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Potentially toxic elements (PTEs) pose a significant threat to the groundwater system and human health. Pollution and the potential risks of PTEs in groundwater in the KÇnqi River Basin (KRB) of the northwest arid zones of China are still unknown. A total of 53 groundwater samples containing eight PTEs (Al, As, Cd, Cu, Mn, Pb, Se, and Zn) were collected from the KRB, and the pollution levels and probabilistic health risks caused by PTEs were assessed based on the Nemerow Index (NI) method and the health risk assessment model. The results revealed that the mean contents of Al, As, and Mn in the groundwater surpassed the Class III threshold of the Standard for Groundwater Quality of China. The overall pollution levels of the investigated PTEs in the groundwater fall into the moderate pollution level. The spatial distributions of contents and pollution levels of different PTEs in the groundwater were different. Health risk assessment indicated that all the investigated PTEs in groundwater in the KRB may pose a probabilistic non-carcinogenic health risk for both adults and children. Moreover, As may pose a non-carcinogenic health risk, whereas the non-carcinogenic health risk posed by the other seven PTEs in groundwater will not have the non-carcinogenic risks. Furthermore, As falls into the low carcinogenic risk level, whereas Cd falls into the very low carcinogenic risk level. Overall, As was confirmed as the dominant pollution factor and health risk factor of groundwater in the KRB. Results of this study provide the scientific basis needed for the prevention and control of PTE pollution in groundwater.
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Heavy metal(loid) (HM) contamination is a significant threat to wetland ecosystem. However, contamination risks of HMs in overlying water of small wetlands, which are easily ignored because of their minor occupancy in an overall area, are nearly unknown. A total of 36 water samples containing six HMs were collected from the urban and rural small wetlands of Urumqi in China, and the contamination levels and probabilistic health risks caused by HMs were assessed using the Nemerow pollution index (NPI) and the health risk assessment model introduced by the US EPA. The results revealed that the average concentration of Hg in the urban and rural small wetlands surpassed the Class II thresholds of the Environmental Quality Standards for Surface Water (GB 3838-2002) by factors of 3.2 and 5.0 times, respectively. The overall contamination levels of HMs in the small wetlands fall into the high contamination level. Results of a health risk assessment indicated that non-carcinogenic health risk of the investigated HMs are found to be lower than the acceptable range for adults, but higher than the acceptable range for children. Meanwhile, As falls into the low carcinogenic risk level, whereas Cd falls into the very low carcinogenic risk level. Overall, HMs in rural small wetlands showed relatively higher contamination levels and probabilistic health risks than that of urban small wetlands. In addition, As was identified as the dominant health risk factor in the overlying water of small wetlands in the study area. Findings of this study provide scientific support needed for the prevention of HM contamination of small wetlands in arid zones.
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Monascus species are functional fermentation fungi with great potential for selenium (Se) supplementation. This study investigated the effects of Se bio-fortification on the growth, morphology, and biosynthesis of Monascus ruber M7. The results demonstrated a significant increase in the yield of orange and red Monascus pigments (MPs) in red yeast rice (RYR) by 38.52% and 36.57%, respectively, under 20 µg/mL of selenite pressure. Meanwhile, the production of citrinin (CIT), a mycotoxin, decreased from 244.47 µg/g to 175.01 µg/g. Transcriptome analysis revealed significant upregulation of twelve genes involved in MPs biosynthesis, specifically MpigE, MpigF, and MpigN, and downregulation of four genes (mrr3, mrr4, mrr7, and mrr8) associated with CIT biosynthesis. Additionally, three genes encoding cysteine synthase cysK (Log2FC = 1.6), methionine synthase metH (Log2FC = 2.2), and methionyl-tRNA synthetase metG (Log2FC = 1.8) in selenocompound metabolism showed significantly upregulated. These findings provide insights into Se biotransformation and metabolism in filamentous fungi.
