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In this study, we introduced a novel dual-laser multi-color imaging system. Integrated with a multi-channel filter wheel, this system compared three spectral decontamination algorithms (nonnegative matrix factorization [NMF], RCAN, and PICASSO) showcasing its efficacy in achieving four-color imaging with only two laser sources. Combined with a reliable image reconstruction algorithm, the spatial resolution of four channels super-resolution four-color images reached 130, 125, 133, and 132 nm, respectively. Lipid droplets, mitochondria, lysosomes, and nuclei from the mouse hepatocytes (AML12), human neuroblastoma cells (SH-SY5Y), mouse hippocampal neuronal cells (HT-22), and immortalized murine bone marrow-derived macrophages were imaged. At the same time, the chromatin condensation, nuclear contraction, DNA fragmentation, apoptotic body formation, as well as the fusion of Mito and Lyso involved in mitochondrial autophagy were observed in HT-22 and SH-SY5Y cells suffering oxidative stress. Our multi-color SIM imaging system establishes a powerful platform for dynamic organelle studies and other high-resolution investigations in live cells.
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The mitogen-activated protein kinase (MAPK) cascade (MAPKKK-MAPKK-MAPK) plays a critical role in biotic and abiotic stress responses and abscisic acid (ABA) signalling. A previous study has shown that the ABA-activated MKK1-MPK1 cascade is essential in regulating ABA response and stress tolerance in rice. However, the specific MAPKKK upstream of the MKK1-MPK1 cascade in ABA signalling remains unknown. Here, we identified that MAPKKK28, a previously uncharacterized member of the rice MEKK family, is involved in regulating ABA responses, including seed germination, root growth, stomatal closure, and the tolerance to oxidative stress and osmotic stress. We found that MAPKKK28 directly interacts with and phosphorylates MKK1. Further analysis indicated that the activation of both MKK1 and MPK1 depends on MAPKKK28 in ABA signalling. Genetic analysis revealed that MAPKKK28 functions upstream of the MKK1-MPK1 cascade to positively regulate ABA responses and enhance tolerance to oxidative and osmotic stress. These results not only reveal a new complete MAPK cascade in plants but also uncover its importance in ABA signalling.
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BACKGROUND: Highly reactive oxygen species (ROS) could lead to serious damage in living cells and are associated with many diseases like cancers. Metal cluster with strong fluorescence has great potential in biosensing and many thiolate ligands-protected clusters have been applied in ROS sensing. RESULTS: In this work, we synthesized levonorgestrel protected Au10 cluster with specific sensing ability for highly ROS via crystal transformation from Au8 cluster, demonstrating the significance of inner core structure on detecting performance. The detection limit of Au10 cluster for ClO- could reach as low as 0.1 µM. This fluorescent probe not only achieving detection of exogenous ClO- in living cells and zebrafish, but also successful imaging of endogenous ClO- in HeLa and HepG2 cells. SIGNIFICANCE: In comparison to previously reported cluster-based sensors for ROS, this work proposes a different reaction mechanism of metal nanoclusters for ROS detection (breakage of gold-alkynyl bond and oxidation of alkynyl group). This provides new directions for designing specific ROS probes and broadens the applications of metal clusters in disease diagnostics.
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Corantes Fluorescentes , Ouro , Ácido Hipocloroso , Levanogestrel , Peixe-Zebra , Humanos , Ouro/química , Células HeLa , Ácido Hipocloroso/análise , Animais , Células Hep G2 , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Levanogestrel/química , Imagem Óptica , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/análise , Nanopartículas Metálicas/químicaRESUMO
Vertical transistors, in which the source and drain are aligned vertically and the current flow is normal to the wafer surface, have attracted considerable attention recently. However, the realization of high-density vertical transistors is challenging, and could be largely attributed to the incompatibility between vertical structures and conventional lateral fabrication processes. Here we report a T-shape lamination approach for realizing high-density vertical sidewall transistors, where lateral transistors could be pre-fabricated on planar substrates first and then laminated onto vertical substrates using T-shape stamps, hence overcoming the incompatibility between planar processes and vertical structures. Based on this technique, we vertically stacked 60 MoS2 transistors within a small vertical footprint, corresponding to a device density over 108 cm-2. Furthermore, we demonstrate two approaches for scalable fabrication of vertical sidewall transistor arrays, including simultaneous lamination onto multiple vertical substrates, as well as on the same vertical substrate using multi-cycle layer-by-layer laminations.
