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Hepatic ischemia-reperfusion injury (IRI) is a major cause of liver damage during hepatic resection, transplantation, and other surgical procedures, often leading to graft failure and liver dysfunction. Recent studies have identified ferroptosis, a form of regulated cell death characterized by iron-dependent lipid peroxidation, as a key contributor to IRI. In this study, we investigated the protective effects of Ticlopidine, a thienopyridine compound and platelet aggregation inhibitor, on hepatic IRI. Using a C57BL/6J mouse model, we demonstrated that prophylactic Ticlopidine treatment significantly reduced necrotic and fibrotic areas in liver tissues, as well as serum levels of alanine transaminase (ALT) and aspartate aminotransferase (AST). Prussian Blue staining revealed that Ticlopidine pretreatment decreased iron accumulation in hepatic tissues, whereas markers of lipid peroxidation (malondialdehyde and 4-hydroxynonenal) and ferroptosis (PTGS2) were significantly downregulated. Additionally, Ticlopidine ameliorated inflammatory infiltration as indicated by reduced Gr-1 staining. In vitro, Ticlopidine dose-dependently inhibited ferroptosis induced by various inducers in liver cancer cell lines HUH7 and fibrosarcoma cells HT1080. The protective effects involved partial rescue of lipid peroxidation, significant reduction of ferrous iron levels, and strong protection against mitochondrial damage. These findings suggested that Ticlopidine acts as a broad-spectrum ferroptosis inhibitor, offering a promising therapeutic approach for protecting the liver against IRI.
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Ferroptose , Fígado , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão , Ticlopidina , Animais , Ferroptose/efeitos dos fármacos , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/tratamento farmacológico , Masculino , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Ticlopidina/farmacologia , Ticlopidina/análogos & derivados , Camundongos , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Linhagem Celular Tumoral , Ferro/metabolismoRESUMO
Azines are valuable synthons or target molecules in organic synthesis. In this work, we report that CBZ6 could work as a photoreductive catalyst for the N-N homocoupling of oximes in high efficiency. This therefore enabled convenient access to a large variety of azines from the corresponding aryl and alkyl ketones, as well as aryl aldehydes in up to 99% yield. 2,4-Dinitrophenoxyl was used as the recyclable auxiliary and the CBZ6 photocatalyst could also be recycled. These together with the low catalyst loading (2 mol % of CBZ6), the short reaction time (4 h), and the nontoxic DMSO solvent make the current process a sustainable and practical alternative to the classic methods.
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The root of Aconitum carmichaelii Debx. (Fuzi) is an herbal medicine used in China that exerts significant efficacy in rescuing patients from severe diseases. A key toxic compound in Fuzi, aconitine (AC), could trigger unpredictable cardiotoxicities with high-individualization, thus hinders safe application of Fuzi. In this study we investigated the individual differences of AC-induced cardiotoxicities, the biomarkers and underlying mechanisms. Diversity Outbred (DO) mice were used as a genetically heterogeneous model for mimicking individualization clinically. The mice were orally administered AC (0.3, 0.6, 0.9 mg· kg-1 ·d-1) for 7 d. We found that AC-triggered cardiotoxicities in DO mice shared similar characteristics to those observed in clinic patients. Most importantly, significant individual differences were found in DO mice (variation coefficients: 34.08%-53.17%). RNA-sequencing in AC-tolerant and AC-sensitive mice revealed that hemoglobin subunit beta (HBB), a toxic-responsive protein in blood with 89% homology to human, was specifically enriched in AC-sensitive mice. Moreover, we found that HBB overexpression could significantly exacerbate AC-induced cardiotoxicity while HBB knockdown markedly attenuated cell death of cardiomyocytes. We revealed that AC could trigger hemolysis, and specifically bind to HBB in cell-free hemoglobin (cf-Hb), which could excessively promote NO scavenge and decrease cardioprotective S-nitrosylation. Meanwhile, AC bound to HBB enhanced the binding of HBB to ABHD5 and AMPK, which correspondingly decreased HDAC-NT generation and led to cardiomyocytes death. This study not only demonstrates HBB achievement a novel target of AC in blood, but provides the first clue for HBB as a novel biomarker in determining the individual differences of Fuzi-triggered cardiotoxicity.
