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Atrial fibrillation (AF) is the most common clinical sustained arrhythmia; clinical therapeutic drugs have low atrial selectivity and might cause more severe ventricle arrhythmias while stopping AF. As an anti-AF drug target with high selectivity on the atrial muscle cells, the undetermined crystal structure of Kv1.5 potassium channel impeded further new drug development. Herein, with the simulated 3D structure of Kv1.5 as the drug target, a series of 3-morpholine linked aromatic amino substituted 1H-indoles as novel Kv1.5 channel inhibitors were designed and synthesized based on target–ligand interaction analysis. The synthesis route was practical, starting from commercially available material, and the chemical structures of target compounds were characterized. It was indicated that compounds T16 and T5 (100 μM) exhibited favorable inhibitory activity against the Kv1.5 channel with an inhibition rate of 70.8 and 57.5% using a patch clamp technique. All compounds did not exhibit off-target effects against other drug targets, which denoted some selectivity on the Kv1.5 channel. Interestingly, twelve compounds exhibited favorable vasodilation activity on pre-contracted arterial rings in vitro using KCl or phenylephrine (PE) by a Myograph. The vasodilation rates of compounds T16 and T4 (100 μM) even reached over 90%, which would provide potential lead compounds for both anti-AF and anti-hypertension new drug development.

The ultrastrongly coupling (USC) system has very important research significance in quantum simulation and quantum computing. In this paper, the ultranarrow spectrum of a circuit QED system with two qubits ultrastrongly coupled to a single-mode cavity is studied. In the regime of USC, the JC model breaks down and the counter-rotating terms in the quantum Rabi Hamiltonian leads to the level anti-crossing in the energy spectrum. Choosing a single-photon driving field at the point of avoided-level crossing, we can get an equivalent four-level dressed state model, in which the dissipation of the two intermediate states is only related to the qubits decay. Due to the electron shelving of these two metastable states, a narrow peak appears in the cavity emission spectrum. Furthermore, we find that the physical origin for the spectral narrowing is the vacuum-induced quantum interference between two transition pathways. And this interference effect couples the slowly decaying incoherent components of the density matrix into the equations of the sidebands. This result provides a possibility for the study of quantum interference effect in the USC system.

Parecoxib plays an important role in inhibition of human cancer. However, the effect of parecoxib on esophageal squamous cell carcinoma (ESCC) is still not well known. The purpose of this study was to investigate the effect of parecoxib on ESCC and its underlying mechanism.RNA-sequence analysis was performed to identify functional alterations and mechanisms. Cell cycle, proliferation, invasion, and migration were assessed using flow cytometry, CCK-8 assay, colony formation, transwell, and wound healing assays. Extracellular matrix (ECM) degradation was detected by substrate gel zymography and 3D cell culture assay. Western blotting was used to detect parecoxib-dependent mechanisms involving cell cycle, proliferation, invasion, and migration. Tumor formation in vivo was detected by mouse assay.Functional experiments indicated that parecoxib induced ESCC cell cycle arrest in G2 phase, and inhibited cell proliferation, invasion, and migration in vitro. Western blotting revealed that parecoxib downregulated the phosphorylation levels of AKT and PDK1, as well as the expression of the mutant p53, cyclin B1, and CDK1, while upregulating p21waf1. Parecoxib inhibited matrix metalloproteinase-2 (MMP2) secretion and invadopodia formation, which were related to ECM degradation. Furthermore, we found that parecoxib suppressed ESCC growth in heterotopic tumor models.Parecoxib inhibits ESCC progression, including cell cycle, proliferation, invasion, and migration, via the PDK1-AKT signaling pathway.

Background: The exact morbidity of myocarditis is unknown, as the treatment is generally delayed in virtue of misdiagnosis or missed diagnosis. Aim: The aim of this study was to identify prognostic factors of left-ventricular remodeling on CMRI performed in patients with pathological proven myocarditis. Methods: Sixty-two cases with various presentations of myocarditis (39 cases with heart failure; 23 cases with arrhythmias) were selected. All patients, who underwent coronary angiography, endomyocardial biopsy, were divided into positive-remodeling and negative-remodelling groups to analyse LGE and cardiac cine parameters at presentation and subsequent to 3 months. Results: Comparison of two subgroups in CMRI is as follows: positive LGE (65.6% vs. 86.7%; p Conclusion: LGE-MRI is rewarding as an independent predictor in left-ventricular positive and negative remodelling of myocarditis.

