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1.
Genes Dev ; 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32115408

RESUMO

Dysregulation of early neurodevelopment is implicated in macrocephaly/autism disorders. However, the mechanism underlying this dysregulation, particularly in human cells, remains poorly understood. Mutations in the small GTPase gene RAB39b are associated with X-linked macrocephaly, autism spectrum disorder (ASD), and intellectual disability. The in vivo roles of RAB39b in the brain remain unknown. We generated Rab39b knockout (KO) mice and found that they exhibited cortical neurogenesis impairment, macrocephaly, and hallmark ASD behaviors, which resembled patient phenotypes. We also produced mutant human cerebral organoids that were substantially enlarged due to the overproliferation and impaired differentiation of neural progenitor cells (NPCs), which resemble neurodevelopmental deficits in KO mice. Mechanistic studies reveal that RAB39b interacts with PI3K components and its deletion promotes PI3K-AKT-mTOR signaling in NPCs of mouse cortex and cerebral organoids. The mTOR activity is robustly enhanced in mutant outer radial glia cells (oRGs), a subtype of NPCs barely detectable in rodents but abundant in human brains. Inhibition of AKT signaling rescued enlarged organoid sizes and NPC overproliferation caused by RAB39b mutations. Therefore, RAB39b mutation promotes PI3K-AKT-mTOR activity and alters cortical neurogenesis, leading to macrocephaly and autistic-like behaviors. Our studies provide new insights into neurodevelopmental dysregulation and common pathways associated with ASD across species.

2.
Nature ; 579(7797): 32-33, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32132685
3.
Adv Mater ; : e1905578, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32101356

RESUMO

The rate-determining process for electrochemical energy storage is largely determined by ion transport occurring in the electrode materials. Apart from decreasing the distance of ion diffusion, the enhancement of ionic mobility is crucial for ion transport. Here, a localized electron enhanced ion transport mechanism to promote ion mobility for ultrafast energy storage is proposed. Theoretical calculations and analysis reveal that highly localized electrons can be induced by intrinsic defects, and the migration barrier of ions can be obviously reduced. Consistently, experiment results reveal that this mechanism leads to an enhancement of Li/Na ion diffusivity by two orders of magnitude. At high mass loading of 10 mg cm-2 and high rate of 10C, a reversible energy storage capacity up to 190 mAh g-1 is achieved, which is ten times greater than achievable by commercial crystals with comparable dimensions.

4.
Adv Mater ; 32(5): e1901958, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31273850

RESUMO

The programmable nature of smart textiles makes them an indispensable part of an emerging new technology field. Smart textile-integrated microelectronic systems (STIMES), which combine microelectronics and technology such as artificial intelligence and augmented or virtual reality, have been intensively explored. A vast range of research activities have been reported. Many promising applications in healthcare, the internet of things (IoT), smart city management, robotics, etc., have been demonstrated around the world. A timely overview and comprehensive review of progress of this field in the last five years are provided. Several main aspects are covered: functional materials, major fabrication processes of smart textile components, functional devices, system architectures and heterogeneous integration, wearable applications in human and nonhuman-related areas, and the safety and security of STIMES. The major types of textile-integrated nonconventional functional devices are discussed in detail: sensors, actuators, displays, antennas, energy harvesters and their hybrids, batteries and supercapacitors, circuit boards, and memory devices.

