeding. To efficiently transfer PmJM809 into different genetic backgrounds, 13 of 19 closely linked markers were confirmed to be suitable for marker-assisted selection. Using these markers, a series of wheat breeding lines with harmonious disease resistance and agronomic performance were selected from the crosses of Jimai 809 and several susceptible cultivars. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01467-8.
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Endothelial senescence, aging-related inflammation, and mitochondrial dysfunction are prominent features of vascular aging and contribute to the development of aging-associated vascular disease. Accumulating evidence indicates that DNA damage occurs in aging vascular cells, especially in endothelial cells (ECs). However, the mechanism of EC senescence has not been completely elucidated, and so far, there is no specific drug in the clinic to treat EC senescence and vascular aging. Here we show that various aging stimuli induce nuclear DNA and mitochondrial damage in ECs, thus facilitating the release of cytoplasmic free DNA (cfDNA), which activates the DNA-sensing adapter protein STING. STING activation led to a senescence-associated secretory phenotype (SASP), thereby releasing pro-aging cytokines and cfDNA to further exacerbate mitochondrial damage and EC senescence, thus forming a vicious circle, all of which can be suppressed by STING knockdown or inhibition. Using next-generation RNA sequencing, we demonstrate that STING activation stimulates, whereas STING inhibition disrupts pathways associated with cell senescence and SASP. In vivo studies unravel that endothelial-specific Sting deficiency alleviates aging-related endothelial inflammation and mitochondrial dysfunction and prevents the development of atherosclerosis in mice. By screening FDA-approved vasoprotective drugs, we identified Cilostazol as a new STING inhibitor that attenuates aging-related endothelial inflammation both in vitro and in vivo. We demonstrated that Cilostazol significantly inhibited STING translocation from the ER to the Golgi apparatus during STING activation by targeting S162 and S243 residues of STING. These results disclose the deleterious effects of a cfDNA-STING-SASP-cfDNA vicious circle on EC senescence and atherogenesis and suggest that the STING pathway is a promising therapeutic target for vascular aging-related diseases. A proposed model illustrates the central role of STING in mediating a vicious circle of cfDNA-STING-SASP-cfDNA to aggravate age-related endothelial inflammation and mitochondrial damage.
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Senescencia Celular , Cilostazol , Inflamación , Proteínas de la Membrana , Ratones Endogámicos C57BL , Mitocondrias , Animales , Proteínas de la Membrana/metabolismo , Cilostazol/farmacología , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Humanos , Inflamación/metabolismo , Inflamación/tratamiento farmacológico , Senescencia Celular/efectos de los fármacos , Ratones , Envejecimiento/metabolismo , Células Endoteliales/metabolismo , Células Endoteliales/efectos de los fármacos , Citosol/metabolismo , ADN/metabolismo , Masculino , Células Endoteliales de la Vena Umbilical Humana , Fenotipo Secretor Asociado a la Senescencia , Células CultivadasRESUMEN
OBJECTIVES: To explore the relationship between cumulative ecological risk and individual risky behavior and multiple forms of aggregated behaviors among adolescents, and examine the gender differences. METHODS: A large-scale, nationally representative, and students-based investigation was conducted in rural and urban areas of eight provinces in China from October to December 2021. A total of 22 868 adolescents with an average age of 14.64 years completely standardized questionnaire in which the sociodemographic characteristics, socio-ecological risk factors and risky behaviors were used to analyze. RESULTS: Of included students, 48.4% encountered the high level of social-ecological risk. The prevalence of breakfast intake not daily, alcohol use (AU), smoking, physical inactivity, prolonged screen time (ST) on weekdays and weekends, suicidal ideation, suicidal plan, suicidal attempt, and non-suicidal self-injury (NSSI) was 41.0%, 11.9%, 3.4%, 61.9%, 15.1%, 51.1%, 27.7%, 13.9%, 6.5% and 27.0% respectively. 22.2% of participants engaged in high-risk behaviors. All were significantly influences of increased cumulative ecological risk on individual behavior and low-risk clustering behaviors separately. The odds ratio of breakfast intake not daily, AU, smoking, physical inactivity, prolonged ST in weekday and weekend, suicidal ideation, suicidal plan, suicidal attempt, and NSSI for the adjusted model in low versus high level of cumulative ecological risk was respectively significant in both boy and girls, and the ratio of odds ratios (ROR) was separately 0.95 (p = 0.228), 0.67 (p < 0.001), 0.44 (p < 0.001), 0.60 (p < 0.001), 0.78 (p = 0.001), 0.83 (p = 0.001), 0.80 (p = 0.001), 0.83 (p = 0.022), 0.71 (p = 0.005), 0.75 (p = 0.001). Girls encountering a high level of cumulative ecological risk were more likely to engage in multiple forms of clustering risky behaviors than boys (RORs: 0.77, p = 0.001). CONCLUSIONS: Research and effective inventions at the social-ecological environment, based on the view of cumulative risk, are needed to promote the healthy development of behaviors in adolescence, and pay more attention to decreasing the occurrence of risky behaviours in girls than boys.
