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It is urgent to develop new antimalarial drugs with good therapeutic effects to address the emergence of drug resistance. Here, the artelinic acid-choline derivative (AD) was synthesized by dehydration reaction and esterification reaction, aimed to avoid the emergence of drug resistance by synergistic effect of artemisinins and choline derivative, which could compete with choline for rate-limiting enzymes in the phosphatidylcholine (PC) biosynthetic pathway. AD was formulated into liposomes (ADLs) by the thin-film hydration method. Efficacy of ADLs was evaluated by Peters 4-day suppression test. The suppression percentage against Plasmodium yoelii BY265 (PyBY265) in ADLs group was higher than those of positive control groups (dihydroartemisinin liposomes, P < 0.05) and other control groups (P ⩽ 0.05) at the doses of 4.4, 8.8, 17.6 µmol (kg·d)-1, respectively. The negative conversion fraction, recrudescence fraction and survival fraction of ADLs group were superior to other control groups. Pharmacokinetics in rats after intravenous injection suggested that ADLs exhibited higher exposure levels (indexed by area under concentration-time curve) than that of AD solution, artelinic acid liposomes or artelinic acid solution (P < 0.01). Taken together, ADLs exhibited promising antimalarial efficacy and pharmacokinetic characteristics.
Assuntos
Artemisininas/química , Colina/química , Lipossomos/farmacologia , Lipossomos/farmacocinética , Plasmodium yoelii/efeitos dos fármacos , Animais , Antimaláricos/farmacocinética , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Artemisininas/farmacocinética , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Colina/farmacocinética , Colina/farmacologia , Colina/uso terapêutico , Lipossomos/química , Lipossomos/uso terapêutico , Malária/tratamento farmacológico , Camundongos , Camundongos Endogâmicos ICR , Ratos , Ratos Sprague-DawleyRESUMO
The dihydroartemisinin-derived dimer (DHA dimer) was synthesized, and its antimalarial activities were evaluated both in vitro and in vivo. The dimer IC50 value of 0.51 ± 0.12 nM in vitro was significantly lower than that of DHA at 1.81 ± 0.70 nM. The dimer ED50 values were 0.44 ± 0.03 and 0.18 ± 0.03 mg/(kg·day) in vivo for intragastric (i.g.) and intravenous (i.v.) groups, respectively, to Plasmodium yoelii rodent malaria. It also performed better relative to those of DHA which had ED50 values of 0.76 ± 0.03 mg/(kg·day) (i.g.) and 0.32 ± 0.03 mg/(kg·day) (i.v.). Moreover, the recrudescence rate, negative conversion rate, and cure rate of the dimer showed superior performance. Furthermore, the metabolites and major metabolic pathways of the dimer in rats were preliminarily investigated using the HPLC-HRMSn method. Twenty-seven metabolites, including DHA, 11 metabolites of DHA, and 15 other novel metabolites, were detected in rats after i.g. administration of dimer. The metabolic pathways of the 15 novel metabolites were inferred: deoxygenation, hydroxylation, and hydroxylation with dehydration.
Assuntos
Artemisininas/metabolismo , Artemisininas/farmacologia , Plasmodium yoelii/efeitos dos fármacos , Animais , Antimaláricos/química , Antimaláricos/metabolismo , Antimaláricos/farmacologia , Artemisininas/química , Cromatografia Líquida de Alta Pressão , Concentração Inibidora 50 , RatosRESUMO
The surface modification of LEDs based on GaAs is realized by super-aligned multiwalled carbon nanotube (SACNT) networks as etching masks. The surface morphology of SACNT networks is transferred to the GaAs. It is found that the light output power of LEDs based on GaAs with a nanostructured surface morphology is greatly enhanced with the electrical power unchanged.
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Semantic segmentation is a critical component for street understanding task in autonomous driving field. Existing various methods either focus on constructing the object's inner consistency by aggregating global or multi-scale context information, or simply combine semantic features with boundary features to refine object details. Despite impressive, most of them neglect the long-range dependences between the inner objects and boundaries. To this end, we present a Boundary Aware Network (BASeg) for semantic segmentation by exploiting boundary information as a significant cue to guide context aggregation. Specifically, a Boundary Refined Module (BRM) is proposed in the BASeg to refine coarse low-level boundary features from a Canny detector by high-level multi-scale semantic features from the backbone, and based on which, the Context Aggregation Module (CAM) is further proposed to capture long-range dependences between the boundary regions and the object inner pixels, achieving mutual gains and enhancing the intra-class consistency. Moreover, our method can be plugged into other CNN backbones for higher performance with a minor computation budget, and obtains 45.72%, 81.2%, and 77.3% of mIoU on the datasets ADE20K, Cityscapes, and CamVid, respectively. Compared with some state-of-the-art ResNet101-based segmentation methods, extensive experiments demonstrate the effectiveness of our method. Our code is available at https://github.com/Lature-Yang/BASeg.
