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Two new glucosidated indole-containing quinazoline alkaloids designated fumigatosides G (1) and H (2) were isolated from mangrove-derived fungus Aspergillus fumigatus SAl12, together with the known analogues fumigatoside B (3) and fumiquinazoline J (4). The planar structures of the new compounds were elucidated by HR-MS and NMR spectroscopic data analyses. The absolute configurations were determined by comparison of electronic circular dichroic (ECD) spectra with that of the known compound fumigatoside B and with the calculated ECD spectrum. All these indole-quinazoline compounds were tested for anti-bacterial and cytotoxic activities.

The first sodium borate-squarate, Na2(C4O4)(H3BO3)(H2O)4·H3BO3, with strong SHG response obtained by the synergy effect between two planar NLO-active motifs.

The outbreak and persistence of coronavirus disease 2019 (COVID-19) threaten human health. B cells play a vital role in fighting the infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite many studies on the immune responses in COVID-19 patients, it is still unclear how B cell receptor (BCR) constituents, including immunoglobulin heavy (IGHs) and light chains (IGLs), respond to SARS-CoV-2 in patients with varying symptoms. In this study, we conducted complementarity-determining region 3 (CDR3) sequencing of BCR IGHs and IGLs from the peripheral blood of COVID-19 patients and healthy donors. The results showed significantly reduced clonal diversity, more expanded clones, and longer CDR3 lengths of IGH and IGL in COVID-19 patients than those in healthy individuals. The IGLs had a much higher percentage of VJ skew usage (47.83% IGLV and 42.86% IGLJ were significantly regulated) than the IGHs (12.09% IGHV and 0% IGHJ) between the healthy individuals and patients, which indicated the importance of BCR light chains. Furthermore, we found a largely expanded

Purpose To use 18 F-FDG microPET dynamic imaging to preliminarily identify the changes of myocardial glucose metabolism corresponding to different functional phenotypes of diabetic cardiomyopathy (DCM) in mice and elucidate their relationships. Methods Left ventricular function was measured by echocardiography in C57BL/KsJ-db/db (db/db) mice and their controls at 8, 12, 16, and 20 weeks of age to divide DCM stages and functional phenotypes. Myocardial histopathology was used to verify the staging accuracy and list-mode microPET dynamic imaging was conducted. The myocardial metabolic rate of glucose (MRglu) and the glucose uptake rate constant (Ki) were derived via Patlak graphical analysis, and the differences in myocardial glucose metabolism levels in different DCM stages were compared. The key proteins involved in myocardial glucose metabolism signaling pathway were analyzed by Western blotting to elucidate the underlying mechanism of abnormal glucose metabolism in DCM. Results Compared with the controls, the ratio of early diastolic transmitral flow velocity to early diastolic mitral annular tissue velocity (E/e’) of db/db mice was significantly increased from the age of 12 weeks, while the left ventricular ejection fraction (LVEF) was significantly decreased from the age of 16 weeks (all P P P > 0.05). MRglu and SUV were moderately negatively correlated with the E/e’ ratio (r=-0.539 and − 0.512, P = 0.007 and 0.011), which were not significantly correlated with LVEF (P > 0.05). Meanwhile, Ki was not significantly correlated with LVEF or E/e’ ratio. The decreased expression of glucose transporter (GLUT) -4 in db/db mice preceded GLUT-1 and was accompanied by decreased phosphorylated AMP-activated protein kinase (p-AMPK) expression. Myocardial MRglu, Ki and SUV were significantly positively correlated with the expression of GLUT-4 (MRglu: r = 0.537; Ki: r = 0.818; SUV: r = 0.491; P = 0.000 ~ 0.046), but there was no significant correlation with GLUT-1 expression (P = 0.238 ~ 0.780). Conclusions During the progression of DCM, with the changes of left ventricular functional phenotype, abnormal and dynamic changes of myocardial glucose metabolism can occur in the early stage.

