Design and experimental realization of triple-band electromagnetically induced transparency terahertz metamaterials employing two big-bright modes for sensing applications.

Multi-band electromagnetically induced transparency (EIT) effects have attracted widespread attention due to their great application prospects. However, their realization is mainly based on the coupling of multiple sub-resonators that typically exceed the number of transparency peaks, resulting in complex structural designs and cumbersome preparation procedures. This paper reports a simple design of a terahertz metamaterial that can produce the triple-band EIT effect using two "big-bright" mode coupling of two sub-resonators. The design adopts the classical two-layer structure. A U-shaped split-ring resonator and a fork-shaped resonator form a periodic array on the surface of the flexible organic polymer material. Three transparency peaks around 0.59 THz, 1.07 THz, and 1.34 THz are experimentally realized, and their formation mechanisms are explored. Furthermore, the triple-band EIT metamaterial was prepared by the photolithography technology and characterized by terahertz time-domain spectroscopy. Theoretical simulation results agree well with experimental results. Sensing characteristics and slow light effects of the terahertz metamaterial are further discussed experimentally. The proposed triple-band EIT metamaterial having excellent properties, including thin size, good flexibility, simple and compact structure, and high sensing sensitivity, could provide guidance for the subsequent design and implementation of multifunctional multi-band EIT metamaterials.

Response of soil microbial community diversity to continuous cucumber cropping in facilities along the Yellow River irrigation area.

Cucumber is an important cash crop; however, continuous cropping obstacles readily occur within the intensive production processes of facility horticulture. This study aimed to determine the effects of continuous cropping on soil quality and the microbial community in the rhizosphere soil of cucumbers. Rhizosphere soil of cucumber planted continuously for 4, 8, and 12 years was investigated, and soil that was not continuously planted was used as the control. Soil physicochemical properties, enzyme activity, microbial diversity, and richness were determined. The results showed that with the increase in continuous cropping years (0, 4, 8, and 12 years), soil total salt content continuously increased, while the pH value significantly decreased. Compared with the control, soil organic matter, alkali-hydrolyzed nitrogen, available phosphorus, available potassium, and nitrate nitrogen contents increased significantly after 4 and 8 years of continuous cropping. Spearman correlation analysis showed that pH was negatively correlated with sucrase or sucrose and available phosphorus was positively correlated with alkaline phosphatase. Compared with the control, the diversity and abundance of bacterial and fungal communities in cucumber rhizosphere soil decreased after 4 and 12 years of continuous cropping. Continuous cropping led to a significant increase in the richness of the dominant phylum of cucumber rhizosphere soil. Principal coordinates analysis showed that, compared with the control, the soil microbial community structure was significantly separated after 4, 8, and 12 years of continuous cropping, and the microbial community structure was most similar after 4 and 8 years of continuous cropping. In addition, redundancy analysis showed that pH was the main driver of soil microbial dominance. In conclusion, continuous cropping of cucumber along the Yellow River irrigation area has led to the deterioration of soil nutrients and microbial communities in that region. This experiment provides a theoretical foundation for addressing the challenges associated with continuous cropping in cucumber cultivation.

Activin A directly impairs human cardiomyocyte contractile function indicating a potential role in heart failure development.

Activin A has been linked to cardiac dysfunction in aging and disease, with elevated circulating levels found in patients with hypertension, atherosclerosis, and heart failure. Here, we investigated whether Activin A directly impairs cardiomyocyte (CM) contractile function and kinetics utilizing cell, tissue, and animal models. Hydrodynamic gene delivery-mediated overexpression of Activin A in wild-type mice was sufficient to impair cardiac function, and resulted in increased cardiac stress markers (N-terminal pro-atrial natriuretic peptide) and cardiac atrophy. In human-induced pluripotent stem cell-derived (hiPSC) CMs, Activin A caused increased phosphorylation of SMAD2/3 and significantly upregulated SERPINE1 and FSTL3 (markers of SMAD2/3 activation and activin signaling, respectively). Activin A signaling in hiPSC-CMs resulted in impaired contractility, prolonged relaxation kinetics, and spontaneous beating in a dose-dependent manner. To identify the cardiac cellular source of Activin A, inflammatory cytokines were applied to human cardiac fibroblasts. Interleukin -1ß induced a strong upregulation of Activin A. Mechanistically, we observed that Activin A-treated hiPSC-CMs exhibited impaired diastolic calcium handling with reduced expression of calcium regulatory genes (SERCA2, RYR2, CACNB2). Importantly, when Activin A was inhibited with an anti-Activin A antibody, maladaptive calcium handling and CM contractile dysfunction were abrogated. Therefore, inflammatory cytokines may play a key role by acting on cardiac fibroblasts, causing local upregulation of Activin A that directly acts on CMs to impair contractility. These findings demonstrate that Activin A acts directly on CMs, which may contribute to the cardiac dysfunction seen in aging populations and in patients with heart failure.

