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1.
Neurochem Res ; 2021 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-33586092

RESUMEN

Alzheimer's disease (AD) is a growing health concern worldwide. MicroRNAs (miRNAs) have been extensively studied in many diseases, including AD. To identify differentially expressed miRNAs (DEmiRNAs) and genes specific to AD, we used bioinformatic analyses to investigate candidate miRNA-mRNA pairs involved in the pathogenesis of AD. We focused on differentially expressed genes (DEGs) that are targets of DEmiRNAs. The GEO2R tool and the HISAT2-DESeq2 software were used to identify DEmiRNAs and DEGs. Bioinformatic tools available online, such as TAM and the Database for Annotation, Visualization and Integrated Discovery (DAVID), were used to perform functional annotation and enrichment analysis. Targets of miRNAs were predicted using the miRTarBase. The Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape, which are available online, were utilized to construct protein-protein interaction (PPI) networks and identify hub genes. Furthermore, transcription factors (TFs) encoded by the DEGs were predicted using the TransmiR database and TF-miRNA-mRNA networks were constructed. Finally, the expression profile of a hub gene in peripheral blood mononuclear cells was compared between healthy individuals and AD patients. We identified 26 correlated miRNA-mRNA pairs. In the parietal lobe, miRNA-mRNA pairs involved in protein folding were enriched, and in the frontal lobe, miRNA-mRNA pairs involved in synaptic transmission, abnormal protein degradation, and apoptosis were enriched. In addition, HSP90AB1 in peripheral blood mononuclear cells was found to be significantly downregulated in AD patients, and this was consistent with its expression profile in the parietal lobe of AD patients. Our results provide brain region-specific changes in miRNA-mRNA associations in AD patients, further our understanding of potential underlying molecular mechanisms of AD, and reveal promising diagnostic and therapeutic targets for AD.

2.
Proc Natl Acad Sci U S A ; 118(9)2021 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-33627404

RESUMEN

Long-term potentiation (LTP) has long been considered as an important cellular mechanism for learning and memory. LTP expression involves NMDA receptor-dependent synaptic insertion of AMPA receptors (AMPARs). However, how AMPARs are recruited and anchored at the postsynaptic membrane during LTP remains largely unknown. In this study, using CRISPR/Cas9 to delete the endogenous AMPARs and replace them with the mutant forms in single neurons, we have found that the amino-terminal domain (ATD) of GluA1 is required for LTP maintenance. Moreover, we show that GluA1 ATD directly interacts with the cell adhesion molecule neuroplastin-65 (Np65). Neurons lacking Np65 exhibit severely impaired LTP maintenance, and Np65 deletion prevents GluA1 from rescuing LTP in AMPARs-deleted neurons. Thus, our study reveals an essential role for GluA1/Np65 binding in anchoring AMPARs at the postsynaptic membrane during LTP.

3.
Artículo en Inglés | MEDLINE | ID: mdl-33619598

RESUMEN

To isolate endophytic bacterium with the ability to specifically convert ginsenoside Rc from Panax quinquefolius. An endophytic bacterium G9y was isolated from Panax quinquefolius and indentified as Bacillus sp. based on 16s rDNA gene sequence. Ginsenoside Rc was effectively converted to Rd by G9y, which was confirmed by thin-layer chromatography and high performance liquid chromatography (HPLC) analysis. The biotransformation conditions were further optimized as follows: inoculum amount 5%, converting temperature 45 °C, medium beef extract peptone broth at pH of 7, and the time of Rc addition was 4 h after bacterium G9y growth, under which ginsenoside Rc was completely converted to Rd by bacterium G9y within 25 h after inoculation. A strain of G9y with the ability to convert ginsenoside Rc into Rd was screened from endophytic bacteria isolated from P. quinquefolius. The results provide a new microbial resource for preparing ginsenoside Rd via biotransformation, and explore a pathway for Rc utilization, which has great potential application value.