We herein report the first sodium borate-squarate, namely, Na

Reciprocity is a generic feature in various physical systems because it is directly associated to the symmetry of physical laws under time reversal. The breaking of the reciprocity is vitally important in numerous fields, such as the control of energy flux, imaging technologies and topological insulators. For instance, electrical diodes, as a typical nonreciprocal representative in electronic systems, have already contributed to substantial scientific revolutions in many aspects, including integrated circuits, lighting and signal indication. Motivated by the electrical diodes, thermal diodes exhibiting the rectifying effect on thermal energy are achieved in nonlinear lattices. Similarly, the nonreciprocity in photonic systems can be realized by many mechanisms, such as the nonlinearity of optical medium and the mode conversion. Synchronously, the concept of the nonreciprocity further extends to phononic systems. The main means to achieve acoustic nonreciprocity are based on the nonlinearity of acoustic material, dynamic element, and magnetoelastic interaction. However, the nonlinear approach introduces the inherently low conversion efficiency, the dynamic scheme has difficulty in application at high-speed modulation or on nanoscale, and the method based on magnetoelastic interaction has small bandwidth and high frequency, which have severe limitations for practical application of the nonreciprocity. From the perspectives of principles, history, and problems, this paper reviews in detail the progress of the nonreciprocity based on nonlinearity, dynamic components, and magnetoelastic interactions. Some existing problems with these methods were pointed out. For example, the nonreciprocal solution based on nonlinear media has low energy conversion efficiency, it is difficult to miniaturize the nonreciprocal device based on dynamic components because of itself complexity, and the bandwidth of nonreciprocity based on magnetoelastic interaction is narrow. Correspondingly, improvement of the energy conversion efficiency based on the nonlinear medium, more reasonable design of a dynamic modulation system, and widening broadband of nonreciprocity in the magnetoelastic system, can be researched in the future. For example, in order to reduce the nonreciprocal frequency of magnetoelastic system, it is worth studying the unidirectional transmission of sound waves in the magnetoelastic system under a dynamic magnetic field. For the sake of realizing a nonreciprocal system with no external power source and high conversion efficiency, the nonreciprocity of acoustic waves in a magnetoelastic system under a zero magnetic field may become a focus of future research. In addition, since each scheme has its advantages, the combined effects of multiple schemes may overcome the shortcomings of a single scheme and achieve more significant nonreciprocal effects. So far, the combined effects between nonlinearity and dynamic components have not received much attention. We expect that research of nonreciprocity will be extended to both nonlinear and spatiotemporally modulated systems in the future. The combined effects between nonreciprocity and magnetoelastic interaction may become an important content of future research. Finally, considering practical engineering application, there are still many aspects worthy of further study, such as the miniaturization of nonreciprocal devices, optimal design of nonreciprocity based on optimization theory, and adjustable nonreciprocity based on smart materials or structures. In short, the nonreciprocity of acoustic metamaterials is an important field of scientific research, which has potential applications, such as rectification, vibration and noise reduction, sensing, and bioimaging.

In recent years, urgent needs for counting crowds and vehicles have greatly promoted research of crowd counting and density estimation. Benefiting from the rapid development of deep learning, the counting performance has been greatly improved, and the application scenarios have been further expanded. Aiming to deeply understand the development status of crowd counting and density estimation, we introduce and analyze the typical methods in this field and especially focus on elaborating deep learning-based counting methods. We summarize the existing approaches into four categories, i.e., detection-based, regression-based, convolutional neural network based and video-based. Each category is explicated in great detail. To provide more concrete reference, we compare the performance of typical methods on the popular benchmarks. We further elaborate on the datasets and metrics for the crowd counting community and discuss the work of solving the problem of small-sample-based counting, dataset annotation methods and so on. Finally, we summarize various challenges facing crowd counting and their corresponding solutions and propose a set of development trends in the future.

Atherosclerosis (AS) is an essential pathological changes of ischemic cardio-cerebrovascular disease, and monocyte migration and adhesion to endothelial cells are the critical pathological process in AS. Our previous studies demonstrated a beneficial effect of zedoarondiol in AS, but whether the mechanism is associated with monocyte migration and adhesion to endothelial cells remains unclear. In this study, we investigated whether the anti-atherosclerotic effects of zedoarondiol were associated with decreasing migration and adhesion of monocytes. The oil red O staining demonstrated that zedoarondiol ameliorated AS plaques in en face aorta and aortic root of apolipoprotein E gene knocked (apoE