Dl-3-n-butylphthalide attenuates myocardial ischemia reperfusion injury by suppressing oxidative stress and regulating cardiac mitophagy via the PINK1/Parkin pathway in rats.

Background: Acute myocardial infarction (AMI) is one of the leading causes of mortality worldwide. Undesirable myocardial damage may occur during reperfusion of the ischemic myocardium, and this is known as "ischemic reperfusion injury" (IRI). Currently, there are few effective drugs to alleviate IRI. Dl-3-n-butylphthalide (NBP) is recommended for the treatment of acute ischemic stroke in China. This study investigated the effects of NBP on IRI and its underlying mechanisms. Methods: The left anterior descending (LAD) coronary arteries of rats were occluded for 30 minutes and reperfused for 6 hours to establish the ischemia/reperfusion (I/R) model. NBP was administered intraperitoneally 2 hours before modeling and immediately after reperfusion. At 6 hours after reperfusion, 2,3,5-triphenyltetrazolium chloride (TTC) staining, enzyme-linked immunosorbent assay (ELISA), oxidative stress index, myocardial injury index, hematoxylin and eosin (HE) staining, transmission electron microscopy (TEM), real-time polymerase chain reaction (PCR), immunofluorescence staining, and Western blot analyses were performed to investigate the protective effects of NBP against IRI. Results: In the rat I/R model, NBP remarkably reduced the myocardial infarct size, alleviated myocardial injury and oxidative stress, improved the pathological alteration of cardiomyocytes and mitochondria, and upregulated mitophagy. In addition, the study demonstrated that the protective effects of NBP against IRI involved mitophagy mediated by the PTEN-induced putative kinase protein-1 (PINK1)/Parkin signaling pathway. Conclusions: NBP was able to protect the myocardium from IRI in rats through inhibiting oxidative stress and activating mitophagy, mediated by the PINK1/Parkin pathway.

Tunable dielectric metasurfaces by structuring the phase-change material.

Metasurfaces have made great progress in the last decade for generating miniature and integrated optical devices. The optical properties of metasurfaces can be tuned dynamically by integrating with phase-change materials. However, the efficiency of tunable metasurfaces remains a bit low, which is a disadvantage for the realistic applications of metasurfaces. Here, we demonstrate the tunable dielectric metasurfaces by structuring the phase-change material Ge2Sb2Te5. The unit cell of metasurface is composed of several Ge2Sb2Te5 nanopillars with different geometric parameters, and the incident light interacts with different nanopillars at diverse phases of Ge2Sb2Te5, leading to various functions. By elaborately arranging the Ge2Sb2Te5 nanopillars, various tunable optical devices have been realized, including tunable beam steering, reconfigurable metalens and switchable wave plate. The refractive direction, focal length and polarization state can be tuned through the phase transition of Ge2Sb2Te5. The phase-change metasurfaces based on Ge2Sb2Te5 nanostructures could be used in cameras, optical microscopy and adaptive optics.

Switchable transmissive and reflective metadevices based on the phase transition of vanadium dioxide.