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Proteínas Quinases Ativadas por AMP , Aconitina , Cardiotoxicidade , Histona Desacetilases , Animais , Camundongos , Cardiotoxicidade/metabolismo , Cardiotoxicidade/etiologia , Histona Desacetilases/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Masculino , Humanos , Aconitum/química , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Medicamentos de Ervas Chinesas/farmacologiaRESUMO
BACKGROUND: Osteoporosis is currently considered the most common bone disease in the world and is characterized by low bone mass, deterioration of the bone tissue microstructure, and decreased bone strength. With the increasing popularity of smartphones and short videos, many patients search for various types of health information through social media, such as short videos. As one of China's short video giants, TikTok has played a significant role in spreading health information. We found that there are many videos about osteoporosis on TikTok; however, the quality of these short videos has not yet been evaluated. OBJECTIVE: The purpose of this study was to evaluate the information quality of osteoporosis videos on the domestic TikTok platform. METHODS: We retrieved and screened 100 videos about osteoporosis from TikTok, extracted the basic information, encoded the video content, and recorded the source of each video. Two independent raters evaluated the information quality of each video via the DISCERN rating scale. RESULT: The videos were divided into three groups according to their source: medical personnel, science communicators, and news media, with medical personnel posting the most videos. The content of the video is divided into 7 groups, namely, disease prevention, disease diagnosis, disease symptoms, disease overview, life-style, drug knowledge, and drug treatment, with the most videos related to disease overview. The average DISCERN score of the videos is 37.69 (SD = 6.78), mainly within the 'poor' (54/100, 54%) and 'appropriate' (43/100, 43%) rating ranges, with overall quality being low. Further analysis revealed a positive correlation between the number of shares, comments, likes, and favorites, and a positive correlation between the DISCERN score and the number of shares and favorites. CONCLUSION: The overall quality of videos concerning osteoporosis on TikTok is lower, but the quality of videos varies significantly across different sources. We should be selective and cautious when watching videos about osteoporosis on TikTok.
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Osteoporose , Mídias Sociais , Gravação em Vídeo , Humanos , China , Informação de Saúde ao Consumidor/normas , Disseminação de Informação/métodosRESUMO
To synthesize an effective and versatile nano-platform serving as a promising carrier for controlled drug delivery, visible-light-induced diselenide-crosslinked polyurethane micelles were designed and prepared for ROS-triggered on-demand doxorubicin (DOX) release. A rationally designed amphiphilic block copolymer, poly(ethylene glycol)-b-poly(diselenolane diol-co-isophorone diisocyanate)-b-poly(ethylene glycol) (PEG-b-PUSe-b-PEG), which incorporates dangling diselenolane groups within the hydrophobic PU segments, was initially synthesized through the polycondensation reaction. In aqueous media, this type of amphiphilic block copolymer can self-assemble into micellar aggregates and encapsulate DOX within the micellar core, forming DOX-loaded micelles that are subsequently in situ core-crosslinked by diselenides via a visible-light-triggered metathesis reaction of Se-Se bonds. Compared with the non-crosslinked micelles (NCLMs), the as-prepared diselenide-crosslinked micelles (CLMs) exhibited a smaller particle size and improved colloidal stability. In vitro release studies have demonstrated suppressed drug release behavior for CLMs in physiological conditions, as compared to the NCLMs, whereas a burst release of DOX occurred upon exposure to an oxidation environment. Moreover, MTT assay results have revealed that the crosslinked polyurethane micelles displayed no significant cytotoxicity towards HeLa cells. Cellular uptake analyses have suggested the effective internalization of DOX-loaded crosslinked micelles and DOX release within cancer cells. These findings suggest that this kind of ROS-triggered reversibly crosslinked polyurethane micelles hold significant potential as a ROS-responsive drug delivery system.
