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1.
Cell Death Dis ; 11(2): 107, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32034125

RESUMO

Mouse embryonic stem cells (ESCs) are isolated from the inner cell mass of blastocysts, and they exist in different states of pluripotency-naïve and primed states. Pten is a well-known tumor suppressor. Here, we generated Pten-/- mouse ESCs with the CRISPR-Cas9 system and verified that Pten-/- ESCs maintained naïve pluripotency by blocking Gsk3ß activity. Serum/LIF and 2i (MAPK and GSK3 inhibitors) conditions are commonly used for ESC maintenance. We show that the Pten-inhibitor SF1670 contributed to sustaining mouse ESCs and that Pten activation by the S380A, T382A, and T383A mutations (Pten-A3) suppressed the pluripotency of ESCs. The in vivo teratoma formation ability of SF1670-treated ESCs increased, while the Pten-A3 mutations suppressed teratoma formation. Furthermore, the embryoid bodies derived from Pten-deficient ESCs or SF1670-treated wild-type ESCs showed greater expression of ectoderm and pluripotency markers. These results suggest that Pten-mediated Gsk3ß modulates the naïve pluripotency of ESCs and that Pten ablation regulates the lineage-specific differentiation.

2.
Int J Biol Sci ; 16(1): 12-26, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31892842

RESUMO

Adverse cardiac remodeling after myocardial infarction (MI) is associated with extremely high mortality rates worldwide. Although optimized medical therapy, Preservation of lusitropic and inotropic function and protection against adverse remodeling in ventricular structure remain relatively frequent. This study demonstrated that Andrographolide (Andr) significantly ameliorated adverse cardiac remodeling induced by myocardial infarction and improves contractile function in mice with LAD ligation compared with the control group. Briefly, Andr markedly attenuated cardiac fibrosis and relieved inflammation after myocardial infarction. Specifically, Andr significantly blocked oxidative stress and the nuclear translocation of p-P65 following myocardial infarction. At the mechanistic level, antioxidant effect of Andr was achieved through strengthening antioxidative stress capacity and attributed to the activation of Nrf2/HO-1 Signaling. Consistently, H9C2 administrated with Andr showed a decreased oxidative stress caused by hypoxia precondition, but treatment with specific Nrf2 inhibitor (ML385) or the silence of Nrf2 blunted the activation of Nrf2/HO-1 Signaling and removed the protective effects of Andr in vitro. Thus, we suggest that Andr alleviates adverse cardiac remodeling following myocardial infarction through enhancing Nrf2 signaling pathway.

3.
ACS Appl Mater Interfaces ; 11(50): 47106-47111, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31769651

RESUMO

The last two decades have shown an increasing need for GaN-based laser diodes (LDs), which are currently only grown on bulk GaN substrates, which remain to date very expensive and/or only available in small sizes. The ever growing laser market will expand in the coming years, thanks to the development of automotive laser lighting, high-speed Li-Fi optical data transmission, LiDAR sensing for autonomous vehicles and smart cities, head-up displays, and AR/VR systems, in addition to biomedical and further industrial applications. These emerging technologies demand for mass-production of GaN-based lasers to be produced on large-size, low-cost, and industrially compatible substrates. To address this issue, we demonstrate the first electrically injected semipolar 440 nm LD on high-quality and low-defect-density (11-22) GaN templates grown on scalable and low-cost sapphire substrates. The LDs exhibit a threshold current density of 17 kA/cm2, a single facet output power of more than 200 mW at 2 A with a slope efficiency of 0.85 W/A, and a TE polarization having a ratio of 97.6%. These results enable the advancement of ultra-low-cost LDs while benefiting from the inherent advantages of semipolar GaN properties.

