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In consideration of several serious side effects induced by the classical AF-2 involved "lock" mechanism, recently disclosed PPARγ-Ser273 phosphorylation mode of action has become an alternative and mainstream mechanism for currently PPARγ-based drug discovery and development with an improved therapeutic index. In this study, by virtue of structure-based virtual high throughput screening (SB-VHTS), structurally chemical optimization by targeting the inhibition of the PPARγ-Ser273 phosphorylation as well as in vitro biological evaluation, which led to the final identification of a chrysin-based potential hit (YGT-31) as a novel selective PPARγ modulator with potent binding affinity and partial agonism. Further in vivo evaluation demonstrated that YGT-31 possessed potent glucose-lowering and relieved hepatic steatosis effects without involving the TZD-associated side effects. Mechanistically, YGT-31 presented such desired therapeutic index, mainly because it effectively inhibited the CDK5-mediated PPARγ-Ser273 phosphorylation, selectively elevated the level of insulin sensitivity-related Glut4 and adiponectin but decreased the expression of insulin-resistance-associated genes PTP1B and SOCS3 as well as inflammation-linked genes IL-6, IL-1ß and TNFα. Finally, the molecular docking study was also conducted to uncover an interesting hydrogen-bonding network of YGT-31 with PPARγ-Ser273 phosphorylation-related key residues Ser342 and Glu343, which not only gave a clear verification for our targeting modification but also provided a proof of concept for the abovementioned molecular mechanism.
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Hígado Graso , Flavonoides , PPAR gamma , PPAR gamma/metabolismo , PPAR gamma/agonistas , Flavonoides/farmacología , Flavonoides/química , Flavonoides/síntesis química , Relación Estructura-Actividad , Hígado Graso/tratamiento farmacológico , Hígado Graso/metabolismo , Humanos , Estructura Molecular , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Animales , Hipoglucemiantes/farmacología , Hipoglucemiantes/química , Hipoglucemiantes/síntesis química , Simulación del Acoplamiento Molecular , Relación Dosis-Respuesta a Droga , Ratones , Masculino , Evaluación Preclínica de MedicamentosRESUMEN
Electroless plating facilitates the metallization of nonconductive substrate surfaces, and of note, the precise control of the bath stability constant influences the deposition process of metal particles. In this paper, trisodium citrate, potassium sodium tartrate, nitrogen triacetic acid, thiourea, and ethylenediamine tetraacetic acid disodium were selected as coordination agents, and the effect of the metal ion ligand stability constant on the reduction deposition was studied. Coordination bonds can be established between the Cu2+ and O/N/S particles in the ligand because paired electrons in O/N/S hybrid orbitals tend to occupy empty Cu2+ hybrid orbitals and establish coordination bonds. More importantly, the copper-potassium sodium tartrate ligand exhibits the lowest stability constant and lowest reduction barrier. As an exception, a consecutive Cu-plated coating with an excellent crystallinity property was deposited on the cotton surface when potassium sodium tartrate was used as the coordination agent in the plating solution. The deposition amounts are 55.2% and 74.1% after 1 and 4 h of electroless copper plating, respectively. The surface resistivity of Cu-plated cotton is 0.38 Ω/cm2, and additionally, the surface resistivity ratio before and after 1000 cycles fluctuated between 0.9 and 1.1, indicating that the Cu-plated cotton exhibits outstanding flexibility. In this paper, the deposition rate can be optimized by adjusting the copper particle ligand stability constant in the plating solution, aiming to achieve optimal results.
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Functionalized hexagonal boron nitride nanosheets (BNNSs) have arisen as compelling anticorrosive additives, yet the precise mechanism of their corrosion resistance enhancement in coatings remains unclear. Here, polyethylenimine functionalized BNNSs (PEI-BNNSs) with approximately 6-11 layers were prepared through a "one-step" method. Then, the PEI-BNNSs/Waterborne epoxy (WEP) composite coatings were incorporated via the waterborne latex blending method for the anticorrosion of the Q235 substrate. The impedance modulus (|Z|f = 0.01 Hz) of 0.5 wt % PEI-BNNSs/WEP composite coating soaked in 3.5 wt % NaCl solution for 35 days increased by 4 orders of magnitude compared to pure WEP coating, exhibiting exceptional long-term resistance against corrosion. The positron annihilation lifetime spectroscopy and corrosion product analysis demonstrated that the reinforced anticorrosion capabilities are not solely ascribed to the "tortuous path effect" arising from BNNSs impermeability. These mechanisms also encompass the reduction in free volume fraction and radius of the free volume cavities within the composite coating brought about by the PEI molecules. Additionally, the increase in coating adhesion, promoted by PEI, plays an important role in augmenting the barrier properties against corrosive agents. This study provided a full comprehension of the role played by functionalized BNNSs in fortifying the anticorrosion attributes of WEP coatings.