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Perovskite monocrystalline films are regarded as desirable candidates for the integration of high-performance optoelectronics due to their unique photophysical properties. However, the heterogeneous integration of a perovskite monocrystalline film with other semiconductors is fundamentally limited by the lattice mismatch, which hinders direct epitaxy. Herein, the van der Waals (vdW) integration strategy for 3D perovskites is developed, where perovskite monocrystalline films are epitaxially grown on the mother substrate, followed by its peeling off and transferring to arbitrary semiconductors, forming monocrystalline heterojunctions. The as-achieved CsPbBr3-Nb-doped SrTiO3 (Nb:STO) vdW p-n heterojunction exhibited comparable performance to their directly epitaxial counterpart, demonstrating the feasibility of vdW integration for 3D perovskites. Furthermore, the vdW integration could be extended to silicon substrates, rendering the CsPbBr3-n-Si and CsPbCl3-p-Si p-n heterojunction with apparent rectification behaviors and photoresponse. The vdW integration significantly enriches the selections of semiconductors hybridizing with perovskites and provides opportunities for monocrystalline perovskite optoelectronics with complex configurations and multiple functionalities.
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Two-dimensional (2D) semiconductors have shown great potential for monolithic three-dimensional (M3D) integration due to their dangling-bonds-free surface and the ability to integrate to various substrates without the conventional constraint of lattice matching1-10. However, with atomically thin body thickness, 2D semiconductors are not compatible with various high-energy processes in microelectronics11-13, where the M3D integration of multiple 2D circuit tiers is challenging. Here we report an alternative low-temperature M3D integration approach by van der Waals (vdW) lamination of entire prefabricated circuit tiers, where the processing temperature is controlled to 120 °C. By further repeating the vdW lamination process tier by tier, an M3D integrated system is achieved with 10 circuit tiers in the vertical direction, overcoming previous thermal budget limitations. Detailed electrical characterization demonstrates the bottom 2D transistor is not impacted after repetitively laminating vdW circuit tiers on top. Furthermore, by vertically connecting devices within different tiers through vdW inter-tier vias, various logic and heterogeneous structures are realized with desired system functions. Our demonstration provides a low-temperature route towards fabricating M3D circuits with increased numbers of tiers.
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Objective: The objective of this study was to investigate the impact of electro-acupuncture (EA) on sepsis-related intestinal injury and its relationship with macrophage polarization. Methods: A sepsis model was established using cecal ligation and puncture (CLP) to assess the effectiveness of EA. The extent of pathological injury was evaluated using Chiu's score, the expression of ZO-1 and Ocludin, and the impact on macrophage polarization was examined through flow cytometry and immunofluorescence staining. The expression of spermidine, one type of polyamine, and ornithine decarboxylase (ODC) was measured using ELISA and PCR. Once the efficacy was determined, a polyamine depletion model was created, and the role of polyamines was reassessed by evaluating efficacy and observing macrophage polarization. Results: EA treatment reduced the Chiu's score and increased the expression of ZO-1 and Ocludin in the intestinal tissue of septic mice. It inhibited the secretion of IL-1ß and TNF-α, promoted the polarization of M2-type macrophages, increased the secretion of IL-10, and upregulated the expression of Arg-1, spermidine, and ODC. However, after depleting polyamines, the beneficial effects of EA on alleviating intestinal tissue damage and modulating macrophage polarization disappeared. Conclusion: The mechanism underlying the alleviation of intestinal injury associated with CLP-induced sepsis by EA involves with the promotion of M2-type macrophage polarization mediated by spermidine expression.
