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Perovskite is an emerging material with immense potential in the field of optoelectronics. 1D perovskite nanowires are crucial building blocks for the development of optoelectronic devices. However, producing perovskite nanowires with high quality and controlled alignment is challenging. In this study, the direct epitaxial growth of perovskite on oriented carbon nanotube (CNT) templates is presented through a chemical vapor deposition method. The deposition process of lead iodide and methylammonium iodide is systematically investigated, and a layer plus island growth mechanism is proposed to interpret the experimental observations. The aligned long CNTs serve as 1D templates and allow the growth of CNT@perovskite core-shell heterostructure with a high aspect ratio to withstand large deformation. The obtained 1D perovskite materials can be easily manipulated and transferred, enabling the facile preparation of microscale flexible devices. For proof of concept, a photodetector based on an individual CNT@methylammonium lead iodide heterostructure is fabricated. This work provides a new approach to prepare 1D hetero-nanostructure and may inspire the design of novel flexible nanophotodetectors.
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BACKGROUND: Adequate nutritional knowledge and healthy dietary behaviours are essential for promoting rational nutrition for children. However, lack of nutritional knowledge and unhealthy dietary behaviours are common among Chinese children. Therefore, we developed a school-based nutrition education (NE) program to assess its impacts on nutritional knowledge and dietary behaviours in pupils. METHODS: In this trial, one school was assigned as an intervention group (n = 199) and the other two schools were designated as a control group (n = 140). Children in the intervention group received the NE program in addition to their regular health curriculum, whereas the control group continued with their usual health curriculum without any NE program materials. RESULTS: Concerning nutritional knowledge, the mean difference (follow-up minus baseline) of average knowledge scores in the intervention group was significantly higher than that in the control group (1.99 ± 3.22 vs. 0.66 ± 3.60, p = 0.001). However, subgroup analysis revealed that this difference disappeared among boys and students with malnutrition status. Regarding dietary behaviours, the NE program significantly increased the proportion of children exhibiting high frequencies of meat and nuts consumption in the intervention group, along with diverse food choice at breakfast. Additionally, it markedly reduced the proportion of children exhibiting high frequencies of sugar-sweetened beverages and fast food consumption. Structural equation modelling analyses indicated a significant direct effect of NE intervention on nutritional knowledge and an indirect effect on dietary behaviours. CONCLUSIONS: The NE program effectively enhanced nutritional knowledge scores and further improved dietary behaviours among Chinese primary school students. Future NE programs should pay more attention to boys and children with malnutrition.
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Bioelectronics integrates electronics with biological organs, sustaining the natural functions of the organs. Organs dynamically interact with the external environment, managing internal equilibrium and responding to external stimuli. These interactions are crucial for maintaining homeostasis. Additionally, biological organs possess a soft and stretchable nature; encountering objects with differing properties can disrupt their function. Therefore, when electronic devices come into contact with biological objects, the permeability of these devices, enabling interactions and substance exchanges with the external environment, and the mechanical compliance are crucial for maintaining the inherent functionality of biological organs. This review discusses recent advancements in soft and permeable bioelectronics, emphasizing materials, structures, and a wide range of applications. The review also addresses current challenges and potential solutions, providing insights into the integration of electronics with biological organs.