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With the frequent increase and update of electromagnetic interference (EMI) shielding materials, a low-resolution material that can absorb most electromagnetic waves, thereby effectively reducing the secondary pollution, is urgently needed. However, the excellent performance, flexibility, and low cost of these methods are usually incompatible with current reports. To address the above dilemma, we reported a facile solution for fabricating a low-reflection and high-performance EMI shielding composite by means of electroless nickel plating (EP-Ni), electroless copper plating (EP-Cu), annealing, and coating with a polydimethylsiloxane (PDMS) polymer with the structure of a Ni@Cu tube encapsulated with PDMS. The results indicate that the active groups on vegetable wool can act as active sites for the absorption of the Pd catalyst, thereby catalyzing the reduction of Ni2+, Cu2+, and the subsequent deposition on the plant fiber surface. Notably, the Ni@Cu-encapsulated plant fibers decreased during annealing at 100 °C. According to the segregated network and synergistic effect of the porous structure, the as-fabricated EMI shielding material demonstrated high absorption and low reflection, in which the power coefficient of the T value was approximately 0.0001, the R value was about 0.1764 (a decrease of 27.5% compared that of EP-Ni cotton), and the A value was approximately 0.8235.
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In this work, a textile-based triboelectric nanogenerator (TENG) device was developed through electroless plating technology to prepare electrode material. Hydrophilic groups on the fiber surface are able to absorb Ag+, which could play a role in the center of a catalyst to reduce Cu2+ to fabricate Cu-coated cotton toward the fabrication of TENG electrode material. The TENG device established admirable performance and good stabilization, and a maximum voltage at 9.6 V was detected when the stress and strain on the polydimethylsiloxane layer are 82.6 kPa and 5.8%, respectively. In addition, the relationships among device properties and strain/thickness of dielectric materials have been explored in depth as well. The output voltage of the device increases gradually with the enhancement of dielectric strain and stress. As expected, the TENG as-fabricated device was installed to various physical behaviors to illustrate the harvesting of power of knee-jerk movements.
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OBJECTIVE: PM2.5 is closed linked to asthma exacerbation. The Notch1 pathway acts as an important pathway, ultimately inducing T-helper cells that express GATA3 and its corresponding Th2 cytokines. The regulatory effects of miR-139-5p on the Notch1 pathway have been indicated in cancer. However, studies on miR-139-5p have not applied asthma-related models. The role of miR-139-5p and its regulatory effects on the Notch1-GATA3 pathway in asthma exacerbation induced by acute PM2.5 exposure has not been elucidated. We hypothesize that acute PM2.5 exposure induces asthma exacerbation by regulating the expression of miR-139-5p and activating the Notch1-GATA3 pathway. METHODS: We first employed Diseased Human Bronchial Epithelial Cells-Asthma cells to establish an in vitro model of acute exposure to PM2.5, and explored the relationship between the different concentrations and durations of acute PM2.5 exposure and the activation of Notch1-GATA3 pathway. We investigated the protein and mRNA expression changes of Notch1, upstream Jagged1, downstream GATA3, as well as the regulatory effect of miR-139-5p involved in it. RESULTS: The miR-139-5p expression increased within 24 h of PM2.5 exposure. However, if PM2.5 exposure was sustained, miR-139-5p expression turned to decrease, accompanied by upregulations of the mRNA and protein expression of Notch1-GATA3 pathway. Overexpression of miR-139-5p blocked Notch1-GATA3 pathway activation induced by acute PM2.5 exposure. CONCLUSION: Acute PM2.5 exposure can activate Notch1-GATA3 pathway in asthma bronchial epithelial cells model, which might be involved in PM2.5-induced asthma exacerbation. miR-139-5p has a potential protective role of inhibiting PM2.5-induced asthma airway inflammation by targeting Notch1.