5.
Sci Rep ; 9(1): 18264, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31797883

RESUMO

Head and neck lymphedema (HNL) is a disfiguring disease affecting over 90% of patients treated for head and neck cancer. Animal models of lymphedema are used to test pharmacologic and microsurgical therapies; however, no animal model for HNL is described in the literature to date. In this study we describe the first reproducible rat model for HNL. Animals were subjected to two surgical protocols: (1) lymphadenectomy plus irradiation; and (2) sham surgery and no irradiation. Head and neck expansion was measured on post-operative days 15, 30 and 60. Magnetic resonance imaging (MRI) was acquired at the same time points. Lymphatic drainage was measured at day 60 via indocyanine green (ICG) lymphography, after which animals were sacrificed for histological analysis. Postsurgical lymphedema was observed 100% of the time. Compared to sham-operated animals, lymphadenectomy animals experienced significantly more head and neck swelling at all timepoints (P < 0.01). Lymphadenectomy animals had significantly slower lymphatic drainage for 6 days post-ICG injection (P < 0.05). Histological analysis of lymphadenectomy animals revealed 83% greater subcutis thickness (P = 0.008), 22% greater collagen deposition (P = 0.001), 110% greater TGFß1+ cell density (P = 0.04), 1.7-fold increase in TGFß1 mRNA expression (P = 0.03), and 114% greater T-cell infiltration (P = 0.005) compared to sham-operated animals. In conclusion, animals subjected to complete lymph node dissection and irradiation developed changes consistent with human clinical postsurgical HNL. This was evidenced by significant increase in all head and neck measurements, slower lymphatic drainage, subcutaneous tissue expansion, increased fibrosis, and increased inflammation compared to sham-operated animals.

6.
ACS Appl Mater Interfaces ; 11(47): 44214-44222, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31682105

RESUMO

Photoelectrochemical water splitting is a promising approach to enhance the efficiency of water splitting. However, it is still challenging to develop an efficient oxygen evolution reaction (OER) electrocatalyst that can be coupled with light due to inefficient light utilization. Here, we demonstrate that N, Fe-co-doped CoS2 (N, Fe-CoS2) nanorod arrays can act as a highly efficient photo-coupled electrochemical OER catalyst. In dark conditions, the N, Fe-doped CoS2 on self-supported stainless steel (SS) mesh shows a small OER overpotential (215 mV) at a current density of 10 mA cm-2, a reduced Tafel slope (43.2 mV dec-1), and negligible activity decay after 10 000 cycles. Upon visible-NIR light illumination, the N, Fe-doped anode exhibits superior photoelectrochemical performance because of the enhanced photoresponse, excellent light harvesting ability and promoted interfacial kinetics of charge separation. Our well-designed photoelectrochemical OER electrode can not only serve as a light absorption semiconductor but also the active catalytic sites for the OER reaction; the electrode composed of the single phase can efficiently avoid photocarrier recombination at the grain boundary. This study provides an insight into photoanode synthesis for photoelectrochemical OER and offers guidance on the future electrocatalyst design.

7.
PLoS One ; 14(10): e0223879, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31613912

RESUMO

The soft palate is a key component of the oropharyngeal complex that is critical for swallowing, breathing, hearing and speech. However, complete functional restoration in patients with cleft soft palate remains a challenging task. New insights into the molecular signaling network governing the development of soft palate will help to overcome these clinical challenges. In this study, we investigated whether key signaling pathways required for hard palate development are also involved in soft palate development in mice. We described the dynamic expression patterns of signaling molecules from well-known pathways, such as Wnt, Hh, and Fgf, during the development of the soft palate. We found that Wnt signaling is active throughout the development of soft palate myogenic sites, predominantly in cells of cranial neural crest (CNC) origin neighboring the myogenic cells, suggesting that Wnt signaling may play a significant role in CNC-myogenic cell-cell communication during myogenic differentiation in the soft palate. Hh signaling is abundantly active in early palatal epithelium, some myogenic cells, and the CNC-derived cells adjacent to the myogenic cells. Hh signaling gradually diminishes during the later stages of soft palate development, indicating its involvement mainly in early embryonic soft palate development. Fgf signaling is expressed most prominently in CNC-derived cells in the myogenic sites and persists until later stages of embryonic soft palate development. Collectively, our results highlight a network of Wnt, Hh, and Fgf signaling that may be involved in the development of the soft palate, particularly soft palate myogenesis. These findings provide a foundation for future studies on the functional significance of these signaling pathways individually and collectively in regulating soft palate development.

