Fufang Luohanguo Qingfei granules reduces influenza virus susceptibility via MAVS-dependent type I interferon antiviral signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Luohanguo Qingfei granules (LQG) is a Chinese patent medicine, clinically used to treat flu-like symptoms including cough with yellow phlegm, impeded phlegm, dry throat and tongue. However, the protective activity of LQG against influenza infection is indeterminate. AIM OF THE STUDY: This study is to investigate the therapeutic effect of LQG on influenza infection and elucidate its underlying mechanism. MATERIALS AND METHODS: In vivo: A viral susceptible mouse model induced by restraint stress was established to investigate LQG's beneficial effects on influenza susceptibility. MAVS knockout (Mavs-/-) mice were used to verify the potential mechanism of LQG. In vitro: Corticosteroid (CORT)-treated A549 cells were employed to identify the active ingredients in LQG. Mice morbidity and mortality were monitored daily for 21 days. Histopathologic changes and inflammatory cytokines in lung tissues were examined by H&E staining and ELISA. RNA-seq was used to explore the signaling pathway influenced by LQG and further confirmed by qPCR. Immunoblotting and immunohistochemistry (IHC) were used to determine the protein levels. CO-IP and DARTS were applied to detect protein-protein interaction and compound-protein interaction, respectively. RESULTS: LQG effectively attenuated the susceptibility of restrained mice to H1N1 infection. LQG significantly boosted the production of IFN-ß transduced by mitochondrial antiviral-signaling protein (MAVS), while MAVS deficiency abrogated its protective effects on restrained mice infected with H1N1. Moreover, in vitro studies further revealed that mogroside Ⅱ B, amygdalin, and luteolin are potentially active components of LQG. CONCLUSION: These results suggested that LQG inhibited the mitofusin 2 (Mfn2)-mediated ubiquitination of MAVS by impeding the E3 ligase synoviolin 1 (SYVN1) recruitment, thereby enhancing IFN-ß antiviral response. Overall, our work elaborates a potential regimen for influenza treatment through reduction of stress-induced susceptibility.

Marsdenia tenacissima injection induces the apoptosis of prostate cancer by regulating the AKT/GSK3ß/STAT3 signaling axis.

Marsdenia tenacissima injection, a standard Marsdenia tenacissima extract (MTE), has been approved as an adjuvant therapeutic agent for various cancers. Our previous study showed that MTE inhibited the proliferation and metastasis of prostate cancer (PCa) cells. However, the underlying mechanisms and active ingredients of MTE against PCa were not completely understood. This study revealed that MTE induced significant decreases in cell viability and clonal growth in PCa cells. In addition, MTE induced the apoptosis of DU145 cells by reducing the mitochondrial membrane potential and increasing the expression of Cleaved Caspase 3/7, Cyt c, and Bax. In vivo, DU145 xenografted NOD-SCID mice treated with MTE showed significantly decreased tumor size. TUNEL staining and Western blot confirmed the pro-apoptotic effects of MTE. Network pharmacology analysis collected 196 ingredients of MTE linked to 655 potential targets, and 709 PCa-associated targets were retrieved, from which 149 overlapped targets were screened out. Pathway enrichment analysis showed that the HIF-1, PI3K-AKT, and ErbB signaling pathways were closely related to tumor apoptosis. Western blot results confirmed that MTE increased the expression of p-AKTSer473 and p-GSK3ßSer9, and decreased the expression of p-STAT3Tyr705in vitro and in vivo. A total of 13 compounds in MTE were identified by HPLC-CAD-QTOF-MS/MS and UPLC-QTOF-MS/MS. Molecular docking analysis indicated that six compounds may interact with AKT, GSK3ß, and STAT3. In conclusion, MTE induces the endogenous mitochondrial apoptosis of PCa by regulating the AKT/GSK3ß/STAT3 signaling axis, resulting in inhibition of PCa growth in vitro and in vivo.