Hypertension is a major risk factor for cardiovascular disease and Chinese herb monomers could provide new structural skeletons for anti-hypertension new drug development. Paeonol is a Chinese herbal monomer extracted from Cortex moutan, exhibited some anti-hypertensive activity. The study focused on the structural optimization of paeonol to provide promising lead compounds for anti-hypertension new drug development. Herein, twelve new paeonol derivatives (PD) were designed and synthesized and their vasodilation activity was evaluated by in vitro vasodilation drug screening platform based on Myograph. Its anti-hypertension activity, PD-C302 (2-hydroxy-4-methoxyvalerophenone) as a representative with the optimal vasodilation activity, was determined by its response to blood pressure in spontaneously hypertensive rats (SHR) in vivo. Moreover, its molecular mechanism was probed by the vasodilation activity of rat superior mesenteric artery rings with or without endothelium pre-contracted by potassium chloride (KCl) or phenylephrine hydrochloride (PE). It was indicated that PD-C302 significantly reduced the blood pressure in SHR, which would involve in PD-C302-induced vasodilation. Furthermore, endothelium-dependent pathways and endothelium-independent pathways both contributed importantly to PD-C302-induced vasodilation at low concentration of PD-C302. Endothelium-independent pathways (vascular smooth muscle cell-mediated vasodilation), were mainly responsible for the PD-C302-induced vasodilation at high concentration of PD-C302, which involved in opening multiple K

The frequency-resolved correlations of the fluorescence emitted by a four-level system in the $J=1/2$ to $J=1/2$ transition driven by a linearly polarized laser field are theoretically investigated. In the cross two-photon correlation of the $\ensuremath{\pi}$ and ${\ensuremath{\sigma}}^{+}$ transitions, we show that VICs can induce the interference of time orderings between the two-photon paths with different dipole moments, which can serve as a good scheme to exhibit the effects of vacuum-induced coherences (VICs). An external magnetic field can cause frequency differences between two-photon paths with different time orderings. When the differences can be distinguished by detectors, the effects of VICs are destroyed and time asymmetry of the two-photon correlations appears due to the reveal of ``which path'' information. However, the which path information can be erased by tuning the filtering frequencies so the perfect interference effects of time orderings and time symmetry are restored.

Frequency-resolved photon statistics of resonance fluorescence generated from a two-level system driven by a strong laser field and a weak laser field with equal frequencies are studied. The frequency resolution of fluorescent radiation is described by quantum filtering dynamics, which is simulated theoretically by two single-mode quantum optical cavities with tunable frequencies to scan the incident fluorescent radiation. By calculating the two-photon intensity–intensity correlation functions in terms of the cavity modes, we demonstrate that two-color strong correlations of resonance fluorescence can be generated not only between the opposite sidebands, but also between the central band and one of the sidebands: although both sidebands are broadened due to the perturbation of the weak laser field on the strong-field dressed atom. We emphasize that these properties are in contrast to the conventional case of the standard single-atom Mollow triplet. Moreover, if the resonance frequencies of the two filtering cavities are tuned appropriately, broadband two-color strong correlations are predicted, and the physical origin is revealed from the perspective of quantum interference of photon emission dynamics. This can be considered as a feasible scheme for the design of broadband non-classical light sources, and may be beneficial to the quantum precise detection of atomic and molecular dynamics via quantum optical spectroscopy.

BACKGROUND This study aimed to compare multiple quantitative evaluation indices of levels of theoretical knowledge and clinical practice skills in training medical interns in cardiovascular imaging based on the use of the blended teaching (BT) online artificial intelligence (AI) case resource network platform (CRNP), including time and frequency indices and effectiveness of the CRNP. MATERIAL AND METHODS The study included 110 medical interns who were divided into the routine teaching (RT) group (n=55) and the blended teaching (BT) group (n=55). The two were assessed using the mini-clinical evaluation exercise (mini-CEX) that assessed clinical skills, attitudes, and behaviors and using an objective written questionnaire. The following four indices were compared between the RT and BT groups: the X-ray score (XS), the computed tomography angiography (CTA) score (CS), the cardiac magnetic resonance imaging (CMRI) score (MS), and the average score (AS). Seven assessment indicators included: the imaging description (ID), the qualitative diagnosis (QD), the differential diagnosis (DD), examination preparation (EP), interview skill (IS), position display (PD), and human care (HC). Indicators of CRNP use included: number of times (TN), average duration (AD), single maximum duration (SMD), and total duration (TD). RESULTS AS significantly correlated with AD (rAD=0.761) and TD (rTD=0.754), and showed moderate correlation with TN (rTN=0.595), but weak correlation with SMD (rSMD=0.404). CONCLUSIONS Levels of theoretical knowledge and clinical practice skills during medical intern training in cardiovascular imaging based on BT using the CRNP teaching technology improved theoretical knowledge and practical skills.