Metasurfaces have made great progress in the past decade in generating various planar optical devices. However, most metasurfaces exhibit their functions in either reflection mode or transmission mode, with the other mode unutilized. In this work, we demonstrate switchable transmissive and reflective metadevices by combining metasurfaces with vanadium dioxide. The composite metasurface can work as a transmissive metadevice, with one function for vanadium dioxide in the insulating phase, and is changed to a reflective metadevice with another function for vanadium dioxide in the metallic phase. By carefully designing the structures, the metasurface can be switched from a transmissive metalens to a reflective vortex generator, or between a transmissive beam steering and a reflective quarter-wave plate through the phase transition of vanadium dioxide. The switchable transmissive and reflective metadevices have potential applications in imaging, communication, and information processing.

Tunable wave plates based on phase-change metasurfaces.

Wave plates based on metasurfaces have attracted intensive attention over the past decade owing to their compactness and design flexibility. Although various wave plates have been designed, their working wavelengths are fixed once they are made. Here we present a study on tunable wave plates based on phase-change metasurfaces made of Ge2Sb2Te5 nanopillar structures. The Ge2Sb2Te5 nanopillars can work as a high-efficiency transmissive half- or quarter-wave plate depending on their structural parameters. The working wavelength of wave plate can be tuned via the phase transition of Ge2Sb2Te5. Moreover, the polarization state of the transmitted light at a fixed wavelength can be modified by changing the crystallinity of Ge2Sb2Te5. The features suggest that tunable wave plates may have applications in optical modulators, molecular detection, and polarimetric imaging.

Electric Field Tuning of Interlayer Coupling in Noncentrosymmetric 3R-MoS2 with an Electric Double Layer Interface.

Interlayer coupling in two-dimensional (2D) layered materials plays an important role in controlling their properties. 2H- and 3R-MoS2 with different stacking orders and the resulting interlayer coupling have been recently discovered to have different band structures and a contrast behavior in valley physics. However, the role of carrier doping in interlayer coupling in 2D materials remains elusive. Here, based on the electric double layer interface, we demonstrated the experimental observation of carrier doping-enhanced interlayer coupling in 3R-MoS2. A remarkable tuning of interlayer Raman modes can be observed by changing the stacking sequence and carrier doping near their monolayer limit. The modulated interlayer vibration modes originated from the interlayer coupling show a doping-induced blue shift and are supposed to be associated with the interlayer coupling enhancement, which is further verified using our first-principles calculations. Such an electrical control of interlayer coupling of layered materials in an electrical gating geometry provides a new degree of freedom to modify the physical properties in 2D materials.

Micro-RNA-21 rs1292037 A>G polymorphism can predict hepatocellular carcinoma prognosis (HCC), and plays a key role in cell proliferation and ischemia-reperfusion injury (IRI) in HCC cell model of IRI.

OBJECTIVES: To assess the predictive function of miR-21 rs1292037 A greater than G polymorphism in survival and ischemia-reperfusion injury (IRI) in hepatocellular carcinoma (HCC) patients. METHODS: The experiment was carried out between July 2018 and July 2019, whereas the prospective clinical study was carried out between January 2014 and January 2019. In this study, 62 HCC patients with hepatitis B virus (HBV), 17 HCC patients without HBV, and 13 healthy controls were investigated. Micro-RNA-21 levels in the blood were identified using quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and allele specific PCR for miR-21 rs1292037. Partial hepatectomy was performed in all patients, and the tumor development indicators and survival time were evaluated in a subsequent follow-up. Cell-based simulated IRI model of HCC huh7 cell line was used to determine the functions of miR-21 with respect to IRI and proliferation. RESULTS: Micro-RNA-21 levels were significantly increased in HCC patients. Furthermore, an miR- 21 rs1292037 A greater than G polymorphism was found to be significantly associated with HCC prognosis and severity of liver injury after hepatectomy. In vitro study revealed that miR-21 might prevent IRI from occurring, and can induce proliferation in HCC huh7 cells. These functions of miR-21 were demonstrated to be triggered by IL-12A inhibition. CONCLUSION: Micro-RNA-21 rs1292037 A greater than G polymorphism can predict IRI and tumor progression by regulating the miR-21/IL-12A.axis.

Intrinsic magnetic topological insulator phases in the Sb doped MnBi2Te4 bulks and thin flakes.