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Biofortificación , Citrinina , Monascus , Ácido Selenioso , Selenio , Monascus/metabolismo , Monascus/genética , Monascus/crecimiento & desarrollo , Selenio/metabolismo , Ácido Selenioso/metabolismo , Citrinina/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Pigmentos Biológicos/metabolismo , Fermentación , Productos BiológicosRESUMEN
Bimetallic MOF derivatives have shown excellent performance as nano-enzymes in the field of catalysis. Herein, PdCo oxide nanoflowers with three-dimensional flower were prepared by a simple pyrolysis method on a precursor of bimetallic PdCo-MOF. PdCoOx showed excellent peroxidase mimic activity, which could significantly promote the oxidation of TMB by H2O2. Compared with CoOx, the peroxidase mimic activity of the optimized PdCoOx-300 increased by 2.41-fold. PdCoOx-300 has high affinity for TMB and H2O2 with Km values of 0.16 mM and 2.11 mM, which are only 57.03% and 36.87% of HRP, respectively. The highly specific peroxidase mimic activity is conducive to the sensitive detection of H2O2, glucose and ascorbic acid with limit of detection of 10, 100 and 10 nM, respectively. Furthermore, the total antioxidant capacity in the actual beverage samples was conducted, which showed good anti-interference ability and recovery rate.
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Antioxidantes , Peróxido de Hidrógeno , Estructuras Metalorgánicas , Peroxidasa , Antioxidantes/química , Estructuras Metalorgánicas/química , Peroxidasa/química , Peróxido de Hidrógeno/química , Paladio/química , Catálisis , Oxidación-Reducción , Cobalto/química , Nanoestructuras/química , Ácido Ascórbico/química , Ácido Ascórbico/análisis , Glucosa/química , Glucosa/análisis , Óxidos/químicaRESUMEN
This study aimed to investigate the efficacy of supercritical CO2 (SC-CO2) extraction in enhancing the extraction rate, purity, and antioxidant activity of Indocalamus latifolius (Keng) McClure (Poaceae) leaf terpenoids (ILLTs). Crude extracts obtained from leaves were subjected to qualitative and quantitative analyses, revealing neophytadiene, phytol, ß-sitosterol, ß-amyrone, squalene, and friedelin as the primary terpenoid constituents, identified through gas chromatography-mass spectrometry (GC-MS). Compared with steam distillation extraction (SD), simultaneous distillation extraction (SDE), ultra-high pressure-assisted n-hexane extraction (UHPE-Hex), ultra-high pressure-assisted ethanol extraction (UHPE-EtOH), ultrasound-assisted n-hexane extraction (UE-Hex), and ultrasound-assisted ethanol extraction (UE-EtOH), SC-CO2 exhibited a superior ILLT extraction rate, purity, and antioxidant activity. Scanning electron microscopy (SEM) observations of the residues further revealed more severe damage to both the residues and their cell walls after SC-CO2 extraction. Under optimal parameters (4.5 h, 26 MPa, 39 °C, and 20% ethyl alcohol), the ILLT extraction rate with SC-CO2 reached 1.44 ± 0.12 mg/g, which was significantly higher than the rates obtained by the other six methods. The subsequent separation and purification using WelFlash C18-l, BUCHI-C18, and Sephadex LH-20 led to an increase in the purity of the six terpenoid components from 12.91% to 93.34%. Furthermore, the ILLTs demonstrated cytotoxicity against HepG2 cells with an IC50 value of 148.93 ± 9.93 µg/mL. Additionally, with increasing concentrations, the ILLTs exhibited an enhanced cellular antioxidant status, as evidenced by reductions in both reactive oxygen species (ROS) and malondialdehyde (MDA) levels.
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In the study, natural deep eutectic solvents (NADESs) were used as alternatives to traditional chemical solvents for the extraction of polyphenols from Elaeagnus angustifolia L. Nine NADESs were tested for the first time and compared with ethanol and water (traditional solvents) regarding the extraction of phenolic compounds from E. angustifolia L. These solvents were particularly effective at extracting polyphenols, whose low water solubility usually requires high amounts of organic solvents. The solvent based on choline chloride and malonic acid provided optimal results and was selected for further optimization. The effects of material-to-liquid ratio, ultrasound time, and ultrasound temperature on the extraction efficiency were studied through single-factor experiments. These parameters were optimized by Box-Behnken design using response surface methodology. The optimal conditions identified were 49.86 g/mL of material-to-liquid ratio, 31.10 min of ultrasound time, and 62.35 °C of ultrasound temperature, resulting in a high yield of 140.30 ± 0.19 mg/g. The results indicated that the NADES extraction technique provided a higher yield than the conventional extraction process. The antioxidant activity of the extract of polyphenols from E. angustifolia L. was determined, and UPLC-IMS-QTOF-MS was used to analyze the phenolic compounds in it. The results revealed that the scavenging ability of 1,1-diphenyl-2-picryl-hydrazil and 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate) extracted by NADES was higher than that of polyphenols extracted by water and ethanol. Furthermore, a total of 24 phenolic compounds were identified in the extract. To the best of our knowledge, this is the first study in which a green and efficient NADES extraction method has been used to extract bioactive polyphenols from E. angustifolia L., which could provide potential value in pharmaceuticals, cosmetics, and food additives.