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Conductas de Riesgo para la Salud , Conducta Autodestructiva , Masculino , Femenino , Humanos , Adolescente , Intento de Suicidio , Ideación Suicida , Conducta Autodestructiva/epidemiología , Factores de Riesgo , China/epidemiología , Encuestas y CuestionariosRESUMEN
Brain damage caused by ethanol abuse may lead to permanent damage, including severe dementia. The aim of this study was to investigate the effects of ginger powder on ethanol-induced cognitive disorders by examining oxidative damage and inflammation status, and the gene expression of N-methyl-D-aspartate (NMDA) and γ-Aminobutyric acid (GABA)-A receptors in the hippocampus of male rats. 24 adult male Sprague-Dawley rats were allocated randomly to four groups as follows control, ethanol (4g/kg/day, by gavage), ginger (1g/kg/day, by gavage), and ginger-ethanol. At the end of the study, memory and learning were evaluated by the shuttle box test. Moreover, to explore mechanisms involved in ethanol-induced cognitive impairment and the protective effect of ginger, the expression of Nuclear factor kappa B (NF-κB), nuclear factor erythroid 2-related factor 2 (Nrf2), NMDA receptor, and GABA-A receptor was measured along with inflammatory and oxidative biomarkers in the hippocampus tissue. The results showed that ethanol could induce cognitive impairment in the ethanol group, while pretreatment with ginger could reverse it. The gene expression of the NF-κB/ Tumor necrosis factor (TNF)-α/Interleukin (IL)-1ß pathway and NMDA and GABA-A receptors significantly increased in the ethanol group compared to the control group. While pretreatment with ginger could significantly improve ethanol-induced cognitive impairment through these pathways in the ginger-ethanol group compared to the ethanol group (P < 0.05). It can be concluded that ginger powder could ameliorate ethanol-induced cognitive impairment by modulating the expression of NMDA and GABA-A receptors and inhibiting oxidative damage and the NF-κB/TNF-α/IL-1ß pathway in the rat hippocampus.
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Disfunción Cognitiva , Zingiber officinale , Ratas , Animales , Masculino , Ratas Sprague-Dawley , Receptores de GABA-A/metabolismo , N-Metilaspartato/metabolismo , N-Metilaspartato/farmacología , Etanol/toxicidad , FN-kappa B/metabolismo , Receptores de GABA/metabolismo , Polvos/metabolismo , Polvos/farmacología , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Extractos Vegetales/metabolismo , Hipocampo/metabolismo , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
AIM: The relationship between vitamin D status and Kawasaki Disease (KD), as well as coronary artery lesion (CAL), has yet to be established. METHODS: A meta-analysis was conducted to assess the correlation between vitamin D status and KD, as well as the impact of vitamin D status on the progression of KD into CAL. RESULTS: The meta-analysis revealed a consistent and significant association between serum 25(OH)D level and the occurrence KD (studies N = 22; z = -3.51, P < 0.001). Patients with KD had markedly lower levels of vitamin D than healthy controls (SMD: -1.30 ng/mL, 95%CI: -2.05 to -0.55 ng/mL). CONCLUSION: The study provided evidence supporting a significant association between lower serum vitamin D levels and the occurrence of KD, particularly within the Chinese population. However, the findings did not suggest a direct impact of vitamin D on the development of CAL in KD patients.