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Asma , Bronquios , Células Epiteliales , Factor de Transcripción GATA3 , MicroARNs , Material Particulado , Receptor Notch1 , MicroARNs/metabolismo , MicroARNs/genética , Humanos , Asma/genética , Asma/metabolismo , Asma/inducido químicamente , Receptor Notch1/metabolismo , Receptor Notch1/genética , Factor de Transcripción GATA3/metabolismo , Factor de Transcripción GATA3/genética , Material Particulado/efectos adversos , Células Epiteliales/metabolismo , Bronquios/citología , Transducción de Señal , Proteína Jagged-1/genética , Proteína Jagged-1/metabolismo , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/toxicidadRESUMEN
The diverse bacterial populations within the symbiotic microbiota play a pivotal role in both health and disease. Microbiota modulates critical aspects of tumor biology including cell proliferation, invasion, and metastasis. This regulation occurs through mechanisms like enhancing genomic damage, hindering gene repair, activating aberrant cell signaling pathways, influencing tumor cell metabolism, promoting revascularization, and remodeling the tumor immune microenvironment. These microbiota-mediated effects significantly impact overall survival and the recurrence of tumors after surgery by affecting the efficacy of chemoradiotherapy. Moreover, leveraging the microbiota for the development of biovectors, probiotics, prebiotics, and synbiotics, in addition to utilizing antibiotics, dietary adjustments, defensins, oncolytic virotherapy, and fecal microbiota transplantation, offers promising alternatives for cancer treatment. Nonetheless, due to the extensive and diverse nature of the microbiota, along with tumor heterogeneity, the molecular mechanisms underlying the role of microbiota in cancer remain a subject of intense debate. In this context, we refocus on various cancers, delving into the molecular signaling pathways associated with the microbiota and its derivatives, the reshaping of the tumor microenvironmental matrix, and the impact on tolerance to tumor treatments such as chemotherapy and radiotherapy. This exploration aims to shed light on novel perspectives and potential applications in the field.
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OBJECTIVE: This study aimed to investigate the functioning and mechanism of coptisine in acute lung injury (ALI). METHODS: Murine Lung Epithelial 12 (MLE-12) cells were stimulated with lipopolysaccharide (LPS) to construct an in vitro pulmonary injury model to study the functioning of coptisine in sepsis-induced ALI. The viability of MLE-12 cells was assessed by the cell counting kit-8 assay. The cytokine release of tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and IL-1ß was measured by enzyme-linked-immunosorbent serologic assay. The relative expression levels of TNF-α, IL-6, and IL-1ß mRNA were examined by reverse transcription-quantitative polymerase chain reaction. The cell apoptosis of MLE-12 cells was determined by Annexin V/propidium iodide staining and analyzed by flow cytometry. The expressions of apoptosis-related proteins Bax and cleaved Caspase-3 were observed by Western blot analysis. The activation of nuclear factor kappa B (NF-κB) signaling pathway was discovered by the determination of phospho-p65, p65, phospho-nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha (IκBα), and IκBα through Western blot analysis. RESULTS: Coptisine treatment could significantly restore decrease in MLE-12 cell viability caused by LPS stimulation. The release of TNF-α, IL-6, and IL-1ß was significantly inhibited by coptisine treatment. Coptisine treatment inhibited MLE-12 cell apoptosis induced by LPS, and also inhibited the expression levels of Bax and cleaved Caspase-3. Coptisine treatment along with LPS stimulation, significantly reduced the protein level of phospho-IκBα, increased the level of IκBα, and reduced phospho-p65-p65 ratio. CONCLUSION: These results indicated that coptisine attenuated sepsis lung injury by suppressing lung epithelial cell inflammation and apoptosis through NF-κB pathway. Therefore, coptisine may have potential to treat sepsis-induced ALI.
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Lesión Pulmonar Aguda , Neumonía , Sepsis , Humanos , Ratones , Animales , FN-kappa B/metabolismo , Lipopolisacáridos/efectos adversos , Caspasa 3 , Inhibidor NF-kappaB alfa , Interleucina-6/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Proteína X Asociada a bcl-2 , Pulmón/patología , Sepsis/tratamiento farmacológico , Lesión Pulmonar Aguda/tratamiento farmacológico , Células Epiteliales/metabolismo , ApoptosisRESUMEN
Gastric cancer has a high incidence rate, significantly threatening patients' health. Gastric histopathology images can reliably diagnose related diseases. Still, the data volume of histopathology images is too large, making misdiagnosis or missed diagnosis easy. The classification model based on deep learning has made some progress on gastric histopathology images. However, traditional convolutional neural networks (CNN) generally use pooling operations, which will reduce the spatial resolution of the image, resulting in poor prediction results. The image feature in previous CNN has a poor perception of details. Therefore, we design a dilated CNN with a late fusion strategy (DCNNLFS) for gastric histopathology image classification. The DCNNLFS model utilizes dilated convolutions, enabling it to expand the receptive field. The dilated convolutions can learn the different contextual information by adjusting the dilation rate. The DCNNLFS model uses a late fusion strategy to enhance the classification ability of DCNNLFS. We run related experiments on a gastric histopathology image dataset to verify the excellence of the DCNNLFS model, where the three metrics Precision, Accuracy, and F1-Score are 0.938, 0.935, and 0.959.