4.
Thyroid ; 2021 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-33619987

RESUMEN

BACKGROUND: Human chorionic gonadotropin (hCG) is a marker of placental function, which also stimulates the maternal thyroid gland. Maternal thyroid function can be associated with the pathophysiology of gestational diabetes mellitus (GDM). We aimed to study whether there is an association of hCG concentrations in early pregnancy with GDM, and whether it is mediated through maternal thyroid hormones. METHODS: This study included 18,683 pregnant women from a tertiary hospital in Shanghai, China, between January 2015 and December 2016. GDM was diagnosed using a 2-hour, 75-g oral glucose tolerance test (OGTT) according to the American Diabetes Association guidelines. Multivariable logistic or linear regression models were used to identify associations, adjusting for maternal age, education level, family history of diabetes, parity, fetal sex, thyroperoxidase antibody (TPOAb) status and pre-pregnancy body mass index (BMI). RESULTS: Higher hCG concentrations were associated with a lower plasma glucose during OGTT, but not with fasting plasma glucose or hemoglobin A1c concentrations tested during early pregnancy. hCG in early pregnancy was negatively associated with GDM risk (p=0.027). Mediation analysis identified that an estimated 21.4% of the association of hCG-associated GDM risk was mediated through changes in free thyroxine (FT4) concentrations (p<0.05). In sensitivity analysis restricted to TPOAb positive women, hCG was not associated with GDM (p=0.452). CONCLUSIONS: Higher hCG in early pregnancy is associated with a lower risk of GDM. Maternal FT4 may act as an important mediator in this association.

5.
Oxid Med Cell Longev ; 2021: 8836058, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33574981

RESUMEN

A random-pattern skin flap plays an important role in the field of wound repair; the mechanisms that influence the survival of random-pattern skin flaps have been extensively studied but little attention has been paid to endogenous counterinjury substances and mechanism. Previous reports reveal that the apelin-APJ axis is an endogenous counterinjury mechanism that has considerable function in protecting against infection, inflammation, oxidative stress, necrosis, and apoptosis in various organs. As an in vivo study, our study proved that the apelin/APJ axis protected the skin flap by alleviating vascular oxidative stress and the apelin/APJ axis works as an antioxidant stress factor dependent on CaMKK/AMPK/GSK3ß signaling. In addition, the apelin/APJ-manipulated CaMKK/AMPK/GSK3ß-dependent mechanism improves HUVECs' resistance to oxygen and glucose deprivation/reperfusion (OGD/R), reduces ROS production and accumulation, maintained the normal mitochondrial membrane potential, and suppresses oxidative stress in vitro. Besides, activation of the apelin/APJ axis promotes vascular migration and angiogenesis under relative hypoxia condition through CaMKK/AMPK/GSK3ß signaling. In a word, we provide new evidence that the apelin/APJ axis is an effective antioxidant and can significantly improve the vitality of random flaps, so it has potential be a promising clinical treatment.

6.
Arterioscler Thromb Vasc Biol ; : ATVBAHA120315210, 2021 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-33535789

