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The current study aimed to assess the effect of timosaponin Aâ ¢ (T-Aâ ¢) on drug-metabolizing enzymes during anticancer therapy. The in vivo experiments were conducted on nude and ICR mice. Following a 24-day administration of T-Aâ ¢, the nude mice exhibited an induction of CYP2B10, MDR1, and CYP3A11 expression in the liver tissues. In the ICR mice, the expression levels of CYP2B10 and MDR1 increased after a three-day T-Aâ ¢ administration. The in vitro assessments with HepG2 cells revealed that T-Aâ ¢ induced the expression of CYP2B6, MDR1, and CYP3A4, along with constitutive androstane receptor (CAR) activation. Treatment with CAR siRNA reversed the T-Aâ ¢-induced increases in CYP2B6 and CYP3A4 expression. Furthermore, other CAR target genes also showed a significant increase in the expression. The up-regulation of murine CAR was observed in the liver tissues of both nude and ICR mice. Subsequent findings demonstrated that T-Aâ ¢ activated CAR by inhibiting ERK1/2 phosphorylation, with this effect being partially reversed by the ERK activator t-BHQ. Inhibition of the ERK1/2 signaling pathway was also observed in vivo. Additionally, T-Aâ ¢inhibited the phosphorylation of EGFR at Tyr1173 and Tyr845, and suppressed EGF-induced phosphorylation of EGFR, ERK, and CAR. In the nude mice, T-Aâ ¢ also inhibited EGFR phosphorylation. These results collectively indicate that T-Aâ ¢ is a novel CAR activator through inhibition of the EGFR pathway.
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Previous studies have shown that differentiated embryo-chondrocyte expressed gene 1 (DEC1) promotes osteoblast osteogenesis. To investigate the role of DEC1 in postmenopausal osteoporosis (PMOP), we utilized the two types (DEC1 +/+, DEC1 -/-) mice to establish an ovariectomy (OVX) model and found that the bone loss in DEC1 -/- OVX mice were much less than that in DEC1 +/+ OVX mice. The expression levels of RUNX2 and OSX significantly increased in DEC1 -/- OVX mice compared with those in DEC1 +/+ OVX mice. Whereas, NFATc1, c-Fos, CTSK and RANKL/OPG significantly decreased in DEC1 -/- OVX mice compared with those in DEC1 +/+ OVX mice. Likewise, DEC1 deficiency suppressed IL-6 and IL-1ß. Further study showed Runx2, Osx, Alp, and Ocn significantly increased in DEC1 -/- OVX BMSCs compared with those in DEC1 +/+ OVX BMSCs. And the mRNA levels of IL-1ß, IL-6, Tnf-α and Ifn-γ increased significantly in DEC1 +/+ OVX BMMs compared with those in DEC1 +/+ sham BMMs, but not in DEC1 -/- OVX BMMs compared with those in DEC1 -/- sham BMMs. Furthermore, the p-IκBα and p-P65 significantly increased in DEC1 +/+ OVX BMMs compared with those in DEC1 +/+ sham BMMs, but did not increase in DEC1 -/- OVX BMMs compared with those in DEC1 -/- sham BMMs. Taken together, DEC1 deficiency inhibits the NF-κB pathway induced by OVX, thereby decreasing cytokines, and subsequently, inhibits the decrease of osteogenesis and the increase of osteoclastogenesis caused by OVX. The findings provide a novel understanding of postmenopausal osteoporosis development, which offers potential avenues for the intervention strategies.