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Eletrônica , Humanos , Permeabilidade , Dispositivos Eletrônicos Vestíveis , AnimaisRESUMO
Di-2-ethylhexyl phthalate (DEHP), a widely utilized plasticizer, has been described as a potential obesogen based on in vivo disruption of hepatic lipid homeostasis and in vitro promotion of lipid accumulation. However, limited literature exists regarding the specific ramifications of DEHP exposure on obese individuals, and the precise mechanisms underlying the adverse effects of DEHP exposure remain unclear. This study aimed to assess the impact of DEHP on hepatic lipid metabolism in obese mice by comparing them to normal mice. Following a 10-week DEHP exposure period, the obese mice exhibited higher blood lipid levels, more severe hepatic steatosis, and more infiltrations of inflammatory cells in liver tissue than normal mice. Interestingly, the body weight of the mice exhibited no significant alteration. In addition, transcriptomic analyses revealed that both lipogenesis and fatty acid oxidation contributed to hepatic lipid metabolism dysregulation following DEHP exposure. More specifically, alterations in the transcription of genes associated with hepatic lipid metabolism were linked to the different responses to DEHP exposure observed in normal and obese mice. Additionally, the outcomes of in vitro experiments validated the in vivo findings and demonstrated that DEHP exposure could modify hepatic lipid metabolism in normal mice by activating the LXR/SREBP-1c signaling pathway to promote lipogenesis. At the same time, DEHP exposure led to inhibition of the Camkkß/AMPK pathway to suppress ß-fatty acid oxidation. Conversely, in obese mice, DEHP exposure was found to be associated with the stimulation of both lipogenesis and fatty acid oxidation via activation of the LXR/SREBP-1c and PPAR-α signaling pathways, respectively. The findings presented in this study first elucidate the contrasting mechanisms underlying DEHP-induced liver damage in obese and normal mice, thereby offering valuable insights into the pathogenesis of DEHP-induced liver damage in individuals with obesity.
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Dietilexilftalato , Metabolismo dos Lipídeos , Ácidos Ftálicos , Animais , Camundongos , Dietilexilftalato/metabolismo , Ácidos Graxos/metabolismo , Lipídeos , Fígado/metabolismo , Camundongos Obesos , Obesidade/induzido quimicamente , Obesidade/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Transdução de Sinais , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismoRESUMO
BACKGROUND/OBJECTIVES: Previous research has shown maternal betaine supplementation alleviates fetal-derived hepatic steatosis. Therefore, this study examined the anti-inflammatory effect of maternal betaine intake in offspring mice and its mechanism. MATERIALS/METHODS: Female C57BL/6J mice and their offspring were randomly divided into 3 groups according to the treatment received during gestation and lactation: control diet (CD), fatty liver disease (FLD), and fatty liver disease + 1% betaine (FLD-BET). The FLD group was given a high-fat diet and streptozotocin (HFD + STZ), and the FLD-BET group was treated with HFD + STZ + 1% betaine. After weaning, the offspring mice were given a normal diet for 5 weeks and then dissected to measure the relevant indexes. RESULTS: Compared to the CD group, the offspring mice in the FLD group revealed obvious hepatic steatosis and increased serum levels of alanine aminotransferase, interleukin (IL)-6, and tumor necrosis factor (TNF)-α; maternal betaine supplementation reversed these changes. The hepatic mRNA expression levels of IL-6, IL-18, and Caspase-1 were significantly higher in the FLD group than in the CD group. Maternal betaine supplementation reduced the expression of IL-1ß, IL-6, IL-18, and apoptosis-associated speck-like protein containing C-terminal caspase recruitment domain (ASC). Maternal betaine supplementation also reversed the increasing protein expressions of nitric oxide dioxygenase-like receptor family pyrin domain containing 3 (NLRP3), ASC, Caspase-1, IL-1ß, and IL-18 in offspring mice exposed to HFD + STZ. Maternal betaine supplementation decreased the homocysteine (Hcy) and s-adenosine homocysteine (SAH) levels significantly in the livers. Furthermore, the hepatic Hcy concentrations showed significant inverse relationships with the mRNA expression of TNF-α, NLRP3, ASC, and IL-18. The hepatic SAH concentration was inversely associated with the IL-1ß mRNA expression. CONCLUSIONS: The lipotropic and anti-inflammatory effect of maternal betaine supplementation may be associated with the inhibition of NLRP3 inflammasome in the livers of the offspring mice.
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Nature-derived silk fibers possess excellent biocompatibility, sustainability, and mechanical properties, yet producing strong and tough silk fibers in a facile and large-scale manner remains a significant challenge. Herein, we report a simple method for preparing strong and tough silk fibers by feeding silkworms rare earth ion-modified diets. The resulting silk fibers exhibit significantly increased tensile strength and toughness, with average values of 0.85 ± 0.07 GPa and 156 ± 13 MJ m-3, respectively, and maximum values of 0.97 ± 0.04 GPa and 188 ± 19 MJ m-3, approaching those of spider dragline silk. Our findings suggest that the incorporation of rare earth ions (La3+ or Eu3+) into the silk fibers contributes to this enhancement. Structure analysis reveals a reduction in content and an improvement in orientation of ß-sheet nanocrystals in silk fibers. X-ray photoelectron spectroscopy analysis confirms the chemical interaction between rare earth ions with ß-sheet nanocrystals. The structural evolution and chemical interactions lead to the simultaneous enhancement in both strength and toughness. This work presents a simple, scalable, and effective strategy for producing ultra-strong and tough silk fibers with potential applications in areas requiring super structural materials, such as personal protection and aerospace.