RESUMEN

OBJECTIVE: Early detection of aortic degeneration is critical for improving outcomes in patients with aortic aneurysm and dissection. We investigated nanoparticle contrast-enhanced computed tomography for the early detection of aortic injury. Approach and Results: In a mouse model of sporadic aortic aneurysm and dissection, C57BL/6J mice were challenged with a high-fat diet and Ang II (angiotensin II) infusion (n=20). Unchallenged control mice received a standard laboratory diet and saline infusion (n=19). Computed tomography angiography (CTA) was performed to evaluate aortic enlargement, and delayed nanoparticle contrast-enhanced computed tomography (CTD) imaging was performed to detect wall signal enhancement indicative of aortic wall degeneration. Aortic segments that exhibited CTD findings but appeared normal on CTA were termed preclinical aortic disease. Aortic aneurysm and dissection development was determined upon the gross examination of excised aortas. Aortic degeneration and inflammation were examined by performing histological and immunofluorescence analyses. Leakage of Evans blue dye into aortic wall was used to validate changes in vascular permeability. In challenged mice, gross findings of aortic disease were found in 41% of aortic segments. CTA findings of mild disease (dilatation) and advanced disease (aortic aneurysm and dissection with the presence of false lumen) were seen in 33% of aortic segments. CTD findings of wall signal enhancement were seen in 63% of aortic segments. Of those, 48% appeared normal on CTA. Aortic segments with CTD findings showed aortic wall degeneration and inflammation on histological and immunofluorescence analyses. Immunofluorescence analysis and Evans blue dye uptake suggested passive leakage of nanoparticle contrast agent due to endothelial injury as a potential mechanism underlying the detection of aortic disease on CTD. CONCLUSIONS: In mice, CTD imaging exhibits high sensitivity for detecting aortic wall degeneration and inflammation before vessel enlargement becomes evident in CTA.

7.
Artículo en Inglés | MEDLINE | ID: mdl-33554725

RESUMEN

Environmental pollution by heavy metal ions, organic pollutants, oils, pesticides or dyes is a ubiquitous problem adversely affecting human health and environmental ecology. Development and application novel adsorbents in full-scale treatment systems with effectiveness properties could effective ways to facilitate the extraction and adsorption of environment pollutants from wastewater. Graphene materials have drawn much attention due to their extraordinary electron mobilities, high surface areas, good thermal conductivities, and excellent mechanical properties. Three-dimensional graphene materials can provide the inherent advantages of 2D graphene sheets and exhibit micro/nanoporous structures, increased specific surface areas, high electron conductivities, fast mass transport kinetics, and strong mechanical strength. Potential applications for 3D graphene materials include environmental remediation, chemical and biological sensing, catalysis, and super capacitors. Recent advances in the applications of 3D functionalized graphene materials (3D FGMs) doped with heteroatoms for the extraction and adsorption of environmental pollutants in wastewater are summarized in this review.

8.
J Environ Manage ; 284: 112113, 2021 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-33571853

RESUMEN

The improvement of the catalytic performance of sludge-based biochar plays an important role in the catalytic application of biochar. This work aimed to use transition metals and rare earth elements (Fe, Ce, La, Al, Ti) to modify sludge and prepare modified biochar with better catalytic performance through pyrolysis. Through the Fourier transform infrared spectrometer, Raman spectrometer, and X-ray photoelectron spectroscopy, the effects of different metal modifications on the surface morphology, molecular structure, element compositions, and valence of elements of biochar were comprehensively investigated. The results showed that metal elements were successfully modified onto the surface of biochar as metal oxides. Although the highest intensity of persistent free radicals was detected in blank-biochar by electron spin resonance, the intensities of hydroxyl radicals catalyzed by modified biochars in H2O2 system were higher than that catalyzed by blank-biochar, indicating that the catalytic performance of modified biochar was mainly related to the metal oxide loaded and the defect structure on the surface of metal-modified biochar. Furthermore, in the H2O2 system, the degradation efficiencies of tetracycline catalyzed by the biochars within 4 h were 51.7% (blank-biochar), 90.7% (Fe-biochar), 69.0% (Ce-biochar), 59.9% (La-biochar), 58.0% (Al-biochar), 58.0% (Ti-biochar), respectively, suggesting that Fe-biochar not only possessed the best catalytic performance but also shortened the reaction time. This research not only provided the possibility for recycling the waste activated sludge, but also proposed a modification method to improve the catalytic performance of biochar.

