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The functional and sensory augmentation of living structures, such as human skin and plant epidermis, with electronics can be used to create platforms for health management and environmental monitoring. Ideally, such bioelectronic interfaces should not obstruct the inherent sensations and physiological changes of their hosts. The full life cycle of the interfaces should also be designed to minimize their environmental footprint. Here we report imperceptible augmentation of living systems through in situ tethering of organic bioelectronic fibres. Using an orbital spinning technique, substrate-free and open fibre networks-which are based on poly (3,4-ethylenedioxythiophene):polystyrene sulfonate-can be tethered to biological surfaces, including fingertips, chick embryos and plants. We use customizable fibre networks to create on-skin electrodes that can record electrocardiogram and electromyography signals, skin-gated organic electrochemical transistors and augmented touch and plant interfaces. We also show that the fibres can be used to couple prefabricated microelectronics and electronic textiles, and that the fibres can be repaired, upgraded and recycled.
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"Molecular ping-pong," emerging as a control strategy in solid-state nanopore technology, presents a highly promising approach for repetitive measurements of single biomolecules, such as DNA. This paper introduces a high-precision, high-speed nanopore molecular ping-pong control system consisting of a home-built trans-impedance amplifier (TIA), a control system based on a Field Programmable Gate Array (FPGA), and a LabVIEW program operating on the host personal computer. Through feedback compensation and post-stage boosting, the TIA achieves a high bandwidth of about 200 kHz with a gain of 100 MΩ, along with low input-referred current noise of 1.6 × 10-4 pA2/Hz at 1 kHz and 1.1 × 10-3 pA2/Hz at 100 kHz. The FPGA-based control system demonstrates a minimum overall response time (tdelay) of 6.5 µs from the analog input current signal trigger to the subsequent reversal of the analog output drive voltage signal, with a control precision of 1 µs. Additionally, a LabVIEW program has been developed to facilitate rapid data exchange and communication with the FPGA program, enabling real-time signal monitoring, parameter adjustment, and data storage. Successful recapture of individual DNA molecules at various tdelay, resulting in an improvement in capture rate by up to 2 orders of magnitude, has been demonstrated. With unprecedented control precision and capture efficiency, this system provides robust technical support and opens novel research avenues for nanopore single-molecule sensing and manipulation.
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Petal abscission affects the growth, development, and economic value of plants, but the mechanism of ethylene-ROS-induced petal abscission is not clear. Therefore, we treated roses with different treatments (MOCK, ETH, STS, and ETH + STS), and phenotypic characteristics of petal abscission, changed ratio of fresh weight, morphology of cells in AZ and the expression of RhSUC2 were analyzed. On this basis, we measured reactive oxygen species (ROS) content in petals and AZ cells of roses, and analyzed the expression levels of some genes related to ROS production and ROS scavenging. Ethylene promoted the petal abscission of rose through decreasing the fresh weight of the flower, promoting the stacking and stratification of AZ cells, and repressing the expression of RhSUC2. During this process, ethylene induced the ROS accumulation of AZ cells and petals mainly through increasing the expressions of some genes (RhRHS17, RhIDH1, RhIDH-III, RhERS, RhPBL32, RhFRS5, RhRAC5, RhRBOHD, RhRBOHC, and RhPLATZ9) related to ROS production and repressing those genes (RhCCR4, RhUBC30, RhSOD1, RhAPX6.1, and RhCATA) related to ROS scavenging. In summary, ROS and related regulatory factors involved in ethylene induced petal abscission in roses.