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AIM: Fat mass and obesity-associated (FTO) protein, the first discovered N6-methyladenine (m6A) demethylase, played positive roles in bone formation. In this study, the aim was to investigate the function and potential mechanism of Fto in dentine formation. METHODOLOGY: In vivo model, postnatal 12-day (PN12), 4-week-old (4 wk), 6-week-old (6 wk) healthy male C57BL/6J were randomly divided into Fto knockout (Fto-/- ) mice and wild-type (WT) littermates according to their genotypes, with 3-5 mice in each group. The mandibles of Fto-/- mice and WT control littermates were isolated for analysis by micro-computed tomography (micro-CT), 3-dimensional reconstruction and Haematoxylin-eosin (HE) staining. In vitro, mouse dental papilla cells (mDPCs) and human dental stem pulp cells (hDPSCs) were cultured with odontogenetic medium to evaluate differentiation capacity; expression levels of odontoblastic related genes were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR). The inclusion levels of Runt-related transcription factor 2 (RUNX2) exon 5 in mDPCs and hDPSCs were detected by semiquantitative real-time polymerase chain reaction (RT-PCR). The RNA binding motif protein 4 (RBM4) m6A site was verified through m6A methylated RNA immunoprecipitation (MeRIP) and the stability of RBM4 mRNA influenced by FTO knockdown was measured by mRNA stability assay. Differences with p values < .05 were regarded as statistically significant. RESULTS: We discovered that Fto-/- mice showed significant dentine formation defects characterized by widened pulp cavity, enlarged pulp-tooth volume ratio, thinned dentine and pre-dentine layer of root (p < .05). Fto-/- mDPCs and FTO-silencing hDPSCs not only exhibited insufficient mineralization ability and decreased expression levels of odontoblastic mineralization related genes (p < .05), but showed significantly reduced Runx2 exon 5 inclusion level (p < .05). FTO knockdown increased the m6A level of RBM4 and destabilized the mRNA of RBM4, thus contributing to the reduced RBM4 expression level. Moreover, Rbm4 overexpression in Fto-/- mDPCs can partly restore Runx2 exon 5 inclusion level and the differentiation ability disrupted by Fto knockout. CONCLUSION: Thus, within the limitations of this study, the data suggest that FTO promotes odontoblastic differentiation during dentine formation by stabilizing RBM4 mRNA to promote RUNX2 exon 5 inclusion.
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Subunidad alfa 1 del Factor de Unión al Sitio Principal , Odontoblastos , Animales , Humanos , Masculino , Ratones , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/metabolismo , Diferenciación Celular , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Pulpa Dental , Dentina/metabolismo , Exones/genética , Ratones Endogámicos C57BL , ARN Mensajero/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Microtomografía por Rayos XRESUMEN
The theory of cultural capital has long been applied to explain academic achievement. This qualitative study investigated first-year students in higher vocational colleges and, taking this low cultural capital group as an example, explored how cultural capital has affected their past teacher-student interactions. Participants described their experience of interacting with their teachers. We found that these students primarily experienced authoritative and laissez-faire teacher-student interactions. Students' embodied and institutionalized cultural capital profoundly affected different aspects of the teacher-student interaction. In modern China, vocational and academic education are of the same status, so teachers should modify their evaluations based solely on academic achievement. When interacting with students, teachers should be more understanding and interact in a more student-centred way. Teacher training programmes should also be reformed, and training for teachers in general and vocational schools should be distinguished.