9.
Res Vet Sci ; 136: 25-31, 2021 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-33578291

RESUMEN

Pathogenicity of tibial dyschondroplasia (TD) in broiler chickens is not detected yet. Janus Kinase/Signal Transducer and Activator of Transcription (JAK-STAT) signaling pathway-related genes were investigated in thiram induced TD chickens. Real-time qPCR and immunohistochemical (IHC) technique were used to observe the expression changes of STAT3 and SOSC3 gene on days 1, 2, 4, 6 after feeding 100 mg·kg-1 thiram. Morphological, pathological, and histological results of this study suggested that chondrocyte cells were observed more damaged on day 6 than day 1, 2, and 4. Therefore, Lameness and damaged chondrocytes gradually increased from day 1 to 6. The mRNA expression level of STAT3 was observed insignificant (P > 0.05) in thiram induced TD chickens' group of day 1. However, on days 2, 4, and 6, the expression was significant (P < 0.05). SOCS3 increased in thiram group on days 1, 2 and 6, decreased on day 4 (P < 0.05). The p-STAT3 and SOCS3 protein's protein localization was evaluated in the control and thiram-induced TD broiler chickens through IHC, suggesting that SOSC3 protein was observed significantly higher on days 1, 2, and 6 and down-regulated on day 4. p-STAT3 protein on thiram induced group was observed significantly upregulated on days 4 and 6. In conclusion, the differential expression of STAT3 and SOCS3 showed that the JAK-STAT signaling pathway might play an important role in regulating an abnormal proliferation, differentiation, or apoptosis of chondrocytes in TD at an early stage.

10.
PLoS One ; 16(2): e0247107, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33600469

RESUMEN

BACKGROUND: High altitude exposure induces overload of right-sided heart and may further predispose to supraventricular arrhythmia. It has been reported that atrial mechanical dyssynchrony is associated with atrial arrhythmia. Whether high altitude exposure causes higher right atrial (RA) dyssynchrony is still unknown. The aim of study was to investigate the effect of high altitude exposure on right atrial mechanical synchrony. METHODS: In this study, 98 healthy young men underwent clinical examination and echocardiography at sea level (400 m) and high altitude (4100 m) after an ascent within 7 days. RA dyssynchrony was defined as inhomogeneous timing to peak strain and strain rate using 2D speckle-tracking echocardiography. RESULTS: Following high altitude exposure, standard deviation of the time to peak strain (SD-TPS) [36.2 (24.5, 48.6) ms vs. 21.7 (12.9, 32.1) ms, p<0.001] and SD-TPS as percentage of R-R' interval (4.6 ± 2.1% vs. 2.5 ± 1.8%, p<0.001) significantly increased. Additionally, subjects with higher SD-TPS (%) at high altitude presented decreased right ventricular global longitudinal strain and RA active emptying fraction, but increased RA minimal volume index, which were not observed in lower group. Multivariable analysis showed that mean pulmonary arterial pressure and tricuspid E/A were independently associated with SD-TPS (%) at high altitude. CONCLUSION: Our data for the first time demonstrated that high altitude exposure causes RA dyssynchrony in healthy young men, which may be secondary to increased pulmonary arterial pressure. In addition, subjects with higher RA dyssynchrony presented worse RA contractile function and right ventricular performance.

11.
Life Sci ; 272: 119238, 2021 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-33600860

RESUMEN

Non-coding RNAs (ncRNAs) include miRNA, lncRNA, and circRNA. NcRNAs are involved in multiple biological processes, including chromatin remodeling, signal transduction, post-transcriptional modification, cell autophagy, carbohydrate metabolism, and cell cycle regulation. Triple negative breast cancer (TNBC) is notorious for high invasiveness and metastasis, poor prognosis, and high mortality, and it is the most malignant breast cancer, while the effective targets for TNBC treatment are still lacking. NcRNAs act as oncogenes or suppressor genes, as well as promote or inhibit the occurrence and development of TNBC. Here, we reviewed some important miRNAs, lncRNAs, circRNAs, their target(s) and molecular mechanisms in TNBC. It is benefited to understand the occurrence and development of TNBC, further some ncRNAs might be potential targets for TNBC treatment.