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BACKGROUND: Previous studies have found that inflammatory proteins are involved in the pathogenesis of atrial fibrillation (AF). We used mendelian randomization to explore the potential pathogenic inflammatory proteins of AF. METHODS: This study adopts a Mendelian randomization design to primarily assess causal associations using the Wald ratio and the inverse variance weighting method. It leverages protein quantitative trait locus (pQTL) data encompassing 91 types of inflammatory proteins from 14,824 participants of European ancestry. The primary analysis phase utilizes AF GWAS data from 55,106 participants, with an additional 237,690 participants included in the validation stage. Sensitivity analyses, including reverse causality analysis, Bayesian colocalization analysis, and phenotype scanning, were conducted. Finally, the study explores potential targeted drugs. RESULTS: The findings highlight a causal link between 7 inflammatory proteins and AF, with 2 showing positive correlations and 5 exhibiting negative correlations. Among these, fibroblast growth factor 5 (FGF5) emerges as particularly robust in sensitivity analysis. Colocalization analysis indicates a shared genetic variation between FGF5 and AF, supporting its potential as a targeted therapy for AF. Importantly, this causal relationship remains unaffected by reverse causality. Furthermore, significant pleiotropic effects were observed in phenotype scanning. Finally, the causal association between FGF5 and AF was successfully replicated during the validation phase. CONCLUSION: FGF5 may become an intervention target for AF targeted therapy.
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We aimed to investigate the expression and motor modulatory roles of several mechano-sensitive channels (MSCs) in human ureter. Human proximal ureters were obtained from eighty patients subjected to nephrectomy. Expression of MSCs at mRNA, protein and functional levels were examined. Contractions of longitudinal ureter strips were recorded in organ bath. A fluorescent probe Diaminofluoresceins was used to measure nitric oxide (NO). RT-PCR analyses revealed predominant expression of Piezo1 and TRPV2 mRNA in intact ureter and mucosa. Immunofluorescence assays indicate proteins of MSCs (Piezo1/Piezo2, TRPV2 and TRPV4) were mainly distributed in the urothelium. Ca2+ imaging confirmed functional expression of TRPV2, TRPV4 and Piezo1 in cultured urothelial cells. Specific agonists of Piezo1 (Yoda1, 3-300 µM) and TRPV2 (cannabidiol, 3-300 µM) attenuated the frequency of ureteral contractions in a dose-dependent manner while the TRPV4 agonist GSK1016790A (100 nM-1 µM) exerted no effect. The inhibitory effects of Piezo1 and TRPV2 agonists were significantly blocked by the selective antagonists (Dooku 1 for Piezo1, Tranilast for TRPV2), removal of the mucosa, and pretreatment with NO synthase inhibitor L-NAME (10 µM). Yoda1 (30 µM) and cannabidiol (50 µM) increased production of NO in cultured urothelial cells. Our results suggest that activation of Piezo1 or TRPV2 evokes NO production and release from mucosa that may mediate mechanical stimulus-induced reduction of ureter contractions. Our findings support the idea that targeting Piezo1 and TRPV2 channels may be a promising pharmacological strategy for ureter stone passage or colic pain relief.
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Background: N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin widely used to induce PD models, but the effect of MPTP on the cells and genes of PD has not been fully elucidated. Methods: Single-nucleus RNA sequencing was performed in the Substantia Nigra (SN) of MPTP mice. UMAP analysis was used for the dimensionality reduction visualization of the SN in the MPTP mice. Known marker genes highly expressed genes in each cluster were used to annotate most clusters. Specific Differentially Expressed Genes (DEGs) and PD risk genes analysis were used to find MPTP-associated cells. GO, KEGG, PPI network, GSEA and CellChat analysis were used to reveal cell type-specific functional alterations and disruption of cell-cell communication networks. Subset reconstruction and pseudotime analysis were used to reveal the activation status of the cells, and to find the transcription factors with trajectory characterized. Results: Initially, we observed specific DEGs and PD risk genes enrichment in microglia. Next, We obtained the functional phenotype changes in microglia and found that IGF, AGRN and PTN pathways were reduced in MPTP mice. Finally, we analyzed the activation state of microglia and revealed a pro-inflammatory trajectory characterized by transcription factors Nfe2l2 and Runx1. Conclusion: Our work revealed alterations in microglia function, signaling pathways and key genes in the SN of MPTP mice.