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BACKGROUND: Treatment options for T1/2N0M0 anal squamous cell carcinoma include chemotherapy, radiotherapy, chemoradiotherapy, and local excision, although the optimal treatment method has not been determined. METHODS: The National Cancer Institute Surveillance, Epidemiology and Results database was used to search and screen 1465 patients with cT1/2N0M0 anal squamous cell carcinoma who were clinically diagnosed between 2004 and 2016. Survival analysis was performed using the Kaplan-Meier method and log-rank test. Cox proportional hazards regression analysis was performed to screen independent prognostic factors and build a nomogram survival prediction model. According to the risk score, patients were divided into low, medium, and high risk groups using X-tile software. RESULTS: Age, sex, grade and cT stage were identified as independent prognostic factors for cT1/2N0M0 anal squamous cell carcinoma and were included in the nomogram to construct a prediction model. The C-index of the model was 0.770 [95% confidence interval (CI), 0.693-0.856], which was higher than the C-index of T stage 0.565 (95% CI, 0.550-0.612). Low-risk patients benefited from local resection, moderate-risk patients benefited from radiotherapy, and high-risk patients benefited from radiotherapy or chemoradiotherapy. This was confirmed using external validation data from the center. CONCLUSION: The nomogram developed in this study effectively and comprehensively evaluated the prognosis of patients with cT1/2N0M0 squamous cell carcinoma of the anal canal. Local excision is recommended for low risk patients, radiotherapy for moderate-risk patients, and radiotherapy or chemoradiotherapy for high-risk patients.
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Neoplasias del Ano , Carcinoma de Células Escamosas , Humanos , Masculino , Femenino , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/mortalidad , Persona de Mediana Edad , Neoplasias del Ano/terapia , Neoplasias del Ano/patología , Neoplasias del Ano/mortalidad , Anciano , Nomogramas , Pronóstico , Estadificación de Neoplasias , Adulto , Programa de VERF , Anciano de 80 o más AñosRESUMEN
Although post-translational lipidation is prevalent in eukaryotes, its impact on the liquid-liquid phase separation of disordered proteins is still poorly understood. Here, we examined the thermodynamic phase boundaries and kinetics of aqueous two-phase system (ATPS) formation for a library of elastin-like polypeptides modified with saturated fatty acids of different chain lengths. By systematically altering the physicochemical properties of the attached lipids, we were able to correlate the molecular properties of lipids to changes in the thermodynamic phase boundaries and the kinetic stability of droplets formed by these proteins. We discovered that increasing the chain length lowers the phase separation temperature in a sigmoidal manner due to alterations in the unfavorable interactions between protein and water and changes in the entropy of phase separation. Our kinetic studies unveiled remarkable sensitivity to lipid length, which we propose is due to the temperature-dependent interactions between lipids and the protein. Strikingly, we found that the addition of just a single methylene group is sufficient to allow tuning of these interactions as a function of temperature, with proteins modified with C7-C9 lipids exhibiting non-Arrhenius dependence in their phase separation, a behavior that is absent for both shorter and longer fatty acids. This work advances our theoretical understanding of protein-lipid interactions and opens avenues for the rational design of lipidated proteins in biomedical paradigms, where precise control over the phase separation is pivotal.
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Polipéptidos Similares a Elastina , Ácidos Grasos , Cinética , Separación de Fases , Termodinámica , ProteínasRESUMEN
Cancer immunotherapy has revolutionized the treatment of lung adenocarcinoma (LUAD); however, a significant proportion of patients do not respond. Recent transcriptomic studies to understand determinants of immunotherapy response have pinpointed stromal-mediated resistance mechanisms. To gain a better understanding of stromal biology at the cellular and molecular level in LUAD, we performed single-cell RNA sequencing of 256,379 cells, including 13,857 mesenchymal cells, from 9 treatment-naïve patients. Among the mesenchymal cell subsets, FAP+PDPN+ cancer-associated fibroblasts (CAF) and ACTA2+MCAM+ pericytes were enriched in tumors and differentiated from lung-resident fibroblasts. Imaging mass cytometry revealed that both subsets were topographically adjacent to the perivascular niche and had close spatial interactions with endothelial cells (EC). Modeling of ligand and receptor interactomes between mesenchymal and ECs identified that NOTCH signaling drives these cell-to-cell interactions in tumors, with pericytes and CAFs as the signal receivers and arterial and PLVAPhigh immature neovascular ECs as the signal senders. Either pharmacologically blocking NOTCH signaling or genetically depleting NOTCH3 levels in mesenchymal cells significantly reduced collagen production and suppressed cell invasion. Bulk RNA sequencing data demonstrated that NOTCH3 expression correlated with poor survival in stroma-rich patients and that a T cell-inflamed gene signature only predicted survival in patients with low NOTCH3. Collectively, this study provides valuable insights into the role of NOTCH3 in regulating tumor stroma biology, warranting further studies to elucidate the clinical implications of targeting NOTCH3 signaling. SIGNIFICANCE: NOTCH3 signaling activates tumor-associated mesenchymal cells, increases collagen production, and augments cell invasion in lung adenocarcinoma, suggesting its critical role in remodeling tumor stroma.