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Síndrome Mucocutáneo Linfonodular , Deficiencia de Vitamina D , Vitamina D , Síndrome Mucocutáneo Linfonodular/sangre , Síndrome Mucocutáneo Linfonodular/complicaciones , Humanos , Vitamina D/sangre , Vitamina D/análogos & derivados , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/sangre , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/etiología , Enfermedad de la Arteria Coronaria/epidemiología , Progresión de la EnfermedadRESUMEN
Tissue-on-chip systems represent promising platforms for monitoring and controlling tissue functions in vitro for various purposes in biomedical research. The two-dimensional (2D) layouts of these constructs constrain the types of interactions that can be studied and limit their relevance to three-dimensional (3D) tissues. The development of 3D electronic scaffolds and microphysiological devices with geometries and functions tailored to realistic 3D tissues has the potential to create important possibilities in advanced sensing and control. This study presents classes of compliant 3D frameworks that incorporate microscale strain sensors for high-sensitivity measurements of contractile forces of engineered optogenetic muscle tissue rings, supported by quantitative simulations. Compared with traditional approaches based on optical microscopy, these 3D mechanical frameworks and sensing systems can measure not only motions but also contractile forces with high accuracy and high temporal resolution. Results of active tension force measurements of engineered muscle rings under different stimulation conditions in long-term monitoring settings for over 5 wk and in response to various chemical and drug doses demonstrate the utility of such platforms in sensing and modulation of muscle and other tissues. Possibilities for applications range from drug screening and disease modeling to biohybrid robotic engineering.
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Técnicas de Cultivo Tridimensional de Células/métodos , Imagenología Tridimensional/métodos , Músculos/metabolismo , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Acetilcolina/farmacología , Actinina/metabolismo , Animales , Cafeína/farmacología , Técnicas de Cultivo Tridimensional de Células/instrumentación , Diferenciación Celular , Línea Celular , Dantroleno/farmacología , Ratones , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Mioblastos/citología , Mioblastos/metabolismo , Miosinas/metabolismo , Ingeniería de Tejidos/instrumentación , Vasodilatadores/farmacologíaRESUMEN
Powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is a serious threat to wheat (Triticum aestivum L.) production. Narrow genetic basis of common wheat boosted the demand for diversified donors against powdery mildew. Aegilops tauschii Coss (2n = 2x = DD) and emmer wheat (2n = 4x = AABB), as the ancestor species of common wheat, are important gene donors for genetic improvement of common wheat. In this study, a total of 71 Ae. tauschii and 161 emmer wheat accessions were first evaluated for their powdery mildew resistance using the Bgt isolate E09. Thirty-three Ae. tauschii (46.5%) and 108 emmer wheat accessions (67.1%) were resistant. Then, all these accessions were tested by the diagnostic markers for 21 known Pm genes. The results showed that Pm2 alleles were detected in all the 71 Ae. tauschii and only Pm4 alleles were detected in 20 of 161 emmer wheat accessions. After haplotype analysis, we identified four Pm4 alleles (Pm4a, Pm4b, Pm4d, and Pm4f) in the emmer wheat accessions and three Pm2 alleles (Pm2d, Pm2e, and Pm2g) in the Ae. tauschii. Further resistance spectrum analysis indicated that these resistance accessions displayed different resistance reactions to different Bgt isolates, implying they may have other Pm genes apart from Pm2 and/or Pm4 alleles. Notably, a new Pm2 allele, Pm2S, was identified in Ae. tauschii, which contained a 64-bp deletion in the first exon and formed a new termination site at the 513th triplet of the shifted reading frame compared with reported Pm2 alleles. The phylogenetic tree of Pm2S showed that the kinship of Pm2S was close to Pm2h. To efficiently and accurately detect Pm2S and distinguish with other Pm2 alleles in Ae. tauschii background, a diagnostic marker, YTU-QS-3, was developed, and its effectiveness was verified. This study provided valuable Pm alleles and enriched the genetic diversity of the powdery mildew resistance in wheat improvement.
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Aegilops , Ascomicetos , Resistencia a la Enfermedad , Enfermedades de las Plantas , Triticum , Triticum/genética , Triticum/microbiología , Triticum/inmunología , Ascomicetos/fisiología , Ascomicetos/genética , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/inmunología , Enfermedades de las Plantas/genética , Resistencia a la Enfermedad/genética , Aegilops/genética , Aegilops/microbiología , Genes de Plantas/genética , Alelos , HaplotiposRESUMEN
Astragalus membranaceus saponins are the main components of A. membranaceus, a plant widely used in traditional Chinese medicine. Recently, research on the anti-cancer effects of A. membranaceus saponins has received increasing attention. Numerous in vitro and in vivo experimental data indicate that A. membranaceus saponins exhibit significant anti-cancer effects through multiple mechanisms, especially in inhibiting tumor cell proliferation, migration, invasion, and induction of apoptosis, etc. This review compiles relevant studies on the anti-cancer properties of A. membranaceus saponins from various databases over the past two decades. It introduces the mechanism of action of astragalosides, highlighting their therapeutic benefits in the management of cancer. Finally, the urgent problems in the research process are highlighted to promote A. membranaceus saponins as an effective drug against cancer.