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Antioxidantes , Elaeagnaceae , Extractos Vegetales , Polifenoles , Polifenoles/química , Polifenoles/aislamiento & purificación , Extractos Vegetales/química , Antioxidantes/química , Antioxidantes/farmacología , Antioxidantes/aislamiento & purificación , Elaeagnaceae/química , Disolventes Eutécticos Profundos/química , Tecnología Química Verde , Solventes/químicaRESUMEN
BACKGROUND: To improve phytol bioavailability, a novel method of magnetic stirring and high-pressure homogenization (HPH) combination was used to prepare zein/fucoidan-coated phytol nanoliposomes (P-NL-ZF). The characterization, the simulated in vitro digestion, and the antioxidant activity of these phytol nanoliposomes from the different processes have been studied. RESULTS: Based on the results of dynamic light scattering (DLS) and gas chromatography-mass spectrometer (GC-MS) analysis, P-NL-ZF prepared through the combination of magnetic stirring and HPH exhibited superior encapsulation efficiency at 76.19% and demonstrated exceptional physicochemical stability under a series of conditions, including storage, pH, and ionic in comparison to single method. It was further confirmed that P-NL-ZF by magnetic stirring and HPH displayed a uniform distribution and regular shape through transmission electron microscopy (TEM). Fourier-transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) analysis showed that electrostatic interactions and hydrogen bonding were the primary driving forces for the formation of composite nanoliposomes. Additionally, an in vitro digestion study revealed that multilayer composite nanoliposomes displayed significant and favorable slow-release properties (58.21%) under gastrointestinal conditions compared with traditional nanoliposomes (82.36%) and free phytol (89.73%). The assessments of chemical and cell-based antioxidant activities demonstrated that the coating of zein/fucoidan on phytol nanoliposomes resulted in enhanced effectiveness in scavenging activity of ABTS free radical and hydroxyl radical and mitigating oxidative damage to HepG2 cells. CONCLUSION: Based on our studies, the promising delivery carrier of zein/fucoidan-coated nanoliposomes is contributed to the encapsulation of hydrophobic natural products and enhancement of their biological activity. © 2024 Society of Chemical Industry.
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Antioxidantes , Liposomas , Nanopartículas , Fitol , Zeína , Antioxidantes/química , Antioxidantes/farmacología , Liposomas/química , Zeína/química , Fitol/química , Nanopartículas/química , Humanos , Tamaño de la Partícula , Estabilidad de Medicamentos , Composición de Medicamentos/métodos , Polisacáridos/química , Portadores de Fármacos/química , Liberación de FármacosRESUMEN
To solve the large size faultiness of Oryza sativa recombinant human serum albumin nanoparticle (OsrHSA NP), the structural discrepancies between OsrHSA and plasma-derived human serum albumin (pdHSA) were analyzed deeply in this research. It demonstrated that there were some subtle structural discrepancies located in subdomain IA and IIA between OsrHSA and pdHSA, which included peptide backbone, disulphide bridge and some amino acids. Firstly, the structural discrepancies were investigated through literature comparison, it inferred that the structural discrepancies resulted from the fatty acid (FA) binding to OsrHSA at site 2 of subdomain IA and IIA. To form a cavity for accommodation of FA molecule in OsrHSA, the peptide backbone structure of subdomain IA and IIA would change, accompanied by the conformational transition of disulphide bridges and side chain structure change of some amino acids in subdomain IA and IIA. These alterations induced the exposure of tryptophan (Trp) and tyrosine (Tyr) residues in subdomain IA and IIA and the decrease of net negative charges of molecular surface. The former would promote more OsrHSA molecules aggregate, and the latter would weaken the electrostatic repulsion. As a result, the size of OsrHSA NP was more extensive than that of pdHSA NP (175.84 ± 15.63 nm vs. 31.67 ± 1.31 nm) when the concentration of Dimethyl Sulphoxide (DMSO) was 30% (v/v). In this study, the experimental scheme of OsrHSA NP preparation was improved. There were two changes in the enhanced preparation scheme: pH 8.2 PBS buffer and 63% DMSO. It indicated that the improved OsrHSA NP carrier was comparable to the pdHSA NP carrier. The size and drug loading of paclitaxel-loaded improved OsrHSA NP were 53.57 ± 3.63 nm and 7.25 ± 0.46% (w/w), and those of docetaxel-loaded improved OsrHSA NP were 44.75 ± 2.26 nm and 8.43 ± 0.74% (w/w). Moreover, both NPs exhibited good stability for 168 h at 7.4 pH values. It is established that the improved OsrHSA NP is comparable to the pdHSA NP as a taxane delivery system.