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Modelos Animais de Doenças , Eletroacupuntura , Macrófagos , Poliaminas , Sepse , Animais , Sepse/terapia , Sepse/metabolismo , Sepse/imunologia , Camundongos , Macrófagos/imunologia , Macrófagos/metabolismo , Eletroacupuntura/métodos , Poliaminas/metabolismo , Masculino , Ativação de Macrófagos , Intestinos/patologia , Intestinos/imunologia , Camundongos Endogâmicos C57BL , Citocinas/metabolismoRESUMO
Two-dimensional (2D) semiconductors hold great promises for ultra-scaled transistors. In particular, the gate length of MoS2 transistor has been scaled to 1 nm and 0.3 nm using single wall carbon nanotube and graphene, respectively. However, simultaneously scaling the channel length of these short-gate transistor is still challenging, and could be largely attributed to the processing difficulties to precisely align source-drain contact with gate electrode. Here, we report a self-alignment process for realizing ultra-scaled 2D transistors. By mechanically folding a graphene/BN/MoS2 heterostructure, source-drain metals could be precisely aligned around the folded edge, and the channel length is only dictated by heterostructure thickness. Together, we could realize sub-1 nm gate length and sub-50 nm channel length for vertical MoS2 transistor simultaneously. The self-aligned device exhibits on-off ratio over 105 and on-state current of 250 µA/µm at 4 V bias, which is over 40 times higher compared to control sample without self-alignment process.
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van der Waals heterostructures (vdWHs) based on two-dimensional (2D) semiconductors have attracted considerable attention. However, the reported vdWHs are largely based on vertical device structure with large overlapping area, while the realization of lateral heterostructures contacted through 2D edges remains challenging and is majorly limited by the difficulties of manipulating the lateral distance of 2D materials at nanometer scale (during transfer process). Here, we demonstrate a simple interfacial sliding approach for realizing an edge-by-edge lateral contact. By stretching a vertical vdWH, two 2D flakes could gradually slide apart or toward each other. Therefore, by applying proper strain, the initial vertical vdWH could be converted into a lateral heterojunction with intimately contacted 2D edges. The lateral contact structure is supported by both microscope characterization and in situ electrical measurements, exhibiting carrier tunneling behavior. Finally, this approach can be extended to 3D thin films, as demonstrated by the lateral 2D/3D and 3D/3D Schottky junction.
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Recently, the underlying mechanisms of acupuncture on the effects of Alzheimer's disease (AD) treatment have not been fully elucidated. Defects in ALP (autophagy-lysosomal pathway) and TFEB (transcription factor EB) play critical roles in AD. Our previous studies have demonstrated that electroacupuncture (EA) can ameliorate both ß-amyloid (Aß) pathology and cognitive function in APP/PS1 mice. However, the effects of EA on the expression of ALP and TFEB and their potential mechanisms require further investigation. Twenty-eight male APP/PS1 mice were randomly divided into Tg and Tg + EA groups, and 14 C57BL/6 mice served as the wild-type (WT) group. After 1 week of adaptation to the living environment, mice in the Tg + EA group were restrained in mouse bags and received manual acupuncture at Baihui (GV20) acupoint and EA stimulation at bilateral Yongquan (KI1) acupoints, using the same restraint method for WT and Tg groups. The intervention was applied for 15 min each time, every other day, lasting for six weeks. After intervention, the spatial learning and memory of the mice was assessed using the Morris water maze test. Hippocampal Aß expression was detected by immunohistochemistry and ELISA. Transmission electron microscopy (TEM) was used to observe autophagic vacuoles and autolysosomes in the hippocampus. Immunofluorescence method was applied to examine the expression of TFEB in CA1 region of the hippocampus and the co-localization of CTSD or LAMP1 with Aß. Western blot analysis was performed to evaluate the changes of LC3, p62, CTSD, LAMP1, TFEB and n-TFEB (nuclear TFEB) in the hippocampus. The findings of behavioral assessment indicated that EA alleviated the cognitive impairment of APP/PS1 mice. Compared with the WT group, the Tg group showed significant cognitive decline and abnormalities in ALP and TFEB function (P < 0.01 or P < 0.05). However, these abnormal changes were alleviated in the Tg + EA group (P < 0.01 or P < 0.05). The Tg group also showed more senile plaques and ALP dysfunction features, compared with the WT group, and these changes were alleviated by EA. In conclusion, this study highlights that EA ameliorated Aß pathology-related cognitive impairments in the APP/PS1 model associated with ALP and TFEB dysfunction.