12.
Water Res ; 194: 116915, 2021 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-33607387

RESUMEN

In this study, visible light (VL) was adopted for permanganate (PM) activation without additional catalyst, where sulfamethazine (SMT) was selected as the probe compound. Experiment results showed that the VL/PM system can effectively degrade SMT through pseudo-first-order reaction kinetics. Influencing factors including PM dosage, solution pH, humid acid (HA) and coexisting anions (CO32-, SO42-, Cl- and NO3-) which affect SMT photo-degradation were also examined. Pyrophosphate (PP) had an inhibitory effect on SMT degradation due to the complexation of PP with Mn (III). Electron spin resonance (ESR) spectrometry and UV-Vis spectrophotometer proved that VL can activate PM to generate ·O2- and Mn (III) reactive species. Furthermore, based on the active site prediction, intermediates identification and Density Functional Theory (DFT) calculation, two main degradation pathways involving SMT molecular rearrangement and cleavage of S-N bond were proposed. Moreover, the energy barriers of the two degradation pathways were also calculated. This study offers a novel approach for aqueous SMT removal and deepens our understanding of the degradation mechanism of SMT through DFT calculation, which hopes to shed light on the future development of VL/PM treatment.

13.
Cancer Biol Med ; 18(1): 155-171, 2021 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-33628591

RESUMEN

Objective: Patients with cancer pain are highly dependent on morphine analgesia, but studies have shown a negative correlation between morphine demand and patient outcomes. The long-term use of morphine may result in abnormally elevated serum morphine-3-glucuronide (M3G) levels. Hence, the effects of M3G on tumor progression are worth studying. Methods: The effects of M3G on PD-L1 expressions in human non-small cell lung cancer (NSCLC) cell lines were first evaluated. Activation of TLR4 downstream pathways after M3G treatment was then determined by Western blot. The effects of M3G on human cytotoxic T lymphocytes (CTL) cytotoxicity and INF-γ release was also detected. Finally, the LLC murine lung adenocarcinoma cell line were used to establish a murine lung cancer model, and the effects of M3G on tumor growth and metastasis were determined. Results: M3G promoted the expressions of PD-L1 in the A549 and H1299 cell lines in a TLR4-dependent manner (P < 0.05). M3G activated the PI3K and the NFκB signaling pathways, and this effect was antagonized by a TLR4 pathway inhibitor. A PI3K pathway inhibitor reversed the M3G-mediated PD-L1 upregulation. M3G inhibited the cytotoxicity of CTL on A549 cells and decreased the level of INF-γ. Repeated M3G intraperitoneal injections promoted LLC tumor growth and lung metastasis through the upregulation of tumor expressed PD-L1 and the reduction of CTL in the tumor microenvironment. Conclusions: M3G specifically activated TLR4 in NSCLC cells and upregulated PD-L1 expression through the PI3K signaling pathway, thereby inhibiting CTL cytotoxicity and finally promoting tumor immune escape.

14.
Gene ; : 145521, 2021 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-33631236

RESUMEN

SPINDLIN1-Z (SPIN1Z), a member of the Spin/Ssty(Y-linked spermiogenesis specific transcript) protein family, participates in the early embryonic development process. Our previous RNA-seq analysis indicates that the level of Spin1z was abundantly expressed in male embryonic stem cells (ESCs) and primitive germ cells (PGCs), we speculate that Spin1z may play an important role in chicken male differentiation. Therefore, the loss- and gain-of-function experiments provide solid evidence that Spin1z is both necessary and sufficient to initiate male development in chicken. Furthermore, chromatin immunoprecipitation (ChIP) assay and the dual-luciferase assay was performed to further confirm that Spin1z contributed to chicken male differentiation by inhibiting the Tcf4 transcription. Our findings provide a novel insight into the molecular mechanism for chicken male differentiation.