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Nanopartículas , Oryza , Proteínas Recombinantes , Albúmina Sérica Humana , Humanos , Oryza/química , Albúmina Sérica Humana/química , Proteínas Recombinantes/química , Nanopartículas/química , Taxoides/química , Sistemas de Liberación de MedicamentosRESUMEN
Metabolism regulates the phenotype and function of macrophages. After recruitment to local tissues, monocytes are influenced by the local microenvironment and differentiate into various macrophages depending on different metabolic pathways. However, the metabolic mechanisms underlying decidual macrophage differentiation remain unknown. Interleukin-10 (IL-10) is an important decidual macrophage inducer and promotes oxidative phosphorylation (OXPHOS) of bone marrow-derived macrophages. In this study, we mainly investigate the metabolic changes involved in IL-10-generated macrophages from monocytes using in vitro models. We demonstrate that exposure of monocytes (either peripheral or THP-1) to IL-10 altered the phenotype and function of resultant macrophages that are linked with OXPHOS changes. Interleukin-10 enhanced the mitochondrial complex I and III activity of THP-1 cell-differentiated macrophages and increased the mitochondrial membrane potential, intracellular adenosine triphosphate, and reactive oxygen species levels. Oxidative phosphorylation blockage with oligomycin changed the cell morphology of IL-10-generated macrophages and the expression levels of cytokines, such as transforming growth factor beta, tumor necrosis factor-alpha, interferon gamma, and IL-10, apart from changes in the expression level of the surface markers CD206, CD209, and CD163. Moreover, in vivo IL-10 administration reduced the lipopolysaccharide (LPS)-induced embryo resorption rate, and this effect was diminished when OXPHOS was inhibited, demonstrating that OXPHOS is important for the improved pregnancy outcomes of IL-10 in LPS-induced abortion-prone mice. Our findings provide deep insights into the roles of IL-10 in macrophage biology and pregnancy maintenance. Nevertheless, the direct evidence that OXPHOS is involved in decidual macrophage differentiation needs further investigations.
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Diferenciación Celular , Interleucina-10 , Macrófagos , Fosforilación Oxidativa , Femenino , Animales , Interleucina-10/metabolismo , Fosforilación Oxidativa/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Ratones , Embarazo , Diferenciación Celular/efectos de los fármacos , Resultado del Embarazo , HumanosRESUMEN
This study involved the preparation of Metal Organic Frameworks (MOF)-derived Co8FeS8@Co1-xS nanoenzymes with strong interfacial interactions. The nanoenzymes presented the peroxidase (POD)-like activity and the oxidation activity of reduced glutathione (GSH). Accordingly, the dual activities of Co8FeS8@Co1-xS provided a self-cascading platform for producing significant amounts of hydroxyl radical (â¢OH) and depleting reduced glutathione, thereby inducing tumor cell apoptosis and ferroptosis. More importantly, the Co8FeS8@Co1-xS inhibited the anti-apoptosis protein B-cell lymphoma-2 (Bcl-2) and activated caspase family proteins, which caused tumor cell apoptosis. Simultaneously, Co8FeS8@Co1-xS affected the iron metabolism-related genes such as Heme oxygenase-1 (Hmox-1), amplifying the Fenton response and promoting apoptosis and ferroptosis. Therefore, the nanoenzyme synergistically killed anti-apoptotic tumor cells carrying Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations. Furthermore, Co8FeS8@Co1-xS demonstrated good biocompatibility, which paved the way for constructing a synergistic catalytic nanoplatform for an efficient tumor treatment.
