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Targeting ferroptosis, a type of cell death elicited by Fe2+ and lipid reactive oxygen species (L-ROS), provides a novel strategy for cancer therapy. Selenium has the potential to treat cancers by acting as a pro-oxidative agent, thus leading to cancer cell death. Here, we found that the triple negative breast cancer (TNBC) MDA-MB-231 cells were more sensitive to ferroptosis induced by sodium selenite (Na2SeO3) than that of non-TNBC MCF-7 cells. Na2SeO3 significantly elevated the level of L-ROS, MDA and Fe2+, decreased the content of GSH and the enzyme activity of GPx, disrupted the expression of ferroptosis related proteins such as GPx4 and FTH1, as well as compromised mitochondrial morphology in MDA-MB-231 cells. Moreover, ATM was activated by Na2SeO3 in MDA-MB-231 cells. Notably, Na2SeO3-induced ferroptosis was inhibited by ATM kinase inhibitor KU55933 or siATM, suggesting that Na2SeO3-induced ferroptosis was mediated by ATM protein in MDA-MB-231 cells. Our findings suggest a therapeutic strategy by ferroptosis against TNBC and deepened our understanding of ATM function.
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The onerous health and economic burden associated with head and neck squamous cell carcinoma (HNSCC) is a global predicament. Despite the advent of novel surgical techniques and therapeutic protocols, there is an incessant need for efficacious diagnostic and therapeutic targets to monitor the invasion, metastasis and recurrence of HNSCC due to its substantial morbidity and mortality. The differential expression patterns of histone deacetylases (HDACs), a group of enzymes responsible for modifying histones and regulating gene expression, have been demonstrated in neoplastic tissues. However, there is limited knowledge regarding the role of HDACs in HNSCC. Consequently, this review aims to summarize the existing research findings and explore the potential association between HDACs and HNSCC, offering fresh perspectives on therapeutic approaches targeting HDACs that could potentially enhance the efficacy of HNSCC treatment. Additionally, the Cancer Genome Atlas (TCGA) dataset, CPTAC, HPA, OmicShare, GeneMANIA and STRING databases are utilized to provide supplementary evidence on the differential expression of HDACs, their prognostic significance and predicting functions in HNSCC patients.
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Neoplasias de Cabeça e Pescoço , Inibidores de Histona Desacetilases , Histona Desacetilases , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Histona Desacetilases/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/enzimologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/enzimologia , Inibidores de Histona Desacetilases/uso terapêutico , Inibidores de Histona Desacetilases/farmacologia , Terapia de Alvo Molecular , Regulação Neoplásica da Expressão GênicaRESUMO
INTRODUCTION: The efficacy of root canal treatment is greatly impacted by a thorough understanding of root canal anatomy. This systematic review and meta-analysis aim to thoroughly investigate the root morphology and canal configuration (RMCC) of permanent premolars (PMs). METHODOLOGY: A comprehensive analysis was conducted following the PRISMA guidelines. Literature exploration was carried out across four electronic databases (PubMed, Embase, Cochrane, and Web of Science). The risk of bias assessment was conducted for the included studies utilizing the Anatomical Quality Assessment (AQUA) tool. Data analysis was performed utilizing SPSS and RevMAN5.3.3. The meta-analysis was applied with a 95% confidence interval to calculate odds ratios (OR). RESULTS: Among the 82 selected studies, 59 studies exhibited potential bias in domain one (objective(s) and subject characteristics), followed by domain three (methodology characterization). The majority of maxillary PM1s had either single root (46.7%) or double roots (51.9%), while three-rooted variants were uncommon (1.4%). Conversely, most other PMs exhibited a single root. In terms of canal configuration, maxillary PM1s predominantly featured double distinct canals (87.2%), with the majority of maxillary PM2s displaying either a single canal (51.4%) or double canals (48.3%). Mandibular PMs were primarily characterized by single canals, accounting for 78.3% of mandibular PM1s and 90.3% of mandibular PM2s. Subgroup analyses revealed higher incidences of single-rooted and single-canalled PMs among Asians compared to Caucasians. Additionally, women exhibited a higher incidence of single-rooted PMs, while men showed a greater frequency of double-rooted PMs. CONCLUSIONS: The comprehensive analysis indicated that maxillary PM1s predominantly possess double roots and double canals, whereas maxillary PM2s and mandibular PMs were primarily characterized by single-rooted with a single canal. Notably, single root and single canal were more prevalent among women and Asian samples.