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Doença de Alzheimer , Disfunção Cognitiva , Eletroacupuntura , Animais , Masculino , Camundongos , Doença de Alzheimer/terapia , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Disfunção Cognitiva/terapia , Disfunção Cognitiva/metabolismo , Modelos Animais de Doenças , Hipocampo/metabolismo , Camundongos Endogâmicos C57BL , Camundongos TransgênicosRESUMO
Two-dimensional (2D) semiconductors have generated considerable attention for high-performance electronics and optoelectronics. However, to date, it is still challenging to mechanically exfoliate large-area and continuous monolayers while retaining their intrinsic properties. Here, we report a simple dry exfoliation approach to produce large-scale and continuous 2D monolayers by using a Ag film as the peeling tape. Importantly, the conducting Ag layer could be converted into AgOx nanoparticles at low annealing temperature, directly decoupling the conducting Ag with the underlayer 2D monolayers without involving any solution or etching process. Electrical characterization of the monolayer MoS2 transistor shows a decent carrier mobility of 42 cm2 V-1 s-1 and on-state current of 142 µA/µm. Finally, a plasmonic enhancement photodetector could be simultaneously realized due to the direct formation of Ag nanoparticles arrays on MoS2 monolayers, without complex approaches for nanoparticle synthesis and integration processes, demonstrating photoresponsivity and detectivity of 6.3 × 105 A/W and 2.3 × 1013 Jones, respectively.
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MHC-E restricted CD8 T cells show promise in vaccine settings, but their development and specificity remain poorly understood. Here we focus on a CD8 T cell population reactive to a self-peptide (FL9) bound to mouse MHC-E (Qa-1b) that is presented in response to loss of the MHC I processing enzyme ERAAP, termed QFL T cells. We find that mature QFL thymocytes are predominantly CD8αß+CD4-, show signs of agonist selection, and give rise to both CD8αα and CD8αß intraepithelial lymphocytes (IEL), as well as memory phenotype CD8αß T cells. QFL T cells require the MHC I subunit ß-2 microglobulin (ß2m), but do not require Qa1b or classical MHC I for positive selection. However, QFL thymocytes do require Qa1b for agonist selection and full functionality. Our data highlight the relaxed requirements for positive selection of an MHC-E restricted T cell population and suggest a CD8αß+CD4- pathway for development of CD8αα IELs.