8.
Sci Adv ; 5(10): eaax4961, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31646177

RESUMO

Artificial synaptic devices that can be stretched similar to those appearing in soft-bodied animals, such as earthworms, could be seamlessly integrated onto soft machines toward enabled neurological functions. Here, we report a stretchable synaptic transistor fully based on elastomeric electronic materials, which exhibits a full set of synaptic characteristics. These characteristics retained even the rubbery synapse that is stretched by 50%. By implementing stretchable synaptic transistor with mechanoreceptor in an array format, we developed a deformable sensory skin, where the mechanoreceptors interface the external stimulations and generate presynaptic pulses and then the synaptic transistors render postsynaptic potentials. Furthermore, we demonstrated a soft adaptive neurorobot that is able to perform adaptive locomotion based on robotic memory in a programmable manner upon physically tapping the skin. Our rubbery synaptic transistor and neurologically integrated devices pave the way toward enabled neurological functions in soft machines and other applications.

9.
Research (Wash D C) ; 2019: 9490413, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31549096

RESUMO

The continuous development of electron devices towards the trend of "More than Moore" requires functional diversification that can collect data (sensors) and store (memories) and process (computing units) information. Considering the large occupation proportion of image data in both data center and edge devices, a device integration with optical sensing and data storage and processing is highly demanded for future energy-efficient and miniaturized electronic system. Two-dimensional (2D) materials and their heterostructures have exhibited broadband photoresponse and high photoresponsivity in the configuration of optical sensors and showed fast switching speed, multi-bit data storage, and large ON/OFF ratio in memory devices. In addition, its ultrathin body thickness and transfer process at low temperature allow 2D materials to be heterogeneously integrated with other existing materials system. In this paper, we overview the state-of-the-art optoelectronic random-access memories (ORAMs) based on 2D materials, as well as ORAM synaptic devices and their applications in neural network and image processing. The ORAM devices potentially enable direct storage/processing of sensory data from external environment. We also provide perspectives on possible directions of other neuromorphic sensor design (e.g., auditory and olfactory) based on 2D materials towards the future smart electronic systems for artificial intelligence.

10.
Small ; 15(45): e1904507, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31532888

RESUMO

The improvement of activity of electrocatalysts lies in the increment of the density of active sites or the enhancement of intrinsic activity of each active site. A common strategy to realize dual active sites is the use of bimetal compound catalysts, where each metal atom contributes one active site. In this work, a new concept is presented to realize dual active sites with tunable electron densities in monometal compound catalysts. Dual Co2+ tetrahedral (Co2+ (Td )) and Co3+ octahedral (Co3+ (Oh )) coordination active sites are developed and adjustable electron densities on the Co2+ (Td ) and Co3+ (Oh ) are further achieved by phosphorus incorporation (P-Co9 S8 ). The experimental results and density functional theory calculations show that the nonmetal P doping can systematically modulate charge density of Co2+ (Td ) and Co3+ (Oh ) in P-Co9 S8 and simultaneously improve the electrical conductivity of Co9 S8 , which substantially enhances oxygen evolution reaction performance of P-Co9 S8 .

11.
ACS Nano ; 13(10): 11469-11476, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31545026

RESUMO

Valence engineering has been proved an effective approach to modify the electronic property of a catalyst and boost its oxygen evolution reaction (OER) activity, while the limited number of elements restricts the structural diversity and the active sites. Also, the catalyst performance and stability are greatly limited by cationic dissolution, ripening, or crystal migration in a catalytic system. Here we employed a widely used technique to fabricate heteroepitaxial pyrite selenide through dual-cation substitution and a boron dopant to achieve better activity and stability. The overpotential of Ni-pyrite selenide catalyst is decreased from 543 mV to 279.8 mV at 10 mA cm-2 with a Tafel slope from 161 to 59.5 mV dec-1. Our theoretical calculations suggest both cation and boron doping can effectively optimize adsorption energy of OER intermediates, promote the charge transfer among the heteroatoms, and improve their OER property. This work underscores the importance of modulating surface electronic structure with the use of multiple elements and provides a general guidance on the minimization of activity loss with valence engineering.