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Dente Pré-Molar , Tomografia Computadorizada de Feixe Cônico , Cavidade Pulpar , Raiz Dentária , Humanos , Tomografia Computadorizada de Feixe Cônico/métodos , Dente Pré-Molar/diagnóstico por imagem , Dente Pré-Molar/anatomia & histologia , Raiz Dentária/diagnóstico por imagem , Raiz Dentária/anatomia & histologia , Cavidade Pulpar/diagnóstico por imagem , Cavidade Pulpar/anatomia & histologiaRESUMO
BACKGROUND: Sodium dehydroacetate (DHA-S) is a common food additive, which can combine with serum proteins in the plasma, but the interaction mechanism between DHA-S and human serum albumin (HSA) is unclear. In this study, multiple spectroscopy techniques, isothermal titration calorimetry (ITC), molecular docking and esterase activity test were employed to investigate the interaction mechanism of DHA-S and HSA. RESULTS: A DHA-S-HSA complex was formed and the structure of HSA were altered by DHA-S. Since DHA-S changed the tight structure of the hydrophobic subdomain IIA where tryptophan (Trp) was placed, the hydrophobicity of the microenvironment of HSA was enhanced. With the addition of DHA-S, the skeleton structure of HSA became loose and the solvent shell on the HSA surface was destroyed. DHA-S altered the secondary structure of HSA, resulting in the decreased α-helix and increased ß-sheet contents. The interaction was exothermic and spontaneous driven by van der Waals and hydrogen bonding. DHA-S inhibited the esterase activity of HSA. Molecular docking demonstrated that the binding site of DHA-S on HSA located at the cavity of subdomains IIA and IIIA, but the amino acids related to esterase activity of HSA were not in the binding pocket, indicating that the mechanism by which DHA-S inhibited HSA esterase activity was the change in protein structure. CONCLUSION: This study illustrated that DHA-S interacted with HSA and the structure and function of HSA were affected by DHA-S. This research could help to understand the toxicity of DHA-S and provide basic data for safe use of food additives. © 2021 Society of Chemical Industry.
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Esterases , Albumina Sérica Humana , Sítios de Ligação , Dicroísmo Circular , Esterases/metabolismo , Humanos , Ligação de Hidrogênio , Simulação de Acoplamento Molecular , Ligação Proteica , Pironas , Albumina Sérica Humana/química , Albumina Sérica Humana/metabolismo , Espectrometria de Fluorescência , TermodinâmicaRESUMO
Due to the rapid development of industrial society, air pollution is becoming a serious problem which has being a huge threat to human health. Ultrafine particles (UFPs), one of the major air pollutants, are often the culprits of human diseases. At present, most of the toxicological studies of UFPs focus on their biological effects on lung cells and tissues, but there are less researches taking aim at the negative effects on functional proteins within the body. Therefore, we experimentally explored the effects of ultrafine carbon black (UFCB) on the structure and function of trypsin. After a short-term exposure to UFCB, the trypsin aromatic amino acid microenvironment, protein backbone and secondary structure were changed significantly, and the enzyme activity showed a trend that rose at first, then dropped. In addition, UFCB interacts with trypsin in the form of a complex. These studies demonstrated the negative effects of UFCB on trypsin, evidencing potential effects on animals and humans.
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Material Particulado/toxicidade , Fuligem/toxicidade , Tripsina/química , Tripsina/metabolismo , Animais , Bovinos , Dicroísmo Circular , Regulação da Expressão Gênica/efeitos dos fármacos , Modelos Moleculares , Tamanho da Partícula , Estrutura Secundária de Proteína/efeitos dos fármacos , Análise Espectral , Tripsina/efeitos dos fármacosRESUMO
This study investigated the adverse effects of perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) on mouse primary hepatocytes by conducting cell viability, apoptosis, intracellular oxidative stress level, superoxide dismutase (SOD), catalase (CAT) activity and glutathione level assays. It was shown that PFOA and PFOS altered antioxidant enzymes activities and triggered oxidative stress, and thus exhibited cytotoxicity to the hepatocytes. Molecular mechanisms of SOD activities were measured and structural changes were explored by isothermal titration calorimetry and multiple spectroscopy. PFOA and PFOS bind to SOD via electrostatic forces with 7.634⯱â¯0.06 and 9.7⯱â¯0.4 sites, respectively, leading to structural and conformational changes. The overall results demonstrated that PFOS and PFOA are able to interact with SOD directly, resulting in producing oxidative stress and induce apoptosis.