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Ferroptosis , Neoplasias , Humanos , Apoptosis , Neoplasias/tratamiento farmacológico , Antioxidantes , Glutatión/metabolismo , Línea Celular Tumoral , Peróxido de HidrógenoRESUMEN
Given the current increases in the divorce rate and the number of single-parent families, the development of gender roles among children from single-parent families has received more and more attention. This study investigated how single parents influenced the formation of their children's gender roles and family-related factors that benefited the development of gender roles in single-parent children. Through in-depth interviews with 24 pairs of parents and children from single-parent families, we investigated single parents' and their children's cognition on gender roles, parents' parenting attitudes and behaviors during their children's gender role development, and communication and interaction between parents and children. Results showed intergenerational consistency in the gender role concepts of parents and their children in single-parent families. However, the children's gender role concepts were not completely and directly inherited from their parents, and could be affected by their subjective initiative. Additionally, single parenting did not necessarily negatively impact children's gender role development, which depends on their parent's parenting style. The study's limitations are discussed, and future directions for in-depth research are suggested.
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OBJECTIVE(S): The emergence of antibiotic resistance has led to suboptimal treatment outcomes for Mycoplasma pneumoniae pneumonia (MPP). Exploring naturally occurring drug components that are both effective against MPP and non-toxic may be a promising choice. This study aimed to investigate the therapeutic effect of andrographolide nanoparticles on pneumonia caused by Mycoplasma pneumoniae infection. METHODS: Andrographolide alginate-poloxamer nanoparticles (AND-ALG-POL/NPs) were obtained by wet medium grinding, and the characterization and in vitro release of the prepared andrographolide nanoparticles were examined by high performance liquid chromatography, particle size analyzer, zeta potential meter and transmission electron microscopy. The cytotoxicity and anti-inflammatory effects of AND-ALG-POL/NPs were evaluated in vitro by MP-infected lung epithelial cells BEAS-2B. Symptoms of pneumonia, total cell count, total protein content and inflammatory factor levels in BALF were assessed by MP-induced pneumonia in BALB/c mice treated with AND-ALG-POL/NPs, and histopathological studies were performed on lung tissues from experimental animals. RESULTS: The results showed that the prepared AND-ALG-POL/NPs were homogeneous spherical with a diameter of 180 ± 23 nm, a zeta potential of (-14.4 ± 2.1) mV, an average encapsulation rate of 87.74 ± 0.87 %, and an average drug loading of 13.17 ± 0.54 %. AND-ALG-POL/NPs were capable of slow release in vitro and showed significant inhibitory ability against MP (P < 0.001). However, AND-ALG-POL/NPs were not cytotoxic to normal cells and alleviated MP infection-induced apoptosis and elevated inflammatory factors. In the in vivo experiments, AND-ALG-POL/NPs alleviated the symptoms of pneumonia in MPP mice, reduced the abnormally elevated total cell count, total protein content and inflammatory factor levels in BALF, and alleviated lung tissue edema, inflammatory cell infiltration and apoptosis (P < 0.001). Meanwhile, the therapeutic effects of AND-ALG-POL/NPs on MPP were similar to those of azithromycin (AZM) and higher than those of andrographolide (AND) free monotherapy (P < 0.001). CONCLUSION: In summary, the prepared AND-ALG-POL/NPs can effectively inhibit MPP in vitro and in vivo, and the effect is similar to that of AZM. Therefore, AND- ALG - POL/NPs have the potential to replace AZM as a potential drug for the treatment of MPP.