Assuntos
Condução de Veículo , SemânticaRESUMO
Transition-metal dichalcogenides are promising challengers to conventional semiconductors owing to their remarkable electrical performance and suppression of short-channel effects (SCEs). In particular, monolayer molybdenum disulfide has exhibited superior suppression of SCEs owing to its atomic thickness, high effective carrier mass, and low dielectric constant. However, difficulties still remain in large-scale stable fabrication of nanometer-scale channels. Herein, a method to fabricate electrodes with sub-10 nm gaps was demonstrated using horizontally aligned single-walled carbon nanotubes as an evaporation mask. The widths of the nanogaps exhibit robust stability to various process parameters according to the statistical results. Based on these nanogaps, ultrashort-channel length monolayer MoS2 field-effect transistors were produced. Monolayer MoS2 devices with a 7.5 nm channel length and a 10 nm thick HfO2 dielectric layer exhibited excellent performances with an ON/OFF ratio up to 107, a mobility of 17.4 cm2/V·s, a subthreshold swing of about 120 mV/dec, and a drain-induced barrier lowering of about 140 mV/V, all of which suggest a superior suppression of SCEs. This work provides a universal and stable method for large-scale fabrication of ultrashort-channel 2D-material transistors.
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Both p-type and n-type MoTe2 transistors are needed to fabricate complementary electronic and optoelectronic devices. In this study, we fabricate air-stable p-type multi-layered MoTe2 transistors using Au as electrode and achieve the conversion of p-type transistor to n-type by annealing it in vacuum. Temperature-dependent in situ measurements assisted by the results given by first-principle simulations indicate that n-type conductance is an intrinsic property, which is attributed to tellurium vacancies in MoTe2, while the device in air experiences a charge transfer which is caused by oxygen/water redox couple and is converted to air-stable p-type transistor. Based on p-type and n-type multi-layered MoTe2 transistors, we demonstrate a complementary inverter with gain values as high as 9 at VDD = 5 V.
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A flexible and transparent film assembled from the cross-nanoporous structures of Au on PET (CNS of Au@PET) is developed as a versatile and effective SERS substrate for rapid, on-site trace analysis with high sensitivity. The fabrication of the CNS of Au can be achieved on a large scale at low cost by employing an etching process with super-aligned carbon nanotubes as a mask, followed by metal deposition. A strongly enhanced Raman signal with good uniformity can be obtained, which is attributed to the excitation of "hot spots" around the metal nanogaps and sharp edges. Using the CNS of Au@PET film as a SERS platform, real-time and on-site SERS detection of the food contaminant crystal violet (CV) is achieved, with a detection limit of CV solution on a tomato skin of 10-7 M. Owing to its ability to efficiently extract trace analytes, the resulting substrate also achieves detection of 4-ATP contaminants and thiram pesticides by swabbing the skin of an apple. A SERS detection signal for 4-ATP has a relative standard deviation of less than 10%, revealing the excellent reproducibility of the substrate. The flexible, transparent and highly sensitive substrates fabricated using this simple and cost-effective strategy are promising for practical application in rapid, on-site SERS-based detection.
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We have fabricated carbon nanotube and MoS2 field-effect transistors with asymmetric contact forms of source-drain electrodes, from which we found the current directionality of the devices and different contact resistances under the two current directions. By designing various structures, we can conclude that the asymmetric electrical performance was caused by the difference in the effective Schottky barrier height (ΦSB) caused by the different contact forms. A detailed temperature-dependent study was used to extract and compare the ΦSB for both contact forms of CNT and MoS2 devices; we found that the ΦSB for the metal-on-semiconductor form was much lower than that of the semiconductor-on-metal form and is suitable for all p-type, n-type, or ambipolar semiconductors. This conclusion is meaningful with respect to the design and application of nanomaterial electronic devices. Additionally, using the difference in barrier height caused by the contact forms, we have also proposed and fabricated Schottky barrier diodes with a current ratio up to 104; rectifying circuits consisting of these diodes were able to work in a wide frequency range. This design avoided the use of complex chemical doping or heterojunction methods to achieve fundamental diodes that are relatively simple and use only a single material; these may be suitable for future application in nanoelectronic radio frequency or integrated circuits.
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We introduce a simple and cost-effective approach for fabrication of effective surface-enhanced Raman spectroscopy (SERS) substrates. It is shown that the as-fabricated substrates show excellent SERS effects in various probe molecules with high sensitivity, that is, picomolar level detection, and also good reliability. With a SERS enhancement factor beyond 108 and excellent reproducibility (deviation less than 5%) of signal intensity, the fabrication of the SERS substrate is realized on a four-inch wafer and proven to be effective in pesticide residue detection. The SERS substrate is realized first through the fabrication of quasi-periodic nanostructured silicon with dimension features in tens of nanometers using superaligned carbon nanotubes networks as an etching mask, after which a large amount of hot spots with nanometer gaps are formed through deposition of a gold film. With rigorous nanostructure design, the enhanced performance of electromagnetic field distribution for nanostructures is optimized. With the advantage of cost-effective large-area preparation, it is believed that the as-fabricated SERS substrate could be used in a wide variety of actual applications where detection of trace amounts is necessary.