Objective The deficit of dopaminergic neurons in the nigrostriatal pathway is one of the pathological features of Parkinson's disease (PD). The decline of vesicular monoamine transporter type 2 (VMAT2) has been verified to relate with the severity of PD. The purpose of this study was to evaluate the ability of [18F]fluoropropyl-(+)-dihydrotetrabenazine ([18F]FP-(+)-DTBZ) to detect dopaminergic neuron dysfunction in a standard rat model of PD using PET imaging. Specifically, two different doses of 6-hydroxydopamine (6-OHDA) were injected unilaterally into the medial forebrain bundle (MFB) to create the models with two different severities. Methods Male Sprague-Dawley rats were intracranially injected with 8 μg 6-OHDA (partial lesion group), 16 μg 6-OHDA (full lesion group) and vehicle (sham group) into MFB, respectively. Thirty minutes static [18F]FP-(+)-DTBZ microPET scanning was performed to determine the dopaminergic neuron integrity on the 28th day post-injection and the behavioral tests were carried out in the next two days. Then, the rats were decapitated, and the brains were collected for biogenic amines content analysis or dissected for autoradiography and immunohistochemical (IHC) staining. The correlations of PET results to the behavioral, biological, histological, autoradiography results were analyzed, respectively. Results The standardized uptake value ratio (ST to CB) of [18F]FP-(+)-DTBZ in the ipsilateral striata decreased significantly in partial lesion group and full lesion group. Compared with the sham group, the ratio of the standardized uptake value in ipsilateral striatum to that in contralateral striatum decreased by 57.09 ± 2.30% (full lesion group) and 25.31 ± 5.70% (partial lesion group), respectively. The dopaminergic neuronal dysfunction was corroborated by in vitro autoradiography, IHC, and quantitative analysis of DA as well as its metabolites concentration tests. The motor function impairments of 6-OHDA-treated animals were manifested by a series of behavioral tests. The results of microPET imaging were linearly correlated with behavioral, biological, histological, and autoradiography results, respectively. Conclusion Our data suggest that [18F]FP-(+)-DTBZ may be useful for detecting different degrees of dopaminergic neuronal lesions by PET imaging in PD models induced by 6-OHDA.

In recent years, applications of face recognition have increased significantly. Despite the successful application of deep convolutional neural network (DCNN), training such networks is still a challenging task that needs a lot of experience and carefully tuning. Based on the Inception-ResNet network, we propose a novel method to mitigate the difficulty of training such deep convolutional neural network and improve its performance simultaneously. The residual scaling factor used in the Inception-ResNet module is a manually set fixed value. We believe that changing the value to a trainable parameter and initializing it to a small value can improve the stability of the model training. We further adopted a small trick of alternating the ReLU activation function with the Leaky ReLU and PReLU. The proposed model slightly increased the number of training parameters but improved training stability and performance significantly. Extensive experiments are conducted on VGGFace2, MS1MV2, IJBB and LFW datasets. The results show that the proposed trainable residual scaling factor (TRSF) and PReLU can promote the accuracy notably while stabilizing training process.

Two new spirotetronate natural products, lobophorin L (1) and lobophorin M (2), together with three known lobophorin-like spirotetronate antibiotics (3–5) and two known ansamycins (6–7), were isolated from the marine-derived Streptomyces sp. 4506. The structures of 1 and 2 were established on the basis of HRESIMS as well as 1D and 2D NMR datasets. Antibacterial assay showed that, compounds 1 and 3–5 exhibited strong to moderate antibacterial activities against Micrococcus luteus and Bacillus thuringiensis with MIC values ranging from 0.0625 to 8 μg/mL, while compounds 3 and 6 showed weak antibacterial activities against Staphylococcus aureus and MRSA. The antibacterial activities of the lobophorins in this study indicated that the more substitution number of the sugar moieties at C-9 of the lobophorin, the stronger antimicrobial properties it may deserve, and the higher the oxidation degree of substituent group at C-3D, the better antibacterial activities of its corresponding compound could be.