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Doxorrubicina , Luz , Micelas , Polímeros , Espécies Reativas de Oxigênio , Doxorrubicina/química , Doxorrubicina/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Humanos , Polímeros/química , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Portadores de Fármacos/química , Células HeLa , Polietilenoglicóis/química , Sobrevivência Celular/efeitos dos fármacos , Tamanho da PartículaRESUMO
We establish a facile electrochemical approach for detecting miRNA. Programmable DNA tetrahedron is designed using thiol groups for electrode modification, the amino group for the localization of electrochemical species and a hairpin structure that responds to target miRNA. In addition, duplex-specific nuclease-assisted amplification helps improve the sensitivity of this biosensor. The target-initiated partial collapse of the DNA tetrahedron event integrates recognition, electrode immobilization, signal recruitment and amplification. By measuring the sharp silver stripping peak, the highly sensitive detection of miRNA is achieved, which also performs satisfactorily challenging biological samples. This method is featured with simple operation, high sensitivity and practical utility, exhibiting great application potential in clinical diagnosis.
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Técnicas Biossensoriais , MicroRNAs , MicroRNAs/genética , MicroRNAs/química , DNA/genética , DNA/química , Técnicas Biossensoriais/métodos , Endonucleases , Eletrodos , Técnicas Eletroquímicas/métodos , Limite de DetecçãoRESUMO
Objective: COVID-19 has evolved into a major global public health event. The number of people reporting insomnia is growing exponentially during the pandemic. This study aimed to explore the relationship between aggravated insomnia and COVID-19-induced psychological impact on the public, lifestyle changes, and anxiety about the future. Methods: In this cross-sectional study, we used the questionnaires from 400 subjects who were obtained from the Department of Encephalopathy of the Wuhan Hospital of Traditional Chinese Medicine between July 2020 and July 2021. The data collected for the study included demographic characteristics of the participants and psychological scales consisting of the Spiegel Sleep Questionnaire, the Fear of COVID-19 Scale (FCV-19S), the Zung Self-Rating Anxiety Scale (SAS), and the Zung Self-Rating Depression Scale (SDS). The independent sample t-test and one-way ANOVA were used to compare the results. Correlation analysis of variables affecting insomnia was performed using Pearson correlation analysis. The degree of influence of the variables on insomnia was determined using linear regression, and a regression equation was derived. Results: A total of 400 insomnia patients participated in the survey. The median age was 45.75 ± 15.04 years. The average score of the Spiegel Sleep Questionnaire was 17.29 ± 6.36, that of SAS was 52.47 ± 10.39, that of SDS was 65.89 ± 8.72, and that of FCV-19S was 16.09 ± 6.81. The scores of FCV-19S, SAS, and SDS were closely related to insomnia, and the influencing degree was in the following order: fear, depression, and anxiety (OR = 1.30, 0.709, and 0.63, respectively). Conclusion: Fear of COVID-19 can be one of the primary contributors to worsening insomnia.
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COVID-19 , Distúrbios do Início e da Manutenção do Sono , Humanos , Adulto , Pessoa de Meia-Idade , Modelos Lineares , Qualidade do Sono , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Pandemias , Estudos Transversais , COVID-19/epidemiologia , Análise de Regressão , Ansiedade/epidemiologia , Depressão/epidemiologiaRESUMO
This study investigated the effect of the prone trunk extension test (PTE) on lumbar and lower limb muscle stiffness to explore the optimal angle for lumbar muscle training, understand the peripheral muscle force transmission effect, and determine the modulation strategy and interaction mode of different muscles during PTE. Twenty healthy young females were recruited for this study, and the stiffness of the erector spinae (ES), semitendinosus (ST), biceps femoris (BF), medial head of the gastrocnemius (MG), and lateral head of the gastrocnemius (LG) was measured by MyotonPRO under four angular PTE conditions (0° horizontal position, 10°, 20°, and 30°). With the increasing angle, the stiffness of ES decreased gradually, while ST and BF increased first and then decreased. The stiffness of MG and LG increased first, then decreased, then increased. There was a moderate to strong negative correlation between ES stiffness variation and ST (r = -0.819 to -0.728, p < 0.001), BF (r = -0.620 to -0.527, p < 0.05), MG (r = -788 to -0.611, p < 0.01), and LG (r = -0.616 to -0.450, p < 0.05). Horizontal PTE maximizes the activation of ES. There is a tension transfer between the ES, hamstrings, and gastrocnemius, mainly between the ES, ST, and LG. The study provides data to explore the effect of peripheral muscle force transmission and the modulation strategies of different muscles during trunk extension.