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Zanthoxyli radix is a popular tea among the elderly, and it is believed to have a positive effect on Alzheimer's disease. In this study, a highly effective three-step strategy was proposed for comprehensive analysis of the active components and biological functions of Zanthoxylum nitidum (ZN), including high-resolution LC-Q-TOF mass spectrometry (HRMS), multivariate statistical analysis for heterogeneity (MSAH), and experimental and virtual screening for bioactivity analysis (EVBA). A total of 117 compounds were identified from the root, stem, and leaf of ZN through HRMS. Bioactivity assays showed that the order of acetylcholinesterase (AChE) inhibitory activity from strong to weak was root > stem > leaf. Nitidine, chelerythrine, and sanguinarine were found to be the main differential components of root, stem, and leaf by OPLS-DA. The IC50 values of the three compounds are 0.81 ± 0.02, 0.14 ± 0.01, and 0.48 ± 0.01 µM respectively, indicating that they are potent and high-quality AChE inhibitors. Molecular docking showed that pi-pi T-shaped interactions and pi-lone pairs played important roles in AChE inhibition. This study not only explains the biological function of Zanthoxyli radix in alleviating Alzheimer's disease to some extent, but also lays the foundation for the development of stem and leaf of ZN.
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Acetilcolinesterasa , Inhibidores de la Colinesterasa , Espectrometría de Masas , Simulación del Acoplamiento Molecular , Hojas de la Planta , Zanthoxylum , Zanthoxylum/química , Inhibidores de la Colinesterasa/química , Inhibidores de la Colinesterasa/farmacología , Acetilcolinesterasa/química , Acetilcolinesterasa/metabolismo , Hojas de la Planta/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Raíces de Plantas/química , Tallos de la Planta/química , Cromatografía Líquida de Alta Presión , Humanos , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacologíaRESUMEN
The discovery of negative differential conductance (NDC) in a single molecule and mechanism controlling this phenomenon are important for molecular electronics. We investigated the electronic properties of a typical radical molecule 3-carbamoyl-2,2,5,5-tetramethyl-3-pyrrolin-1-yloxy (CTPO) on an Au(111) surface using low-temperature scanning tunneling microscopy (STM) and inelastic electron tunneling spectroscopy. Large NDC was observed in single CTPO molecules at the boundary of the crystal monolayer. The origin of observed NDC is revealed as the inelastic electron-phonon scattering during tunneling, and the strong spatial variation of the NDC over the single molecule illustrates the nature of the localized radical group. In addition, the NDC can be transformed into a positive differential conductance peak by tuning coupling strengths between different tunneling channels. An empirical multi-channel model has been developed to describe the competition between the valley-shaped NDC and peak-shaped positive differential conductance. The unique electronic property and giant conductance change observed in this radical molecule is valuable for designing novel molecular devices in the future.
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Mitigating the growth of dendritic lithium (Li) metal on silicon (Si) anodes has become a crucial task for the pursuit of long-term cycling stability of high energy density Si-based lithium-ion batteries (LIBs) under fast charging or other specific conditions. While it is widely known that Li metal plating on Si-based anodes may introduce inferior cycling stability and cause safety concerns, the evolution of the anode/material structure and electrochemical performance with Li metal plating remains largely unexplored. A comprehensive quantitative investigation of the hybrid Li storage mechanism, combining the Li alloying/dealloying mechanism and plating/stripping mechanism, has been conducted to explore the effect of Li plating on Si-based anodes. The findings reveal that Li plating/stripping accounts for the decay of the overall Coulombic efficiency and cycling stability of the hybrid Li storage mechanism. Furthermore, alloying reactions occurring below 0â V encourage the formation of crystalline Li15Si4, which subsequently exacerbates voltage hysteresis. The performance decay is amplified as the ratio of Li plating/stripping capacity increases, or in other words, as the over-lithiation level rises, thereby posing a threat to the battery's cycling stability. These results provide valuable insights into the design of advanced Si-based electrodes for high energy density LIBs.
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Rare earth elements (REEs) are a new type of material resource which have attracted significant attention in recent years. REEs have emerged as essential metals in modern-day technology due to their unique functions. The long-term, large-scale mining and utilization of rare earths has caused serious environmental pollution and constitutes a global health issue, which has raised concerns regarding the safety of human health. However, the toxicity profile of suspended particulate matter in REEs in the environment, which interacts with the human body, remains largely unknown. Studies have shown that REEs can enter the human body through a variety of pathways, leading to a variety of organ and system dysfunctions through changes in genetics, epigenetics, and signaling pathways. Through an extensive literature search and critical analysis, we provide a comprehensive overview of the available evidence, identify knowledge gaps, and make recommendations for future research directions.