15.
BMC Cancer ; 21(1): 198, 2021 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-33632155

RESUMEN

BACKGROUND: The unprecedented efficacy of chimeric antigen receptor T (CAR-T) cell immunotherapy of CD19+ B-cell malignancies has opened a new and useful way for the treatment of malignant tumors. Nonetheless, there are still formidable challenges in the field of CAR-T cell therapy, such as the biodistribution of CAR-T cells in vivo. METHODS: NALM-6, a human B-cell acute lymphoblastic leukemia (B-ALL) cell line, was used as target cells. CAR-T cells were injected into a mice model with or without target cells. Then we measured the distribution of CAR-T cells in mice. In addition, an exploratory clinical trial was conducted in 13 r/r B-cell non-Hodgkin lymphoma (B-NHL) patients, who received CAR-T cell infusion. The dynamic changes in patient blood parameters over time after infusion were detected by qPCR and flow cytometry. RESULTS: CAR-T cells still proliferated over time after being infused into the mice without target cells within 2 weeks. However, CAR-T cells did not increase significantly in the presence of target cells within 2 weeks after infusion, but expanded at week 6. In the clinical trial, we found that CAR-T cells peaked at 7-21 days after infusion and lasted for 420 days in peripheral blood of patients. Simultaneously, mild side effects were observed, which could be effectively controlled within 2 months in these patients. CONCLUSIONS: CAR-T cells can expand themselves with or without target cells in mice, and persist for a long time in NHL patients without serious side effects. TRIAL REGISTRATION: The registration date of the clinical trial is May 17, 2018 and the trial registration numbers is NCT03528421 .

16.
Artículo en Inglés | MEDLINE | ID: mdl-33547622

RESUMEN

High altitude (HA) exposure has been considered as a cardiac stress and might impair ventricular diastolic function. Atrial contraction is involved in ventricular passive filling, however the atrial performance to HA exposure is poorly understood. This study aimed to evaluate the effect of short-term HA exposure on bi-atrial function. Physiological and 2D-echocardiographic data were collected in 82 healthy men at sea level (SL, 400 m) and 4100 m after an ascent within 7 days. Atrial function was measured using volumetric and speckle-tracking analyses during reservoir, conduit and contractile phases of cardiac cycle. Following HA exposure, significant decreases of reservoir and conduit function indexes were observed in bi-atria, whereas decreases of contractile function indexes were observed in right atrium (RA), estimated via RA active emptying fraction (SL 41.7 ± 13.9% vs. HA 35.4 ± 12.2%, p = 0.001), strain during the contractile phase [SL 13.5 (11.4, 17.8) % vs. HA 12.3 (9.3, 15.9) %, p = 0.003], and peak strain rate during the contractile phase [SL - 1.76 (- 2.24, - 1.48) s-1 vs. HA - 1.57 (- 2.01, - 1.23) s-1, p = 0.002], but not in left atrium (LA). In conclusion, short-term HA exposure of healthy individuals impairs bi-atrial performance, mostly observed in RA. Especially, atrial contractile function decreases in RA rather than LA, which seems not to compensate for decreased ventricular filling after HA exposure. Our findings may provide a novel evidence for right-sided heart dysfunction to HA exposure.

17.
Anal Chem ; 93(7): 3378-3385, 2021 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-33560116

RESUMEN

Thienoisoindigo as a popular conjugated skeleton has been constantly applied in the construction of organic optoelectronic materials. Exploring its new applications in fluorescent sensors and bioimaging is helpful to extend its potential. In this work, a thienoisoindigo fluorophore was first selected as a building block to be applied in the construction of the near-infrared fluorescent materials with an aggregation-induced emission manner through introducing triarylamine, thiophene-bridged triarylamine, and N,N-dimethyl styrene, respectively. These fluorescent agents showed the near-infrared emission and possessed typical aggregation-induced emission behavior. Although they had low band gaps and near-infrared emission, they presented remarkable photostability. Especially, thiophene-bridged triarylamine and N,N-dimethyl styrene-coated thienoisoindigos exhibited strong lysosomal targeting capability, and they could also serve for fluorescence imaging in vivo.