Total flavonoids of Litchi seed attenuate stem cell-like properties in breast cancer by regulating Notch3 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Breast cancer has been the most commonly-diagnosed cancer worldwide, and the treatment and prognosis of which are often limited by breast cancer stem cells (BCSCs). Litchi seeds have shown good anti-cancer activity in various cancers including prostate cancer, lung cancer and breast cancer. However, the activity and underlying mechanism of Litchi seeds against BCSCs remain unknown. AIM OF THE STUDY: To investigate the activity and mechanism of total flavonoids of litchi seed (TFLS) against BCSCs in vitro and in vivo. MATERIALS AND METHODS: Two orthotopic xenograft mouse models were established using HCC1806 cells pretreated or untreated with TFLS to determine whether TFLS could target BCSCs in vivo. Mammosphere formation and flow cytometry assays were employed to evaluate the effect of TFLS on BCSCs in vitro. The underlying mechanism was investigated using RT-qPCR, Western blot, immunohistochemistry and immunofluorescence experiments. RESULTS: TFLS could significantly inhibit the viability of HCC1806, MCF-7 and HCC1937 cells in vitro and suppress the growth of HCC1806 cells in vivo. TFLS attenuated stem cell-like properties of breast cancer through reducing the percentage of CD44+CD24-/low cells, inhibiting the mammospheres formation and down-regulating the mRNA and protein levels of cancer stem cells related markers (Oct4, Nanog, Sox2) in MCF-7 and HCC1806 cells. Meanwhile, TFLS suppressed the tumor-initiating ability of BCSCs via reducing the percentage of CD44+CD24-/low cells in tumor and lowering tumor incidence rate in orthotopic xenograft mice. In addition, TFLS treatments restricted the expression and nuclear translocation of Notch3, subsequently down-regulated Hes1 and Runx2 expressions. CONCLUSIONS: TFLS could suppress the growth of breast cancer and eliminate breast cancer stem cells by inhibiting the Notch3 signaling pathway.

A network pharmacology-based approach to explore the active ingredients and molecular mechanism of Lei-gong-gen formula granule on a spontaneously hypertensive rat model.

BACKGROUND: Lei-gong-gen formula granule (LFG) is a folk prescription derived from Zhuang nationality, the largest ethnic minority among 56 nationalities in China. It consists of three herbs, namely Eclipta prostrata (L.) L., Smilax glabra Roxb, and Centella asiatica (L.) Urb. It has been widely used as health protection tea for hundreds of years to prevent hypertension in Guangxi Zhuang Autonomous Region. The purpose of this study is to validate the antihypertensive effect of LFG on the spontaneously hypertensive rat (SHR) model, and to further identify the effective components and anti-hypertension mechanism of LFG. METHODS: The effects of LFG on blood pressure, body weight, and heart rate were investigated in vivo using the SHR model. The levels of NO, ANG II, and ET-1 in the serum were measured, and pathological changes in the heart were examined by H&E staining. The main active components of LFG, their corresponding targets, and hypertension associated pathways were discerned through network pharmacology analysis based on the Traditional Chinese Medicine Systems Pharmacology (TCMSP), Traditional Chinese Medicine Integrated Database (TCMID), and the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM). Then the predicted results were further verified by molecular biology experiments such as RT-qPCR and western blot. Additionally, the potential active compounds were predicted by molecular docking technology, and the chemical constituents of LFG were analyzed and identified by UPLC-QTOF/MS technology. Finally, an in vitro assay was performed to investigate the protective effects of potential active compounds against hydrogen peroxide (H2O2) induced oxidative damage in human umbilical vein endothelial cells (HUVEC). RESULTS: LFG could effectively reduce blood pressure and increase serum NO content in SHR model. Histological results showed that LFG could ameliorate pathological changes such as cardiac hypertrophy and interstitial inflammation. From network pharmacology analysis, 53 candidate active compounds of LFG were collected, which linked to 765 potential targets, and 828 hypertension associated targets were retrieved, from which 12 overlapped targets both related to candidate active compounds from LFG and hypertension were screened and used as the potential targets of LFG on antihypertensive effect. The molecular biology experiments of the 12 overlapped targets showed that LFG could upregulate the mRNA and protein expressions of NOS3 and proto-oncogene tyrosine-protein kinase SRC (SRC) in the thoracic aorta. Pathway enrichment analysis showed that the PI3K-AKT signaling pathway was closely related to the expression of NOS3 and SRC. Moreover, western blot results showed that LFG significantly increased the protein expression levels of PI3K and phosphorylated AKT in SHR model, suggesting that LFG may active the PI3K-AKT signaling pathway to decrease hypertension. Molecular docking study further supported that p-hydroxybenzoic acid, cedar acid, shikimic acid, salicylic acid, nicotinic acid, linalool, and histidine can be well binding with NOS3, SRC, PI3K, and AKT. UPLC-QTOF/MS analysis confirmed that p-hydroxybenzoic acid, shikimic acid, salicylic acid, and nicotinic acid existed in LFG. Pre-treatment of HUVEC with nicotinic acid could alleviate the effect on cell viability induced by H2O2 and increase the NO level in cell supernatants. CONCLUSIONS: LFG can reduce the blood pressure in SHR model, which might be attributed to increasing the NO level in serum for promoting vasodilation via upregulating SRC expression level and activating the PI3K-AKT-NOS3 signaling pathway. Nicotinic acid might be the potential compound for LFG antihypertensive effect.