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Linfócitos T CD8-Positivos , Receptores de Antígenos de Linfócitos T alfa-beta , Animais , Camundongos , Peptídeos/metabolismo , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Timócitos/metabolismo , Genes MHC da Classe IIRESUMO
To the best of our knowledge, no previous study has quantitatively estimated the dynamics and cumulative susceptibility to influenza infections after the widespread lifting of COVID-19 public health measures. We constructed an imitated stochastic susceptible-infected-removed model using particle-filtered Markov Chain Monte Carlo sampling to estimate the time-dependent reproduction number of influenza based on influenza surveillance data in southern China, northern China, and the United States during the 2022-2023 season. We compared these estimates to those from 2011 to 2019 seasons without strong social distancing interventions to determine cumulative susceptibility during COVID-19 restrictions. Compared to the 2011-2019 seasons without a strong intervention with social measures, the 2022-2023 influenza season length was 45.0%, 47.1%, and 57.1% shorter in southern China, northern China, and the United States, respectively, corresponding to an 140.1%, 74.8%, and 50.9% increase in scale of influenza infections, and a 60.3%, 72.9%, and 45.1% increase in population susceptibility to influenza. Large and high-intensity influenza epidemics occurred in China and the United States in 2022-2023. Population susceptibility increased in 2019-2022, especially in China. We recommend promoting influenza vaccination, taking personal prevention actions on at-risk populations, and monitoring changes in the dynamic levels of influenza and other respiratory infections to prevent potential outbreaks in the coming influenza season.
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COVID-19 , Influenza Humana , Humanos , Estados Unidos/epidemiologia , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , COVID-19/epidemiologia , Estações do Ano , Pandemias , China/epidemiologiaRESUMO
Primary kidney neuroendocrine tumors (NETs) are rare renal malignancies. However, detecting and monitoring neuroendocrine neoplasms remains challenging because of their nonspecific nature. We herein present a case involving a 53-year-old woman who experienced episodes of intermittent abdominal pain, dizziness, and nausea for a period of 5 days. Computed tomography urography revealed a small (approximately 19- × 16-mm) nodular shadow in the left kidney. The nodular shadow exhibited slightly lower density than the surrounding tissue as well as enhancement, with a portion protruding into the renal sinus region. Histological and immunohistochemical analyses of the biopsy specimen from the mass indicated a well-differentiated NET. After analysis of this case, we performed a literature review and herein discuss various techniques for imaging and pathological diagnosis of renal NETs. Additionally, we provide insights into the treatment options and prognosis for affected patients. By combining this case study with the existing published literature, we aim to offer a valuable reference for clinicians treatment patients diagnosed with renal NETs.
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Neoplasias Renais , Tumores Neuroendócrinos , Feminino , Humanos , Pessoa de Meia-Idade , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/patologia , Rim/diagnóstico por imagem , Rim/patologia , Neoplasias Renais/diagnóstico por imagem , Prognóstico , Dor AbdominalRESUMO
OBJECTIVE: To explore the mechanism of electroacupunctureï¼EAï¼ in improving learning-memory ability in Alzheimer's disease ï¼ADï¼ mice from the perspective of endosomal-lysosomal system. METHODS: Male APP/PS1 transgenic mice were randomly divided into model group and EA group ï¼n=10 in each groupï¼ and 10 male C57BL/6 wild mice were taken as the normal group. EA ï¼1 Hz/50 Hz, 1 mAï¼ was applied at bilateral "Yongquan"ï¼KI1ï¼ and acupuncture was applied at "Baihui" ï¼GV20ï¼ for 15 min. The mice of the model and normal groups were subjected to restriction with the same method as those of the EA group for 15 min. The treatment was conducted once every other day for 6 weeks. The spatial learning-memory ability ï¼shown by escape latency of place navigation test and the time of crossing the target platform and total swimming distance in the target quadrant in 1 min of spatial probe test ï¼ was detected by Morris water maze test. The immunoactivity of senile plaques ï¼SPï¼ in the hippocampus tissue was detected by immunohistochemistry. The ultrastructural characters of hippocampal neurons were observed by transmission electron microscope, and the expression levels of Ras-related protein 5 ï¼Rab5ï¼, Ras-related protein 7 ï¼Rab7ï¼ and cathepsin D ï¼CTSDï¼ in the hippocampus were detected by Western blot, separately. RESULTS: Compared with the normal group, the escape latency, SP immunoactivity, and protein expression levels of Rab5, Rab7 and CTSD were significantly increased ï¼P<0.05, P<0.01ï¼, while the number of crossing the original platform and the total swimming distance in the platform quadrant were considerably reduced ï¼P<0.05ï¼ in the model group. In contrast to the model group, the EA group had a marked decrease in the escape latency, SP immunoactivity, and protein expression levels of Rab5, Rab7 and CTSD ï¼P<0.05, P<0.01ï¼, and a striking increase in the number of crossing the original platform and the swimming distance in the platform quadrant ï¼P<0.05ï¼. Results of transmission electron microscope showed an accumulation of endosome, lysosome, and endolysosomes in the hippocampal neurons in the model group, which was evidently milder in the EA group. CONCLUSION: EA of GV20 and KI1 can improve the learning-memory ability of AD mice, which may be related to its function in reducing hippocampal Aß deposition and down-regulating endosomal-lysosomal system activity.