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Ácidos Alcanossulfônicos , Caprilatos , Fluorocarbonos , Hepatócitos , Superóxido Dismutase , Ácidos Alcanossulfônicos/metabolismo , Ácidos Alcanossulfônicos/toxicidade , Animais , Apoptose/efeitos dos fármacos , Caprilatos/metabolismo , Caprilatos/toxicidade , Fluorocarbonos/metabolismo , Fluorocarbonos/toxicidade , Hepatócitos/efeitos dos fármacos , Camundongos , Superóxido Dismutase/metabolismoRESUMO
Perfluorodecanoic acid (PFDA) has been widely used in production of many daily necessities because of its special nature. Althoughtoxic effects of PFDA to organisms have been reported, there is little research on the genotoxicity induced by oxidative stress of PFDA on the cellular and molecular levels simultaneously. Thus, we investigated the DNA oxidative damage caused by PFDA in mouse hepatocytes. On the cellular level, an increase in ROS content indicated that PFDA caused oxidative stress in mouse hepatocytes. In addition, after PFDA exposure, the comet assay confirmed DNA strand breaks and an increased 8-OHdG content demonstrated DNA oxidative damage. On the molecular level, the microenvironment of aromatic amino acids, skeleton and secondary structure of catalase (CAT) were varied after PFDA exposure and the enzyme activity was reduced because PFDA bound near the heme groups of CAT. Moreover, PFDA was shown to interact with DNA molecule by groove binding. This study suggests that PFDA can cause genotoxicity by inducing oxidative stress both on the cellular and molecular levels.
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Dano ao DNA , Ácidos Decanoicos/toxicidade , Poluentes Ambientais/toxicidade , Fluorocarbonos/toxicidade , Hepatócitos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Sítios de Ligação , Catalase/química , Catalase/metabolismo , Células Cultivadas , Ensaio Cometa , DNA/química , Hepatócitos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Oxirredução , Estresse Oxidativo/genética , Cultura Primária de Células , Estrutura Secundária de Proteína , Espécies Reativas de Oxigênio/metabolismoRESUMO
As a promising biolabeling biomaterials, quantum dots (QDs) present a great potential. However, the toxicity of QDs to organisms has attracted wide attention. In our research, we introduced an in vitro method to study the molecular mechanisms for the structure and activity alterations of Candida rugosa lipase (CRL) with the binding of 3-mercaptopropionic acid-capped CdTe QDs. Multiple spectroscopic methods, isothermal titration calorimetry, and enzyme activity measurements were used in this paper. QDs statically quenched the intrinsic fluorescence of CRL with the quenching constant decreases from 2.46 × 1013 to 1.64 × 1013 L mol-1 second-1 (298 to 310 K). It binds to CRL through hydrophobic force with 1 binding site, unfolding and loosening the skeleton and changed its secondary structure. Rather than aggregating on the surface, it enters the pocket of the CRL to interact with Ser-209 (2.43 Å) and the residues surrounding Ser-209, making the catalytic triad more exposed. Furthermore, the activity of CRL was inhibited by approximately 15%. This work demonstrates that 3-mercaptopropionic acid-capped CdTe QDs may cause negative effects to CRL and obtains a molecular mechanism on QD-induced toxicity to proteins in vitro.