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BACKGROUND: RUNX2 (Runt-related transcription factor 2) acts as a key regulator in the odontogenic differentiation of human dental pulp stem cells (hDPSCs). Moreover, the inclusion of exon 5 is important for RUNX2 function. Our previous study showed that Y-Box Binding Protein 1 (YBX1) promoted RUNX2 exon 5 inclusion and mineralization of hDPSCs. However, the regulatory mechanism of RUNX2 exon 5 alternative splicing needed further exploration. METHODS: The expression level of heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) during the odontogenic differentiation of hDPSCs was analyzed by RT-PCR and Western blot. The roles of hnRNP A1 in the alternative splicing of RUNX2 exon 5 and the odontogenic differentiation of dental mesenchymal cells were analyzed by gain- and loss-of-function experiments. RESULTS: Surprisingly, we found an alternative splicing factor, hnRNP A1, which had an opposite role to YBX1 in regulating RUNX2 exon 5 inclusion and odontogenic differentiation of hDPSCs. Through gain- and loss-of-function assay, we found that hnRNP A1 suppressed the inclusion of RUNX2 exon 5, resulting in the inhibition of odontoblastic differentiation. The overexpression of hnRNP A1 can inhibit the expression of ALP (alkaline phosphatase) and OCN (osteocalcin), and the formation of mineralized nodules during the odontogenic differentiation of both hDPSCs and mouse dental papilla cells (mDPCs), whereas the opposite results were obtained with an hnRNP A1 knockdown preparation. CONCLUSIONS: The present study indicated that hnRNP A1 suppressed RUNX2 exon 5 inclusion and reduced the odontogenic differentiation ability of hDPSCs and mDPCs.
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Subunidad alfa 1 del Factor de Unión al Sitio Principal , Células Madre , Animales , Humanos , Ratones , Diferenciación Celular/genética , Células Cultivadas , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Pulpa Dental/metabolismo , Exones/genética , Ribonucleoproteína Nuclear Heterogénea A1/metabolismo , Células Madre/metabolismoRESUMEN
Textile-based triboelectric nanogenerator (T-TENG) devices, particularly, narrow-gap mode, have been conceived and developed for obtaining energy harvesting and tactile sensing devices unaffected by the external environment. Enhancing the interfacial area of T-TENG materials offers exciting opportunities to improve the device output performance. In this work, a narrow-gap T-TENG was fabricated with a facile process, and a new strategy for improving the device output is proposed. The new structural sensor (polydimethylsiloxane (PDMS)-encapsulated electroless copper plating (EP-Cu) cotton) with multiple electricity generation mechanism was designed and fabricated for enhancing recognition accuracy. The result shows that only PDMS layer strain was established at an external stress of 1.24-12.4 kPa and the fibers laterally slip at a stress of 12.4-139 kPa; more importantly, the output performance of the TENG displayed a linear relationship under corresponding stress ranges. The as-fabricated device demonstrated the ability to convert different energies such as vibration, raindrops, wind and human motions into electrical energy with excellent sensitivity. Interestingly, the output signal of the as-fabricated TENG device is a combination of output signals from PDMS/EP-Cu and PDMS/recognition object devices. To be precise, there are two TENG devices (PDMS/EP-Cu and PDMS/recognition object) that work when the as-fabricated TENG device is under 12.4-139 kPa stress. Accompanied by unique characteristics, the generated TENG signals are capable of recognition of contact materials. Combining the TENG signal and deep learning technology, we explore a strategy that can enable the as-fabricated device to recognize 8 different materials with 99.48% recognition accuracy in the natural environment.
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The exploration of flexible resistive sensors with excellent performance remains a challenge. In this paper, a nickel-coated carbon tube with a textured structure was prepared as a conductive sensitive material and inserted into the poly(dimethylsiloxane) (PDMS) polymer; interestingly, the sensor performance was controlled by the elastic modulus of the matrix resin. The results show that Pd2+ may be adsorbed by the active groups on the surface of a plant fiber as a catalytic center for the reduction of Ni2+. After 300 °C annealing, the inner plant fiber would be carbonized and attached to the outside of the nickel tube; to be precise, the textured Ni-encapsulated C tube was fabricated successfully. It is worth noting that the C tube serves as a layer of support for the external Ni coating, providing sufficient mechanical strength. In addition, resistance sensors with different properties were prepared by controlling the elasticity modulus of the PDMS polymer by introducing different contents of curing agents. The limit uniaxial tensile strain was enhanced from 42 to 49% and sensitivity reduced from 0.2 to 2.0% with the elasticity modulus of the matrix resin increasing from 0.32 to 2.2 MPa. As expected, the sensor is obviously appropriate for the detection of elbow joints, human speaking, and human joints with the reduction of the elasticity modulus of the matrix resin. To be precise, the optimal elastic modulus of the sensor matrix resin would facilitate the improvement of its sensitivity to monitor different human behaviors.