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With the continuous development of new energy vehicles, the number of decommissioned lithium iron phosphate (LiFePO4) batteries has been constantly increasing. Therefore, it is necessary to recover metal from spent LiFePO4 batteries due to the high potential for environmental protection and high resource value. In this study, sodium persulfate (Na2S2O8) was selected as the oxidant to regulate and control the oxidation state and proton activity of the leaching solution through its high oxidizing ability. Selective recovery of lithium from LiFePO4 batteries was achieved by oxidizing LiFePO4 to iron phosphate (FePO4) during the leaching process. This paper reports an extensive investigation of the effects of various factors, including the acid concentration, initial volume fraction of the oxidant, reaction temperature, solid-liquid ratio, and reaction time, on lithium leaching. Li+ reached a high leaching rate of 93.3% within 5 minutes even at a low concentration of sulphuric acid (H2SO4), and high-purity lithium carbonate (Li2CO3) was obtained through impurity removal and precipitation reactions. In addition, the leaching mechanism was analysed by both X-ray diffraction and X-ray photoelectron spectroscopy characterization. The results show that the obtained high lithium-ion (Li+) leaching efficiency and fast Li+ leaching time can be ascribed to the superior oxidizing properties of Na2S2O8 and the stability of the crystal structure of LiFePO4 during the oxidative leaching process. The adopted method has significant advantages in terms of safety, efficiency and environmental protection, which are conducive to the sustainable development of lithium batteries.
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Lítio , Metais , Metais/química , Fontes de Energia Elétrica , Reciclagem/métodos , Oxidantes , Ferro , FosfatosRESUMO
This report presents nanoparticles composed of a liquid gallium core with a reduced graphene oxide (RGO) shell (Ga@RGO) of tunable thickness. The particles are produced by a simple, one-pot nanoprobe sonication method. The high near-infrared absorption of RGO results in a photothermal energy conversion of light to heat of 42.4%. This efficient photothermal conversion, combined with the large intrinsic thermal expansion coefficient of liquid gallium, allows the particles to be used for photoacoustic imaging, that is, conversion of light into vibrations that are useful for imaging. The Ga@RGO results in fivefold and twofold enhancement in photoacoustic signals compared with bare gallium nanoparticles and gold nanorods (a commonly used photoacoustic contrast agent), respectively. A theoretical model further reveals the intrinsic factors that affect the photothermal and photoacoustic performance of Ga@RGO. These core-shell Ga@RGO nanoparticles not only can serve as photoacoustic imaging contrast agents but also pave a new way to rationally design liquid metal-based nanomaterials with specific multi-functionality for biomedical applications.
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Gálio , Grafite , Nanopartículas , Técnicas Fotoacústicas , Meios de Contraste , Ouro , Técnicas Fotoacústicas/métodos , Fototerapia/métodosRESUMO
Circulating tumor DNA (ctDNA) serves as a powerful noninvasive and viable biomarker for the diagnosis of cancers. The abundance of ctDNA in patients with advanced stages is significantly higher than that in patients with early stages. Herein, a ratiometric electrochemical biosensor for the detection of ctDNA is developed by smart design of DNA probes and recycles of DNAzyme activation. The conformational variation of DNA structures leads to the changes of two types of electrochemical species. This enzyme-free sensing strategy promotes excellent amplification efficiency upon target recognition. The obtained results assure good analytical performances and a limit of detection as low as 25 aM is achieved. Additionally, this method exhibits outstanding selectivity and great application prospects in biological sample analysis.