4.
Opt Express ; 27(21): 31062-31074, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31684346

RESUMO

Traditional absorbers are usually sandwich structures in which a metallic ground plane is employed to prevent the transmission. Such absorbers suffer from a major drawback that incident light can only irradiate from the front of the absorbers. In this paper, a novel absorber with bulk Dirac semimetal (BDS)-AlCuFe quasicrystals is proposed to realize bidirectional and dynamically tunable terahertz (THz) perfect absorption. The proposed structure consists of two layers of AlCuFe plates with rectangular apertures and a dielectric spacer. By adjusting transverse distance between the top and bottom rectangular apertures, perfect absorption could be realized under TM polarization. Simulation results show that perfect absorption can be obtained whether light irradiates from the front or back of the system, indicating a performance of bidirectional absorption. In addition, benefiting from the variable Fermi level of AlCuFe, the resonance frequency can be dynamically tuned in the THz range. Our work will stimulate more investigations on BDS-based bidirectional absorbers and optical modulators.

5.
Food Sci Nutr ; 7(9): 3017-3029, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31572595

RESUMO

Volatile flavor compounds (VFCs) and nutrients in Viscum articulatum Burm.f. parasitic on ancient tea trees (named TM) were studied in this research by headspace solid-phase microextraction (HS-SPME)/gas chromatography-mass spectrometry (GC-MS) and conventional methods. Sixty-six volatile compounds belonging to different classes were identified by GC-MS. The ketones, alcohols, and aldehydes were the principal aroma groups in TM according to principle component analysis (PCA). The most abundant aroma components in TM included benzaldehyde (9.64%), geranylacetone (7.92%), epoxy-ß-ionone (7.71%), ß-linalool (7.35%), methyl salicylate (6.96%), and hotrienol (6.14%), significantly higher than CKs (p < .05). The positive PC1 and PC2 in TM were correlated with benzaldehyde, hotrienol, methyl salicylate, and geranylacetone. The mistletoes could be differentiated from CKs due to the difference in aroma compounds. Clean and fresh, woody and nutty odor with minor floral scent was the characteristics of TM. Analysis of the nutritional components showed that contents of polyphenols and catechins in TM were at trace levels, significantly lower than CKs (p < .05). The total contents of polyphenols, amino acids, carbohydrates, and caffeine in TM were significantly lower from the total soluble solids (p < .05), indicating that there were still lots of compounds undetected in TM. The sensory test showed that the taste and aroma in TM can be accepted, which indicates TM could be developed into alternative tea drinks in the future.

6.
Opt Express ; 27(17): 24154-24160, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31510309

RESUMO

We investigated the electrical and optical performances of semipolar (11-22) InGaN green µLEDs with a size ranging from 20 × 20 µm2 to 100 × 100 µm2, grown on a low defect density and large area (11-22) GaN template on patterned sapphire substrate. Atom probe tomography (APT) gave insights on quantum wells (QWs) thickness and indium composition and indicated that no indium clusters were observed in the QWs. The µLEDs showed a small wavelength blueshift of 5 nm, as the current density increased from 5 to 90 A/cm2 and exhibited a size-independent EQE of 2% by sidewall passivation using atomic-layer deposition, followed by an extremely low leakage current of ~0.1 nA at -5 V. Moreover, optical polarization behavior with a polarization ratio of 40% was observed. This work demonstrated long-wavelength µLEDs fabricated on semipolar GaN grown on foreign substrate, which are applicable for a variety of display applications at a low cost.

7.
Opt Express ; 27(17): 24717-24723, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31510356

RESUMO

A nonpolar edge emitting thin film InGaN laser diode has been separated from its native substrate by mechanical tearing with adhesive tape, combining the benefits of Epitaxial Lateral Overgrowth (ELO) and cleavability of nonpolar GaN crystal. The essence of ELO is mainly to weakening strength between native substrate and the fabricated laser device on top of it. We report a 3 mm long laser bar removed from its native GaN substrate. We confirmed edge emitting lasing operation after cleaving facets on a separated thin bar. Threshold current density of the laser was measured to be as low as 2.15 kA/cm2.