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With the popularity of smart terminals, wearable electronic devices have shown great market prospects, especially high-sensitivity pressure sensors, which can monitor micro-stimuli and high-precision dynamic external stimuli, and will have an important impact on future functional development. Compressible flexible sensors have attracted wide attention due to their simple sensing mechanism and the advantages of light weight and convenience. Sensors with high sensitivity are very sensitive to pressure and can detect resistance/current changes under pressure, which has been widely studied. On this basis, this review focuses on analyzing the performance impact of device structure design strategies on high sensitivity pressure sensors. The design of structures can be divided into interface microstructures and three-dimensional framework structures. The preparation methods of various structures are introduced in detail, and the current research status and future development challenges are summarized.
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Glycolysis is vital for the excessive proliferation of keratinocytes in psoriasis, and uridine phosphorylase-1 (UPP1) functions as an enhancer of cancer cell proliferation. However, little is known about whether UPP1 promotes keratinocyte proliferation and accelerates psoriasis development. This study revealed that UPP1 facilitates cell viability and cell-cycle progression in human epidermal keratinocytes (HEKs) by modulating the glycolytic pathway. Bioinformatics analysis of UPP1 gene expression and its correlation with the Reactome revealed that UPP1 mRNA expression, cell-cycle progression, the interleukin-6 (IL-6)/Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathway and glycolysis were positively associated with psoriasis. Cell proliferation, the cell cycle and glycolysis were evaluated after UPP1 was silenced or overexpressed. The results showed that UPP1 overexpression increased cell proliferation, cell-cycle progression and glycolysis, which was contrary to the effects of UPP1 silencing. However, the STAT3 inhibitor diminished UPP1 expression because STAT3 can bind to the UPP1 promoter. In conclusion, UPP1 was significantly activated by the IL-6/STAT3 pathway and could modulate glycolysis to regulate cell proliferation and cell-cycle progression in keratinocytes during the development of psoriasis.
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Ciclo Celular , Supervivencia Celular , Glucólisis , Queratinocitos , Factor de Transcripción STAT3 , Uridina Fosforilasa , Humanos , Proliferación Celular , Epidermis/metabolismo , Epidermis/patología , Interleucina-6/metabolismo , Interleucina-6/genética , Queratinocitos/metabolismo , Psoriasis/patología , Psoriasis/metabolismo , Psoriasis/genética , Transducción de Señal , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/genética , Uridina Fosforilasa/metabolismo , Uridina Fosforilasa/genéticaRESUMEN
BACKGROUND: Alcoholic liver disease (ALD), a public health challenge worldwide caused by long-term persistent drinking, is life-threatening with minimal approved therapies. Hepatic steatosis accompanied by inflammation is an initial and inevitable stage in the complex progression of simple alcoholic liver injury to more severe liver diseases such as hepatitis, liver fibrosis, cirrhosis and liver cancer. PURPOSE: We aimed to identify the therapeutic role of Bruceine A (BA) in ALD whilst attempting to explore whether its protective effects depend specifically on the farnesoid X receptor (FXR). METHODS: Autodock was applied to detect the affinity between BA and FXR. Lieber-DeCarli liquid diet with 5 % ethanol (v/v) was adopted to establish the mouse ALD model. The lentivirus mediating FXR (LV-FXR) was injected into mice via the tail vein to establish FXR-overexpressed mice. FXR silencing or overexpression plasmids were transfected into AML-12 cells prior to ethanol stimulation. Quantitative real-time PCR, Western blotting and immunofluorescence assays were employed to determine the expression of related genes. We subjected liver sections to H&E and Oil Red O staining to evaluate the liver histological injury and the deposition of lipid droplets. RESULTS: BA significantly reduced body weight and liver-to-body weight ratios as well as biochemical indexes in mice. Ethanol-induced liver damage and lipid accumulation could be alleviated by BA treatment. BA bound to FXR by two hydrogen bonds. There was a positive correlation between BA administration and FXR expression. BA inhibited the expression of lipid synthesis genes and enhanced the expression of lipid metabolism genes by activating FXR, thus alleviating steatosis in ALD. Moreover, BA exerted an ameliorative effect against inflammation by inhibiting the activation of absent in melanoma 2 (AIM2) inflammasome by activating FXR. FXR overexpression possessed the ability to counter the accumulation of lipid and the activation of AIM2 inflammasome caused by ethanol. FXR deficiency exacerbated ethanol-induced liver steatosis and inflammation. The hepatoprotective effect of BA could be disrupted by FXR antagonist guggulsterone (GS) in vivo and FXR siRNA in vitro. CONCLUSION: BA alleviated alcoholic liver disease by inhibiting AIM2 inflammasome activation through an FXR-dependent mechanism. This study may potentially represent a new therapeutic approach for ALD.