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Bombyx , Seda , Animais , Seda/química , Bombyx/metabolismo , Resistência à Tração , Íons/metabolismo , DietaRESUMO
Escherichia coli O157:H7, Staphylococcus aureus, and Salmonella are major foodborne pathogens that are widespread in nature and responsible for several outbreaks of food safety accidents. Thus, a rapid and practical technique (PMA-mPCR) was developed for the simultaneous detection of viable E. coli O157:H7, S. aureus, and Salmonella in pure culture and in a food matrix. To eliminate false positive results, propidium monoazide (PMA) was applied to selectively suppress the DNA amplification of dead cells. The results showed the optimum concentration of PMA is 5.0 µg/mL. The detection limit of this assay by mPCR was 103 CFU/mL in the culture broth, and by PMA-mPCR was 104 CFU/mL both in pure culture and a food matrix (milk and ground beef). In addition, the detection of mixed viable and dead cells was also explored in this study. The detection sensitivity ratio of viable and dead counts was less than 1:10. Therefore, the PMA-mPCR assay proposed here might provide an efficient detection tool for the simultaneous detection of viable E. coli O157:H7, S. aureus, and Salmonella and also have great potential for the detection and concentration assessment of VBNC cells.
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Escherichia coli O157 , Staphylococcus aureus , Animais , Bovinos , Staphylococcus aureus/genética , Escherichia coli O157/genética , Microbiologia de Alimentos , Salmonella/genética , Propídio , AzidasRESUMO
Continuous and reliable monitoring of blood pressure and cardiac function is of great importance for diagnosing and preventing cardiovascular diseases. However, existing cardiovascular monitoring approaches are bulky and costly, limiting their wide applications for early diagnosis. Here, we developed an intelligent blood pressure and cardiac function monitoring system based on a conformal and flexible strain sensor array and deep learning neural networks. The sensor has a variety of advantages, including high sensitivity, high linearity, fast response and recovery, and high isotropy. Experiments and simulation synergistically verified that the sensor array can acquire high-precise and feature-rich pulse waves from the wrist without precise positioning. By combining high-quality pulse waves with a well-trained deep learning model, we can monitor blood pressure and cardiac function parameters. As a proof of concept, we further constructed an intelligent wearable system for real-time and long-term monitoring of blood pressure and cardiac function, which may contribute to personalized health management, precise and early diagnosis, and remote treatment.
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Aprendizado Profundo , Dispositivos Eletrônicos Vestíveis , Pressão Sanguínea , Monitorização Fisiológica , Frequência CardíacaRESUMO
Few-walled carbon nanotube (FWCNT) is composed of a few coaxial shells of CNTs with different diameters. The shells in one tube can slide relatively to each other under external forces, potentially leading to regulated electrical properties, which are never explored due to experimental difficulties. In this work, the electromechanical response induced by inter-shell sliding of individual CNTs is studied and revealed the linear electrical current variation for the first time. Based on centimeter-long FWCNTs grown through chemical vapor deposition, controllable and reversible inter-shell sliding is realized while simultaneously recording the electrical current. Reversible and linear current variation with inter-shell sliding is observed, which is consistent with the proposed inter-shell tunneling model. Further, a silk fibroin-assisted transfer technique is developed for long CNTs and realized the fabrication of FWCNT-based flexible devices. Tensile stress can be applied on the FWCNTs@silk film encapsulated in elastic silicone to induce inter-shell sliding and thus controls electrical current, which is demonstrated to serve as a new human-machine interface with high reliability. Besides, it is foreseen that the electromechanical behaviors induced by inter-layer sliding in 1D nanotubes may also be extended to 2D layered materials, shedding new light on the fabrication of novel electronics.