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Doença de Alzheimer , Eletroacupuntura , Masculino , Camundongos , Animais , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Doença de Alzheimer/genética , Doença de Alzheimer/terapia , Endossomos , Lisossomos/genética , Placa AmiloideRESUMO
Intranasal insulin reduces lesion size and enhances memory capacity in traumatic brain injury (TBI) models, but the molecular mechanisms behind this neuroprotective action not yet understood. Here we used Feeney's free-falling method to construct TBI mouse models and administrated intranasal insulin, rapamycin, insulin and rapamycin, or normal saline to assess their effects on neurological functions, cerebral edema, and the expression of Iba1 in microglia through immunofluorescence assay. We also measured concentrations of interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) in the brain using enzyme immunosorbent assay, investigated apoptosis with TUNEL staining and Western blotting, and evaluated autophagy, endoplasmic reticulum (ER) stress, and PI3K/Akt/mTOR signaling pathway with Western blotting. The autophagosome was assessed through transmission electron microscopy. Our findings demonstrated that intranasal insulin promoted neurological recovery, decreased brain swelling, and reduced injury lesions on days 1, 3, and 7 post TBI. Moreover, intranasal insulin reduced microglia activation and the concentration of IL-1ß or TNF-α on the same days. Through Western blotting and transmission electron microscopy, we observed that intranasal insulin suppressed autophagy while activating the PI3K/AKT/mTOR signaling pathway on days 1 and 3 post TBI. TUNEL assay and Western blotting also indicated that intranasal insulin inhibited ER stress-mediated apoptosis. Interestingly, the mTOR inhibitor rapamycin partially blocked the pro-autophagy and anti-apoptosis effects of intranasal insulin both on days 1 and 3 post TBI. Our results suggest that intranasal insulin can ameliorate TBI by regulating autophagy and ER stress-mediated apoptosis through the PI3K/AKT/mTOR signaling pathway, providing a promising therapeutic strategy for TBI.
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Lesões Encefálicas Traumáticas , Proteínas Proto-Oncogênicas c-akt , Animais , Camundongos , Apoptose , Autofagia , Lesões Encefálicas Traumáticas/metabolismo , Estresse do Retículo Endoplasmático , Insulina/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
In the absence of a new transistor technology to replace CMOS, design specialization has emerged as one of the most immediate options for achieving high-performance computing [...].
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Vertical field effect transistors (VFETs) have attracted considerable interest for developing ultra-scaled devices. In particular, individual VFET can be stacked on top of another and does not consume additional chip footprint beyond what is needed for a single device at the bottom, representing another dimension for high-density transistors. However, high-density VFETs with small pitch size are difficult to fabricate and is largely limited by the trade-offs between drain thickness and its conductivity. Here, a simple approach is reported to scale the drain to sub-10 nm. By combining 7 nm thick Au with monolayer graphene, the hybrid drain demonstrates metallic behavior with low sheet resistance of ≈100 Ω sq-1 . By van der Waals laminating the hybrid drain on top of 3 nm thick channel and scaling gate stack, the total VFET pitch size down to 20 nm and demonstrates a higher on-state current of 730 A cm-2 . Furthermore, three individual VFETs together are vertically stacked within a vertical distance of 59 nm, representing the record low pitch size for vertical transistors. The method pushes the scaling limit and pitch size limit of VFET, opening up a new pathway for high-density vertical transistors and integrated circuits.