Glioblastoma multiforme (GBM) is the most malignant form of glioma, and the overall survival time of patients with GBM is usually less than 14 months. Therefore, it is urgent to find new and effective medicine for GBM. Recently, marine natural products have been shown to exhibit strong inhibitory effects on cancer cells, providing a new avenue for exploring novel drugs for GBM treatment. In this study, we investigated the inhibitory effect of the Grincamycin (GCN) B-F, newly isolated from marine-derived Streptomyces Lusitanus SCSIO LR32, on GBM cells, and evaluated the mechanism of GCN B on GBM. The results, for the first time, showed that GCN B acted as a potent inhibitor to suppress growth and invasion of two human GBM cell lines U251 and 091214 in vitro. In addition, GCN B could effectively target GSCs in GBM evidenced by attenuated formation of tumor spheres and decrease of several markers of GSCs. Furthermore, we performed gene expression microarray followed by Signal-Net analysis. The result revealed that RHOA and PI3K/AKT axis played critical roles for a GCN B-mediated inhibitory effect on GSCs. Altogether, our findings highlighted GCN B as a promising inhibitor for GSCs via targeting RHOA and PI3K/AKT.

Face detection is one of the important tasks of object detection. Typically detection is the first stage of pattern recognition and identity authentication. In recent years, deep learning-based algorithms in object detection have grown rapidly. These algorithms can be generally divided into two categories, i.e., two-stage detector like Faster R-CNN and one-stage detector like YOLO. Although YOLO and its varieties are not so good as two-stage detectors in terms of accuracy, they outperform the counterparts by a large margin in speed. YOLO performs well when facing normal size objects, but is incapable of detecting small objects. The accuracy decreases notably when dealing with objects that have large-scale changing like faces. Aimed to solve the detection problem of varying face scales, we propose a face detector named YOLO-face based on YOLOv3 to improve the performance for face detection. The present approach includes using anchor boxes more appropriate for face detection and a more precise regression loss function. The improved detector significantly increased accuracy while remaining fast detection speed. Experiments on the WIDER FACE and the FDDB datasets show that our improved algorithm outperforms YOLO and its varieties.

In this paper, the transient turbulent cavitating flow around a marine propeller behind a ship was investigated experimentally with emphasis on how vortex generator (VG) influences propeller cavitation and hull pressure fluctuations. The experiments were carried out in China Large Cavitation Channel with the closed test section covering 10.5 m in length and cross-section of 2.2 m2 ϗ 2.0 m2. The experiment recorded instantaneous cavitation photos of the propeller and pressure fluctuations on the hull surface. The results demonstrate that without vortex generator, the sheet cavitation inception begins at −50° (310°), and then from −50° (310°) to 30°, the extent and area of sheet cavitation increase. When vortex generator installed on the hull, the sheet cavitation inception occurs in advance at −60° (300°), and the sheet cavitation expands to larger rotation range due to the vortex generator. It is shown that the vortex generator with proper geometry and installed location may contribute the highly nonuniform wake to be more uniform, and can make the change of propeller cavitation to be milder, which decrease the pressure fluctuations in this study. Further analysis indicates that the vortex generator may promote the energy distribution to be more uniform in physical and spectral space in some degree.

Platelet-derived exosomes (PLT-Exos) are the main subtype of extracellular vesicles secreted by platelets, which carry proteins, nucleotides, lipids, and other substances to acceptor cells, playing an important role in intercellular communication. PLT-Exos increase with platelet activation and are involved in the process of atherothrombosis by delivering cargo to acceptor cells. Atherosclerotic plaque rupture, causing thrombosis and arterial occlusion, is the basic pathological change leading to cardiovascular events. PLT-Exos from different donors have different functions. PLT-Exos secreted by healthy volunteer or mice can inhibit platelet activation and inflammation of endothelial cells, thus exerting an antithrombotic effect, while PLT-Exos derived from some patients induce endothelial apoptosis and an inflammatory response to promote atherothrombosis. Furthermore, increased PLT-Exos reflect platelet activation and their cargoes also are derived from platelets; therefore, PLT-Exos can also be used as a biomarkers for the diagnosis and prognosis of cardiovascular disease. This article reviews the characteristics of PLT-Exos and discusses their role in cell-to-cell communication and atherothrombosis.

Two new phthalide derivatives (1-2) and four known phthalide compounds (3-6) were purified from the culture of a mangrove endophytic fungus Pestalotiopsis sp. SAS4. Their chemical structures were established by analyses of 1D and 2D nuclear magnetic resonance (NMR) and high resolution mass spectrometry (HR-MS) spectroscopic data. All of these compounds were evaluated in vitro for antibacterial, cytotoxicity, and resistance to hypoxic-ischemic injury activities.