12.
ACS Appl Mater Interfaces ; 11(35): 32449-32459, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31405273

RESUMO

A series of Cr-doped In2-xCrxO3 (ICO) semiconductor thin films were epitaxially grown on (111)-oriented 0.71Pb(Mg1/3Nb2/3)O3-0.29PbTiO3 (PMN-0.29PT) single-crystal substrates by the pulsed laser deposition. Upon the application of an electric field to the PMN-0.29PT substrate along the thickness direction, we realized in situ, reversible, and nonvolatile control of the electronic properties and Fermi level of the films, which are manifested by abundant physical phenomena such as the n-type to p-type transformation, metal-semiconductor transition, metal-insulator transition, crossover of the magnetoresistance (MR) from negative to positive, and a large nonvolatile on-and-off ratio of 5.5 × 104% at room temperature. We also strictly disclose that both the sign and the magnitude of MR are determined by the electron carrier density of ICO films, which could modify the s-d exchange interaction and weak localization effect. Our results demonstrate that the ferroelectric gating approach using PMN-PT can be utilized to gain deeper insight into the carrier-density-related electronic properties of In2O3-based semiconductors and provide a simple and energy efficient way to construct multifunctional devices which can utilize the unique properties of composite materials.

13.
Nanoscale ; 11(32): 15029-15036, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31263822

RESUMO

Low dimensional materials (LDMs) have drawn world-wide attention as potential candidates applied in flexible and wearable electronics. It is an attractive research topic to systematically integrate all-LDMs to realize flexible electronics. However, it is difficult to pattern LDMs by conventional photolithography and plasma etching without harming the other overlapped analogous components. Here, we propose and realize independent-operation all-LDM flexible transistors integrated into a 2-inch substrate using the proposed photolithography incorporated filtration (PIF) platform. The transistors consisting of only one-dimensional carbon nanotubes and two-dimensional graphene oxide show an ultralow operating voltage of less than -1 V, an extraordinary subthreshold swing (SS) of 170 mV dec-1, a low threshold voltage (Vth) of -0.3 V and a high carrier mobility up to 105 cm2 V-1 s-1. Moreover, the device shows a small bending radius of 1 mm and a transistor transparency of 94%. The full room-temperature process further demonstrates the great potential of applying the proposed devices and the PIF platform to future high-performance flexible transparent electronics. This work provides a novel route to tackle the difficulty in integrating solution processed LDMs.

14.
Nat Nanotechnol ; 14(8): 776-782, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31308498

RESUMO

Neuromorphic visual systems have considerable potential to emulate basic functions of the human visual system even beyond the visible light region. However, the complex circuitry of artificial visual systems based on conventional image sensors, memory and processing units presents serious challenges in terms of device integration and power consumption. Here we show simple two-terminal optoelectronic resistive random access memory (ORRAM) synaptic devices for an efficient neuromorphic visual system that exhibit non-volatile optical resistive switching and light-tunable synaptic behaviours. The ORRAM arrays enable image sensing and memory functions as well as neuromorphic visual pre-processing with an improved processing efficiency and image recognition rate in the subsequent processing tasks. The proof-of-concept device provides the potential to simplify the circuitry of a neuromorphic visual system and contribute to the development of applications in edge computing and the internet of things.