Research of a Radar Imaging Algorithm Based on High Pulse Repetition Random Frequency Hopping Synthetic Wideband Waveform.

Aiming at the imaging algorithm of high-pulse-repetition random-frequency-hopping synthetic wideband radar on a supersonic/hypersonic aircraft platform, this study established an echo simulation model of target and clutter, analyzed the special range-Doppler coupling effect and its influence on imaging, and proposes a method of imaging with pipeline-parallel processing based on generalized 2D matched-filtering and Doppler pre-processing. In the method, Doppler-beam-sharpening was advanced to be performed with the pulse compression process in each frame, and the special range-Doppler coupling effect caused by high dynamic motion of platform and random frequency hopping in bandwidth synthesis was well suppressed; several modes of random frequency hopping were designed and the pipeline-parallel image processing algorithm was optimized for each mode. Theoretical analysis and simulation results show that the proposed imaging method can effectively avoid the divergence of 2D range-Doppler images in the range direction, and can meet the requirements of real-time imaging.

3D-GIoU: 3D Generalized Intersection over Union for Object Detection in Point Cloud.

Three-dimensional (3D) object detection is an important research in 3D computer vision with significant applications in many fields, such as automatic driving, robotics, and human-computer interaction. However, the low precision is an urgent problem in the field of 3D object detection. To solve it, we present a framework for 3D object detection in point cloud. To be specific, a designed Backbone Network is used to make fusion of low-level features and high-level features, which makes full use of various information advantages. Moreover, the two-dimensional (2D) Generalized Intersection over Union is extended to 3D use as part of the loss function in our framework. Empirical experiments of Car, Cyclist, and Pedestrian detection have been conducted respectively on the KITTI benchmark. Experimental results with average precision (AP) have shown the effectiveness of the proposed network.

The Spectral Prediction of Original Primary Pigment Based on Constrained Non-Negative Matrix Factorization.

With direct prediction in the spectral reflectance space with principal component analysis, the numbers of eigenvectors will surpass the numbers of real primary pigments while the eigenvectors and the corresponding coefficients have negative value, which can not directly presented original primary pigment spectral characteristics and corresponding concentration. We proposed an innovative spectral prediction method in which a complete linear spectral space was created according to optical properties of originals pigment. A constrained non-negative matrix factorization algorithm to predict the numbers and spectral curve shapes of real primary pigments was used in the space. So, this paper designed an overall research plan and implementation process about spectral prediction method firstly, and studied how to select and establish a spectral linear space which was conformed to optical properties of originals; taking transparent pigments as example, and spectra constrained non-negative matrix factorization (SCNMF) algorithm was established to predict primary pigment spectra based on basic non-negative matrix factorization algorithm (BNMF). Aiming at realizing multiple optimal solution of BNMF and improving the prediction accuracy as well as make the matrix decomposition results to be clearly physically meaningful; the proposed SCNMF needs to satisfy four constraints: non negative constraint, additive constraint, smoothness constraint and sparseness constraint. The objective function and iterative algorithm to meet four constraints were set up. The prediction results show that the proposed method can realize accurate prediction of original primary pigments' numbers and spectra effectively.

[The Research of Spectral Dimension Reduction Method Based on Human Visual Characteristics].