Human leukocyte antigen (HLA) polymorphism is hypothesized to be associated with diverse immune responses toward infectious diseases. Herein, by comparing against multiple subpopulation groups as control, we confirmed that HLA-B*15:27 and HLA-DRB1*04:06 were associated with coronavirus disease 2019 susceptibility in China. Both alleles were predicted to have weak binding affinities toward viral proteins.

The first commercial interface for hyphenating liquid chromatography with isotope ratio mass spectrometry (LC-IRMS) was not available until 2004, and it was commercialized under the name LC IsoLink by Thermo Finnigan. LC-IRMS, a method of compound-specific isotope analysis, has enabled the detection of stable carbon isotope ratios (

Topological elastic metamaterials have emerged as a new frontier in the quest of topological phases in condensed matter physics. Their exotic topological properties open a wealth of promising engineering-oriented applications that are difficult to realize with traditional elastic metamaterials, such as robust and defect insensitive waveguiding, signal sensing, and splitting. In this review, we retrospectively examine the underlying physical concept of topologically ordered states of elastic waves, starting from the one-dimensional (1D) example based on the Su–Schrieffer–Heeger (SSH) model. We then move on to two-dimensional (2D) topological metamaterials, discussing elastic analogues of quantum Hall, pseudospin-Hall, valley-Hall phases. Finally, we survey the latest developments in the field including three-dimensional (3D) elastic topological phases and higher-order topological insulators (TIs). Altogether, this paper provides a comprehensive overview of the flourishing research frontier on topological elastic metamaterials, and highlights prominent future directions in this field.

Four new hydroxamate-containing natural product cyclopeptides designated acremonpeptides A-D (1-4), together with Al(III)-acremonpeptide D (5) were obtained from the marine fungus Acremonium persicinum SCSIO 115. The planar structures of 1-5 were established on the basis of HRMS as well as 1D and 2D NMR data sets. Moreover, the amino acid absolute configurations were determined using Marfey's method. Compounds 1-5 all feature three 2-amino-5-(N-hydroxyacetamido)pentanoic acid (N5-hydroxy-N5-acetyl-l-ornithine) metal ion chelating moieties. Beyond their discovery and structure elucidation, in vitro bioassays revealed acremonpeptides A (1), B (2), and Al(III)-acremonpeptide D (5) as moderate antiviral agents for herpes simplex virus 1 with EC50 values of 16, 8.7, and 14 μM, respectively.

The topological transport of Lamb wave in phononic crystal slabs provides a great potential in reinforcing nondestructive testing, high sensitivity sensing, and information processing. In this paper, the authors investigate the pseudospins edge states of fundamental antisymmetric Lamb waves in a snowflakelike phononic slab. Significantly, the fourfold Dirac degeneracy for antisymmetric Lamb mode is accidentally formed at the Γ point with the critical angle of the snowflakelike holes, which does not require the folding of the lattices. Meanwhile, based on the rotating-scatterer mechanism, the mirror symmetry is broken and the topological multipole phase transitions are well induced during the gradual change of the scattering strength among the scatterers with the rotation angle. The topologically protected edge states and its unidirectional robust propagation are further demonstrated. The proposed topological phononic slabs will be a more hopeful option to apply in engineering practices.

The remarkable properties of topological insulators have inspired numerous studies on topological transport for bulk waves, but the demonstrations of topological edge states with tunable frequency are few attempts. Here, we report on the active frequency tunability of topologically protected edge states for in-plane bulk waves by applying a thermal field. We find that the center frequency of topological band gap is shifted down and the band width is enlarged as the temperature increases. Meanwhile, the frequency range of topologically protected edge states is also shifted to low frequency region with the higher temperature. Furthermore, the robust propagation of in-plane bulk waves along a desired path is demonstrated within different frequency bands. The tunable frequency for both topological band gaps and topologically protected edge states achieves the active control of the transport for in-plane bulk waves, which may dramatically facilitate practical applications of novel phononic devices.