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Diterpenos , Nanopartículas , Neumonía por Mycoplasma , Ratones , Animales , Neumonía por Mycoplasma/tratamiento farmacológico , Mycoplasma pneumoniae , Pulmón/metabolismo , Nanopartículas/química , AzitromicinaRESUMEN
BACKGROUND: Cry1Ab has emerged as a bio-insecticide to control Spodoptera litura (Lepidoptera: Noctuidae). However, the sublethal effects of Cry1Ab on the physiological changes and molecular level of S. litura have not been well documented. Our aims in this study were to assess the sublethal effect of Cry1Ab on S. litura, including midgut and Malpighian tubules as targets. RESULTS: After sublethal Cry1Ab exposure, distinct histological alterations were mainly observed in the midgut. Furthermore, the results of comparative RNA sequencing and tandem mass tag-based proteomics showed that, in the midgut, most differential expression genes (DEGs) were up-regulated and significantly enriched in the serine protease activity pathway, and up-regulated differential expression proteins (DEPs) were mainly associated with the oxidative phosphorylation pathway, whereas the down-regulated involved in the ribosome pathways. In the Malpighian tubules, DEGs and DEPs were significantly enriched in the ribosome pathway. We proposed that ribosome may act as a universal target in energy metabolism with other pathways via the results of protein-protein interaction analysis. Further, by verification of the mRNA expression of some Cry protein receptor and detoxification genes after Cry1Ab treatment, it was suggested that the ribosomal proteins (RPs) possibly participate in influencing the Bt-resistance of S. litura larvae under sublethal Cry1Ab exposure. CONCLUSION: Under sublethal Cry1Ab exposure, the midgut of S. litura was damaged, and the proteotranscriptomic analysis elucidated that Cry1Ab disrupted the energy homeostasis of larvae. Furthermore, we emphasized the potential role of ribosomes in sublethal Cry1Ab exposure. © 2024 Society of Chemical Industry.
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Toxinas de Bacillus thuringiensis , Endotoxinas , Proteínas Hemolisinas , Larva , Túbulos de Malpighi , Spodoptera , Animales , Spodoptera/efectos de los fármacos , Spodoptera/genética , Spodoptera/metabolismo , Spodoptera/crecimiento & desarrollo , Túbulos de Malpighi/efectos de los fármacos , Túbulos de Malpighi/metabolismo , Larva/efectos de los fármacos , Larva/genética , Larva/crecimiento & desarrollo , Larva/metabolismo , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Proteínas de Insectos/metabolismo , Proteínas de Insectos/genética , Transcriptoma , Tracto Gastrointestinal/efectos de los fármacos , Tracto Gastrointestinal/metabolismo , Insecticidas/toxicidad , Proteoma , Proteómica , Sistema Digestivo/efectos de los fármacos , Sistema Digestivo/metabolismoRESUMEN
The clinical application of oncology therapy is hampered by high glutathione concentrations, hypoxia, and inefficient activation of cell death mechanisms in cancer cells. In this study, Fe and Mo bimetallic sulfide nanomaterial (FeS2@MoS2) based on metal-organic framework structure is rationally prepared with peroxidase (POD)-, catalase (CAT)-, superoxide dismutase (SOD)-like activities and glutathione depletion ability, which can confer versatility for treating tumors and mending wounds. In the lesion area, FeS2@MoS2 with SOD-like activity can facilitate the transformation of superoxide anions (O2 -) to hydrogen peroxide (H2O2), and then the resulting H2O2 serves as a substrate for the Fenton reaction with FMS to produce highly toxic hydroxyl radicals (âOH). Simultaneously, FeS2@MoS2 has an ability to deplete glutathione (GSH) and catalyze the decomposition of nicotinamide adenine dinucleotide phosphate (NADPH) to curb the regeneration of GSH from the source. Thus it can realize effective tumor elimination through synergistic apoptosis-ferroptosis strategy. Based on the alteration of the H2O2 system, free radical production, glutathione depletion and the alleviation of hypoxia in the tumor microenvironment, FeS2@MoS2 NPS can not only significantly inhibit tumors in vivo and in vitro, but also inhibit multidrug-resistant bacteria and hasten wound healing. It may open the door to the development of cascade nanoplatforms for effective tumor treatment and overcoming wound infection.