15.
Elife ; 82019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31259687

RESUMO

Patterning is a critical step during organogenesis and is closely associated with the physiological function of organs. Tooth root shapes are finely tuned to provide precise occlusal support to facilitate the function of each tooth type. However, the mechanism regulating tooth root patterning and development is largely unknown. In this study, we provide the first in vivo evidence demonstrating that Ezh2 in the dental mesenchyme determines patterning and furcation formation during dental root development in mouse molars. Mechanistically, an antagonistic interaction between epigenetic regulators Ezh2 and Arid1a controls Cdkn2a expression in the dental mesenchyme to regulate dental root patterning and development. These findings indicate the importance of balanced epigenetic regulation in determining the tooth root pattern and the integration of roots with the jaw bones to achieve physiological function. Collectively, our study provides important clues about the regulation of organogenesis and has general implications for tooth regeneration in the future.


Assuntos
Padronização Corporal , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Dente Molar/embriologia , Raiz Dentária/embriologia , Fatores de Transcrição/metabolismo , Processo Alveolar/embriologia , Processo Alveolar/metabolismo , Animais , Epitélio/embriologia , Epitélio/metabolismo , Defeitos da Furca/patologia , Histonas/metabolismo , Mesoderma/embriologia , Mesoderma/metabolismo , Metilação , Camundongos Transgênicos , Odontoblastos/metabolismo , Ligamento Periodontal/embriologia , Ligamento Periodontal/metabolismo
16.
J Cell Physiol ; 234(12): 23658-23666, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31187495

RESUMO

Glioblastoma (GBM), a malignant and lethal tumor, remains a big threat to human health and life. Increasing explorations have confirmed that long noncoding RNAs are involved in the tumorigenesis and development of multiple cancers. Nevertheless, the regulatory mechanism of (long intergenic nonprotein coding RNA 1579 LINC01579) in GBM remains to be investigated. In this study, the expression of LINC01579 was upregulated in GBM cells and LINC01579 knockdown inhibited cell proliferation as well as promoted cell apoptosis. Additionally, LINC01579 acted as a sponge for miR-139-5p in GBM and eukaryotic translation initiation factor 4 gamma 2 (EIF4G2) was found to be a downstream target of miR-139-5p. Furthermore, the positive correlation of LINC01579 and EIF4G2 as well as the converse correlation between miR-139-5p and LINC01579 (or EIF4G2) were revealed by the experiments. Based on rescue assays, EIF4G2 overexpression or miR-139-5p inhibitor partially recovered the function of LINC01579 knockdown on cell proliferation and apoptosis. In summary, the results of this study verified that LINC01579 modulated cell proliferation and cell apoptosis in GBM by competitively binding with miR-139-5p to regulate EIF4G2, which provided a new clue to figure out potential therapy for patients suffered from GBM.

17.
Curr Top Dev Biol ; 133: 91-118, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30902260

RESUMO

Jaw bones and teeth originate from the first pharyngeal arch and develop in closely related ways. Reciprocal epithelial-mesenchymal interactions are required for the early patterning and morphogenesis of both tissues. Here we review the cellular contribution during the development of the jaw bones and teeth. We also highlight signaling networks as well as transcription factors mediating tissue-tissue interactions that are essential for jaw bone and tooth development. Finally, we discuss the potential for stem cell mediated regenerative therapies to mitigate disorders and injuries that affect these organs.

18.
Nano Lett ; 19(4): 2634-2640, 2019 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-30841699

RESUMO

Two-dimensional material indium selenide (InSe) has offered a new platform for fundamental research in virtue of its emerging fascinating properties. Unlike 2H-phase transition-metal dichalcogenides (TMDs), ε phase InSe with a hexagonal unit cell possesses broken inversion symmetry in all the layer numbers, and predicted to have a strong second harmonic generation (SHG) effect. In this work, we find that the as-prepared pure InSe, alloyed InSe1- xTe x and InSe1- xS x ( x = 0.1 and 0.2) are ε phase structures and exhibit excellent SHG performance from few-layer to bulk-like dimension. This high SHG efficiency is attributed to the noncentrosymmetric crystal structure of the ε-InSe system, which has been clearly verified by aberration-corrected scanning transmission electron microscopy (STEM) images. The experimental results show that the SHG intensities from multilayer pure ε-InSe and alloyed InSe0.9Te0.1 and InSe1- xS x ( x = 0.1 and 0.2) are around 1-2 orders of magnitude higher than that of the monolayer TMD systems and even superior to that of GaSe with the same thickness. The estimated nonlinear susceptibility χ(2) of ε-InSe is larger than that of ε-GaSe and monolayer TMDs. Our study provides first-hand information about the phase identification of ε-InSe and indicates an excellent candidate for nonlinear optical (NLO) applications as well as the possibility of engineering SHG response by alloying.