Although photothermal therapy (PTT) has been extensively applied in the treatment of cancer using various types of nanomaterials, low penetration of excitation light, low nanoparticle concentration enrichment and abominable nanoparticle permeation still remain huge obstacles in cancer therapy. Herein, we synthesized stable cupric sulfide nanoparticles (CuS NPs) with small size, which after functionalization with a MnO2 coating, were employed for diagnosing and treating tumors. After reacting with an RGD peptide, the nanoparticles were able to target and focus on tumor sites. Once the nanoparticles were enriched in tumors by RGD targeting, the MnO2 coating decomposed to Mn2+ ions in the tumor microenvironment. Meanwhile, the decomposition of MnO2 allowed the dispersion of aggregated CuS NPs to enter deep tumors, and a 1064 nm laser with powerful penetration was utilized to activate CuS NPs in deep tumors for PTT. More importantly, the generated Mn2+ ions were used for stimuli-enhanced T1-weighted magnetic resonance imaging (T1-MRI) and agminated CuS NPs in tumors were accepted for computed tomography (CT) imaging. It was found that these nanocomposites can accurately indicate tumor sites after being intravenously injected, and in vitro and in vivo experiments illustrated the tremendous potential of these nanoplatforms for use in imaging-guided PTT against HepG2 tumors.

To determine factors associated with delayed discharge of hospitalized patients with coronavirus disease (COVID-19). This retrospective cohort study included 47 patients with COVID-19 admitted to three hospitals in Quanzhou City, Fujian Province, China, between January 21, 2020 and March 6, 2020. Univariate and multivariate logistic regression analyses were conducted to identify factors associated with delayed discharge. The median length of hospital stay was 22 days. Patients in the delayed discharge group (length of hospital stay ≥ 21 days, n = 27) were more likely to have diarrhea, anorexia, decreased white blood cell counts, increased complement C3 and C-reactive protein levels, air bronchograms, undergo thymalfasin treatment, and take significantly longer to convert to a severe acute respiratory syndrome coronavirus (SARS-CoV-2) RNA-negative status than those in the control group (length of hospital stay, P = 0.01) and complement C3 levels (OR 1.14 95% CI 1.02–1.27, P = 0.03) were the only risk factors independently associated with delayed discharge from the hospital. Dynamic monitoring of complement C3 and SARS-CoV-2 RNA levels is useful for predicting delayed discharge of patients.

Additional file 1: Correlation test between various diagnostic indicators and adverse outcomes. Relationship between 24 h urine protein cutoff value based on ROC curve and pregnant outcomes. Fig1. 24 h proteinuria cutoff value to determing hypoproteinemia. Fig2. 24 h proteinuria cutoff value to determine adverse outcomes.

Beauvericin (BEA), a cyclic hexadepsipeptide mycotoxin, is a potent inhibitor of the acyl-CoA: cholesterol acyltransferase enzyme 1 (ACAT1), involved in multiple tumor-correlated pathways. However, the binding mechanisms between BEA and ACAT1 were not elucidated.BEA was purified from a mangrove entophytic Fusarium sp. KL11. Single-crystal X-ray diffraction was used to determine the structure of BEA. Wound healing assays of BEA against KB cell line and MDA-MB-231 cell line were evaluated. Inhibitory potency of BEA against ACAT1 was determined by ELISA assays. Molecular docking was carried out to illuminate the bonding mechanism between BEA and ACAT1.The structure of BEA was confirmed by X-ray diffraction, indicating a monoclinic crystal system with P21 space group (α = 90°, β = 92.2216(9)°, γ= 90°). BEA displayed migration-inhibitory activities against KB cells and MDA-MB-231 cells In Vitro. ELISA assays revealed that the protein expression level of ACAT1 in KB cells was significantly decreased after BEA treatment (P ＜0.05). Molecular docking demonstrated that BEA formed hydrogen bond with His425 and pi-pi staking with Tyr429 in ACAT1.BEA sufficiently inhibited the proliferation and migration of KB cells and MDA-MB-231 cells by downregulating ACAT1 expression. In addition, BEA potentially possessed a strong binding affinity with ACAT1. BEA may serve as a potential lead compound for the development of a new ACAT1-targeted anticancer drug.

Two new spirotetronate natural products, lobophorin L (

Reciprocity is a fundamental property of wave propagation in linear time-invariant media. However, it is substantially harder to break reciprocity for elastic waves in a linear elastic system with the help of a magnetostatic field, since elastic waves are spinless in nature. Here, we realize nonreciprocal elastic waves in one-dimensional linear magnetoelastic phononic crystal slabs by an external magnetostatic field. The asymmetric dispersion of spin waves, which is induced by the simultaneous breaking of the time-reversal and spatial-inversion symmetries, results in an efficient elastic wave diode effect in a periodic system due to magnetoelastic interactions. Remarkably, a bidirectional nonreciprocity of elastic waves is achieved based on the folding-back effect of the periodic structure. Our proposed scheme opens up avenues for the design of nonreciprocal devices, such as on-chip tunable diodes, rectifiers, and topological insulators.