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Adenocarcinoma del Pulmón , Fibroblastos Asociados al Cáncer , Neoplasias Pulmonares , Invasividad Neoplásica , Receptor Notch3 , Análisis de la Célula Individual , Células del Estroma , Microambiente Tumoral , Humanos , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/genética , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/patología , Comunicación Celular , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Receptor Notch3/metabolismo , Receptor Notch3/genética , Transducción de Señal , Células del Estroma/metabolismo , Células del Estroma/patologíaRESUMEN
Developing high-performance electromagnetic interference (EMI) shielding materials that are lightweight and flexible and have excellent mechanical properties is an ideal choice for modern integrated electronic devices and microwave protection. Herein, we report the preparation of core-shell polyaniline (PANI)-based nanofiber membranes for EMI shielding through seed polymerization. Electrospinning a PANI solution leads to homogeneously dispersed PANI on the nanofiber surface, with abundant attachment sites for aniline through electrostatic adsorption and hydrogen bonding interaction, allowing PANI to grow on the nanofiber surfaces. This stable core-shell heterostructure provides more interfaces for reflecting and absorbing microwaves. The PANI/PVDF@PANI membranes achieved a shielding efficiency (SE) of 44.7 dB at a thickness of only 1.2 mm, exhibiting an exceptionally high specific EMI shielding effectiveness (SE/t) of 372.5 dB cm-1. Furthermore, the composite membrane exhibits outstanding mechanical stability, durability, air permeability, and moisture permeability, also making it suitable for applications such as EM shielding clothing.
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Background: Ischemic stroke (IS) represents a major cause of morbidity and mortality across the globe. The aberrant expression of miR-365 has been found to be implicated in a wide array of human diseases, including atherosclerosis and cancer. Studies on single-nucleotide polymorphisms (SNPs) in miRNA genes can help gain insight into the susceptibility to the condition. This study aimed to examine the relationship between miR-365 SNPs and the risk of IS. Methods: The study recruited 215 IS patients and 220 controls. The SNPscans genotyping was employed to genotype three polymorphic loci (rs121224, rs30230, and rs178553) of miR-365. The relative expression of miR-365 in peripheral blood mononuclear cells of the patients and controls was determined by using real-time quantitative PCR. Results: The miR-365 rs30230 polymorphism exhibited a significant association with the risk of developing IS (TC vs. CC: adjusted OR = 0.55, 95% CI: 0.33-0.92, P = 0.022; TT vs. CC: adjusted OR = 0.34, 95% CI: 0.14-0.85, P = 0.021; TC +TT vs. CC: adjusted OR = 0.51, 95% CI: 0.31-0.83, P = 0.007; T vs. C: adjusted OR = 0.57, 95% CI: 0.39-0.83, P = 0.004). Haplotype analysis revealed that the C-T-G haplotype was associated with a decreased risk of IS (OR = 0.68, 95% CI: 0.46-1.00, P = 0.047). Furthermore, miR-365 expression was significantly higher in IS patients than in controls (P < 0.001). Interestingly, patients with rs30230 TC or TT genotypes had lower miR-365 levels compared to their counterparts with CC genotypes (P < 0.001). Conclusions: The miR-365 rs30230 polymorphism might bear an association with IS susceptibility in the Chinese population, and the rs30230 TC/TT genotype might be a protective factor against IS.