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Técnicas Biossensoriais , DNA Tumoral Circulante , DNA Catalítico , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Humanos , Limite de DetecçãoRESUMO
BACKGROUND: A hydatidiform mole is a condition caused by abnormal proliferation of trophoblastic cells. MicroRNA miR-30a acts as a tumor suppressor gene in most tumors and participates in the development of various cancers. However, its role in hydatidiform moles is not clear. METHODS: Quantitative real-time reverse transcription PCR was used to verify the expression level of miR-30a and STOX2 (encoding storkhead box 2). Flow cytometry assays were performed to detect the cell cycle in cell with different expression levels of miR-30a and STOX2. Cell Cycle Kit-8, 5-ethynyl-2'-deoxyuridine, and colony formation assays were used to detect cell proliferation and viability. Transwell assays was used to test cell invasion and migration. Dual-luciferase reporter assays and western blotting were used to investigate the potential mechanisms involved. RESULT: Low miR-30a expression promoted the proliferation, migration, and invasion of trophoblastic cells (JAR and HTR-8). Dual luciferase assays confirmed that STOX2 is a target of miR-30a and resisted the effect of upregulated miR-30a in trophoblastic cells. In addition, downregulation of STOX2 by miR-30a could activate ERK, AKT, and P38 signaling pathways. These results revealed a new mechanism by which ERK, AKT, and P38 activation by miR-30a/STOX2 results in excessive proliferation of trophoblast cells in the hydatidiform mole. CONCLUSIONS: In this study, we found that miR-30a plays an important role in the development of the hydatidiform mole. Our findings indicate that miR-30a might promote the malignant transformation of human trophoblastic cells by regulating STOX2, which strengthens our understanding of the role of miR-30a in regulating trophoblastic cell transformation.
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Due to its excellent programmability and biocompatibility, DNA molecule has unique advantages in cell surface engineering. Recent progresses provide a reliable and feasible way to engineer cell surfaces with diverse DNA molecules and DNA nanostructures. The abundant form of DNA nanostructures has greatly expanded the toolbox of DNA-based cell surface engineering and gave rise to a variety of novel and fascinating applications. In this review, we summarize recent advances in DNA-based cell surface engineering and its biological applications. We first introduce some widely used methods of immobilizing DNA molecules on cell surfaces and their application features. Then we discuss the approaches of employing DNA nanostructures and dynamic DNA nanotechnology as elements for creating functional cell surfaces. Finally, we review the extensive biological applications of DNA-based cell surface engineering and discuss the challenges and prospects of DNA-based cell surface engineering.
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DNA , Nanoestruturas , DNA/química , Nanotecnologia , Nanoestruturas/química , Engenharia CelularRESUMO
DNA is a type of promising material for the construction of sensors owing to its sequence programmability to control the formation of certain structures. MicroRNA (miRNA) can be applied as promising biomarkers for the diagnosis of a range of diseases. Herein, a novel fluorescent sensing strategy for miRNA is proposed combining duplex-specific nuclease (DSN)-mediated amplification and dumbbell DNA structural switch. Gold nanoparticles (AuNPs) are employed, which provide a 3D reaction interface. They also act as effective fluorescence quenchers. The proposed sensor exhibits high sensitivity (sub-femtomolar level) with a wide dynamic range. In addition, excellent selectivity to distinguish homology sequences is achieved. It also performs satisfactorily in biological samples. Overall, this fluorescent sensor provides a powerful tool for the analysis of miRNA levels and can be applied for related biological studies and clinical diagnosis.