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Ultra fine particles (UFP) cover the size range of both nucleation mode particles (NUC, Dp < 25 nm) and Aitken mode particles (AIT, 25 nm < Dp < 100 nm), and play important roles in radiative forcing and human health. In this study, we identified new particle formation (NPF) events and undefined events, explored their potential formation mechanism, and quantified their contributions to UFP number concentration (NUFP) in urban Dongguan of the Pearl River Delta (PRD) region. Field campaigns were carried out in four seasons in 2019 to measure particle number concentration in the size range of 4.7-673.2 nm, volatile organic compounds (VOCs), gaseous pollutants, chemical compositions in PM2.5, and meteorological parameters. The frequency of the occurrence of NPF, as indicated by a significant increase in NUC number concentration (NNUC), was 26 %, and that of the undefined event, as indicated by substantial increases in NNUC or AIT number concentration (NAIT), was 32 % during the whole campaign period. The NPF events mainly occurred in autumn (with a frequency of 59 %) and winter (33 %) and only occasionally in spring (4 %) and summer (4 %). On the contrary, the frequencies of the undefined events were higher in spring (52 %) and summer (38 %) than in autumn (19 %) and winter (22 %). The burst periods of the NPF events mainly occurred before 11:00 Local Time (LT), while those of the undefined events mainly occurred after 11:00 LT. Accompanied to NPF events were low concentrations of VOCs and high concentrations of O3. The undefined events by NUC or AIT were associated with the upwind transport of newly formed particles. Source apportionment analysis suggested that NPF and undefined events were the largest contributor to NNUC (51 ± 28 %), NAIT (41 ± 26 %), and NUFP (45 ± 27 %), while coal combustion and biomass burning, and traffic emission were the second largest contributor to NNUC (22 ± 20 %) and NAIT (39 ± 28 %), respectively.
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Contaminantes Atmosféricos , Material Particulado , Humanos , Material Particulado/análisis , Contaminantes Atmosféricos/análisis , Estaciones del Año , Tamaño de la Partícula , Monitoreo del Ambiente , Atmósfera/química , China , Aerosoles/análisisRESUMEN
Previous studies have debated whether the ability for bilinguals to mentally control their languages is a consequence of their experiences switching between languages or whether it is a specific, yet highly-adaptive, cognitive ability. The current study investigates how variations in the language-related gene FOXP2 and executive function-related genes COMT, BDNF, and Kibra/WWC1 affect bilingual language control during two phases of speech production, namely the language schema phase (i.e., the selection of one language or another) and lexical response phase (i.e., utterance of the target). Chinese-English bilinguals (N = 119) participated in a picture-naming task involving cued language switches. Statistical analyses showed that both genes significantly influenced language control on neural coding and behavioral performance. Specifically, FOXP2 rs1456031 showed a wide-ranging effect on language control, including RTs, F(2, 113) = 4.00, FDR p = .036, and neural coding across three-time phases (N2a: F(2, 113) = 4.96, FDR p = .014; N2b: F(2, 113) = 4.30, FDR p = .028, LPC: F(2, 113) = 2.82, FDR p = .060), while the COMT rs4818 (ts >2.69, FDR ps < .05), BDNF rs6265 (Fs >5.31, FDR ps < .05), and Kibra/WWC1 rs17070145 (ts > -3.29, FDR ps < .05) polymorphisms influenced two-time phases (N2a and N2b). Time-resolved correlation analyses revealed that the relationship between neural coding and cognitive performance is modulated by genetic variations in all four genes. In all, these findings suggest that bilingual language control is shaped by an individual's experience switching between languages and their inherent genome.