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Candida/enzimologia , Lipase/química , Pontos Quânticos/química , Ácido 3-Mercaptopropiônico/química , Compostos de Cádmio/química , Candida/química , Ligação Proteica , Proteínas/química , Pontos Quânticos/toxicidade , Análise Espectral , Telúrio/química , Água/químicaRESUMO
This study presents the fabrication and evaluation of a sinusoidal extended depth-of-focus (EDoF) intraocular lens (IOL) based on our previously proposed design approach. The power, through-focus MTF, and surface profile were measured using commercial instruments. Through-focus images of a United States Air Force (USAF) 1951 resolution target formed by the fabricated IOL were compared with Symfony and AR40E under monochromatic and polychromatic light using optical bench testing. Simulations assessed visual acuity (VA) of a pseudophakic model eye with the EDoF IOL, including evaluation of tilt and decentration effects. Results indicate that the base power, add power, and the through-focus MTF@50 lp/mm of the fabricated IOL at a 3 mm pupil size align with the design specifications. The extended-depth-of-focus and imaging performance for the far vision of the fabricated IOL under both monochromatic and polychromatic light conditions at a 3.0 mm pupil diameter is comparable to that of Symfony. In addition, the fabricated IOL exhibits a similar extended-depth-of-focus for three discrete wavelengths. The pseudophakic model eye with the designed EDoF IOL demonstrates a VA exceeding 0.1 logMAR within a defocus range of 2.44 D. The VA is tolerant to both IOL tilt and decentration. These findings demonstrate the promising potential of the sinusoidal EDoF IOL design for future applications in cataract surgery.
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Córnea/fisiopatologia , Aberrações de Frente de Onda da Córnea/fisiopatologia , Pressão Intraocular/fisiologia , Hipertensão Ocular/fisiopatologia , Adulto , Fenômenos Biomecânicos , Topografia da Córnea , Elasticidade/fisiologia , Feminino , Voluntários Saudáveis , Humanos , Masculino , Modelos Biológicos , Postura , Fatores de Tempo , Tonometria Ocular , Adulto JovemRESUMO
Nanoplastics are emerging pollutants that pose a potential threat to the environment and organisms and are widely distributed in environmental samples and food chains. The accumulation of polystyrene nanoplastics (PS-NPs) in an organism can cause oxidative stress. Currently, toxicity studies of PS-NPs mainly focus on the individual and cellular levels, whereas few studies have been conducted on the molecular mechanisms of the interaction between PS-NPs and catalase (CAT). Based on this, CAT was chosen as the target receptor for molecular toxicity research to reveal the interaction mechanism at the molecular level between PS-NPs and CAT by using various spectroscopic means and enzyme activity detection methods. The results indicated that PS-NPs destroyed the secondary structure of CAT, causing its protein skeleton to loosen and unfold, increasing the content of α-helices, decreasing the content of ß-sheets, and exposing the position of the heme group. After exposure to PS-NPs, the internal fluorophore of CAT underwent fluorescence sensitization, resulting in a micelle-like structure, which enhanced the hydrophobicity of aromatic amino acids but did not change their polarity. In addition, the aggregation state of CAT was altered upon binding to PS-NPs, and the volume was further increased. Finally, these structural changes led to a gradual decrease in CAT activity. This study presents a comprehensive assessment of the toxicity of PS-NPs at the molecular level, which can provide more experimental support for the study of the biotoxicological efficacy of PS-NPs.
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Nanopartículas , Poluentes Químicos da Água , Poliestirenos/toxicidade , Poliestirenos/química , Microplásticos , Catalase , Estresse Oxidativo , Nanopartículas/química , Poluentes Químicos da Água/toxicidadeRESUMO
Microplastics (MPs) undergo physical, chemical, and biological aging in the environment, leading to changes in their physicochemical properties, affecting migration characteristics and toxicity. Oxidative stress effects induced by MPs in vivo have been extensively studied, but the toxicity difference between virgin and aged MPs and the interactions between antioxidant enzymes and MPs in vitro have not been reported yet. This study investigated the structural and functional changes of catalase (CAT) induced by virgin and aged PVC-MPs. It was shown that light irradiation aged the PVC-MPs, and the aging mechanism was photooxidation, resulting in a rough surface and appearing holes and pits. Because of the changes in physicochemical properties, aged MPs had more binding sites than virgin MPs. Fluorescence and synchronous fluorescence spectra results suggested that MPs quenched the endogenous fluorescence of CAT and interacted with tryptophane and tyrosine residues. The virgin MPs had no significant effect on the skeleton of CAT, while the skeleton and the polypeptide chains of CAT became loosened and unfolded after binding with the aged MPs. Moreover, the interactions of CAT with virgin/aged MPs increased the α-helix and decreased the ß-sheet contents, destroyed the solvent shell, and resulted in a dispersion of CAT. Due to the large size, MPs cannot enter the interior of CAT and have no effects on the heme groups and activity of CAT. The interaction mechanism between MPs and CAT may be that MPs adsorb CAT to form the protein corona, and aged MPs had more binding sites. This study is the first comprehensive investigation of the effect of aging on the interaction between MPs and biomacromolecules and highlights the potential negative effects of MPs on antioxidant enzymes.