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In this study, an expanded graphite (EG) with nano-CuS (EG/CuS) support material with a special morphology was prepared, with EG/CuS filled with different ratios of palmitic acid (PA). Finally, a PA/EG/CuS composite phase change thermal storage material with photothermal conversion performance was synthesized. The superb chemical and thermal stability of PA/EG/CuS was demonstrated by characterization and analysis of the experiments. EG, a multi-layer structured material, provides rich binding sites for PA and nano-CuS and constructs rich thermal conductivity paths, which effectively improves the thermal conductivity of PA/EG/CuS. It is noted that the maximum thermal conductivity of PA/EG/CuS reached 0.372 W m-1 K-1 and the maximum phase change thermal storage capacity reached 260.4 kJ kg-1, which proved the excellent thermal storage properties of PA/EG/CuS. In addition, PA/EG/CuS exhibits excellent photothermal conversion performance, and the experimental results demonstrated that the best photothermal conversion efficiency of PA/EG/CuS reached 81.4%. The PA/EG/CuS developed in this study provides a promising method for fabricating excellent conductive and low leakage composite phase change materials for solar energy utilization and energy storage.
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Catalytic transfer hydrogenation (CTH) based on non-noble-metal catalysts has emerged as an environmentally friendly way for the utilization of biomass resources. However, the development of efficient and stable non-noble-metal catalysts is crucially challenging due to their inherent inactivity. Herein, a metal-organic framework (MOF)-transformed CoAl nanotube catalyst (CoAl NT160-H) with unique confinement effect was developed via a "MOF transformation and reduction" strategy, which exhibited excellent catalytic activity for the CTH reaction of levulinic acid (LA) to γ-valerolactone (GVL) with isopropanol (2-PrOH) as the H donor. Comprehensive characterizations and experimental investigations uncovered that the confined effect of the ultrathin amorphous Al2O3 nanotubes could modulate the electronic structure and enhance the Lewis acidity of Co nanoparticles (NPs), thus contributing to the adsorption and activation of LA and 2-PrOH. The synergy between the electropositive Co NPs and Lewis acid-base sites of the CoAl NT160-H catalyst facilitated the transfer of α-H in 2-PrOH to the C atom of carbonyl in LA during the CTH process via a Meerwein-Ponndorf-Verley mechanism. Moreover, the confined Co NPs embedded on am-Al2O3 nanotubes endowed the CoAl NT160-H catalyst with superior stability and the catalytic activity was nearly unchanged for at least ten cycles, far surpassing that of the Co/am-Al2O3 catalyst prepared by the traditional impregnation method.
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Background: An increasing number of studies have reported associations between single nucleotide polymorphisms (SNPs) and ovarian cancer (OC) risk. However, some of the findings were inconsistent. The objective of this umbrella review was to evaluate the associations comprehensively and quantitatively. Methods: The protocol of this review was registered in PROSPERO (No. CRD42022332222). We searched the PubMed, Web of Science, and Embase databases to identify related systematic reviews and meta-analyses from inception to 15 October 2021. In addition to estimating the summary effect size by using fixed and random effects models and calculating the 95% prediction interval, we evaluated the cumulative evidence for associations with nominally statistical significance based on the Venice criteria and false positive report probability (FPRP). Results: Forty articles were included in this umbrella review, which referred to a total of 54 SNPs. The median number of original studies per meta-analysis was four, while the median number of total subjects was 3455. All included articles had greater than moderate methodological quality. A total of 18 SNPs were nominally statistically associated with OC risk; 6 SNPs (8 genetic models), 5 SNPs (7 genetic models), and 16 SNPs (25 genetic models) were identified as strong, moderate, and weak cumulative evidence, respectively. Conclusion: This umbrella review revealed associations between SNPs and OC risk and suggested strong cumulative evidence of associations of six SNPs (eight genetic models) with OC risk.