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Antineoplásicos , Estructuras Metalorgánicas , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Animales , Antiinfecciosos/farmacología , Antiinfecciosos/química , Peróxido de Hidrógeno/metabolismo , Peróxido de Hidrógeno/química , Línea Celular Tumoral , Ratones , Glutatión/metabolismo , Hierro/química , Hierro/metabolismo , Apoptosis/efectos de los fármacos , Molibdeno/química , Molibdeno/farmacología , Nanoestructuras/química , Ferroptosis/efectos de los fármacosRESUMEN
Citrinin (CIT), a secondary metabolite produced by the filamentous fungi Monascus species, exhibits nephrotoxic, hepatotoxic, and carcinogenic effects in mammals, remarkably restricting the utilization of Monascus-derived products. CIT synthesis is mediated through the pksCT gene and modified by multiple genetic factors. Here, the regulatory effects of two pksCT transcripts, pksCTα, and pksCTß, generated via pre-mRNA alternative splicing (AS), were investigated using hairpin RNA (ihpRNA) interference, and their impact on CIT biosynthesis and the underlying mechanisms were assessed through chemical biology and transcriptome analyses. The CIT yield in ihpRNA-pksCTα and ihpRNA-pksCT (α + ß) transformants decreased from 7.2 µg/mL in the wild-type strain to 3.8 µg/mL and 0.08 µg/mL, respectively. Notably, several genes in the CIT biosynthetic gene cluster, specifically mrl3, mrl5, mrr1, and mrr5 in the ihpRNA-pksCT (α + ß) transformant, were downregulated. Transcriptome results revealed that silencing pksCT has a great impact on carbohydrate metabolism, amino acid metabolism, lipid metabolism, and AS events. The key enzymes in the citrate cycle (TCA cycle) and glycolysis were significantly inhibited in the transformants, leading to a decrease in the production of biosynthetic precursors, such as acetyl-coenzyme-A (acetyl-coA) and malonyl-coenzyme-A (malonyl-coA). Furthermore, the reduction of CIT has a regulatory effect on lipid metabolism via redirecting acetyl-coA from CIT biosynthesis towards lipid biosynthesis. These findings offer insights into the mechanisms underlying CIT biosynthesis and AS in Monascus, thus providing a foundation for future research.
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Early maladaptive schemas (EMSs) may be closely related to nonsuicidal self-injury (NSSI). The present study aimed to discuss the relationship between EMS and a personal history of NSSI. This was a retrospective study. A total of 1339 Chinese college students between 16 and 29 years old were asked to complete a questionnaire survey regarding their personal history of NSSI and EMSs. 116 college students reported a history of NSSI (NSSI group), who differed significantly in terms of all EMS-related scores than non-NSSI group(nâ =â 1223). Logistic regression analysis showed that the scores in the disconnection/rejection schema domain exhibited by subjects who were the only child in their family could help differentiate between college students with or without NSSI. The emotional deprivation schema was significantly associated with the lifetime frequency of NSSI behaviors; the vulnerability to harm or illness schema was significantly associated with the internal emotion regulation function and pain associated with NSSI; and the enmeshment/underdeveloped self schema was significantly associated with the addictive features of NSSI. The self-sacrifice schema was significantly associated with the external emotion regulation function of NSSI; the enmeshment/underdeveloped self schema was positively related with the sensation-seeking function of NSSI; and the abandonment/instability schema was negatively related the sensation-seeking function of NSSI. The disconnection/rejection schema domain was highly related with NSSI behaviors. EMS is significantly associated with the history, functions, addictive features, and severity of NSSI. Every EMS is worthy of further investigation and discussion with patients in the context of NSSI behaviors during clinical therapy.
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Emociones , Conducta Autodestructiva , Niño , Humanos , Adolescente , Adulto Joven , Adulto , Estudios Retrospectivos , Estudiantes/psicología , Encuestas y Cuestionarios , Conducta Autodestructiva/epidemiología , Conducta Autodestructiva/psicologíaRESUMEN
OBJECTIVE: This study was designed to explore the effects of low-dose levothyroxine (LT4) on levels of atrial natriuretic peptide (ANP) and c-type natriuretic peptide (CNP) in neonates with hypothyroidism (NH). METHODS: In this retrospective study, a total of 90 cases of NH screened out and confirmed by the First Affiliated Hospital of Zhejiang Chinese Medical University from October 2014 to February 2018 were selected as a study group. 80 healthy children who underwent physical examination during the same time period were enrolled as controls. Before and after treatment with LT4, the changes in the levels of serum thyroid stimulating hormone (TSH) and free thyroxine (FT4) were observed, and the changes in the levels of ANP and CNP and their relationships to clinical efficacy were evaluated. Additionally, the growth and development of body and the scores of the China-Wechsler Younger Children Scale of Intelligence (C-WYCSI) were compared before and after the treatment, and the changes in the cardiac functions of children in the study group were evaluated. Independent risk factors for mental abnormality after treatment were analyzed by logistic regression. RESULTS: After treatment, TSH levels in patients declined, while the levels of T3, T4, free triiodothyronine (FT3), and FT4 increased, without significant differences between groups. After treatment, ANP levels in patients increased but CNP levels decreased. ANP levels were negatively correlated with clinical efficacy, but CNP levels were positively correlated with it. Ultrasonic cardiography showed the improved cardiac functions. After treatment, the growth and development of body and the C-WYCSI scores increased compared to those before treatment. First visit date, T3, FT4, TSH were independent risk factors for mental disorders in children. CONCLUSION: For children with NH, low-dose LT4 can correct the level of thyroid function, promote physical and mental development, and improve the levels of ANP and CNP.