18.
Food Chem ; 349: 129112, 2021 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-33581437

RESUMEN

Zein/low-acyl gellan gum (GG) composite particles (ZGPs) were fabricated to stabilize Pickering emulsions (termed "ZGPEs"). The wettability of ZGPs was manipulated simply by adjusting the concentration of GG. The effects of GG concentration, oil fraction and pH on ZGPEs were systematically evaluated by confocal laser scanning microscopy (CLSM), cryo-scanning electron microscopy (cryo-SEM), dynamic light scattering technique, stimulated emission depletion (STED) nanoscopy and rheology. The results showed that ZGPEs exhibited robust colloidal properties and distinct advantage over other previously reported zein-polysaccharide-based Pickering emulsions. CLSM, STED and cryo-SEM analyses revealed that the network structures formed by GG and ZGPs at the continuous phase and oil-water interface were the main contributors to the emulsion's characteristics. This study provides insights into the fabrication of food-grade Pickering emulsions with distinct characteristics that impart favorable properties to various foods and bioactive delivery systems.

19.
Artículo en Inglés | MEDLINE | ID: mdl-33601883

RESUMEN

Flexible pressure sensors have attracted intense attention because of their widespread applications in electronic skin, human-machine interfaces, and healthcare monitoring. Conductive porous structures are always utilized as active layers to improve the sensor sensitivities. However, flexible pressure sensors derived from traditional foaming techniques have limited structure designability. Besides, random pore distribution causes difference in structure and signal repeatability between different samples even in one batch, therefore limiting the batch production capabilities. Herein, we introduce a structure designable lattice structure pressure sensor (LPS) produced by bottom-up digital light processing (DLP) 3D printing technique, which is capable of efficiently producing 55 high fidelity lattice structure models in 30 min. The LPS shows high sensitivity (1.02 kPa-1) with superior linearity over a wide pressure range (0.7 Pa to 160 kPa). By adjusting the design parameters such as lattice type and layer thickness, the electrical sensitivities and mechanical properties of LPS can be accurately controlled. In addition, the LPS endures up to 60000 compression cycles (at 10 kPa) without any obvious electrical signal degradation. This benefits from the firm carbon nanotubes (CNTs) coating derived from high-energy ultrasonic probe and the subsequent thermal curing process of UV-heat dual-curing photocurable resin. For practical applications, the LPS is used for real time pulse monitoring, voice recognition and Morse code communication. Furthermore, the LPS is also integrated to make a flexible 4 × 4 sensor arrays for detecting spatial pressure distribution and a flexible insole for foot pressure monitoring.

20.
PLoS One ; 16(2): e0245832, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33529238

RESUMEN

HER2 amplification greatly contributes to the tumorigenesis of multiple cancers. Intronic miR-4728-5p is transcribed along with its host gene HER2. However, little is known about the role of miR-4728-5p in cancer. This study aims to elucidate the potential role of miR-4728-5p and the underlying mechanism in breast cancer. Kaplan-Meier analysis showed that higher expression of HER2 led to worse survival outcomes in breast cancer patients. The TCGA dataset revealed that compared to normal breast tissues, HER2 and miR-4728-5p levels were significantly upregulated in breast cancer tissues with a positive correlation. In functional assays, miR-4728-5p was confirmed to promote the proliferation and migration in breast cancer cell BT474. EBP1 was identified as a direct target of miR-4728-5p via bioinformatics and luciferase reporter assays. miR-4728-5p was further demonstrated to increase HER2 expression and promote cell proliferation and migration by directly inhibiting EBP1 in breast cancer. Taken together, the HER2-intronic miR-4728-5p/EBP1/HER2 feedback loop plays an important role in promoting breast cancer cell proliferation and migration. Our study provides novel insights for targeted therapies of breast cancer.

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