8.
J Opt Soc Am A Opt Image Sci Vis ; 36(8): 1306-1311, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31503555

RESUMO

An H-type-graphene-based slow-light metamaterial is proposed to produce a dual plasmon-induced transparency phenomenon, which can be effectively modulated by Fermi level, carrier mobility of graphene, and the medium environment. The data calculated by coupled mode theory and results of numerical simulation show prominent agreement. In addition, both the simplicity and continuity of the units of graphene-based metamaterial are extraordinary advantages. Furthermore, the slow-light characteristics of the proposed structure show that the group refractive index is as high as 237, which is more competitive than some other slow-light devices.

9.
Theor Appl Genet ; 132(11): 3047-3062, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31399756

RESUMO

KEY MESSAGE: One QTL qLRI4 controlling leaf rolling index on chromosome 4 was finely mapped, and ZmOCL5, a member of the HD-Zip class IV genes, is likely a candidate. Leaf rolling is an important agronomic trait related to plant architecture that can change the light condition and photosynthetic efficiency of the population. Here, we isolated one EMS-induced mutant in Chang7-2 background with extreme abaxial rolling leaf, named abrl1. Histological analysis showed that the increased number and area of bulliform cells may contribute to abaxial rolling leaf in abrl1. The F2 and F2:3 populations derived from Wu9086 with flat leaves and abrl1 were developed to map abrl1. Non-Mendelian segregation of phenotypic variation was observed in these populations and five genomic regions controlling the leaf rolling index (LRI) were identified, which could be due to the phenotypic difference between Chang7-2 and Wu9086. Moreover, one major QTL qLRI4 on chromosome 4 was further validated and finely mapped to a genetic interval between InDel13 and InDel10, with a physical distance of approximately 277 kb using NIL populations, among which one 602-bp insertion was identified in the promoter region of HD-Zip class IV gene Zm00001d049443 (named as ZmOCL5) of abrl1 compared with wild-type Chang7-2. Remarkably, the 602-bp InDel was associated with LRI in an F2 population developed by crossing abrl1 mutant and its wild-type. In addition, the 602-bp insertion increased ZmOCL5 promoter activity and expression. Haplotype analysis demonstrated that the 602-bp insertion was a rare mutation event. Taken together, we propose that the rolled leaf in the abrl1 mutant may be partially attributed to the 602-bp insertion, which may be an attractive target for the genetic improvement of LRI in maize.

10.
Biomed Rep ; 11(3): 110-114, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31423305

RESUMO

The aim of the present study was to establish a mouse model of acute hyperglycemia, which may be utilized to detect the glucose concentration-dependent hypoglycemic activity of the glucagon-like peptide-1 derivative, 6-KTP. The results demonstrated that the first 30 min following the intraperitoneal injection of 2 g/kg glucose into C57BL/6J mice was the optimum time for assessing the hypoglycemic activity of potential therapeutic methods for diabetes. There was a linear association between the dose of 6-KTP and hypoglycemic activity between 0.2 and 1.2 mg/kg. The resulting model may serve as template for developing cost-effective in vivo models to test similar therapeutics.