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Microplásticos , Poluentes Químicos da Água , Microplásticos/toxicidade , Plásticos , Catalase , Antioxidantes , Estresse Oxidativo , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análiseRESUMO
Microplastics are harmful pollutants that widely exist worldwide and pose a severe threat to all types of organisms. The effects of polystyrene microplastics (PS-MPs) on organisms have been extensively studied, but the interaction mechanism between PS-MPs and superoxide dismutase (SOD) at the molecular level has not been reported yet. Therefore, based on multiple spectroscopic methods and enzyme activity measurements, the molecular mechanism of the interaction between PS-MPs and SOD was investigated. The multispectral results showed that the protein skeleton and secondary structure of SOD were altered by PS-MPs, resulting in decreased α-helix and ß-sheet content. After PS-MPs exposure, fluorescence sensitization occurred, and micelles were formed, along with the enhanced hydrophobicity of aromatic amino acids in SOD. Moreover, the resonance light scattering (RLS) spectra result suggested that the PS-MPs and SOD combined to form a larger complex. Eventually, the activity of SOD was increased due to these structural changes, and the concentration of PS-MPs is positively correlated with SOD activity. This study can provide experimental support for studying the toxicological effects of PS-MPs.
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Poliestirenos , Poluentes Químicos da Água , Poliestirenos/metabolismo , Microplásticos , Plásticos , Superóxido Dismutase , Poluentes Químicos da Água/metabolismo , Análise EspectralRESUMO
Microplastics (MPs) can affect phytoplankton and its photosynthetic performance in many but often in negative ways. Phytoplankton is an important source of dissolved organic matter (DOM) in aquatic ecosystems, but the impact of MPs on the algal production of DOM is poorly known. We investigated the impacts of polyvinyl chloride MPs on the growth and DOM production by Chlamydomonas reinhardtii microalgae in a 28-day-long experiment. During the exponential growth phase of C. reinhardtii, MPs slightly affected algal growth and DOM production. At the end of experiment, MPs decreased the biomass of C. reinhardtii by 43 % in the treatment with MPs exposed to simulated solar radiation prior the experiment (light-aged) and more than in the treatment with virgin MPs. The light-aged MPs decreased algal DOM production by 38 % and modified the chemical composition of DOM. According to spectroscopic analyses, the light-aged MPs increased aromaticity, average molecular weight and fluorescence of DOM produced by C. reinhardtii. The elevated fluorescence was associated with humic-like components identified by a 5-component parallel factor analysis (PARAFAC) from the excitation-emission matrices. We conclude that although MPs can leach DOM to aquatic ecosystems, they potentially modify the aquatic DOM more by interfering with the algal production of DOM and changing the composition of produced DOM.
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Microalgas , Plásticos , Microplásticos , Matéria Orgânica Dissolvida , Ecossistema , Fitoplâncton , Espectrometria de Fluorescência/métodos , Substâncias Húmicas/análise , Análise FatorialRESUMO
Insulin resistance is associated with many pathological conditions, and an in-depth understanding of the mechanisms involved is necessary to improve insulin sensitivity. Here, we show that ZFYVE28 expression is decreased in insulin-sensitive obese individuals but increased in insulin-resistant individuals. Insulin signaling inhibits ZFYVE28 expression by inhibiting NOTCH1 via the RAS/ERK pathway, whereas ZFYVE28 expression is elevated due to impaired insulin signaling in insulin resistance. While Zfyve28 overexpression impairs insulin sensitivity and causes lipid accumulation, Zfyve28 knockout in mice can significantly improve insulin sensitivity and other indicators associated with insulin resistance. Mechanistically, ZFYVE28 colocalizes with early endosomes via the FYVE domain, which inhibits the generation of recycling endosomes but promotes the conversion of early to late endosomes, ultimately promoting phosphorylated insulin receptor degradation. This effect disappears with deletion of the FYVE domain. Overall, in this study, we reveal that ZFYVE28 is involved in insulin resistance by promoting phosphorylated insulin receptor degradation, and ZFYVE28 may be a potential therapeutic target to improve insulin sensitivity.