Objective To investigate the clinical value of multi-slice spiral CT(MSCT) in the diagnosis of mild digestive tract hemorrhage. Methods Thirty-five patients with mild gastrointestinal hemorrhage were examined by enhanced MSCT.CT signs were observed and compared with pathologic examination findings.Results Diseases in these 35 patients included gastric and duodenal ulcer and inflammation(n=4,11.4%),esophagogastric variceal rupture(n=7,20.0%),gastric carcinoma(n=3,8.6%),gastric stromal tumor(n=3,8.6%),gastric polyp(n=1,2.9%),colonic malignancy(n=5,14.2%),small intestinal stromal tumor(n=6,17.1%),rectal cancer(n=2,5.7%),intestinal Crohn disease(n=3,8.6%),and jejunum diverticulum combined with hemorrhage(n=1,2.9%).All of them were diagnosed by endoscopy of the digestive tract and confirmed by operation and pathology.The accuracy rate of CT was 100%.The coincidence rate of CT diagnosis was 97.1%.Conclusion MSCT is a promising technique in the localization,qualitative diagnosis,and clinical treatment of mild gastrointestinal hemorrhage.

The first concise synthesis of the bidesmosidic oleanolic acid saponins 1–3 isolated from Fadogia ancylantha (Makoni tea) have been accomplished through a ‘one-pot sequential glycosylation’ strategy with two glycosyl 1-(trichloroacetimidate)s as glycosyl donors. The synthesized natural products 1–3 were then evaluated for their inhibitory activities against α-glucosidase, α-amylase, and lipase. Among the assayed compounds 1–3, compound 1 showed strong α-glucosidase and α-amylase inhibition, with IC50 values of 160 and 180 μM, respectively. Moreover, compounds 2 and 3 showed strong inhibition against α-glucosidase and lipase, with the respective IC50 values of 170 and 190 μM, and 190 and 200 μM.

Sixteen naturally occurring oleanolic acid saponins and their derivatives were synthesized in an efficient and practical strategy, and their inhibitory activities against α-glucosidase and α-amylase were evaluated in vitro. Among all the compounds, 28-O-monoglucoside 8 exhibited remarkably potent inhibitory activity against α-glucosidase with an IC50 value of 87.3 µM, which was fivefold stronger than that of the antidiabetic acarbose. Based on the preliminary structure-activity relationships, for 28-O-monoglucosides, the presence of a terminal α-l-rhamnopyranosyl residue enhanced the α-glucosidase and α-amylase inhibitory activities. Furthermore, for 3,28-O-bidesmosides, sugar-substituted moieties attached to the C-3 and C-28 positions of the oleanolic acid scaffold are helpful to increase the inhibitory activities against α-amylase and α-glucosidase.

Studying the reproductive attributes of pests is central to understanding their life cycle history and in crafting management strategies to regulate, if not bring down, their population below threshold levels. In this article, the morphology of the male reproductive tract, topology of the spermatozoa, and salient features of spermiogenesis in the Chinese white pine beetle, Dendroctonus armandi Tsai and Li was studied to provide baseline information for further pest management studies. Results showed that male reproductive tract of this species differs from those documented in other Coleopterans by having 20 testicular tubules in each testis and the presence of two types of accessory glands. The spermatozoon is seen having peculiar characteristics such as an "h"-shaped acrosomal vesicle with a "puff"-like expansion, one centriole, one large spongy body, and two accessory bodies. Despite with some morphological differences of the male reproductive organ, spermatogenesis in this organism is similar to other Coleopterans. Overall, detailed studies regarding the components of the primary male reproductive organ of this beetle species would expand the knowledge on the less-understood biology of Coleopteran pests and would help in designing regulatory measures to conserve endemic and indigenous pine trees in China.

We investigate squeezing of the resonance fluorescence of a laser-driven quantum dot (QD) close to a graphene sheet. The coupling between the QD and the surface plasmon around the graphene sheet is frequency dependent in the terahertz region, which can be adjusted by the laser intensity. Distinct decay rates in different transition channels of dressed QDs can be achieved due to the tailored photon reservoir, which can be used to improve the squeezing. It is found that increases in both the dephasing rate and the environmental temperature are harmful to the squeezing. Meanwhile, an enhancement in the QD-plasmon coupling strength may reduce the fragility of squeezing against the decoherence process. Additionally, in the strong light-matter coupling region, squeezing can be largely enhanced by tuning the strength of the pump field and its detuning from the QD.