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Técnicas Biossensoriais , Nanopartículas Metálicas , MicroRNAs , DNA/química , Endonucleases/química , Ouro/química , Limite de Detecção , Nanopartículas Metálicas/química , MicroRNAs/análise , Técnicas de Amplificação de Ácido NucleicoRESUMO
Transmissible gastroenteritis virus (TGEV) is a coronavirus causing diarrhea with high incidence in swine herds. Its persistent infection might lead to epithelial-mesenchymal transition (EMT) of swine intestinal epithelial cells, followed by subsequent infections of other pathogens. Enterococcus faecalis (E. faecalis) is a member of the enteric microorganisms and an opportunistic pathogen. There is no report of secondary E. faecalis infection to TGEV, even though they both target to the intestinal tracts. To investigate the interactions between TGEV and E. faecalis, we set up an in vitro infection model by the swine IPEC-J2 cells. Dynamic changes of cell traits, including EMT and cell motility, were evaluated through qPCR, Western blot, electronic microscopy, scratch test, Transwell migration test and invasion test, respectively. The adhesion and invasion tests of E. faecalis were taken to verify the impact of the preceding TGEV infection. The cell morphology and molecular marker evaluation results showed that the TGEV persistent infection induced EMT on IPEC-J2 cells; increased cellular motility and invasion potential were also observed. Spontaneously, the expression levels of fibronectin (FN) and the membrane protein integrin-α5, which are dominant bacterial receptors on IPEC-J2 cells, were upgraded. It indicated that the bacteria E. faecalis adhered to IPEC-J2 cells through the FN receptor, and then invaded the cells by binding with the integrin-α5, suggesting that both molecules were critical for the adhesion and invasion of E. faecalis to IPEC-J2 cells. Additionally, it appeared that E. faecalis alone might trigger certain EMT phenomena, implying a vicious circle might occur. Generally, bacterial and viral co-infections are frustrating yet common in both human and veterinary medicines, and our observations on enteric TGEV and E. faecalis interactions, especially the diversity of bacterial invasion strategies, might provide new insights into the mechanisms of E. faecalis pathogenicity.
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Infecções Bacterianas , Vírus da Gastroenterite Transmissível , Animais , Humanos , Suínos , Enterococcus faecalis , Infecção Persistente , Intestinos , Células Epiteliais/microbiologia , IntegrinasRESUMO
Nutritional conditions of activated sludge had a significant influence on nitrification inhibition response. This study comprehensively investigated the inhibition of 3,5-dichlorophenol (3,5-DCP) on nitrification of activated sludge with different C/N ratios and carbon source types. The corresponding extracellular polymeric substances (EPS), microbial communities and functional genes were analysed. The results indicated that the addition of carbon source would reduce the nitrification activity and nitrification sensitivity to 3,5-DCP, and the order of the EC50 was sequenced as sodium acetate > methanol > glucose. The response mechanisms of activated sludge under diverse carbon source conditions to 3,5-DCP were summarised as follows. When the 3,5-DCP content was increased from 0.4 mg/L to 0.8 mg/L, the protein content increased from 73.2 ± 2.6 mg/g SS â¼122.4 ± 4 mg/g SS to 92.2 ± 11.2 mg/g SS â¼130.8 ± 9.6 mg/g SS in the tightly bound EPS (TB-EPS). The increase of protein content was attributed to cellular self-protection mechanisms. Furthermore, fluorescence characteristic analysis revealed that tyrosine and tryptophan in loosely bound EPS (LB-EPS) might account for higher EC50 in activated sludge fed with methanol and sodium acetate. In addition, the redundancy analyses (RDA) showed activated sludge with organics enriched the resistant species, such as Proteobacteria and Patescibacteria, while activated sludge without organics enriched the sensitive species, such as Ferruginibacter. Finally, the nitrification genes were found to be consistent with nitrification activity. Thus, the findings provide new insights into nitrification inhibition mechanism under different carbon source conditions.