19.
Hum Mol Genet ; 28(10): 1726-1737, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30689861

RESUMO

Mutations in IRF6, TFAP2A and GRHL3 cause orofacial clefting syndromes in humans. However, Tfap2a and Grhl3 are also required for neurulation in mice. Here, we found that homeostasis of Irf6 is also required for development of the neural tube and associated structures. Over-expression of Irf6 caused exencephaly, a rostral neural tube defect, through suppression of Tfap2a and Grhl3 expression. Conversely, loss of Irf6 function caused a curly tail and coincided with a reduction of Tfap2a and Grhl3 expression in tail tissues. To test whether Irf6 function in neurulation was conserved, we sequenced samples obtained from human cases of spina bifida and anencephaly. We found two likely disease-causing variants in two samples from patients with spina bifida. Overall, these data suggest that the Tfap2a-Irf6-Grhl3 genetic pathway is shared by two embryologically distinct morphogenetic events that previously were considered independent during mammalian development. In addition, these data suggest new candidates to delineate the genetic architecture of neural tube defects and new therapeutic targets to prevent this common birth defect.


Assuntos
Proteínas de Ligação a DNA/genética , Fatores Reguladores de Interferon/genética , Neurulação/genética , Fator de Transcrição AP-2/genética , Fatores de Transcrição/genética , Animais , Sequência Conservada/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Humanos , Camundongos , Mutação , Tubo Neural/crescimento & desenvolvimento , Tubo Neural/patologia , Defeitos do Tubo Neural/genética , Defeitos do Tubo Neural/patologia , Transdução de Sinais/genética , Disrafismo Espinal/genética , Disrafismo Espinal/patologia
20.
J Sci Food Agric ; 99(6): 2793-2801, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30430591

RESUMO

BACKGROUND: Maillard reaction products contribute to the amelioration of the biological functions or physical properties of foods and can be used to make dependable antioxidant wall materials for microcapsules of pine nut oil. The present study aimed to analyze the effects of temperature on the Maillard reaction of dry heat processes using gelatin/gum arabic (GE/GA) or gelatin/gum arabic/maltodextrin (GE/GA/MD) models and the products of the Maillard reaction as encapsulants to protect pine nut oil, as well as to evaluate the characteristics of the microcapsules. RESULTS: The grafting degree of the product increased with the temperature increments during the Maillard reaction. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that the polysaccharide covalently linked to the protein. The antioxidant capability of the Maillard products at 80 °C was the highest. The 2,2-diphenyl-1-picrylhydrazyl radical-scavenging activity, lipid peroxidation-inhibiting activity and reducing power of the GE/GA/MD model were higher than those of the GE/GA model. With in vitro digestion of Maillard products, GE/GA/MD pine nut oil microcapsules exhibited greater oil release in artificial gastric and enteric juices. Microencapsulated pine nut oil had more stable oxygen, which protected the oil, compared to unencapsulated pine nut oil. CONCLUSION: Temperature affects the degree of the Maillard reaction on GE/GA and GE/GA/MD models. © 2018 Society of Chemical Industry.


Assuntos
Antioxidantes/química , Cápsulas/química , Reação de Maillard , Pinus/química , Óleos Vegetais/química , Sementes/química , Peroxidação de Lipídeos
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