11.
Int J Biol Sci ; 15(7): 1523-1532, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31337981

RESUMO

Background: The phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway is hyperactivated in lung cancer and regulates a broad range of cellular processes, including proliferation, survival, angiogenesis, and metastasis. Thus PI3K is considered a promising target for therapy. To date, PI3K inhibitors have not been approved for lung cancer. Recent studies showed that the antipsychotic agent flupentixol induced apoptosis of lung cancer cell, however the anti-tumor mechanism of flupentixol remains unclear. Methods: (1) The idock software simulated the molecular docking between the PI3Kα protein and flupentixol. (2) Inhibition of PI3Kα by the flupentixol was examined by in vitro kinase assays. (3) The cytotoxicity of flupentixol on the NSCLC cell lines was tested by MTT assays. (4) We treated A549 and H661 cells with flupentixol and then measured the percentage of apoptotic cells by the Annexin V/PI analysis. (5) We investigated the effect of flupentixol on the expression of critical PI3K/AKT signaling pathway proteins, further analyzed on the cleavage of PARP and caspase-3 by Western blotting. (6) BALB/C nude mice were subcutaneously injected with A549 cells to evaluate the effect of flupentixol on the growth of lung carcinoma. Results: Structural analysis of the predicted binding conformation suggested that flupentixol docks to the ATP binding pocket of PI3Kα. Kinase assays demonstrate that flupentixol indeed inhibited the PI3Kα kinase activity. Flupentixol exhibited cytotoxicity in lung cancer cell lines A549 and H661 in a dose- and time-dependent manner. Furthermore, flupentixol more strongly inhibited the phosphorylation of AKT (T308 and S473) and the expression of its downstream target gene Bcl-2 than two known PI3K inhibitors (BYL719 and BKM120). Flupentixol induced apoptosis as measured by PARP and caspase-3 cleavage. Finally, flupentixol significantly suppressed A549 xenograft growth in BALB/C nude mice. Conclusions: Flupentixol could be docked to the PI3Kα protein and specifically inhibit the PI3K/AKT pathway and survival of lung cancer cells in vitro and in vivo. As an old drug, flupentixol is a new PI3K inhibitor that may be used for the treatment of lung cancers.

12.
BMC Bioinformatics ; 20(1): 408, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31357929

RESUMO

BACKGROUND: Understanding the phenotypic drug response on cancer cell lines plays a vital role in anti-cancer drug discovery and re-purposing. The Genomics of Drug Sensitivity in Cancer (GDSC) database provides open data for researchers in phenotypic screening to build and test their models. Previously, most research in these areas starts from the molecular fingerprints or physiochemical features of drugs, instead of their structures. RESULTS: In this paper, a model called twin Convolutional Neural Network for drugs in SMILES format (tCNNS) is introduced for phenotypic screening. tCNNS uses a convolutional network to extract features for drugs from their simplified molecular input line entry specification (SMILES) format and uses another convolutional network to extract features for cancer cell lines from the genetic feature vectors respectively. After that, a fully connected network is used to predict the interaction between the drugs and the cancer cell lines. When the training set and the testing set are divided based on the interaction pairs between drugs and cell lines, tCNNS achieves 0.826, 0.831 for the mean and top quartile of the coefficient of determinant (R2) respectively and 0.909, 0.912 for the mean and top quartile of the Pearson correlation (Rp) respectively, which are significantly better than those of the previous works (Ammad-Ud-Din et al., J Chem Inf Model 54:2347-9, 2014), (Haider et al., PLoS ONE 10:0144490, 2015), (Menden et al., PLoS ONE 8:61318, 2013). However, when the training set and the testing set are divided exclusively based on drugs or cell lines, the performance of tCNNS decreases significantly and Rp and R2 drop to barely above 0. CONCLUSIONS: Our approach is able to predict the drug effects on cancer cell lines with high accuracy, and its performance remains stable with less but high-quality data, and with fewer features for the cancer cell lines. tCNNS can also solve the problem of outliers in other feature space. Besides achieving high scores in these statistical metrics, tCNNS also provides some insights into the phenotypic screening. However, the performance of tCNNS drops in the blind test.


Assuntos
Antineoplásicos/uso terapêutico , Aprendizado Profundo , Neoplasias/tratamento farmacológico , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Bases de Dados Factuais , Genômica , Humanos , Concentração Inibidora 50 , Especificidade de Órgãos/efeitos dos fármacos , Fenótipo , Análise de Regressão
13.
Opt Express ; 27(13): 17718-17728, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31252728

RESUMO

We have proposed a simple metal-dielectric-metal (MDM) waveguide system side-coupled with single-mode and multimode resonators. This proposed structure can achieve a typical dual plasmon-induced transparency (PIT) effect in the transmission spectra. The two PIT peaks exhibit opposite evolution tendencies with the increase in the depth of stubs. A multimode-coupled mode theory (M-CMT), confirmed by simulated results, is originally introduced to investigate the coupling effects of the proposed structure. Compared to the previous reported multichannel filters, the proposed structure includes obvious advantages, such as structural simplicity and ease of fabrication. In addition, the sensing characteristics of the proposed structure based on PIT effects are discussed numerically. The results demonstrate that the proposed structure is suitable for applications in multichannel filters, optical switches, and sensors.