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How Tibetan red deer (Cervus elaphus wallichii) acclimates to high altitude environment during the withered grass period is one of the challenges in maintaining their nutrient intake. It is an important basis to study the nutritional ecology of wild large ungulates in alpine ecosystems by investigating the changes in plant communities with altitude during the withered grass period and how these changes affect the food composition of Tibetan red deer. In this study, we selected the Tibetan red deer in Sangri County, Shannan region of Tibet as the research subject. We carried out field surveys on the altitude, plant communities, and feeding traces of the Tibetan red deer in March of 2021 and 2022 during the withered grass period on the Tibetan Plateau. Detrended correspondence analysis and canonical correspondence analysis were used to study altitudinal variations in plant communities and the regularity of food composition. The results showed that during the period of withered grass, Tibetan red deer ate primarily Salix daltoniana, Rosa macrophylla var. glandulifera and Dasiphora parvifolia. S. daltoniana accounted for more than 50% of the food composition, as the main food resources for red deer in withered grass period. In the low altitude area (4100-4300 m), plant community included Caragana versicolor, R. macrophylla and Berberis temolaica, and Tibetan red deer mainly ate R. macrophylla, C. versicolor and Artemisia wellbyi. In higher altitude area (4300-4600 m), plant community consisted of Rhododendron nivale, Rhododendron fragariiflorum, and Sibiraea angustata, and Tibetan red deer mainly fed on S. daltoniana, Salix obscura, and Carex littledalei. At different altitudes, the dominant plant species were the main food of Tibetan red deer. It is suggested that the changes of plant community composition with altitude directly affected food composition of Tibetan red deer, indicating different food composition patterns with altitude gradients.
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Cervos , Poaceae , Animais , Tibet , Ecossistema , Altitude , China , PlantasRESUMO
The mechanoelectrical transduction (MET) channel of cochlear hair cells is gated by the tip link, but the mechanisms that establish the exquisite force sensitivity of this MET channel are not known. Here, we show that the tetraspan lipoma HMGIC fusion partner-like 5 (LHFPL5) directly couples the tip link to the MET channel. Disruption of these interactions severely perturbs MET. Notably, the N-terminal cytoplasmic domain of LHFPL5 binds to an amphipathic helix in TMC1, a critical gating domain conserved between different MET channels. Mutations in the amphipathic helix of TMC1 or in the N-terminus of LHFPL5 that perturb interactions of LHFPL5 with the amphipathic helix affect channel responses to mechanical force. We conclude that LHFPL5 couples the tip link to the MET channel and that channel gating depends on a structural element in TMC1 that is evolutionarily conserved between MET channels. Overall, our findings support a tether model for transduction channel gating by the tip link.
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Mecanotransdução Celular , Proteínas de Membrana , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Mecanotransdução Celular/fisiologia , Células Ciliadas Auditivas/metabolismo , Tetraspaninas/genética , Tetraspaninas/metabolismo , MutaçãoRESUMO
Maternal betaine supplementation has been proven to alleviate non-alcoholic fatty liver disease (NAFLD) in offspring caused by maternal high-fat diet (MHFD). The gut-liver axis plays an important role in NAFLD pathogenesis. However, whether maternal betaine supplementation can alleviate NAFLD in offspring by the gut-liver axis is unknown. C57BL/6J mice were fed with high-fat diet for 4 weeks before mating, and supplemented with 1% betaine during pregnancy and lactation. After weaning, offspring mice were fed with standard diet to 10 weeks. Maternal betaine supplementation reduced hepatic triglyceride content and alleviated hepatic steatosis in offspring mice exposed to MHFD. Furthermore, the mRNA expression of PPARα, CPT1α and FATP2 was increased and TNFα was reduced by maternal betaine supplementation. Maternal betaine intake decreased the relative abundances of Proteobateria, Desulfovibrio and Ruminococcus, but increased the relative abundances of Bacteroides and Parabacteroides. Moreover, maternal betaine intake increased the concentrations of short-chain fatty acids (SCFAs), including acetic acid, butyric acid and valeric acid, in the feces. Gut microbiota and SCFAs were significantly correlated with hepatic triglyceride content and expression of the above genes. Maternal betaine intake had no effect on other gut microbiota-related metabolites (bile acid and trimethylamine-n-oxide). Altogether, maternal betaine supplementation ameliorated MHFD-induced NAFLD possibly through regulating gut microbiota and SCFAs in offspring mice.