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In order to study the effect of both greenhouse and forest cultivating environments on Stropharia rugosoannulata, its volatile aroma compounds were measured by a headspace solid phase micro extractions-gas chromatograph-mass spectrometer (SPME-GC-MS). The optimal adsorption temperature was 75 °C and the optimal adsorption time was 40 min. A total of 36 volatile aroma compounds were identified by GC-MS, including 8 aldehydes, 2 ketones, 4 alcohols, 15 alkenes, and 4 alkanes. Hexanal, 3-Octanone, 2-Undecanone, (E)-Nerolidol, and (Z)-ß-Farnesene made great aromatic contributions. Among them, Hexanal, 3-Octanone, 2-Undecanone were the key aroma compounds for which odor activity values (OAVs) were more than 1. (E)-Nerolidol showed odor modification in the forest samples and showed a key aroma effect in greenhouse samples. (Z)-ß-Farnesene showed odor modification in greenhouse samples. 3-Octanone was the largest contributing compound for which the OAV was more than 60. The total content of volatile aroma compounds first increased and then decreased with growth time; it reached the highest level at 48 h: 2203.7 ± 115.2 µg/kg for the forest environment and 4516.6 ± 228.5 µg/kg for the greenhouse environment. The aroma was the most abundant at this time. All samples opened their umbrella at 84 h and become inedible. Principal component analysis (PCA), hierarchical cluster analysis (HCA), and orthogonal partial least squares discriminant analysis (OPLS-DA) were combined to analyze the aroma difference of S. rugosoannulata under two cultivation modes. PCA and HCA could effectively distinguish the aroma difference in different growth stages. Under different culturing methods, the aroma substances and their changes were different. The samples were divided into two groups for forest cultivation, while the samples were divided into three groups for greenhouse cultivation. At the end of growth, the aroma of S. rugosoannulata with the two cultivation modes was very similar. OPLS-DA clearly distinguished the differences between the two cultivation methods; 17 key aroma difference factors with variable importance projection (VIP) > 1 were obtained from SPLS-DA analysis.
RESUMEN
Purpose: Among all ischemic stroke patients, more than half are mild and rapidly improving acute ischemic stroke (MaRAIS) patients. However, many MaRAIS patients do not recognize the disease early on, and thus they delay access to the treatment that would be most effective if provided earlier. This is especially true in rural areas. The aim of this study was to develop and validate a late hospital arrival risk nomogram in a rural Chinese population of patients with MaRAIS. Methods: We developed a prediction model based on a training dataset of 173 MaRAIS patients collected from September 9, 2019 to May 13, 2020. Data analyzed included demographics and disease characteristics. A least absolute shrinkage and selection operator (LASSO) regression model was used to optimize feature selection for the late hospital arrival risk model. Multivariable logistic regression analysis was applied to build a prediction model incorporating the features selected in the LASSO regression models. The discrimination, calibration, and clinical usefulness of the prediction model were assessed using the C-index, calibration plot, and decision curve analysis, respectively. Internal validation was then assessed using bootstrapping validation. Results: Variables contained in the prediction nomogram included transportation mode, history of diabetes, knowledge of stroke symptoms, and thrombolytic therapy. The model had moderate predictive power with a C-index of 0.709 (95% confidence interval: 0.636-0.783) and good calibration. In the internal validation, the C-index reached 0.692. The risk threshold was 30-97% according to the analysis of the decision curve, and the nomogram could be applied in clinical practice. Conclusion: This novel nomogram, which incorporates transportation mode, history of diabetes, knowledge of stroke symptoms, and thrombolytic therapy, was conveniently applied to facilitate individual late hospital arrival risk prediction among MaRAIS patients in a rural area of Shanghai, China.