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Endossomos , Resistência à Insulina , Insulina , Receptor de Insulina , Animais , Camundongos , Proteínas de Transporte/metabolismo , Endossomos/metabolismo , Insulina/metabolismo , Receptor de Insulina/genética , Receptor de Insulina/metabolismo , Transdução de Sinais , Humanos , ObesidadeRESUMO
White adipose tissue browning can promote lipid burning to increase energy expenditure and improve adiposity. Here, we show that Slc35d3 expression is significantly lower in adipose tissues of obese mice. While adipocyte-specific Slc35d3 knockin is protected against diet-induced obesity, adipocyte-specific Slc35d3 knockout inhibits white adipose tissue browning and causes decreased energy expenditure and impaired insulin sensitivity in mice. Mechanistically, we confirm that SLC35D3 interacts with the NOTCH1 extracellular domain, which leads to the accumulation of NOTCH1 in the endoplasmic reticulum and thus inhibits the NOTCH1 signaling pathway. In addition, knockdown of Notch1 in mouse inguinal white adipose tissue mediated by orthotopic injection of AAV8-adiponectin-shNotch1 shows considerable improvement in obesity and glucolipid metabolism, which is more pronounced in adipocyte-specific Slc35d3 knockout mice than in knockin mice. Overall, in this study, we reveal that SLC35D3 is involved in obesity via NOTCH1 signaling, and low adipose SLC35D3 expression in obesity might be a therapeutic target for obesity and associated metabolic disorders.
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Tecido Adiposo Marrom , Tecido Adiposo Branco , Obesidade , Receptores Notch , Animais , Camundongos , Adipócitos/metabolismo , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Dieta Hiperlipídica , Metabolismo Energético , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/metabolismo , Transdução de Sinais , Receptores Notch/metabolismoRESUMO
With the rapid development of social economy and Internet of Things, the society has entered the era of networking, digitalization, and intelligence, bringing great convenience to people's life; Internet of Things music system also has begun to get people's extensive attention. Due to the influence of such factors as strong music professionalism, complex music theory knowledge, and diverse changes, it is difficult to identify music features. In order to strengthen the user's personal experience of the music system, the multimusic systems are interconnected through information technology to realize the connection between objects and people. The system uses an embedded processor to realize the central control module and then according to network standard the sensor network is built, through radio frequency identification (RFID) technology for light, sound, infrared sensor, temperature, and other sensors for information reading. Music selection logic is designed based on the theory of music psychology and user behavior log, so as to select the best music for users to improve their mood and improve their life quality and work and study efficiency. At the same time, the system uses voice recognition technology to enhance user interaction, through the system, to provide the website to share their own music data and comments on songs and view song information, and the system runs stably and can collect high quality music signals and correctly identify the characteristics of music form and emotional characteristics.
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Internet das Coisas , Música , Humanos , Internet , Reconhecimento Psicológico , TecnologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Senegenin (SEN), an active compound extracted from the traditional Chinese herb Polygala tenuifolia Willd. (a species in the genus Polygala, family Polygalaceae), could nourish neurons and resist neuronal damage in mouse models of Alzheimer's disease (AD). Amyloid-ß (Aß) depositions in neuronal cells may cause pathological changes such as oxidative stress which one return could cause severe damage to mitochondria in AD patients or animal models. Mitophagy is an important mechanism to selectively remove damaged mitochondria. In neurons, this process is mainly mediated by PTEN-induced putative kinase 1 (PINK1)/Parkin pathway. Previous studies have shown that SEN could reduce mitochondrial damage and inhibit apoptosis in neurons. Therefore, this study speculated that SEN might activate mitophagy to clear damaged mitochondria, thereby mitigating Aß-induced cell damage in neuronal cells. AIM OF THE STUDY: This study aimed to determine the effects of SEN on Aß-induced cell damage, and further to explore whether SEN could induce mitophagy. Moreover, the regulatory role of mitophagy in the neuroptrotective effect of SEN would be elucidated. MATERIALS AND METHODS: This study established an in vitro cell damage model using Aß1-42 to treat mouse hippocampal neuron HT22 cells. The effects of SEN on cell