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Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica , Gravidez , Feminino , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Hepatopatia Gordurosa não Alcoólica/metabolismo , Dieta Hiperlipídica/efeitos adversos , Betaína/farmacologia , Betaína/metabolismo , Camundongos Endogâmicos C57BL , Fígado/metabolismo , Suplementos Nutricionais , Triglicerídeos/metabolismoRESUMO
Numerous studies have shown flexible electronics play important roles in health management. The way of power supply is always an essential factor of devices and self-powered ones are very attractive because of the fabrication easiness, usage comfort and aesthetics of the system. In this work, based on the metal-air redox reaction, which is usually used in designing metal-air batteries, we design a self-powered chemoelectric humidity sensor where a silk fibroin (SF) and LiBr gel matrix containing parallel aligned graphene oxide (GO) flakes serve as the electrolyte. The abundant hydrophilic groups in GO/SF and the hygroscopicity of LiBr lead to tight dependence of the output current on the humidity, enabling the sensor high sensitivity (0.09 µA/s/1%), fast response (1.05 s) and quick recovery (0.80 s). As proofs of concept, we design an all-in-one respiratory monitoring-diagnosing-treatment system and a non-contact human-machine interface, demonstrating the applications of the chemoelectric humidity sensor in health management.
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Fibroínas , Grafite , Humanos , Umidade , Metais , OxirreduçãoRESUMO
OBJECTIVE: To explore the clinical characteristics and genetic characteristics of the combined oxidative phosphorylation defect type 21 (COXPD21) caused by the TARS2 compound heterozygous varians, and to improve clinicians' awareness of the disease. METHODS: The clinical performance, diagnosis and treatment process and gene characteristics of COXPD21 caused by TARS2 were reviewed and analyzed and reviewed combined with the literature. RESULTS: The proband was a girl, the first birth, with repeated refractory hypokalemia, hearing impairment, developmental delay and intellectual disabilityï¼development backwardness after infection, high limb muscle tension, and increased serum lactate as the clinical phenotype. Two heterozygous varians in the TARS2 gene were detected by whole exome sequencing, one of which was c.1679(exon14) A > C (p.Asp560Ala) missense , which was derived from the mother, and the other was c.1036(exon10)C >T (p.Arg346Cys) missense variant, derived from the father, the child was diagnosed with COXPD21. The literature collected from the CNKI, Wanfang data and biomedical literature database (PubMed) until November 2021 were searched and reviewed with the key words "mitochondrial encephalomyopathy", "TARS2" and "combined oxidative phosphorylation deficiency type 21". A total of four complete domestic and foreign cases were collected from the literature search. CONCLUSION: COXPD21 onset by complex heterozygous variant of TARS2 causes refractory hypokalemia, which is rarely reported at home and abroad.
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Transparent conductive films are widely used in electronic products and industrial fields. Ultra-thin Ag conductive nanofilm (ACF) was prepared on a soda lime silica glass (ordinary architectural glass) substrate with industrial magnetron sputtering equipment with AZO (Al2O3 doped ZnO) as the crystal bed and wetting layer. In order to improve the corrosion resistance and conductivity of the ACF, graphene nanosheets were modified on the surface of the ACF by electrospraying for the first time. The results show that this graphene modification could be carried out continuously on a meter scale. With the modification of the graphene layer, the corrosion rate of graphene-decorated ACF (G/ACF) can be reduced by 74.56%, and after 72 h of salt spray test, the conductivity of ACF samples without modification of graphene can be reduced by 34.1%, while the conductivity of G/ACF samples with modification of graphene can be reduced by only 6.5%. This work proves the potential of graphene modified ACF to prepare robust large-area transparent conductive film.