The manipulation of the Goos–Hanchen (GH) shifts of the reflected and transmitted probe beams through a cavity containing ∆-configuration artificial or realistic atomic medium is investigated. Adjusting the coherent control fields of atomic medium, the electromagnetically induced transparency with amplification (EITA) can be yielded. When the frequency of probe beam is around EITA, the negative as well as positive GH shifts of the reflected and transmitted probe beams can be greatly enhanced by EITA. Meantime, the GH shift can be switched between the considerably large positive and negative values by adjusting the collective phase of the external fields.

The interference property of the fluorescence field from two nonidentical atoms driven by a laser field is investigated. It is found that there are differences for the intensity and the second-order correlation function between the two identical atoms system and the two nonidentical atoms system. It is shown that the intensity and the second-order correlation function have different behaviors under the weak laser field and the strong case for two identical atoms and two nonidentical atoms systems.

As a target of insect growth regulators, the ecdysone receptor complex binds ecdysone agonists to regulate gene transcription, development, and growth. To understand the response of Lymantria dispar to methoxyfenozide, we studied receptor complex transcription profiles following larval exposure to methoxyfenozide, and observed important variations amongst post-embryonic stages. After the exposure of 2nd and 3rd instar larvae to LC5 and LC20 methoxyfenozide for 72 h, the transcription levels of ecdysone receptor complex genes were mainly upregulated in 2nd instar larvae, but downregulated in 3rd instar larvae. These results provide expression characteristics of the ecdysone receptor complex in L. dispar larvae after methoxyfenozide exposure.

An exciton–photon interacting system in quantum well inside a microcavity coupled to a squeezed bath is considered. Using the method of characteristic function, we solve analytically the master equation under the consideration of different dissipations of the exciton and the cavity field. It is found that this system evolves in a mixed two-mode Gaussian state. The dynamical behavior of quantum properties of this system such as the purity of the exciton, the entanglement between the exciton and the cavity field, and the squeezing of the exciton and the cavity field are discussed in detail.

A scheme for generating two-mode photon-added SU(2) coherent state by means of conditional measurement is proposed. Feeding three uncorrelated Fock states into three input ports of two cascade placed lossless beam splitters respectively and counting photons in one of the output channels, the conditional state in the other two output channels is a two-mode photon-added SU(2) coherent state. The quantum nonlocality property for this state is investigated using parity measurement.

A series of 5,7-disubstituted chrysin, 7-monosubstituted chrysin, 5-monosubstituted chrysin derivatives were synthesized by alkylation, acetylation, benzoylation, carboxymethylation, and evaluated on their antitumor activity of H22 cells in the search for potential antitumor agents. Among them, compound 3 (5,7-diacetyl chrysin) displayed the most potent antitumor activity with IC50 value of 141 μM. Moreover, there is significant up-regulation of G2 in cell cycle of H22.

Colon carcinoma is a multistage disease. Most malignancies arise from pre-existing benign tumors. Multiple chromosomal defects affecting oncogene and tumor suppressor gene function are associated with disease progression. These aberrations result in an imbalance between the normal positive and negative growth effectors, which contribute further to disease progression. We have studied how changes in the expression of TGF alpha and TGF beta affect colon carcinoma cell behavior. Overexpression of the stimulatory factor TGF alpha in a relatively benign cell line with weak TGF alpha autocrine activity converted the cell type to an aggressive, progressed phenotype in vivo and in vitro. In contrast, disruption of TGF alpha expression by constitutive expression of TGF alpha antisense RNA in a progressed cell line with a strong, internalized autocrine loop resulted in the development of clones with decreased tumorigenicity in vitro and in vivo. Suppression of the inhibitory effects of TGF beta by constitutive expression of TGF beta antisense RNA increased the tumorigenicity of the cell lines in vitro and in vivo. None of these alterations in TGF alpha or TGF beta expression affected the doubling time of the cells. The changes in tumorigenicity were due to effects on the lag phase of growth. We conclude that TGF beta functions to maintain the cells in a quiescent state while TGF alpha drives reentry into the cell cycle. We have identified a unique cis-element that mediates TGF alpha autoregulation. The transcription factor binding this element is also involved in the cell-cycle regulation of TGF alpha expression. We hypothesize that this factor may be a convergent point TGF alpha and TGF beta interact in controlling movement into and out of quiescence.