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Rheumatoid arthritis (RA) is one of the most common autoimmune diseases and affects almost 1% of the population. Differentiated embryo-chondrocyte expressed gene-1 (DEC1) has been associated with both osteogenesis and osteoclastogenesis. RA condition is marked by inflammatory hyperplasia, and DEC1 is known to support inflammatory reactions and implicated in antiapoptosis and cell invasion. Here, our goal was to test the hypothesis that DEC1 enhances RA development induced by collagen-induced arthritis (CIA), a well-recognized protocol for developing RA animal models. DEC1+/+ and DEC1-/- mice were subjected to CIA protocol, and the development of RA condition was monitored. We found that CIA robustly induced RA phenotypes (e.g., synovial hyperplasia) and greatly increased the expression of proinflammatory cytokines such as TNF-α. However, these changes were detected in DEC1+/+ but not DEC1-/- mice. Interestingly, these very cytokines strongly induced DEC1, and such a dual role of DEC1, as an inducer for and being induced by proinflammatory cytokines, constitutes a DEC1-amplifying circuit for inflammation. Knockdown of DEC1 in human MH7A cells strongly decreased cell migration and invasion as well as the expression of genes related to RA phenotypes. The combination of DEC1-directed migration and invasion in vitro with synovial hyperplasia in vivo mechanistically establishes cellular bases on how DEC1 is involved in the development of RA phenotypes. In addition to inflammatory signaling, DEC1 functionally interacted with PI3KCA(p110α)/Akt/GSK3ß, Wnt/ß-catenin, and NFATc1. Such engagement in multiple signaling pathways suggests that DEC1 plays coordinated and integral roles in developing RA, one of the most common autoimmune diseases.
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Artritis Experimental , Artritis Reumatoide , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Proteínas de Homeodominio , Animales , Humanos , Ratones , Artritis Experimental/inducido químicamente , Artritis Experimental/genética , Artritis Reumatoide/genética , Colágeno , Citocinas/metabolismo , Fibroblastos/metabolismo , Hiperplasia/patología , Inflamación/patología , Membrana Sinovial/patología , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Proteínas de Homeodominio/metabolismoRESUMEN
Fusarium oxysporum is the main pathogen of Panax notoginseng root rot, and chemical fungicides remain the primary measures to control the disease. Plant essential oil (EO) is a volatile plant secondary metabolic product that does not produce any residue to replace chemical pesticide. To comprehensively understand the antifungal mechanism of Alpinia officinarum Hance EO, the physiological indicators, proteome and metabolome were analyzed using F. oxysporum spores and hyphae treated with different EO concentrations. The cell membrane was damaged after both low and high concentrations of EO treatment, along with leakage of the cell contents. To resist the destruction of membrane structure, fungi can increase the function of steroid biosynthesis and expression of these catalytic enzymes, including squalene monooxygenase (SQLE), sterol 14alpha-demethylase (CYP51, CYP61A), delta14-sterol reductase (TM7SF2, ERG4), methylsterol monooxygenase (MESO1), and sterol 24-C-methyltransferase (SMT1). Furthermore, the tricarboxylic acid cycle (TCA) was influenced by inhibiting the expression of glutamate synthase (GLT1), 4-aminobutyrate aminotransferase (ABAT), and succinate-semialdehyde dehydrogenase (gabD); increasing malate and gamma-aminobutyric acid (GABA); and decreasing citrate content. The spore germination rate and mycelia growth were decreased because the expression of cohesin complex subunit SA-1/2 (IRR1) and cohesion complex subunit (YCS4, BRN1, YCG1) were inhibited. Particularly, under high EO concentrations, cyclin-dependent kinase (CDC28) and DNA replication licensing factor (MCM) were further inhibited to disrupt the cell cycle and meiosis, thus affecting cell division. The results of this study will enrich the understanding of the antifungal mechanism of EOs and provide an important basis to develop new plant-derived fungicides.
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Due to the great threat of chemical pesticides to the ecosystem environment, it is a long-term goal to find environmentally friendly green pesticides. Essential oils (EOs) are considered weapons in plant chemical defense and are important sources of green pesticides. Therefore, the antifungal effects and action mechanisms of Cymbopogom citratus (C. citratus) EOs against seven kinds of Panax notoginseng (P. notoginseng) pathogenic fungi were investigated. Oxford Cup results showed that C. citratus EOs had an excellent detraction effects against seven fungi of P. notoginseng. Gas chromatography-mass spectrometry (GC-MS) was used to construct the chemical profiles of C. citratus EOs, disclosed that the main categories are terpenes and oxygenated terpenes. In addition, compared with the hymexazol, the minimum inhibitory concentration (MIC) showed that EOs and their main components had strong antifungal activities. Besides, EOs had a synergistic effect with hymexazol (a chemical pesticide). The antifungal mechanism of C. citratus EOs was studied by using Fusarium oxysporum (F. oxysporum) as the dominant pathogen. C. citratus EOs may affect the metabolism of fungi and induce mycotoxins to destroy the cell wall to achieve antifungal effects. Finally, EOs were found to significantly retard P. notoginseng infection by F. oxysporum. According to our research, C. citratus EOs are potential green antifungal agent that can be used in the cultivation of P. notoginseng.