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Inflamasomas , Hepatopatías Alcohólicas , Ratones Endogámicos C57BL , Receptores Citoplasmáticos y Nucleares , Animales , Receptores Citoplasmáticos y Nucleares/metabolismo , Hepatopatías Alcohólicas/tratamiento farmacológico , Inflamasomas/metabolismo , Inflamasomas/efectos de los fármacos , Masculino , Ratones , Modelos Animales de Enfermedad , Hígado/efectos de los fármacos , Hígado/patología , Hígado/metabolismo , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , EtanolRESUMEN
Umami peptides are known for enhancing the taste experience by binding to oral umami T1R1 and T1R3 receptors. Among them, small peptides (composed of 2-4 amino acids) constitute nearly 40% of reported umami peptides. Given the diversity in amino acids and peptide sequences, umami small peptides possess tremendous untapped potential. By investigating 168,400 small peptides, we screened candidates binding to T1R1/T1R3 through molecular docking and molecular dynamics simulations, explored bonding types, amino acid characteristics, preferred binding sites, etc. Utilizing three-dimensional molecular descriptors, bonding information, and a back-propagation neural network, we developed a predictive model with 90.3% accuracy, identifying 24,539 potential umami peptides. Clustering revealed three classes with distinct logP (-2.66 ± 1.02, -3.52 ± 0.93, -2.44 ± 1.23) and asphericity (0.28 ± 0.12, 0.26 ± 0.11, 0.25 ± 0.11), indicating significant differences in shape and hydrophobicity (P < 0.05) among potential umami peptides binding to T1R1/T1R3. Following clustering, nine representative peptides (CQ, DP, NN, CSQ, DMC, TGS, DATE, HANR, and STAN) were synthesized and confirmed to possess umami taste through sensory evaluations and electronic tongue analyses. In summary, this study provides insights into exploring small peptide interactions with umami receptors, advancing umami peptide prediction models.
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Simulación del Acoplamiento Molecular , Péptidos , Receptores Acoplados a Proteínas G , Gusto , Receptores Acoplados a Proteínas G/química , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Péptidos/química , Péptidos/metabolismo , Humanos , Sitios de Unión , Simulación de Dinámica Molecular , Unión Proteica , Secuencia de AminoácidosRESUMEN
In China, Fusarium pseudograminearum has emerged as a major pathogen causing Fusarium crown rot (FCR) and caused significant losses. Studies on the pathogen's properties, especially its mating type and trichothecene chemotypes, are critical with respect to disease epidemiology and food/feed safety. There are currently few available reports on these issues. This study investigated the species composition, mating type idiomorphs, and trichothecene genotypes of Fusarium spp. causing FCR in Henan, China. A significant shift in F. pseudograminearum-induced FCR was found in the present study. Of the 144 purified strains, 143 were F. pseudograminearum, whereas only 1 Fusarium graminearum was identified. Moreover, a significant trichothecene-producing capability of F. pseudograminearum strains from Henan was observed in this work. Among the 143 F. pseudograminearum strains identified, F. pseudograminearum with a 15ADON genotype was found to be predominant (133 isolates), accounting for 92.36% of all strains, followed by F. pseudograminearum with a 3ADON genotype, whereas only one NIV genotype strain was detected. Overall, a relatively well-balanced 1:1 ratio of the F. pseudograminearum population was found in Henan. To the best of our knowledge, this is the first study that has examined the Fusarium populations responsible for FCR across the Henan wheat-growing region.
