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Background: Dayuan Yin (DYY) is a classical formula used for treating plague, known for anti-inflammatory and antioxidant effects. It has shown potential in alleviating acute lung injury (ALI), though its mechanisms remain unclear. This study aimed to investigate the effects and mechanisms of DYY in treating ALI. Methods: Network pharmacology and molecular docking techniques were used to elucidate the potential targets and mechanisms of DYY in treating ALI. Subsequently, in vivo experiment was performed to verify the findings from bioinformatics analysis. λ-Carrageenan (λ-Car) was used to establish the ALI model. At 1 h before 2% λ-Car injection, 3 g/kg or 9 g/kg DYY were administered orally. 4 h after λ-Car-induced injury, the efficacy of DYY in treating ALI was assessed using several methods, including Wright-Giemsa staining to examine inflammatory cells in mouse pleural exudates, hematoxylin and eosin staining of lung tissues, and serum cytokine levels, cytokine mRNA levels in lung tissues, key protein levels were detected. Results: Network pharmacology and molecular docking analyses suggested that signal transducer and activator of transcription 3 (STAT3), interleukin-6, and tumor necrosis factor alpha might be the key regulated proteins, while the nuclear factor kappa-B (NF-κB) pathway could be the pathway involved. In vivo, the lung injury score of mice decreased to 0.78 from 3.44 after treating 9 g/kg DYY. Compared with the λ-Car group, the number of inflammatory cells in the DYY groups were decreased by 63 - 73% in pleural effusion. Further analysis showed that DYY could reduce the release of inflammatory cytokines, inhibit the activation of NF-κB signaling pathway, and downregulate the expression of p-janus kinase 2 (JAK2), p-STAT3, and matrix metalloproteinase-9 (MMP-9), thereby protecting against ALI. Conclusion: The study revealed remarkable potential of DYY in alleviating λ-Car-induced ALI through inhibiting the JAK2/STAT3/MMP-9 and NF-κB signaling pathways.

Raw data simulation is very important for system parameter design, performance evaluation, and route planning of bistatic synthetic aperture radar (SAR). However, most conventional simulation methods focus on improving the efficiency of echo simulation, without considering the impact of terrain fluctuations, resulting in insufficient fidelity of simulated echoes. In this article, a raw data simulation framework under undulating terrain for bistatic SAR with arbitrary configuration is proposed. In the framework, based on the prior information of digital elevation model of undulating terrain and the small facet theory, the time-variant scattering coefficient is computed first with the empirical formula related with the angle variation of transmitter and receiver for bistatic SAR. Then the shadow is judged from the perspectives of transmitter and receiver, respectively, and the formation of double shadow is discussed. At last, the above process was embedded into the time domain pulse by the pulse echo simulation algorithm, forming a framework for simulating bistatic SAR raw data under undulating terrain with arbitrary configuration, and the simulated and measured data experiments are illustrated to verify the effectiveness of the proposed framework.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases with limited treatment options. Moreover, its prevalence is doubled in type 2 diabetes mellitus (T2DM). Kaempferol (KAP) is a flavonoid compound that has been suggested to have beneficial effects on NAFLD, but studies on the mechanism are lacking, especially in the diabetic state. Herein, we investigated the effect of KAP on NAFLD associated with T2DM and its underlying mechanism in vitro and in vivo. The results of in vitro studies indicated that KAP treatment (10−8–10−6 M) significantly reduced lipid accumulation in oleic acid-induced HepG2 cells. Moreover, in the T2DM animal model of db/db mice, we confirmed that KAP (50 mg/kg) significantly reduced lipid accumulation and improved liver injury. Mechanistic studies in vitro and in vivo showed that Sirtuin 1 (Sirt1)/AMP-activated protein kinase (AMPK) signal was involved in KAP regulation of hepatic lipid accumulation. KAP treatment activated Sirt1 and AMPK, upregulated the levels of fatty acid oxidation-related protein proliferator activated receptor gamma coactivator 1α (PGC1α); and downregulated lipid synthesis-related proteins, including acetyl-coA carboxylase (ACC), fatty acid synthase (FASN), and sterol regulatory element-binding protein 1 (SREBP1). Furthermore, the curative effect of KAP on lipid accumulation was abolished by siRNA-mediated knockdown of either Sirt1 or AMPK. Collectively, these findings suggest that KAP may be a potential therapeutic agent for NAFLD associated with T2DM by regulating hepatic lipid accumulation through activation of Sirt1/AMPK signaling.