damage were determined by MTT assay and lactate dehydrogenase (LDH) release assay. Reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were detected by Cytation™5 cell imaging microplate detection system. The apoptotic rate was analyzed by flow cytometry. The effects of SEN on mitophagy were detected by transmission electron microscope, immunofluorescence and immunoblotting. RESULTS: Firstly, HT22 cells were treated with 30 µM Aß1-42 for 24 h to establish the damage model. It was found that 30 µM Aß1-42 caused neuronal damages as evidenced by reduced cell viability, increased LDH release and ROS, collapsed MMP and elevated apoptosis. Secondly, Aß1-42-incubated cells were treated with 10, 20, 40 and 60 µM SEN for 24 h. SEN significantly reduced the damage of Aß1-42-incubated cells as shown by recovered cell viability and MMP, reduced apoptosis and ROS. Notably, SEN induced the formation of mitophagosomes and mitolysosomes, and elevated the conversion of LC3 I to LC3 II. Moreover, SEN down-regulated the expression of p62, promoted the accumulation of full-length PINK1 and the translocation of Parkin to mitochondria, decreased the expression of mitochondrial matrix protein HSP60, thus activating the PINK1/Parkin-mediated mitophagy. However, when cells were pretreated with 5 µM CsA (Cyclosporine A, a mitophagy inhibitor) for 2 h and then co-treated with 20 and 40 µM SEN for 24 h, the protective effects of SEN were compromised. CONCLUSIONS: The present study demonstrated that SEN could alleviate Aß1-42-induced cell damage through PINK1/Parkin-mediated mitophagy. Our findings justify the traditional use of P. tenuifolia in China with anti-aging or anti-neurodegenerative effects.
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Mitofagia , Proteínas Quinases , Animais , Humanos , Camundongos , Peptídeos beta-Amiloides , Medicamentos de Ervas Chinesas , Fragmentos de Peptídeos , Proteínas Quinases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ubiquitina-Proteína Ligases/metabolismoRESUMO
The preparation of the wavelength-scale micropores on metallic surfaces is limited by the high opacity of metal. At present, most micropores reported in the literature are more than 20 µm in diameter, which is not only large in size, but renders them inefficient for processing so that it is difficult to meet the needs of some special fields, such as aerospace, biotechnology, and so on. In this paper, the rapid laser fabrications of the wavelength-scale micropores on various metallic surfaces are achieved through femtosecond MHz burst Bessel beam ablation. Taking advantage of the long-depth focal field of the Bessel beam, high-density micropores with a diameter of 1.3 µm and a depth of 10.5 µm are prepared on metal by MHz burst accumulation; in addition, the rapid fabrication of 2000 micropores can be achieved in 1 s. The guidelines and experimental results illustrate that the formations of the wavelength-scale porous structures are the result of the co-action of the laser-induced periodic surface structure (LIPSS) effect and Bessel beam interference. Porous metal can be used to store lubricant and form a lubricating layer on the metallic surface, thus endowing the metal resistance to various liquids' adhesion. The microporous formation process on metal provides a new physical insight for the rapid preparation of wavelength-scale metallic micropores, and promotes the application of porous metal in the fields of catalysis, gas adsorption, structural templates, and bio-transportation fields.
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The widespread use of antibiotics leads to the increasing drug resistance of bacteria and poses a threat to human health. Therefore, there is an urgent need to develop new antibacterial strategies. Herein, based on the good photothermal properties of Copper sulfide (CuS) nanoparticles under near infrared (NIR) laser, we developed a NIR-â ¡ window triple-mode synergetic antibacterial cCuS (cationic CuS) @Vancomycin (Van) nanoplatform. In the proposed nanoplatform, the positive charge on the surface makes cCuS@Van nanoplatform show better bacterial uptake and membrane damage; vancomycin induces chemical sterilization and provides a targeting effect to the nanoplatform; combined with the strong photothermal effect and deep tissue penetration at the excitation of 1064 nm laser, cCuS@Van nanoplatform can effectively kill bacterial. The photothermal conversion efficiency of the nanoplatform can reach 49.12 % and in vitro experiments show a sterilizing rate of more than 99.5 % to staphylococcus aureus (S. aureus) at the concentration of 3.0 µM, which also demonstrated the synergistic effect of cCuS@Van nanoplatform. In addition, low cytotoxicity to human cells conforms the good biocompatibility of the as-prepared cCuS@Van nanoplatform, which endows it a good application prospect in the field of antibacterial, such as wound healing and implant sterilization.