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Microplastic (MP) residues in marine have become an increasingly serious environmental pollution issue, and in recent years the detection of MPs in marine started to attract worldwide research interests. Optical-fiber-based environmental sensors have been extensively employed for their several merits such as high sensitivity, pressure resistance, compactness and ease of constructing communication networks. However, fiber-optic refractive index sensors are not specifically developed for distinguishing MPs from other inorganic particles suspended in water. In this paper, an metal-organic framework (MOF) ZIF-8 functionalized S-tapered fiber (STF) sensor is proposed for specific detection of polystyrene nanoplastics (PSNPs) in aqueous environment. ZIF-8 coordination nanoporous polymers with different film thickness were immobilized over the surface of the fabricated STF structure based on self-growth technique and yielding a large surface area over the sensor surface. High sensitivity detection can be achieved by converting the concentration perturbation of PSNPs into evanescent waves over the ZIF-8 functionalized STF surface through the strong electrostatic adsorption effect and π-π stacking, while the fabricated sensor is insensitive to gravels with silica as the primary component in water. It is found that the proposed detector with 18 film layers achieves a sensitivity up to 114.1353nm/%(w/v) for the PSNPs concentration range of 0.01 %(w/v) to 0.08 %(w/v).
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BACKGROUND: Hepatocellular carcinoma (HCC) is the most common type of liver malignancy. Despite significant progress in HCC treatment, resistance to chemotherapy and tumor metastasis are the main reasons for the unsatisfactory prognosis of HCC. Circular RNAs (circRNAs) have been extensively documented to play a role in the development of various types of cancer. AIMS: Here, we investigated the role of DEAD-box helicase 17 circRNA (circDDX17) in HCC and its underlying molecular mechanisms. METHODS: Our research employed various techniques including reverse transcription-quantitative polymerase chain reaction (RT-qPCR), cell counting kit-8 (CCK-8), flow cytometry, dual luciferase reporter assay, RNA immunoprecipitation (RIP), and western blot analysis. Additionally, we conducted a tumor xenograft assay to investigate the in vivo function of circDDX17. RESULTS: Firstly, the expression of circDDX17 was downregulated in HCC tissues and cells. Through functional experiments, it was observed that the overexpression of circDDX17 enhanced the sensitivity of sorafenib, promoted apoptosis, and inhibited the process of epithelial-mesenchymal transition (EMT) in vitro. Additionally, in vivo studies revealed that circDDX17 reduced tumor growth and increased sorafenib sensitivity. Mechanically, circDDX17 competitively combined miR-21-5p to suppress PTEN expression and activate the PI3K/AKT pathway. Furthermore, our rescue assays demonstrated that circDDX17 act as a tumor suppressor by blocking sorafenib resistance and tumorigenesis, while the inhibitory effect caused by circDDX17 upregulation was neutralized when miR-21-5p was overexpressed, PTEN was silenced, or the PI3K/AKT pathway was activated. CONCLUSION: Our findings firstly confirmed that circDDX17 suppressed sorafenib resistance and HCC progression by regulating miR-21-5p/PTEN/PI3K/AKT pathway, which may provide novel biomarkers for the diagnosis, treatment and prognosis of HCC.