14.
Opt Express ; 27(10): 13884-13894, 2019 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-31163846

RESUMO

Dual plasmon-induced transparency (PIT) and plasmon-induced absorption (PIA) are simultaneously achieved in an integrated metamaterial composed of single layer of graphene. Electric field distribution and coupled mode theory (CMT) are used to demonstrate the physical mechanism of dual PIT and PIA, and the theoretical result of CMT is highly consistent with the finite-difference time-domain (FDTD) method simulation result. Further research shows that both the dual PIT and PIA phenomenon can be effectively modulated by the Fermi level, the carrier mobility of the graphene and the refractive index of the surrounding environment. It is meaningful that the absorption of the dual PIA spectrum can be abruptly increased to 93.5% when the carrier mobility of graphene is 0.8m2/Vs. In addition, the group index can be as high as 328. Thus, our work can pave new way for developing excellent slow-light and light absorption functional devices.

15.
Biochem Biophys Res Commun ; 516(2): 515-520, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31230744

RESUMO

Glioma is the most common primary brain tumor with high mortality. Given the poor outcomes with standard-of-care treatments, novel treatment strategies are needed. Oncolytic viral therapy for glioma has developed as an exciting therapeutic method in recent years. Zika virus, a member of flavivirus family, has oncolytic activity against glioma cells but the mechanism is unknown. Here, we aimed to determine which viral protein might play a critical role in mitigating glioma cell growth. We examined the tumor suppressor function of four nonstructural proteins NS1, NS3, NS4B and NS5 in human glioma cell line U87. As a result, we found that only NS5 significantly inhibited proliferation, migration and invasion of U87 cells. Moreover, expression of NS5 suppressed tumorigenicity of mouse GL261 glioma cell in vivo. Our findings provide some clues for further exploration of oncolytic Zika virus in the treatment of glioma.

16.
Protein Expr Purif ; 161: 78-83, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31051245

RESUMO

Human cytomegalovirus (HCMV), a member of the human herpesvirus family, is a common opportunistic virus causing severe ailments and deaths in people with immature or compromised immune systems. UL23 is a virion protein found in the tegument and is expressed in the cytoplasm in HCMV infected cells. However, UL23 is dispensable for viral replication in cultured cells and little is currently known about its function. In order to further study of UL23, polyclonal antibody of UL23 was prepared. UL23 gene fragment was cloned from HCMV Towne by PCR and ligated into pET28a (+). The recombinant plasmid pET28a (+)-UL23 was transformed into E.coli BL21(DE3) to induce expression of the target protein. Then we efficiently purified the recombinant protein affinity chromatography under unique denaturation conditions. Recombinant UL23 protein was used as immunogen to inoculate New Zealand white rabbits and the sera was collected after the fourth immunization. UL23 Polyclonal antibody was purified from antisera using CNBr-activated Sepharose 4 beads. Our UL23 Polyclonal antibody showed specific reaction with UL23 in ELISA, Western-blot and immunofluorescence. More importantly, UL23 Polyclonal antibody could specifically recognize UL23 protein in HCMV infected cells, which laid a foundation for further study of HCMV UL23.

17.
Nanoscale Res Lett ; 14(1): 124, 2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30945028

RESUMO

A facile hydrothermal polymerization method has been developed for the preparation of monodisperse carbon spheres (MCSs) using the triblock copolymer F108 as surfactant. The synthesis is based on the ammonia-catalyzed polymerization reaction between phenol and formaldehyde (PF). The resultant MCSs have a perfect spherical morphology, smooth surface, and high dispersity. The particle sizes can be tuned in a wide range of 500~2400 nm by adjusting the dosage of the PF precursor. The activated MCSs with suitable heteroatoms (N and O) doped and a large specific surface area (960 m2 g-1) were obtained. A high-performance electrode of electrical double-layer capacitors fabricated by those active material have an excellent specific capacitance (310 F g-1 at 0.5 A g-1) and outstanding cycling stability (92% capacitance retention after 10,000 cycles). This work provides a new opportunity for the fabrication of MCSs with potential applications.