Two different schemes are proposed for deterministically generating a pure motion-entangled state for two well-separated ions trapped in a cavity. The first one is that through adjusting the amplitudes and the frequencies of transverse lasers, the two ions trapped in a bimodal cavity can unconditionally evolve into a two-mode squeezed vacuum state with the aid of the cavity dissipation. The second one is based on the interactions of two appropriate series of the driving laser pulses with the two ions trapped in a single-mode cavity, it allows us to produce a two-mode squeezed vacuum state for the trapped ions' center-of-mass motion.

The dynamical behavior of the entanglement and the squeezing in the system of two ions trapped in a lossy optical cavity is discussed, in which the vibrational mode of the first ion is coupled to the cavity field via a linear-mixing interaction and the vibrational mode of the second ion is coupled to the cavity field via an effective parametric interaction, respectively. It is found that when the effective strength ${r}_{1}$ of the coupling between the first ion and the cavity field is stronger than the strength ${r}_{2}$ of the coupling between the second ion and the cavity field, the motional state of the two ions develops into a robust two-mode mixed Gaussian entangled state and the two-mode squeezing of phonons appears. But the entanglement between the cavity mode and the vibrational mode of the second ion can only happen periodically in a small time range. When ${r}_{1}l{r}_{2}$, only the entanglement between the two vibrational modes appears but the two-mode squeezing does not exist. And the entanglement between the cavity mode and the motional mode of the second ion can also take place in a small time range.

The time-dependent characteristic function for the vibrational quanta of two ions separately trapped in two cascaded optical cavities is obtained analytically beyond the bad cavity limit, in which the motional mode of the ion in the first cavity is coupled to the cavity field via an effective parametric interaction and that of the ion in the second cavity via a linear-mixing interaction as proposed by Peng and Parkins [Phys. Rev. A 65, 062323 (2002)]. It is found that the two ions develop in a two-mode mixed Gaussian entangled state if there exists a unidirectional coupling from the first cavity to the second one.

The dynamical behavior of entanglement for excitons in two quantum dots placed in two separately single-mode optical cavities driven by an external broadband two-mode squeezed vacuum is studied in the low exciton density regime. It is found that if the field in the two separate cavities is initially prepared in a pure two-mode squeezed vacuum state, the excitons in the two quantum dots can evolve into a pure entangled state only when the dissipation of the cavities and exciton modes is negligible. When the effect of the dissipation is included, the excitons will be in a two-mode Gaussian entangled mixed state whose properties are decided by the externally driven field and the initial field. The dependence of the entanglement property of the excitons in the two quantum dots on the squeezing properties of the fields in the two cavities is also discussed.

We investigate a hybrid quantum system combining cavity quantum electrodynamics and optomechanics, where a photon mode is coupled to a four-level tripod atom and to a mechanical mode via radiation pressure. We find that within the single-photon optomechanics and Lamb-Dicke limit, the presence of the tripod atom alters the optical properties of the cavity radiation field drastically, and gives rise to completely quantum destructive interference effects in the optical scattering. The heating rate can be dramatically suppressed via utilizing the completely destructive interference involving atom, photon and phonon, and the obtained result is analogous to that of the resolved sideband regime. The heating process is only connected to the scattering of cavity damping path, which is also far-off resonance. Meanwhile, the cooling rate assisted by the atomic transitions can be significantly enhanced, where the cooling process occurs through the cavity and atomic dissipation paths. Finally, the ground-state cooling of the movable mirror is achievable and even more robust to heating process and thermal noise.

When a trichromatic laser field is applied to a cavity optomechanical system within the single-photon strong-coupling regime, we find that the motion of mirror can evolve into a dark state such that the cavity field mode cannot absorb energy from the external field. Via tuning three components of the pumping field to be resonant to the carrier, red-sideband and blue-sideband transitions in the displaced representation respectively, the state of mirror motion can exhibit non-classical properties, such as that in the Lamb-Dicke limit, the state evolves into a squeezed coherent state, and beyond the limit, the state can become a squeezed non-Gaussian state.

Spectral and squeezing properties of the resonance fluorescence of two coupled quantum dots forming an effective Λ-type three-level structure and connected with two normal metal leads are studied. We assume that one of the dots is driven by a strong light field and find that by modulating the bias voltage and the dot-lead coupling strengths, the electron can be selectively trapped in one of the two dressed states produced by the light field. The trapped electron possesses large coherence, and the resulting unbalanced dressed-state populations can lead to a significant enhancement or suppression of the sidebands in the resonance fluorescence spectrum. Moreover, a wideband squeezing can be generated that may be significantly enhanced by modulating the gate voltage.