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Aceites Volátiles , Panax notoginseng , Plaguicidas , Antifúngicos/farmacología , Aceites Volátiles/farmacología , Ecosistema , Hongos , TerpenosRESUMEN
Graphene has been widely used as a nanofiller in advanced electronic devices and nanocomposite materials to achieve enhanced electronic, mechanical, and barrier properties. Adequate polymers play the role of the composite matrix and can assist in the liquid-phase exfoliation of pristine graphene without any heavy chemical modification and the detriment of the properties of graphene. This stabilization mechanism is generally attributed to the steric forces formed between the polymer-adsorbed adsorbent. However, the key influence of the polymer concentration on the maximum graphene content in the colloidal solutions is still unclear. In this study, three different molar weights of water-soluble polyvinyl alcohol (PVA) were used for graphene dispersion. The influence of the PVA concentration on the graphene dispersion was systematically studied. Based on Flory's theory, we first proposed a model to describe the polymer adsorption process in the graphene/PVA/water ternary system in the "dilute" regime and simulated the adsorption-free energy changes during this transformation. This model is in good agreement with the experimental results and explains the critical polymer concentration, Cc, allowing the optimization of the graphene/polymer ratio. This fundamental understanding of polymer physisorption on 2D materials provides a simple method for producing nanocomposites with controlled nanosheet/polymer ratios and structures, which are of great interest for energy devices and biomaterials.
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Nanocellulose has lately emerged as one of the most promising "green" materials due to its unique properties. Nanocellulose can be mainly divided into three types, i.e., cellulose nanocrystals (CNCs), cellulose nanofibrils (CNFs), and bacterial cellulose (BC). With the rapid development of technology, nanocellulose has been designed into multidimensional structures, including 1D (nanofibers, microparticles), 2D (films), and 3D (hydrogels, aerogels) materials. Due to its adaptable surface chemistry, high surface area, biocompatibility, and biodegradability, nanocellulose-based composite materials can be further transformed as drug delivery carriers. Herein, nanocellulose-based composite material used for drug delivery was reviewed. The typical drug release behaviors and the drug release mechanisms of nanocellulose-based composite materials were further summarized, and the potential application of nanocellulose-based composite materials was prospected as well.
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In this study, a new cellulose nanofibril (CNF) composite aerogel was fabricated using a green and facile mussel-inspired coating strategy. First, the CNF hydrogel was crosslinked by calcium ion followed by immersion in dopamine solution. Second, the surface of CNF was modified using polydopamine (PDA) to obtain PDA@CNF (PCNF) composite aerogel. The PCNF composite aerogels had large surface areas (368.15 m2/g) and low bulk density (27.2 mg/cm3). The composite aerogel exhibited improved mechanical properties, which were almost three times compared with those of CNF aerogel. Moreover, PCNF composite aerogel had good resilience under a wet state. The PDA functional layer remarkably enhanced the adsorption capacities of the composite aerogel for methylene blue (MB). The maximum adsorption of MB was 208 mg/g at an initial dye concentration of 50 mg/L. The adsorption isotherm and kinetic behaviors of the composite aerogel were consistent with Langmuir and pseudo-second-order models. In addition, the PCNF composite aerogels had a high adsorption capacity over a wide pH range. The reuse experiment showed that the removal efficiency of the composite aerogel remained higher than 85% after five cycles. Therefore, PCNF composite aerogels may have potential application in wastewater treatment due to its environmental sustainability and low energy consumption.