Background: Cerebral ischemia is one of the leading causes of neurological deficit, dementia, and disability globally. Salvianolic acids for injection (SAFI), a multi-component drug derived from Salvia miltiorrhiza L., has been clinically used in China to treat ischemic stroke. Purpose: This study was designed to investigate the mechanisms of SAFI in alleviating cerebral ischemia-induced neurodegeneration, especially its regulatory effects on excessive ER stress. Basic procedures: The rat acute cerebral ischemic injury model was established by a 1.5 h occlusion of the middle cerebral artery followed by 24 h of reperfusion. The neurological deficits, neurobehavior, cerebral infarct volume and edema of rats were examined. Hematoxylin and eosin staining, transmission electron microscopy analysis and TUNEL staining were performed to study the brain injury and cell apoptosis. Western blot and immunofluorescence assay were carried out to study the effects and mechanism of SAFI on ischemic injury. Main findings: Results showed that SAFI significantly inhibited the acute neurodegeneration, reduced brain infarct volumes and decreased brain water content of rats. SAFI also downregulated the relative protein levels of Bax/Bcl-2, Bim, Caspase-12, and reduced the number of TUNEL-positive cells in brain tissue, indicating the anti-apoptotic effects of SAFI. Both of immunofluorescence assay and western blot results showed that SAFI downregulated the expression of endoplasmic reticulum (ER) stress maker GRP78. SAFI dramatically inhibited the ER stress-related PERK/eIF2α/ATF4/CHOP and IRE1α/TRAF2/ASK1/JNK signaling pathways. SAFI also alleviated NF-κB triggered inflammatory response, and inhibited the production of IL-6 and IL-β. Conclusions: Our studies indicated that inhibition of excessive ER stress contributes to the protective effects of SAFI against cerebral ischemia-induced neurodegeneration and neuroinflammation.

The propagation attenuation of surface plasmon polaritons (SPPs) has an important impact on the performance of plasmonic devices, so measuring their propagation length is important for designing plasmonic devices. Here we propose a method using a single nanoslit surrounded on both sides by surface gratings to measure the propagation length of SPPs. In this method, the propagation length of SPPs is obtained by using a narrow-area statistical averaging method to process the data of the intensity ratio of two diffracted light waves, which are converted from two SPPs that have the same initial intensity but travel different distances in opposite directions in a narrow area of a surface of a metal film. We demonstrate experimentally that at the illumination wavelength of 632.8 nm, the mean value of the propagation length of SPPs propagating at the interface between the air and a gold film with a thickness of about 360 nm measured using the proposed method is 9.88 μm, with a standard deviation of 0.23 μm (i.e., 2.33 % of the mean value). In addition, we demonstrate experimentally that the measurement error of the proposed method in measuring the intensity ratio of the two diffracted light waves, which is the dominant error of the proposed method in measuring the propagation length of SPPs, can be smaller than 2 % of its theoretical value.

Abstract Mangiferin is a compound with many pharmacological activities and exists in many natural products. Anhydrous and hydrate of mangiferin have been reported separately in two literatures, but the polymorphism of this compound has not been realized until this paper. In this study, polymorph screening of mangiferin has been carried out and five forms have been obtained including three new forms never reported. Several solid state characterization methods, such as powder X-ray diffraction, differential scanning calorimetry and thermogravimetry, are used to identify and characterize all of mangiferin forms. The comparison of the crystallographic data and hirshfeld surface analysis were first reported for mangiferin anhydrous and hydrate. Furthermore, the studies on stability, transformation and solubility have been undertaken, the results prompt that form V can be used as the dominant polymorph for the development of innovative pharmaceuticals. Graphic Abstract

Salvianolic acid A (SalA) is an effective compound extracted from traditional Chinese medicine Salvia miltiorrhiza Bunge. The Forkhead box O3a (FOXO3a) signaling pathway plays crucial roles in the modulation of ischemia-induced cell apoptosis. However, no information about the regulatory effect of SalA on FoxO3a is available. To explore the anti-cerebral ischemia effect and clarify the therapeutic mechanism of SalA, SH-SY5Y cells and Sprague–Dawley rats were applied, which were exposed to oxygen glucose deprivation/reoxygenation (OGD/R) and middle cerebral artery occlusion/reperfusion (MCAO/R) injuries, respectively. The involved pathway was identified using the specific inhibitor LY294002. Results showed that SalA concentration-dependently inhibited OGD/R injury triggered cell viability loss. SalA reduced cerebral infarction, lowered brain edema, improved neurological function, and inhibited neuron apoptosis in MCAO/R rats, which were attenuated by the treatment of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) specific inhibitor LY294002. SalA time- and concentration-dependently upregulated the phosphorylation levels of protein kinase B (AKT) and its downstream protein FOXO3a. Moreover, the nuclear translocation of FOXO3a was inhibited by SalA both in vivo and in vitro, which was also reversed by LY294002. The above results indicated that SalA fought against ischemia/reperfusion damage at least partially via the AKT/FOXO3a/BIM pathway. KEY WORDS: Salvianolic acid A, Ischemia reperfusion, FOXO3a, BIM, Neuroprotection