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Biologically derived and biologically inspired fibers with outstanding mechanical properties have found attractive technical applications across diverse fields. Despite recent advances, few fibers can simultaneously possess high-extensibility and self-recovery properties especially under wet conditions. Here, we report protein-based fibers made from recombinant scallop byssal proteins with outstanding extensibility and self-recovery properties. We initially investigated the mechanical properties of the native byssal thread taken from scallop Chlamys farreri and reveal its high extensibility (327 ± 32%) that outperforms most natural biological fibers. Combining transcriptome and proteomics, we select the most abundant scallop byssal protein type 5-2 (Sbp5-2) in the thread region, and produce a recombinant protein consisting of 7 tandem repeat motifs (rTRM7) of the Sbp5-2 protein. Applying an organic solvent-enabled drawing process, we produce bio-inspired extensible rTRM7 fiber with high-extensibility (234 ± 35%) and self-recovery capability in wet condition, recapitulating the hierarchical structure and mechanical properties of the native scallop byssal thread. We further show that the mechanical properties of rTRM7 fiber are highly regulated by hydrogen bonding and intermolecular crosslinking formed through disulfide bond and metal-carboxyl coordination. With its outstanding mechanical properties, rTRM7 fiber can also be seamlessly integrated with graphene to create motion sensors and electrophysiological signal transmission electrode.
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Pectinidae , Proteínas , Animais , Proteínas/química , Proteômica , Alimentos Marinhos , SoftwareRESUMO
Silkworm silk, which is obtained from domesticated Bombyx mori (B. mori), can be produced in a large scale. However, the mechanical properties of silkworm silk are inferior to its counterpart, spider dragline silk. Therefore, researchers are continuously exploring approaches to reinforce silkworm silk. Herein, we report a facile and scalable hot stretching process to reinforce natural silk fibers obtained from silkworm cocoons. Experimental results show that the obtained hot-stretched silk fibers (HSSFs) retain the chemical components of the original silk fibers while being endowed with increased ß-sheet nanocrystal content and crystalline orientation, leading to enhanced mechanical properties. Significantly, the average modulus of the HSSFs reaches 21.6 ± 2.8 GPa, which is about twice that of pristine silkworm silk fibers (11.0 ± 1.7 GPa). Besides, the tensile strength of the HSSFs reaches 0.77 ± 0.13 GPa, which is also obviously higher than that of the pristine silk (0.56 ± 0.08 GPa). The results show that the hot stretching treatment is effective and efficient for producing superstiff, strong, and tough silkworm silk fibers. We anticipate this approach may be also effective for reinforcing other natural or artificial polymer fibers or films containing abundant hydrogen bonds.
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OBJECTIVES: Preeclampsia (PE) remains the leading cause of high morbidity and mortality in pregnancy. Injury of human umbilical vein endothelial cells (HUVECs) contributes to PE initiation. This study aims to analyze the molecular mechanism of PE-induced injury in HUVECs. METHODS: HUVECs were cultured with serum collected from PE patients and healthy pregnant women. PE-treated HUVECs were transfected with miR-204-5p inhibitor, si-protein tyrosine phosphatase receptor J (PTPRJ), and FLI-06 (Notch signaling pathway inhibitor). Cell viability, apoptosis, migration, and angiogenesis were determined using the cell counting kit-8 method, flow cytometry, wound healing assay, tube formation assay, and ELISA. The binding relationship between miR-204-5p and PTPRJ 3'UTR sequence was verified using dual-luciferase reporter assay. The expressions of miR-204-5p, PTPRJ, Notch, and HES1 were determined using qRT-PCR and Western blot analysis. RESULTS: miR-204-5p levels were higher in PE serum. PE-treated HUVECs showed elevated miR-204-5p expression and apoptosis and reduced migration, angiogenesis and VEGF level. miR-204-5p inhibition alleviated HUVEC injury and upregulated PTPRJ transcription. Silencing PTPRJ partly reversed the protecting role of miR-204-5p inhibition in HUVECs. PTPRJ downregulation or FLI-06 treatment limited the expressions of Notch and HES1 and blocked the activation of the Notch signaling pathway, consequently promoting HUVEC injury. CONCLUSIONS: miR-204-5p inhibited PTPRJ transcription and the activation of the Notch signaling pathway, thereby enhancing HUVEC injury.