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Carcinoma Hepatocelular , ARN Helicasas DEAD-box , Resistencia a Antineoplásicos , Neoplasias Hepáticas , ARN Circular , Sorafenib , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Humanos , Sorafenib/farmacología , Sorafenib/uso terapéutico , ARN Circular/genética , ARN Circular/metabolismo , Resistencia a Antineoplásicos/genética , ARN Helicasas DEAD-box/genética , ARN Helicasas DEAD-box/metabolismo , Animales , Ratones , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Carcinogénesis/genética , Línea Celular Tumoral , MicroARNs/genética , MicroARNs/metabolismo , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Ratones Desnudos , Apoptosis/efectos de los fármacos , Masculino , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo , Transducción de Señal , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Ovarian cancer is a leading cause of death among gynecologic tumors, often detected at advanced stages. Metabolic reprogramming and increased lipid biosynthesis are key factors driving cancer cell growth. Stearoyl-CoA desaturase 1 (SCD1) is a crucial enzyme involved in de novo lipid synthesis, producing mono-unsaturated fatty acids (MUFAs). Here, we aimed to investigate the expression and significance of SCD1 in epithelial ovarian cancer (EOC). Comparative analysis of normal ovarian surface epithelial (NOSE) tissues and cell lines revealed elevated SCD1 expression in EOC tissues and cells. Inhibition of SCD1 significantly reduced the proliferation of EOC cells and patient-derived organoids and induced apoptotic cell death. Interestingly, SCD1 inhibition did not affect the viability of non-cancer cells, indicating selective cytotoxicity against EOC cells. SCD1 inhibition on EOC cells induced endoplasmic reticulum (ER) stress by activating the unfolded protein response (UPR) sensors and resulted in apoptosis. The addition of exogenous oleic acid, a product of SCD1, rescued EOC cells from ER stress-mediated apoptosis induced by SCD1 inhibition, underscoring the importance of lipid desaturation for cancer cell survival. Taken together, our findings suggest that the inhibition of SCD1 is a promising biomarker as well as a novel therapeutic target for ovarian cancer by regulating ER stress and inducing cancer cell apoptosis.
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Neoplasias Ováricas , Estearoil-CoA Desaturasa , Femenino , Humanos , Estearoil-CoA Desaturasa/metabolismo , Apoptosis , Estrés del Retículo Endoplásmico , Carcinoma Epitelial de Ovario , LípidosRESUMEN
This study employs Latent Dirichlet Allocation (LDA) topic modelling methodology to analyze documents related to renewable energy laws and policies at the central level in China. The objective is to investigate the development and evolution of renewable energy policies in China and to gain insights into the national-level attitudes towards renewable energy development. The study consists of two phases: initially, renewable energy policy documents undergo keyword analysis using word clouds and keyword co-occurrence network analysis to elucidate the focal areas and their interconnections within the legal and policy texts. Subsequently, after determining the optimal number of topics for modelling based on topic perplexity and consistency results, the text undergoes data cleaning to isolate words with practical significance. These words are then incorporated into the LDA topic model to analyze the distribution and content of potential topics within the policies. Lastly, by linearly segmenting the time frame, changes in topic intensity over time are visually examined using heat maps. The findings indicate that energy policies have consistently prioritized "development" and emphasized the significance of "new energy" in renewable energy policies. Moreover, as renewable energy has progressed, governments and policymakers have come to acknowledge the importance of comprehensive energy planning, transitioning to clean energy sources, and regulating the electricity market. This growing awareness has led to efforts to strengthen policy and regulatory measures to foster renewable energy's sustainable development and utilization. In summary, this study highlights the effectiveness of the LDA topic model in analyzing renewable energy policies, advancing its adoption and furthering research in the field.
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Antibiotics cannot be effectively removed by traditional wastewater treatment processes, and have become widespread pollutants in various environments. In this study, a Z-type heterojunction photo-catalyst Pg-C3N4 (PCN)/Nitrogen doped biochar (N-Biochar)/BiVO4 (NCBN) for the degradation of norfloxacin (NOR) was prepared by the hydrothermal method. The specific surface area of the NCBN (42.88 m2/g) was further improved compared to BiVO4 (4.528 m2/g). The photo-catalytic performance of the catalyst was investigated, and the N-Biochar acted as a charge transfer channel to promote carrier separation and form Z-type heterojunctions. Moreover, the NCBN exhibited excellent performance (92.5%) in removing NOR, which maintained 70% degradation after four cycles. The main active substance of the NCBN was â¢O2-, and the possible degradation pathways are provided. This work will provide a theoretical basis for the construction of heterojunction photo-catalysts.