18.
Chem Biol Drug Des ; 94(1): 1390-1401, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30916462

RESUMO

Molecular target prediction can provide a starting point to understand the efficacy and side effects of phenotypic screening hits. Unfortunately, the vast majority of in silico target prediction methods are not available as web tools. Furthermore, these are limited in the number of targets that can be predicted, do not estimate which target predictions are more reliable and/or lack comprehensive retrospective validations. We present MolTarPred ( http://moltarpred.marseille.inserm.fr/), a user-friendly web tool for predicting protein targets of small organic compounds. It is powered by a large knowledge base comprising 607,659 compounds and 4,553 macromolecular targets collected from the ChEMBL database. In about 1 min, the predicted targets for the supplied molecule will be listed in a table. The chemical structures of the query molecule and the most similar compounds annotated with the predicted target will also be shown to permit visual inspection and comparison. Practical examples of the use of MolTarPred are showcased. MolTarPred is a new resource for scientists that require a more complete knowledge of the polypharmacology of a molecule. The introduction of a reliability score constitutes an attractive functionality of MolTarPred, as it permits focusing experimental confirmatory tests on the most reliable predictions, which leads to higher prospective hit rates.

19.
Bioinformatics ; 35(20): 3989-3995, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30873528

RESUMO

MOTIVATION: Studies have shown that the accuracy of random forest (RF)-based scoring functions (SFs), such as RF-Score-v3, increases with more training samples, whereas that of classical SFs, such as X-Score, does not. Nevertheless, the impact of the similarity between training and test samples on this matter has not been studied in a systematic manner. It is therefore unclear how these SFs would perform when only trained on protein-ligand complexes that are highly dissimilar or highly similar to the test set. It is also unclear whether SFs based on machine learning algorithms other than RF can also improve accuracy with increasing training set size and to what extent they learn from dissimilar or similar training complexes. RESULTS: We present a systematic study to investigate how the accuracy of classical and machine-learning SFs varies with protein-ligand complex similarities between training and test sets. We considered three types of similarity metrics, based on the comparison of either protein structures, protein sequences or ligand structures. Regardless of the similarity metric, we found that incorporating a larger proportion of similar complexes to the training set did not make classical SFs more accurate. In contrast, RF-Score-v3 was able to outperform X-Score even when trained on just 32% of the most dissimilar complexes, showing that its superior performance owes considerably to learning from dissimilar training complexes to those in the test set. In addition, we generated the first SF employing Extreme Gradient Boosting (XGBoost), XGB-Score, and observed that it also improves with training set size while outperforming the rest of SFs. Given the continuous growth of training datasets, the development of machine-learning SFs has become very appealing. AVAILABILITY AND IMPLEMENTATION: https://github.com/HongjianLi/MLSF. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

20.
Opt Express ; 27(3): 3598-3608, 2019 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-30732376

RESUMO

We propose a novel simple patterned monolayer graphene metamaterial structure based on tunable terahertz plasmon-induced transparency (PIT). Destructive interference in this structure causes pronounced PIT phenomenon, and the PIT response can be dynamically controlled by voltage since the existence of continuous graphene bands in the structural design. The theoretical transmission of this structure is calculated by coupled mode theory (CMT), and the results are highly consistent with the simulation curve. After that, the influence of the graphene mobility on the PIT response and absorption characteristics is researched. It is found that the absorption efficiency of our designed structure can reach up to 50%, meaning the structure is competent to prominent terahertz absorber. Moreover, the slow-light performance of this structure is discussed via analyzing the group refractive index and phase shift. It shows that the structure possesses a broad group refractive index band with ultra-high value, and the value is up to 382. This work will diversify the designs for versatile tunable terahertz devices and micro-nano slow-light devices.

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