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Carbono , Esgotos , Clorofenóis , Metanol , Esgotos/microbiologia , Acetato de SódioRESUMO
This study aims to observe the differentiating effect of shikonin on Wilms' tumor 1 (WT1)-positive HL-60 cells and investigate the fate of the differentiated leukemia cells. WT1 overexpression unaffected cell viability but promoted resistance to H2O2-induced DNA injury and cell apoptosis. The binding of shikonin to the WT1 protein was confirmed by molecular docking and drug affinity reaction target stability (DARTS). Shikonin at the non-cytotoxic concentration could decrease the WT1 protein and simultaneously reduced the CD34 protein and increased the CD11b protein in a dose-dependent manner in normal HL-60 cells but not in WT1-overexpressed HL-60 cells. Shikonin unaffected HL-60 cell viability in 48 h. However, it lasted for 10 days; could attenuate cell proliferation, mitochondrial membrane potential (MMP), and self-renewal; prevent the cell cycle; promote cell apoptosis. In a mouse leukemia model, shikonin could decrease the WT1 protein to prevent leukemia development in a dose-dependent manner. In this study, we also confirmed preliminarily the protein-protein interactions between WT1 and CD34 in molecular docking and CO-IP assay. Our results suggest that: 1. shikonin can down-regulate the WT1 protein level for leukemia differentiation therapy, and 2. the interaction between WT1 and CD34 proteins may be responsible for granulocyte/monocyte immaturity in HL-60 cells.
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Leucemia , Proteínas WT1 , Animais , Camundongos , Proteínas WT1/genética , Simulação de Acoplamento Molecular , Peróxido de Hidrogênio/farmacologia , Leucemia/metabolismo , Diferenciação Celular , Antígenos CD34/metabolismoRESUMO
Manipulation of cell-cell interactions via cell surface engineering has potential biomedical applications in tissue engineering and cell therapy. However, manipulation of the comprehensive and multiple intercellular interactions remains a challenge and missing elements. Herein, utilizing a DNA triangular prism (TP) and a branched polymer (BP) as functional modules, we fabricate tunable DNA scaffold networks on the cell surface. The responsiveness of cell-cell recognition, aggregation and dissociation could be modulated by aptamer-functionalized DNA scaffold networks with high accuracy and specificity. By regulating the DNA scaffold networks coated on the cell surface, controlled intercellular molecular transportation is achieved. Our tunable network provides a simple and extendible strategy which addresses a current need in cell surface engineering to precisely manipulate cell-cell interactions and shows promise as a general tool for controllable cell behavior.
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DNA/química , Redes Neurais de Computação , Polímeros/química , Comunicação Celular , Células HeLa , Células Hep G2 , HumanosRESUMO
Cell-cell communication plays a vital role in biological activities; in particular, membrane-protein interactions are profoundly significant. In order to explore the underlying mechanism of intercellular signaling pathways, a full range of artificial systems have been explored. However, many of them are complicated and uncontrollable. Herein we designed an artificial signal transduction system able to control the influx of environmental ions by triggering the activation of synthetic transmembrane channels immobilized on giant membrane vesicles (GMVs). A membrane protein-like stimulator from one GMV community (GMVB) stimulates a receptor on another GMV community (GMVA) to release ssDNA messengers, resulting in the activation of synthetic transmembrane channels to enable the influx of ions. This event, in turn, triggers signal responses encapsulated in the GMVA protocell model. By mimicking natural signal transduction pathways, this novel prototype provides a workable tool for investigating cell-cell communication and expands biological signaling systems in general as well as explores useful platforms for addressing scientific problems which involve materials science, chemistry, and medicine.
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Células Artificiais/metabolismo , DNA/metabolismo , Transporte de Íons/fisiologia , Transdução de Sinais/fisiologia , DNA/química , Células HeLa , Humanos , Nanoestruturas/químicaRESUMO
Ferric(III) ions (Fe3+) are one of the most abundant metal ions in environmental and biological systems. The determination of Fe3+ has attracted great attention for healthcare concerns. In this work, we have developed a novel fluorescence method for the sensing and intracellular imaging of Fe3+ based on the prepared red-emissive carbon nanodots. The nanoprobes are synthesized via a microwave method using ammonium fluoride and o-phenylenediamine as carbon precursors, which exhibit excellent optical properties and low toxicity. More importantly, the carbon nanodots show high selectivity towards Fe3+ against other interfering ions. The sensitivity is also high with the limit of detection as low as 0.05 µM. Meanwhile, the carbon nanodots have been successfully used for fluorescence imaging of cells and could be quenched by intracellular Fe3+. These results suggest that the red-emissive carbon nanodots have diverse potential utilities in biomedical fields.