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Total glucosides picrorhizae rhizome (TGPR) is an innovative traditional Chinese medicine, which is a candidate drug for the treatment of nonalcoholic steatohepatitis (NASH). However, there is still lack of deep research on the behaviors of TGPR in vivo. In this study, a reliable, specific, and sensitive liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method has been constructed for simultaneous determination of picroside I, picroside II, vanillic acid, androsin, cinnamic acid and picroside IV, the major active constituents of TGPR, in rat various biological matrices (plasma, tissue, bile, urine and feces) using diphenhydramine hydrochloride and paeoniflorin as the internal standard. All biosamples were prepared using a simple protein precipitation with acetonitrile. Chromatographic separation was achieved on a waters UHPLC® HSS T3 (100×2.1 mm, 1.8 µm) column. The mobile phase consisted of methanol: acetonitrile1(1:1, V/V) and 0.5 mM ammonium formate in water, was employed to separate six components from endogenous interferences. The components were detected with a triple quadrupole mass spectrometer using positive and negative ion multiple reaction monitoring (MRM) mode. The newly developed method was successfully applied to investigate the pharmacokinetics, tissue distribution and excretion of six components in rats. The pharmacokinetic results indicated that the six components in TGPR could be quickly absorbed and slowly eliminated and their bioavailability were less than 12.37%, which implied the poor absorption after intragastric dosing. For tissue distribution, the six components in TGPR were detected in liver and only androsin could penetrate the blood-brain barrier. Meanwhile, the excretion study demonstrated that vanillic acid was mostly excreted as prototype drugs and the remaining five components might be widely metabolized in vivo as the metabolites, the unconverted form was excreted mainly by feces route. The pharmacokinetics, tissue distribution and excretion characteristics of six bioactive components in TGPR were firstly revealed, which will provide references for further clinical application of TGPR as an anti-NASH drug.
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Medicamentos de Ervas Chinesas , Espectrometria de Massas em Tandem , Ratos , Animais , Espectrometria de Massas em Tandem/métodos , Ratos Sprague-Dawley , Cromatografia Líquida de Alta Pressão/métodos , Distribuição Tecidual , Medicamentos de Ervas Chinesas/análise , Rizoma/química , Ácido Vanílico/análise , Glucosídeos/farmacocinéticaRESUMO
Perovskite heterojunctions are essential components of perovskite optoelectronics, but their construction and investigation have been impeded by the instability and severe anion interdiffusion. This work epitaxially deposits p-type CsPbBr3 on n-type Nb:SrTiO3 (STO) to construct a functional perovskite heterojunction with high stability. The lattice match allows epitaxial growth of CsPbBr3 to occur over large scale, resulting in a monocrystalline thin film with excellent crystallinity and uniformity. The highly stable STO prevents the anion migration frequently happening in halide perovskites, forming a sharp interface of two perovskite with opposite conduction type, with which a diode is fabricated and a current rectification ratio of 374 is obtained. The diode is able to work as a photodetector with dark current of 2.01 × 10-12 A at -1 V and responsivity (R) of 8.26 A W-1 , rendering a detectivity (D*) of 2.98 × 1013 Jones. Owing to the all-inorganic architecture, effective photoresponse at temperature as high as 150 °C is guaranteed with D* of ≈1.52 × 1013 Jones. Combining the unique optoelectrical properties of halide perovskite and the rigidity of oxide perovskite, the epitaxy of CsPbBr3 on n-type STO opens up a new method to construct functional perovskite heterojunction for optoelectronics.