The traditional spectral dimension reduction methods are usually carried out by matching the reconstructed spectra to the original spectra mathematically, which will often result in reconstructed spectra of small spectral reconstruction errors but very poor colorimetric accuracy when compared with the original one. In order to minimize both the spectral and colorimetric errors more efficiently, we proposed three spectral dimension reduction methods by introducing the characteristics of human vision. The first method is VPCA, in which we apply spectral luminous efficiency function to the original spectra before reduction; The Second method (LMSPCA) uses a matrix derived from LMS cone sensitivity to weight the original spectra before reduction, and the matrix can be form by two methods, in which the L, M, S cones response offset is calculated by in two different ways: one is computed as the absolute value of each corresponding wave length offset, and the other is calculated as the square of each corresponding wave length offset. The third method is LMSPCAs, which is based on the second method LMSPCA by further applying PCA to the residual spectra. The result shows that the VPCA method produces the poorest perfomance. The two cones response weighted matrixes of LMSPCA method have similar performances by presenting better colorimetric accuracy and low spectral accuracy, while LMSPCAs method which compensates for the spectral loss of LMSPCA method can produce higher spectral and colorimetric reconstruction accuracy and color stability under different light source, and satisfies the requirements of spectral color reproduction.

Short-term effects of intragastric balloon in association with conservative therapy on weight loss: a meta-analysis.

Obesity is an epidemic chronic disease which is a risk factor for a number of serious medical conditions. Intragastric balloon, as an alternative, non-surgical treatment approach for the management of obesity, was rejected in previous evidence-based reviews. The object of this review is updating the data and confirming the safety and efficacy of the procedure. In this review, systematic literature retrieve of MEDLINE, EMBASE, CENTRAL and other information sources was performed from inception to December 2014. The quality of selected studies was assessed and meta-analyses of weighted mean differences were made using the inverse variance method. Meta-analyses presented significant effect sizes of -8.9 kg, -3.1 kg/m(2) and -21.0% for SMG as well as of -1.5 kg and -1.2 kg/m(2) for LSG, favoring the intervention group. Safety analysis showed that minor complications occurred at a high rate in intervention group, however, no serious or fatal complication was reported in these studies. In conclusion, the current review presents that short-term efficacy for 6 months treatment of intragastric balloon in association with conservative therapy is clinically significant.

Application of metabolomics in traditional chinese medicine differentiation of deficiency and excess syndromes in patients with diabetes mellitus.

Metabolic profiling is widely used as a probe in diagnosing diseases. In this study, the metabolic profiling of urinary carbohydrates was investigated using gas chromatography/mass spectrometry (GC/MS) and multivariate statistical analysis. The kernel-based orthogonal projections to latent structures (K-OPLS) model were established and validated to distinguish between subjects with and without diabetes mellitus (DM). The model was combined with subwindow permutation analysis (SPA) in order to extract novel biomarker information. Furthermore, the K-OPLS model visually represented the alterations in urinary carbohydrate profiles of excess and deficiency syndromes in patients with diabetes. The combination of GC/MS and K-OPLS/SPA analysis allowed the urinary carbohydrate metabolic characterization of DM patients with different traditional Chinese medicine (TCM) syndromes, including biomarkers different from non-DM patients. The method presented in this study might be a complement or an alternative to TCM syndrome research.

[Clinical early intervention of Tongxia Huayu Decoction on pancreatic microcirculatory disturbance in severe acute pancreatitis].

OBJECTIVE: To study the mechanisms of Tongxia Huayu Decoction (a Chinese herbal decoction for purgation and removing blood stasis) in prognostic improvement for severe acute pancreatitis by early intervention on pancreatic microcirculatory disturbance. METHODS: Fifty-three patients with severe acute pancreatitis were divided randomly into treatment group (n=28) and control group (n=25). Tongxia Huayu Decoction was given to the patients in treatment group in addition to the normal treatment in control group for one week. The clinical symptoms and signs, hemodiastase, urinary amylase, C-reactive protein (CRP) and endothelin (ET) of the patients in the two groups before and after treatment were observed and detected. RESULTS: The total response rate of the treatment group was 98.4%, while that of the control group was 80%, with significant difference between them (P<0.05). There was no significant difference of the contents of hemodiastase, urinary amylase, CRP and ET between the two groups before treatment, while they were significantly decreased after treatment (P<0.01) with more obvious change in treatment group (P<0.01). CONCLUSION: Tongxia Huayu Decoction brings satisfied therapeutic effect on severe acute pancreatitis. The mechanisms may associate with its reducing function on ET releasing so as to inhibit the pancreatic microcirculatory disturbance and acinar cell injury induced by ET.