The deficit of dopaminergic neurons in the nigrostriatal pathway is one of the pathological features of Parkinson's disease (PD). The decline of vesicular monoamine transporter type 2 (VMAT2) has been verified to relate with the severity of PD. The purpose of this study was to evaluate the ability of [Male Sprague-Dawley rats were intracranially injected with 8 μg 6-OHDA (partial lesion group), 16 μg 6-OHDA (full lesion group) and vehicle (sham group) into MFB, respectively. Thirty minutes static [The standardized uptake value ratio (ST to CB) of [Our data suggest that [

Zero-angle refraction of elastic waves in metamaterials has attracted attention for its extraordinary wave collimation properties. However, earlier implementations relied on the specific flat equifrequency curve of the phononic crystals suffer from a narrow range of incident angles or operating bandwidths, which severely hinders the exploration and design of functional devices. Here, we propose an elastic near-zero refractive index metamaterial of a triangular lattice to realize topological zero refraction with arbitrary angles of incidence and wide working frequency range. Topological robustness of the zero-angle refraction of pseudospin-Hall edge state against defects is experimentally demonstrated. Furthermore, tunable wave mode conversion associated with the zero-angle refraction is revealed and discussed. These results provide a paradigm for the simultaneous control of the refraction properties of longitudinal and transverse waves that can be employed for designing the topological elastic antennas and elastic wave collimator. Topological acoustic systems exhibit exotic properties including zero refraction, but typically only in a small region of frequency space. In this work, a zero-index acoustic metamaterial is proposed and fabricated functioning over a wide frequency regime in the presence of lattice defects.

Therapeutic agents that target both tumor cell and vascular endothelial cell may achieve additional anti-tumor efficacy, particularly in lung cancer due to the critical roles of angiogenesis during lung cancer progression and metastasis. In this work, we showed that pitavastatin, a novel cholesterol-lowering drug, potently inhibited lung cancer cells and angiogenesis. This was achieved by the induction of apoptosis and inhibition of proliferation of lung cancer cells and human lung tumor-associated endothelial cell. Pitavastatin was not only effective to chemo-sensitive but also chemo-resistant lung cancer cells. This was also consistent with the finding that pitavastatin significantly enhanced cisplatin's efficacy in lung cancer xenograft model without causing toxicity in mice. We further showed that pitavastatin inhibited lung tumor angiogenesis in vitro and in vivo through suppressing human lung tumor-associated endothelial cell migration and morphogenesis without affecting adhesion. Mechanistically, we showed that pitavastatin acted on lung cancer cells and human lung tumor-associated endothelial cell through suppressing prenylation-dependent Ras/Raf/MEK and PI3K/Akt/mTOR signaling. Our work is the first to demonstrate the inhibitory effects of pitavastatin on Ras-mediated signaling. Our findings provide pre-clinical evidence to repurpose pitavastatin for the treatment of lung cancer.

Purine nucleoside-based antibiotics are a group of natural products or their derivatives displaying remarkable chemical and biological diversity. Their structural similarity to nucleosides and nucleotides involved in primary metabolism endows purine nucleoside antibiotics with unique biochemical properties and capabilities; accordingly, these natural products can often be extremely influential to the internal workings of living organisms. Not surprisingly, significant effort has been directed to developing purine nucleosides natural products and derivatives as drugs. Indeed, a number of such compounds have seen clinical use for many years. Recent advances in modern biotechnology, especially genomics, metabolomics and related “omics” technologies, have enabled us to significantly expand our understanding of the microbial biosynthetic pathways that afford purine nucleoside antibiotics. In this chapter, we survey recent efforts to characterize, understand and exploit the biosynthetic gene clusters associated with the production of these medicinally important natural products. We then briefly summarize the pharmacological applications and biological activities of the purine nucleosides. In total, we present in this chapter a glimpse of the exciting biology and medicinal chemistry displayed by these important secondary metabolites.