Magnetic topological insulators (MTIs) offer a combination of topologically nontrivial characteristics and magnetic order and show promise in terms of potentially interesting physical phenomena such as the quantum anomalous Hall (QAH) effect and topological axion insulating states. However, the understanding of their properties and potential applications have been limited due to a lack of suitable candidates for MTIs. Here, we grow two-dimensional single crystals of Mn(SbxBi(1-x))2Te4 bulk and exfoliate them into thin flakes in order to search for intrinsic MTIs. We perform angle-resolved photoemission spectroscopy, low-temperature transport measurements, and first-principles calculations to investigate the band structure, transport properties, and magnetism of this family of materials, as well as the evolution of their topological properties. We find that there exists an optimized MTI zone in the Mn(SbxBi(1-x))2Te4 phase diagram, which could possibly host a high-temperature QAH phase, offering a promising avenue for new device applications.

Topological Axion States in the Magnetic Insulator MnBi_{2}Te_{4} with the Quantized Magnetoelectric Effect.

Topological states of quantum matter have attracted great attention in condensed matter physics and materials science. The study of time-reversal-invariant topological states in quantum materials has made tremendous progress. However, the study of magnetic topological states falls much behind due to the complex magnetic structures. Here, we predict the tetradymite-type compound MnBi_{2}Te_{4} and its related materials host topologically nontrivial magnetic states. The magnetic ground state of MnBi_{2}Te_{4} is an antiferromagetic topological insulator state with a large topologically nontrivial energy gap (∼0.2 eV). It presents the axion state, which has gapped bulk and surface states, and the quantized topological magnetoelectric effect. The ferromagnetic phase of MnBi_{2}Te_{4} might lead to a minimal ideal Weyl semimetal.

Discovery of Superconductivity in 2M WS2 with Possible Topological Surface States.

Recently the metastable 1T'-type VIB-group transition metal dichalcogenides (TMDs) have attracted extensive attention due to their rich and intriguing physical properties, including superconductivity, valleytronics physics, and topological physics. Here, a new layered WS2 dubbed "2M" WS2 , is constructed from 1T' WS2 monolayers, is synthesized. Its phase is defined as 2M based on the number of layers in each unit cell and the subordinate crystallographic system. Intrinsic superconductivity is observed in 2M WS2 with a transition temperature Tc of 8.8 K, which is the highest among TMDs not subject to any fine-tuning process. Furthermore, the electronic structure of 2M WS2 is found by Shubnikov-de Haas oscillations and first-principles calculations to have a strong anisotropy. In addition, topological surface states with a single Dirac cone, protected by topological invariant Z2 , are predicted through first-principles calculations. These findings reveal that the new 2M WS2 might be an interesting topological superconductor candidate from the VIB-group transition metal dichalcogenides.

Observation of Coulomb gap in the quantum spin Hall candidate single-layer 1T'-WTe2.

The two-dimensional topological insulators host a full gap in the bulk band, induced by spin-orbit coupling (SOC) effect, together with the topologically protected gapless edge states. However, it is usually challenging to suppress the bulk conductance and thus to realize the quantum spin Hall (QSH) effect. In this study, we find a mechanism to effectively suppress the bulk conductance. By using the quasiparticle interference technique with scanning tunneling spectroscopy, we demonstrate that the QSH candidate single-layer 1T'-WTe2 has a semimetal bulk band structure with no full SOC-induced gap. Surprisingly, in this two-dimensional system, we find the electron-electron interactions open a Coulomb gap which is always pinned at the Fermi energy (EF). The opening of the Coulomb gap can efficiently diminish the bulk state at the EF and supports the observation of the quantized conduction of topological edge states.

The influence of caveolin-1 gene polymorphisms on hepatitis B virus-related hepatocellular carcinoma susceptibility in Chinese Han population: A case-control study.