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Celulosa , Polímeros , Adsorción , Celulosa/química , Indoles/química , Azul de Metileno , Polímeros/químicaRESUMEN
To screen natural drugs with strong inhibitory effects against pathogenic fungi related to P. notoginseng, the antifungal activities of garlic and fennel EOs were studied by targeting P. notoginseng disease-associated fungi, and the possible action mechanisms of garlic and fennel EOs as plant fungicides were preliminarily discussed. At present, the antifungal mechanism of EOs has not been fully established. Therefore, understanding the antifungal mechanism of plant EOs is helpful to address P. notoginseng diseases continuous cropping disease-related obstacles and other agricultural cultivation problems. First, the Oxford cup method and chessboard were used to confirm that the EOs and oxamyl had a significant inhibitory effect on the growth of Fusarium oxysporum. F. oxysporum is the main pathogen causing root rot of P. notoginseng and the preliminary study on the antifungal mechanisms of the EOs against F. oxysporum showed that the inhibition of EOs mainly affects cell membrane permeability and cell processes and affects the enzyme activities of micro-organism, to achieve antifungal effects. Finally, an in vivo model verified that both two EOs could significantly inhibit the occurrence of root rot caused by F. oxysporum.
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Foeniculum , Ingredientes Alimentarios , Ajo , Aceites Volátiles , Panax notoginseng , Antifúngicos/farmacología , Hongos , Aceites Volátiles/farmacología , Panax notoginseng/microbiologíaRESUMEN
Colorectal cancer (CRC) is the second deadly and the third most common malignancy worldwide. It has been projected that annual new cases of CRC will increase by 63% in 2040, constituting an even greater health challenge for decades to come. This study has linked DEC1 (differentiated embryonic chondrocyte expressed gene 1) to the pathogenesis of CRC. Based on the analysis of patient samples and database data, DEC1 is expressed much higher in CRC than the adjacent normal tissues. CRC patients with higher DEC1 expression have a shorter survival time. The carcinogenesis protocol with azoxymethane/dextran sulfate induces a higher number of tumors with larger sizes in DEC1+/+ than DEC1-/- mice. Overexpression of DEC1 increases the expression of proliferation- and antiapoptosis-related genes, but decreases the level of proapoptotic genes. Mechanistically, this study has shown that DEC1 is functionally looped to the IL-6/STAT3 signaling pathway (interleukin-6/signal transducer and activator of transcription 3). IL-6 induces DEC1, and DEC1 enhances the phosphorylation of STAT3, resulting in increased pSTAT3/STAT3 ratio. DEC1 and STAT3 are present in reciprocal immunocomplexes, pointing to physical interactions (presumably with pSTAT3). These findings establish that DEC1 is a CRC enhancer. The enhancement is achieved largely through the IL-6/STAT3 pathway. The potential of the physical interaction between DEC1 and STAT3 will likely serve as a foundation to develop intervention strategies for CRC prevention and therapy.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Neoplasias Colorrectales , Proteínas de Homeodominio , Interleucina-6 , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Carcinogénesis , Condrocitos/metabolismo , Condrocitos/patología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Proteínas de Homeodominio/metabolismo , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Ratones , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Transducción de SeñalRESUMEN
Background: The association between serum cystatin C levels and obesity has not been fully explored in adolescents. This study aimed to explore the association between serum cystatin C levels and obesity in adolescents of different sexes. Methods: We conducted a cross-sectional study including 481 adolescents aged 14-17 years. Cystatin C level was measured by immunoassay. Health examinations data, biochemical parameters, and questionnaire information were collected. The restricted cubic spline model analyzed the association between cystatin C levels and obesity in boys and girls. Results: Boys exhibited significantly higher cystatin C levels than girls, with a mean level of 0.97 ± 0.10 mg/L in boys and 0.86 ± 0.09 mg/L in girls (P < 0.001). The restricted cubic spline model suggested that low or high cystatin C levels were associated with an increased risk of obesity in boys, whereas only higher cystatin C levels were associated with an increased risk of obesity in girls. Conclusions: A U-shaped correlation was observed between serum cystatin C levels and the risk of obesity in boys. However, in girls, the risk of obesity showed a trend of initially increase and then decrease with increasing cystatin C levels. Longitudinal studies should be conducted to further investigate the diagnostic potential of cystatin C in the progression of early obesity in adolescents of different sexes.