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Multilingüismo , Humanos , Factor Neurotrófico Derivado del Encéfalo , Lenguaje , Función Ejecutiva/fisiología , Electroencefalografía , Péptidos y Proteínas de Señalización IntracelularRESUMEN
The exploration of flexible and lightweight electromagnetic interference (EMI) shielding materials with excellent shielding effectiveness, as a means to effectively alleviate electromagnetic pollution, is still a tremendous challenge. This paper proposes a conducting material named the textured Ni-encapsulated carbon tube, which can be applied in EMI shielding material by being inserted in the center of a poly(dimethysiloxane) (PDMS) polymer. We demonstrated that Pd2+ could be absorbed by the active groups on the plant fiber surface to catalyze the reduction of Ni2+ as a catalytic center by means of a textured Ni-encapsulated plant fiber. Owing to the outstanding heat-conducting capability of the Ni coating, the inner plant fiber was carbonized and attached to the Ni-tube inside the surface during annealing. To be precise, the textured Ni-encapsulated C tube was fabricated successfully after annealing at 300 °C. On further increasing the annealing temperature, the C tube disappeared gradually with the Ni coating being oxidized to NiO. Of note, the C tube acted as a support layer for the external Ni coating, providing sufficient mechanical strength. When combined with the coating PDMS layer, a flexible and lightweight EMI shielding material is fabricated successfully. It displays an outstanding EMI shielding effectiveness of 31.34 dB and a higher specific shielding efficiency of 27.5 dB·cm3/g, especially showing excellent mechanical property and flexibility with only 2 mm thickness. This study provides a new method to fabricate outstanding EMI shielding materials.
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Candida albicans is an important human fungal pathogen. Our previous study disclosed that aryloxy-phenylpiperazine skeleton was a promising molecule to suppress C. albicans virulence by inhibiting hypha formation and biofilm formation. In order to deeply understand the efficacy and mechanism of action of phenylpiperazine compounds, and obtain new derivatives with excellent activity against C. albicans, hence, we synthesized three series of (1-heteroaryloxy-2-hydroxypropyl)-phenylpiperazines and evaluated their inhibitory activity against C. albicans both in vitro and in vivo in this study. Compared with previously reported aryloxy-phenylpiperazines, part of these heteroaryloxy derivatives improved their activities by strongly suppressing hypha formation and biofilm formation in C. albicans SC5314. Especially, (9H-carbazol-4-yl)oxy derivatives 25, 26, 27 and 28 exhibited strong activity in reducing C. albicans virulence in both human cell lines in vitro and mouse infection models in vivo. The compound 27 attenuated the virulence of various clinical C. albicans strains, including clinical drug-resistant C. albicans strains. Moreover, additive effects of the compound 27 with antifungal drugs against drug-resistant C. albicans strains were also discussed. Furthermore, the compound 27 significantly improved the composition and richness of the faecal microbiota in mice infected by C. albicans. These findings indicate that these piperazine compounds have great potential to be developed as new therapeutic drugs against C. albicans infection.
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Candida albicans , Candidiasis , Humanos , Animales , Ratones , Candidiasis/tratamiento farmacológico , Candidiasis/microbiología , Antifúngicos/farmacología , Piperazinas/farmacología , BiopelículasRESUMEN
To identify potential sources of fine particles (PM2.5, with aerodynamic diameter (Da) ≤ 2.5 µm) in urban Dongguan of south China, a comprehensive campaign was carried out in the whole 2019. Hourly PM2.5 and its dominant chemical components including organic carbon (OC), elemental carbon (EC), water-soluble inorganic ions (WSIIs) and thirteen elements were measured using online instruments. Gaseous pollutants including NH3, HNO3, NO2, NO and O3 and meteorological parameters were also synchronously measured. PM2.5 was dominated by carbonaceous aerosols in summer and by WSIIs in the other seasons. PM2.5 and its dominant chemical components mostly peaked around noon (10:00-14:00 LST). Furthermore, high PM2.5 levels during the daytime were closely related with the increased NO3- levels. The high mass concentrations of NO3- in urban Dongguan during the daytime were likely related with regional transport of NO3- from suburban Dongguan, which was originated from the reaction between NO2 and O3 under the moisture condition during the nighttime. Seven major source factors for PM2.5 including secondary sulfate, ship emission, traffic emission, secondary nitrate, industrial processes, soil dust and coal combustion were identified by positive matrix factorization (PMF) analysis, which contributed 26 ± 14%, 16 ± 16%, 16 ± 10%, 14 ± 11%, 12 ± 11%, 8 ± 6% and 8 ± 6%, respectively, to annual PM2.5 mass concentration. Although secondary sulfate contributed much more than secondary nitrate to PM2.5 on annual basis, the latter exceeded the former source factor when daily PM2.5 mass concentration was higher than 60 µg m-3, indicating the critical role nitrate played in PM2.5 episode events.