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MicroRNAs , Pré-Eclâmpsia , Feminino , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neovascularização Patológica/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/metabolismo , Gravidez , Proteínas Tirosina Fosfatases Classe 3 Semelhantes a Receptores/metabolismo , Receptores Notch/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Hepatocellular carcinoma (HCC) is an aggressive malignancy, and its effective treatment has been hampered by drug resistance. Extracellular vesicle (EV) delivery of TNF-related apoptosis-inducing ligand (TRAIL) (EV-T) was demonstrated to be superior to recombinant TRAIL (rTRAIL) for cancer treatment previously. And AZD5582, a potent antagonist of inhibitors of apoptosis proteins (IAPs) can potentiate apoptosis-based cancer therapies. However, the combination of EV-T and AZD5582 has never been examined for their possible apoptosis inducing synergism in cancers. In this study, we proposed and tested the combination of EV-T and AZD5582 as a potential novel therapy for effective treatment of HCC. Two HCC lines Huh7 and HepG2 that are both resistant to rTRAIL were examined. The results confirmed that AZD5582 and EV-T are synergistic for apoptosis induction in some cancer lines including Huh7 and HepG2 while sparing normal cells. More importantly, this study revealed that TRAIL sensitization by AZD5582 is mediated through the concomitant suppression of anti-apoptotic factors including cFLIP, MCL-1, and IAPs (XIAP, Survivin and cIAP-1). Particularly the downregulation of cFLIP and IAP's appeared to be essential and necessary for the synergism between AZD5582 and TRAIL. In vivo, we first time demonstrated that the combined therapy with low doses of AZD5582 and EV-Ts triggered drastically enhanced apoptosis leading to the complete eradication of Huh7 tumor development without any apparent adverse side effects examined. We thus have unraveled the important molecular mechanism underlying TRAIL sensitization by AZD5582, rationalizing the next development of a combination therapy with AZD5582 and EV-T for HCC treatment. KEY MESSAGES: It confirmed the TRAIL sensitization by AZD5582, a potent antagonist of IAPs in hepatocarcinoma. It revealed that the sensitization is via the concomitant suppression of antiapoptotic factors including cFLIP, MCL-1, and IAPs. The downregulation of cFLIP and IAPs like Survivin appeared to be essential and necessary for the synergism between AZD5582 and nanosomal TRAIL. In vivo the combined therapy with AZD5582 and nanosomal TRAIL led to complete eradication of hepatocarcinoma tumors. This study has rationalized the next development of a combination therapy with AZD5582 and nanosomal TRAIL for cancer treatment.
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Carcinoma Hepatocelular , Vesículas Extracelulares , Neoplasias Hepáticas , Alcinos , Apoptose , Proteínas Reguladoras de Apoptose/metabolismo , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/genética , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/metabolismo , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Vesículas Extracelulares/metabolismo , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Oligopeptídeos , Survivina/metabolismo , Survivina/farmacologia , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/farmacologiaRESUMO
Unidirectional water transport performance is vital for maintaining human thermal and wet comfort in the field of garment materials. In this work, a 3D orthogonal woven fabric (3DOWF) with excellent one-way transport capacity and mechanical properties is developed via 3D weaving and plasma treatment. The 3DOWF consists of polyester yarns (first layer), cotton yarns (second layer), and viscose yarns (third layer) with successively enhanced water absorption capacity. This allows droplets to penetrate spontaneously from the hydrophobic layer to the hydrophilic layer but not vice versa. Moreover, the Coolmax yarn with the core suction effect in the Z-direction and the plasma-treated polyester of the 3DOWF are shown to efficiently speed up the water transport process. In particular, the water penetration rate of the 3DOWF reaches 25 µl s-1 . In turn, the surface temperature after water absorption is increased by 2.6 °C compared with the cotton fabric, while the tensile strengths in the weft and warp directions of the 3DOWF are 49.62 and 18 MPa, respectively. These values represent the best insulation and mechanical characteristics thus far reported among unidirectional water transport fabrics. Therefore, the 3DOWF has great potential for use in watchbands, backpack belts, insoles, and other functional textiles.