Recently, compressive sensing (CS) has been applied in synthetic aperture radar (SAR) imaging, which is increasingly in the focus of study and shows great potential. In CS-based SAR imaging, motion errors of the moving platform introduce inaccuracies in the observation model, which cause various degradations in the final images. To accomplish accurate motion compensation during CS-based SAR imaging, we propose a fast CS-based SAR imaging integrated with motion compensation method. First, CS-based imaging based on the utilization of inverse observation deduced from the inversion of conventional imaging procedures is applied, which is much more computational efficient than the exact observation model. Then, an improved inverse observation model integrated with motion compensation is derived. In the improved model, spatially variant azimuth phase errors are taken into consideration. Joint SAR imaging and motion compensation are formulated as a sparse recovery problem and solved in an iterative way, wherein each iteration both image formation and motion compensation are carried out. The processing of SAR data shows that the proposed method can obtain better focused images compared with the existing SAR imaging and motion compensation methods.

Puerarin is an isoflavonoid extracted from Pueraria lobate with extensive pharmacological effects in traditional Chinese medicine. The evidence implicates that puerarin mitigates hyperglycemia and various relevant complications. Here, the effect of puerarin on skeletal muscle wasting induced by type 1 diabetes (T1D) was explored. Streptozotocin (STZ)-induced T1D male Sprague Dawley (SD) rats were used in this study. Muscle strength, weight and size were measured. L6 rat skeletal muscle cells were applied for in vitro study. Our results showed that eight-week oral puerarin administration (100 mg/kg) increased muscle strengths and weights accompanied by enhanced skeletal muscle cross-sectional areas in diabetic rats. Simultaneously, puerarin also reduced expressions of several muscle wasting marker genes including F-box only protein 32 (Atrogin-1) and muscle-specific RING-finger 1 (Murf-1) in diabetic group both in vitro and in vivo. Transformation from type I fibers (slow muscle) to type II fibers (fast muscle) were also observed under puerarin administration in diabetic rats. Puerarin promoted Akt/mTOR while inhibited LC3/p62 signaling pathway in skeletal muscle cells. In conclusion, our study showed that puerarin mitigated skeletal muscle wasting in T1D rats and closely related with Akt/mTOR activation and autophagy inhibition. Whether this effect in murine applies to humans remains to be determined.

Drug combinations have been the hotspot of the pharmaceutical industry, but the promising applications are limited by the unmet solubility and low bioavailability. In this work, novel cocrystals, consisting of two antithrombotic drugs with poor solubility and low bioavailability in vivo, namely, apixaban (Apx) and quercetin (Que), were developed to discover a potential method to improve the poor solubility and internal absorption of the drug combination. Compared with Apx, the dissolution behavior of Apx–Que (1:1) and Apx–Que–2ACN (1:1:2) was enhanced significantly, while the physical mixture of the chemicals failed to exhibit the advantages. The dissolution improvements of Apx–Que–2ACN could be explained by the fact that the solid dispersion-like structure and column-shaped cage of Que accelerated the access of the solvent to the inner layer of Apx. The fracture of the hydrogen bonds of Apx, which was the joint of the adjacent Que chains, facilitated the break-up of the structures. Besides, the bioavailability of Apx–Que was increased compared with the physical mixture and Apx, and Apx–Que remained stable in high temperature and illumination conditions. Therefore, a drug–drug cocrystal of two antithrombotic agents with poor solubility was developed, which exhibited greatly improved solubility, bioavailability and superior stability, indicating a novel method to overcome the shortages of drug combination.

With the recent advances of deep learning, automatic target recognition (ATR) of synthetic aperture radar (SAR) has achieved superior performance. By not being limited to the target category, the SAR ATR system could benefit from the simultaneous extraction of multifarious target attributes. In this paper, we propose a new multi-task learning approach for SAR ATR, which could obtain the accurate category and precise shape of the targets simultaneously. By introducing deep learning theory into multi-task learning, we first propose a novel multi-task deep learning framework with two main structures: encoder and decoder. The encoder is constructed to extract sufficient image features in different scales for the decoder, while the decoder is a tasks-specific structure which employs these extracted features adaptively and optimally to meet the different feature demands of the recognition and segmentation. Therefore, the proposed framework has the ability to achieve superior recognition and segmentation performance. Based on the Moving and Stationary Target Acquisition and Recognition (MSTAR) dataset, experimental results show the superiority of the proposed framework in terms of recognition and segmentation.