This study aimed to explore the genetic association of polymorphisms in caveolin-1 gene (CAV1) with hepatitis B virus-related hepatocellular carcinoma (HBV-related HCC) susceptibility in a Chinese Han population.The genotyping of polymorphism was conducted using polymerase chain reaction-restriction fragment length polymorphism method. Whether the genotype distribution of polymorphisms in the healthy controls was consistent with Hardy-Weinberg equilibrium (HWE) was detected. The genotype and allele frequency difference between the 2 groups was compared by chi-square test. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated to show the relative risk of HCC which resulted from genetic variants in CAV1. Moreover, the linkage disequilibrium of CAV1 polymorphisms was analyzed by Haploview.The AG genotype and A allele of rs1049334 showed significantly higher frequency in HCC patients than that of chronic HBV patients and the healthy controls (P < .05); so their carriage obviously increased the susceptibility to HBV-related HCC, irrespective of the fact whether individuals were infected with hepatitis B virus or not (AG vs GG: OR 1.958, 95% CI 1.050-3.650, OR 1.899, 95% CI 1.034-3.487; A vs G: OR 1.667, 95% CI 1.033-2.689, OR 1.777, 95% CI 1.103-2.863). Additionally, A-G haplotype of rs3807989-rs1049334 showed the protective role for HBV-related HCC (OR 0.102, 95% CI 0.035-0.293; OR 0.135, 95% CI 0.046-0.395).CAV1 rs1049334 polymorphism is significantly associated with the occurrence risk of HBV-related HCC, and the interaction of polymorphisms should not be neglected.

Predictive value of microRNA-143 in evaluating the prognosis of patients with hepatocellular carcinoma.

OBJECTIVE: The study aims to evaluate the predictive value of microRNA-143 (miR-143) for the prognosis of patients with hepatocellular carcinoma (HCC). METHODS: Between October 2010 and October 2012, 131 HCC patients were selected as a case group; meanwhile, 122 healthy controls were enrolled as a control group. The miR-143 expression in serum was detected by quantitative real-time polymerase chain reaction (qRT-PCR). These HCC patients were divided into the high miR-143 expression group and the low miR-143 expression group based on the threshold of receiver operating characteristic (ROC) curve. Kaplan-Meier method was applied to analyze the prognosis of HCC patients. RESULTS: MiR-143 exhibited decreased expression in the case group significantly compared to the control group. The areas under the ROC curve (AUC), sensitivity value and specificity value of the miR-143 expression for the diagnosis of HCC were 0.831, 80.30% and 82.40%, respectively. The miR-143 expression was negatively correlated with vascular invasion, TNM staging, tumor recurrence, metastasis and survival of HCC patients. CONCLUSIONS: Our study provides evidence that miR-143 may be negatively correlated with the prognosis of HCC and provides a promising strategy for HCC treatment and prognosis improvement.

Ideal Weyl Semimetals in the Chalcopyrites CuTlSe_{2}, AgTlTe_{2}, AuTlTe_{2}, and ZnPbAs_{2}.

Weyl semimetals are new states of matter which feature novel Fermi arcs and exotic transport phenomena. Based on first-principles calculations, we report that the chalcopyrites CuTlSe_{2}, AgTlTe_{2}, AuTlTe_{2}, and ZnPbAs_{2} are ideal Weyl semimetals, having largely separated Weyl points (∼0.05 Å^{-1}) and uncovered Fermi arcs that are amenable to experimental detections. We also construct a minimal effective model to capture the low-energy physics of this class of Weyl semimetals. Our discovery is a major step toward a perfect playground of intriguing Weyl semimetals and potential applications for low-power and high-speed electronics.

Discovery of a potent, orally bioavailable and highly selective human neuronal nitric oxide synthase (nNOS) inhibitor, N-(1-(piperidin-4-yl)indolin-5-yl)thiophene-2-carboximidamide as a pre-clinical development candidate for the treatment of migraine.

We recently reported a series of 1,6-disubstituted indoline-based thiophene amidine compounds (5) as selective neuronal nitric oxide synthase (nNOS) inhibitors to mitigate the cardiovascular liabilities associated with hERG K(+) channel inhibition (IC(50) = 4.7 µM) with previously reported tetrahydroquinoline-based selective nNOS inhibitors (4). The extended structure-activity relationship studies within the indoline core led to the identification of 43 as a selection candidate for further evaluations. The in vivo activity in two different pain (spinal nerve ligation and migraine pain) models, the excellent physicochemical and pharmacokinetic properties, oral bioavailability (F(po) = 91%), and the in vitro safety profile disclosed in this report make 43 an ideal candidate for further evaluation in clinical applications related to migraine pain.