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Apoptosis , Astragalus propinquus , Proliferación Celular , Neoplasias , Saponinas , Saponinas/farmacología , Saponinas/química , Astragalus propinquus/química , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/metabolismo , Apoptosis/efectos de los fármacos , Animales , Proliferación Celular/efectos de los fármacos , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Movimiento Celular/efectos de los fármacosRESUMEN
BACKGROUND: Professional commitment of nursing students is closely related to the stability of the nursing team. Personality traits and metacognition may be related to professional commitment. We investigate the association between Big Five personality, metacognition, and professional commitment among nursing students, and further explore whether Big Five personality modifies the association between metacognition and professional commitment. METHODS: From December 2023 to January 2024, a cross-sectional study was conducted among 3631 nursing students from 17 universities in China through the online platform Sojump.com by cluster sampling method and using the general information questionnaire, BFI-44 (Big Five Inventory 44) scale, metacognition scale and professional commitment scale to investigate their demographic data, personality traits, level of metacognition and level of professional commitment. Latent profile analysis was employed to identify optimal categories of personality traits. Multivariate logistic regression was used to analyze the association between the personality traits and professional commitment, as well as metacognition and professional commitment in all participants and participants with different personality traits subgroups, adjusting for potential covariates. Furthermore, the potential mediating role of metacognition between personality traits and professional commitment was also investigated. RESULTS: Three distinct personality traits were identified: sensitive-negative personality (65.2%), ordinary personality (26.6%), and open-positive personality (8.2%). Compared with nursing students with sensitive-negative personality, nursing students with ordinary personality and open-positive personality were associated with professional commitment, respectively [OR (95% CI): 7.01 (5.99-8.20), 21.09 (15.43-28.83)]. The p value for trend of personality and professional commitment was < 0.001. Metacognition was associated with professional commitment [OR (95% CI): 5.95 (5.20-6.81); p < 0.001]. Personality traits could modify the association between metacognition and professional commitment (pinteraction = 0.009). The mediating role of metacognition between Big Five personality and professional commitment has also been verified. CONCLUSIONS: Personality traits and metacognition of nursing students need to be paid attention to, and interventions based on metacognition may help nursing students with different personality traits to improve their professional commitment level.
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Highly integrated energy systems are on the rise due to increasing global demand. To capture the underlying physics of such interdisciplinary systems, we need a modern framework that unifies all forms of energy. Here, we apply modified Lagrangian mechanics to the description of multi-energy systems. Based on the minimum entropy production principle, we revisit fluid mechanics in the presence of both mechanical and thermal dissipations and propose using exergy flow as the unifying Lagrangian across different forms of energy. We illustrate our theoretical framework by modeling a one-dimensional system with coupled electricity and heat. We map the exergy loss rate in real space and obtain the total exergy changes. Under steady-state conditions, our theory agrees with the traditional formula but incorporates more physical considerations such as viscous dissipation. The integral form of our theory also allows us to go beyond steady-state calculations and visualize the local, time-dependent exergy flow density everywhere in the system. Expandable to a wide range of applications, our theoretical framework provides the basis for developing versatile models in integrated energy systems.
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BACKGROUND: Paronychia is a prevalent clinical disease affecting the soft tissue surrounding the nails. Most cases of toenail paronychia are commonly associated with ingrown toenails. While conservative treatment is effective for mild cases of ingrown toenails, surgical intervention becomes necessary for moderate to severe cases, particularly when granulomas form. OBJECTIVE: To provide a systematic understanding of these classic and modified procedures for surgeons to select the appropriate surgical interventions for patients suffering from moderate to severe ingrown toenails and discuss this technology's advantages and limitations for dermatologic surgery. METHODS: A literature search was performed using PubMed/MEDLINE and Google Scholar databases. Studies discussing surgical intervention for ingrown toenails were included. Moreover, the surgical steps were meticulously depicted by detailed schematic diagrams. RESULTS: These surgical techniques can be divided into three categories: matrix resection, debulking of periungual soft tissues, and the rotational flap technique. Each approach possesses distinct advantages and limitations. CONCLUSION: For moderate to severe cases, surgical interventions may exhibit superior outcomes, faster recovery times, and lower recurrence rates. The surgeon must possess a comprehensive understanding and proficient skillset in various surgical techniques for ingrown toenails.