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In this study, we fabricate air-stable p-type multi-layered MoTe2 phototransistor using Au as electrodes, which shows pronounced photovoltaic response in off-state with asymmetric contact form. By analyzing the spatially resolved photoresponse using scanning photocurrent microscopy, we found that the potential steps are formed in the vicinity of the electrodes/MoTe2 interface due to the doping of the MoTe2 by the metal contacts. The potential step dominates the separation of photoexcited electron-hole pairs in short-circuit condition or with small V sd biased. Based on these findings, we infer that the asymmetric contact cross-section between MoTe2-source and MoTe2-drain electrodes is the reason to form non-zero net current and photovoltaic response. Furthermore, MoTe2 phototransistor shows a faster response in short-circuit condition than that with higher biased V sd within sub-millisecond, and its spectral range can be extended to the infrared end of 1550 nm.
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A vertical point heterostructure (VPH) is constructed by sandwiching a two-dimensional (2D) MoS2 flake with two cross-stacked metallic single-walled carbon nanotubes. It can be used as a field-effect transistor with high on/off ratio and a light detector with high spatial resolution. Moreover, the hybrid 1D-2D-1D VPHs open up new possibilities for nanoelectronics and nano-optoelectronics.
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Two-dimensional (2D) materials have attracted interest because of their excellent properties and potential applications. A key step in realizing industrial applications is to synthesize wafer-scale single-crystal samples. Until now, single-crystal samples, such as graphene domains up to the centimeter scale, have been synthesized. However, a new challenge is to efficiently characterize large-area samples. Currently, the crystalline characterization of these samples still relies on selected-area electron diffraction (SAED) or low-energy electron diffraction (LEED), which is more suitable for characterizing very small local regions. This paper presents a highly efficient characterization technique that adopts a low-energy electrostatically focused electron gun and a super-aligned carbon nanotube (SACNT) film sample support. It allows rapid crystalline characterization of large-area graphene through a single photograph of a transmission-diffracted image at a large beam size. Additionally, the low-energy electron beam enables the observation of a unique diffraction pattern of adsorbates on the suspended graphene at room temperature. This work presents a simple and convenient method for characterizing the macroscopic structures of 2D materials, and the instrument we constructed allows the study of the weak interaction with 2D materials.
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We have proposed and fabricated stable and repeatable, flexible, single-walled carbon nanotube (SWCNT) thin film transistor (TFT) complementary metal-oxide-semiconductor (CMOS) integrated circuits based on a three-dimensional (3D) structure. Two layers of SWCNT-TFT devices were stacked, where one layer served as n-type devices and the other one served as p-type devices. On the basis of this method, it is able to save at least half of the area required to construct an inverter and make large-scale and high-density integrated CMOS circuits easier to design and manufacture. The 3D flexible CMOS inverter gain can be as high as 40, and the total noise margin is more than 95%. Moreover, the input and output voltage of the inverter are exactly matched for cascading. 3D flexible CMOS NOR, NAND logic gates, and 15-stage ring oscillators were fabricated on PI substrates with high performance as well. Stable electrical properties of these circuits can be obtained with bending radii as small as 3.16 mm, which shows that such a 3D structure is a reliable architecture and suitable for carbon nanotube electrical applications in complex flexible and wearable electronic devices.
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Single-walled carbon nanotube (SWNT) thin-film transistors hold great potential for flexible electronics. However, fabrication of air-stable n-type devices by methods compatible with standard photolithography on flexible substrates is challenging. Here, we demonstrated that by using a bilayer dielectric structure of MgO and atomic layer deposited (ALD) Al2O3 or HfO2, air-stable n-type devices can be obtained. The mechanism for conduction type conversion was elucidated and attributed to the hole depletion in SWNT, the decrease of the trap state density by MgO assimilating adsorbed water molecules in the vicinity of SWNT, and the energy band bending because of the positive fixed charges in the ALD layer. The key advantage of the method is the relatively low temperature (120 or 90 °C) required here for the ALD process because we need not employ this step to totally remove the absorbates on the SWNTs. This advantage facilitates the integration of both p-type and n-type transistors through a simple lift off process and compact CMOS inverters were demonstrated. We also demonstrated that the doping of SWNTs in the channel plays a more important role than the Schottky barriers at the metal contacts in carbon nanotube thin-film transistors, unlike the situation in individual SWNT-based transistors.
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We report on the experimental realization of using super-aligned carbon nanotubes (SACNTs) as etching masks for the fabrication of large area nanoscale metal meshes. This method can easily be extended to different metals on both rigid and flexible substrates. The as-fabricated metal meshes, including the ones made of gold, copper, and aluminum, are suitable for use as transparent conductive layers (TCLs). The metal meshes, which are similar to the SACNT networks in their dimensional features of tens of nanometers, exhibit compatible performance in terms of optical transmittance and sheet resistance. Moreover, because the metal meshes are fabricated as an integrated material, there is no junction resistance between the interconnected metal nanostructures, which markedly lowers their sheet resistance at high temperatures. The fabrication of such an effective etching mask involves a simple drawing process of the SACNT networks prepared and a common deposition process. This approach should be easy to extend to various research fields and has broad prospects in commercial applications.