First-in-class, dual-action, 3,5-disubstituted indole derivatives having human nitric oxide synthase (nNOS) and norepinephrine reuptake inhibitory (NERI) activity for the treatment of neuropathic pain.

A family of different 3,5-disubstituted indole derivatives having 6-membered rings were designed, synthesized, and demonstrated inhibition of human nitric oxide synthase (NOS) with norepinephrine reuptake inhibitory activity (NERI). The structure-activity relationship (SAR) within the cyclohexane ring showed the cis-isomers to be more potent for neuronal NOS and selective over endothelial NOS compared to their trans-counterparts. Compounds, such as cis-(+)-37, exhibited dual nNOS and NET inhibition (IC(50) of 0.56 and 1.0 µM, respectively) and excellent selectivity (88-fold and 12-fold) over eNOS and iNOS, respectively. The lead compound (cis-(+)-37) showed lack of any direct vasoconstriction or inhibition of ACh-mediated vasorelaxation in isolated human coronary arteries. Additionally, cis-(+)-37 was effective at reversing both allodynia and thermal hyperalgesia in a standard Chung (spinal nerve ligation) rat neuropathic pain model. Overall, the data suggest that cis-(+)-37 is a promising dual action development candidate having therapeutic potential for the treatment of neuropathic pain.

1,2,3,4-tetrahydroquinoline-based selective human neuronal nitric oxide synthase (nNOS) inhibitors: lead optimization studies resulting in the identification of N-(1-(2-(methylamino)ethyl)-1,2,3,4-tetrahydroquinolin-6-yl)thiophene-2-carboximidamide as a preclinical development candidate.

Numerous studies have shown that selective nNOS inhibitors could be therapeutic in many neurological disorders. Previously, we reported a series of 1,2,3,4-tetrahydroquinoline-based potent and selective nNOS inhibitors, highlighted by 1 ( J. Med. Chem. 2011 , 54 , 5562 - 5575 ). Despite showing activity in two rodent pain models, 1 suffered from low oral bioavailability (18%) and moderate hERG channel inhibition (IC(50) = 4.7 µM). To optimize the properties of 1, we synthesized a small focused library containing various alkylamino groups on the 1-position of the 1,2,3,4-tetrahydroquinoline scaffold. The compounds were triaged based on their activity in the NOS and hERG manual patch clamp assays and their calculated physicochemical parameters. From these studies, we identified 47 as a potent and selective nNOS inhibitor with improved oral bioavailability (60%) and no hERG channel inhibition (IC(50) > 30 µM). Furthermore, 47 was efficacious in the Chung model of neuropathic pain and has an excellent safety profile, making it a promising preclinical development candidate.

Discovery of N-(3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indol-6-yl) thiophene-2-carboximidamide as a selective inhibitor of human neuronal nitric oxide synthase (nNOS) for the treatment of pain.

3,6-Disubstituted indole derivatives were designed, synthesized, and evaluated as inhibitors of human nitric oxide synthase (NOS). Bulky amine containing substitution on the 3-position of the indole ring such as an azabicyclic system showed better selectivity over 5- and 6-membered cyclic amine substitutions. Compound (-)-19 showed the best selectivity for neuronal NOS over endothelial NOS (90-fold) and inducible NOS (309-fold) among the current series. Compounds 16 and (-)-19 were shown to be either inactive or very weak inhibitors of human cytochrome P450 enzymes, indicating a low potential for drug-drug interactions. Compound 16 was shown to reverse thermal hyperalgesia in vivo in the Chung model of neuropathic pain. Compound 16 was also devoid of any significant vasoconstrictive effect in human coronary arteries, associated with the inhibition of human eNOS. These results suggest that 16 may be a useful tool for evaluating the potential role of selective nNOS inhibitors in the treatment of pain such as migraine and CTTH.