Background/Aims: Diabetes mellitus (DM) characterized by hyperglycemia contributes to macrovascular and microvascular complications. Salvianolic acid A (SalA) is a polyphenolic compound isolated from the root of Salvia miltiorrhiza Bunge, which is a traditional Chinese medicine widely used to treat cardiovascular diseases. However, little is known about its antidiabetic effect. Our study aimed to investigate the in vivo and in vitro antidiabetic effect of SalA and the underlying mechanisms. Methods: Alloxan-induced type 1 diabetic mice and high-fat diet (HFD) and low-dose streptozotocin (STZ)-induced type 2 diabetic rats received SalA treatment. Blood glucose, oral glucose tolerance test (OGTT), 24-h food and water intake were monitored. In vitro, glucose consumption and uptake were measured in HepG2 cells and L6 myotubes. Mitochondrial function was detected in hepatic and skeletal muscle mitochondria. AMP-activated protein kinase (AMPK) and Akt were analyzed by western blot. Results: In both type 1 and type 2 diabetic animals, SalA lowered fasting blood glucose (FBG) and fed blood glucose in dose-dependent manner, as well as reduced 24-h food and water intake. In vitro, SalA caused dose-dependent increase in glucose consumption and enhanced glucose uptake. SalA significantly increased ATP production from 10 min to 12 h in HepG2 cells and L6 myotubes. Interestingly, SalA decreased mitochondrial membrane potential (MMP) in HepG2 cells. Furthermore, SalA improved hepatic and skeletal muscle mitochondrial function, increased ATP production, and concurrently decreased MMP. In particularly, SalA activated AMPK phosphorylation through Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ)/AMPK signaling pathway, independent of liver kinase 1 (LKB1)/AMPK pathway. However, SalA didn't show any effect on insulin secretagogue and activation of PI3K/Akt signaling pathway. Conclusion: SalA exhibits the antidiabetic effects in diabetic animal models through improving mitochondrial function, increasing ATP production, and decreasing MMP via CaMKKβ/AMPK signaling pathway.

Bistatic forward-looking SAR (BFSAR) is a kind of bistatic synthetic aperture radar (SAR) system that can image forward-looking terrain in the flight direction of an aircraft. Until now, BFSAR imaging theories and methods for a stationary scene have been researched thoroughly. However, for moving-target imaging with BFSAR, the non-cooperative movement of the moving target induces some new issues: (I) large and unknown range cell migration (RCM) (including range walk and high-order RCM); (II) the spatial-variances of the Doppler parameters (including the Doppler centroid and high-order Doppler) are not only unknown, but also nonlinear for different point-scatterers. In this paper, we put forward an adaptive moving-target imaging method for BFSAR. First, the large and unknown range walk is corrected by applying keystone transform over the whole received echo, and then, the relationships among the unknown high-order RCM, the nonlinear spatial-variances of the Doppler parameters, and the speed of the mover, are established. After that, using an optimization nonlinear chirp scaling (NLCS) technique, not only can the unknown high-order RCM be accurately corrected, but also the nonlinear spatial-variances of the Doppler parameters can be balanced. At last, a high-order polynomial filter is applied to compress the whole azimuth data of the moving target. Numerical simulations verify the effectiveness of the proposed method.

Free of the constraints of orbit mechanisms, weather conditions and minimum antenna area, synthetic aperture radar (SAR) equipped on near-space platform is more suitable for sustained large-scene imaging compared with the spaceborne and airborne counterparts. Terrain observation by progressive scans (TOPS), which is a novel wide-swath imaging mode and allows the beam of SAR to scan along the azimuth, can reduce the time of echo acquisition for large scene. Thus, near-space TOPS-mode SAR (NS-TOPSAR) provides a new opportunity for sustained large-scene imaging. An efficient full-aperture imaging scheme for NS-TOPSAR is proposed in this paper. In this scheme, firstly, two-step processing (TSP) is adopted to eliminate the Doppler aliasing of the echo. Then, the data is focused in two-dimensional frequency domain (FD) based on Stolt interpolation. Finally, a modified TSP (MTSP) is performed to remove the azimuth aliasing. Simulations are presented to demonstrate the validity of the proposed imaging scheme for near-space large-scene imaging application.