Boosting Convolutional Neural Networks with Middle Spectrum Grouped Convolution

This paper proposes a novel module called middle spectrum grouped convolution (MSGC) for efficient deep convolutional neural networks (DCNNs) with the mechanism of grouped convolution. It explores the broad "middle spectrum" area between channel pruning and conventional grouped convolution. Compared with channel pruning, MSGC can retain most of the information from the input feature maps due to the group mechanism; compared with grouped convolution, MSGC benefits from the learnability, the core of channel pruning, for constructing its group topology, leading to better channel division. The middle spectrum area is unfolded along four dimensions: group-wise, layer-wise, sample-wise, and attention-wise, making it possible to reveal more powerful and interpretable structures. As a result, the proposed module acts as a booster that can reduce the computational cost of the host backbones for general image recognition with even improved predictive accuracy. For example, in the experiments on ImageNet dataset for image classification, MSGC can reduce the multiply-accumulates (MACs) of ResNet-18 and ResNet-50 by half but still increase the Top-1 accuracy by more than 1%. With 35% reduction of MACs, MSGC can also increase the Top-1 accuracy of the MobileNetV2 backbone. Results on MS COCO dataset for object detection show similar observations. Our code and trained models are available at https://github.com/hellozhuo/msgc.Comment: 13 pages, 11 figures, submitted to IEEEE Transactions on xx

Distributed Robust Partial State Consensus Control for Chain Interconnected Delay Systems

Partial state consensus (PSC) is investigated for chain interconnected systems with time-varying delays and parameter uncertainties. A novel design philosophy of PSC control is proposed and a sequential calculation method is presented to guarantee the robustness of the controller. A sufficient condition based on linear matrix inequalities (LMIs) is derived and the stability is proven by the Lyapunov method. The proposed approach can ensure that the states which are subject to a consensus constraint achieve consensus, while those without a consensus constraint track their own set points. Finally, numerical simulations and a solution proportioning experiment are developed to validate the effectiveness of the proposed method

Protective effect of dehydroandrographolide on obstructive cholestasis in bile duct-ligated mice

Background: Dehydroandrographolide (DA) is the main contributor to the therapeutic properties of the medicinal plant Andrographis paniculata (AP). However, it is unknown whether DA has a hepatoprotective effect on obstructive cholestasis in mice and humans. Methods: We administered DA to mice for 5 days prior to bile duct ligation (BDL) and for the 7 days. Liver function markers, liver histology and necrosis, compensatory responses of hepatocytes, liver fibrosis and the expression of hepatic fibrogenesis markers were evaluated in BDL mice and/or human LX-2 cells. Results: Mice treated with DA demonstrated lower levels of serum alanine transarninase (ALT), milder liver damage, liver necrosis and fibrosis formation than in vehicle control with carboxymethylcellulose (CMC) mice after BDL. DA treatment also enhanced the Mrp3 expression of hepatocytes but not Mrp4 following BDL. Further, DA treatment in BDL mice significantly reduced liver mRNA and/or protein expression of Tgf-β, Col1a1, α-Sma and Mmp2. This result was also supported by hydroxyproline analysis. The molecular mechanisms of DA treatment were also assessed in human hepatic stellate cell line (LX-2 cell). DA treatment significantly inhibited Tgf-β-induced Col1a1, Mmp2 and α-Sma expression in human LX-2 cells. These data suggested that DA treatment reduced liver damage through development of a hepatic adaptive response and inhibition of the activation of HSCs, which led to a reduction in liver fibrosis formation in BDL mice. Conclusions: DA treatment protected against liver damage and fibrosis following BDL and might be an effective therapy for extrahepatic cholestasis due to bile duct obstruction

Anti-Inflammatory Activity of Dehydroandrographolide by TLR4/NF-κB Signaling Pathway Inhibition in Bile Duct-Ligated Mice

Background/Aims: Clinically, biliary obstruction is often accompanied by progressive inflammation. Dehydroandrographolide (DA) possesses anti-inflammatory properties. However, the anti-inflammatory activities of DA in cholestatic liver injury remain unclear. Methods: Mice were administered with DA by intraperitoneal injection after bile duct ligation (BDL) on day 1. Then mice were subjected to an ileocecal vein injection of lipopolysaccharide (LPS). Liver function markers, histology, pro-inflammatory cytokine levels, NF-κB activation and fibrosis formation were evaluated in BDL mice with LPS. LPS binding to primary Kupffer cells was examined by high-content cytometers. Results: DA was shown to greatly lower initially higher than normal levels of alanine aminotransferase (ALT) and total bilirubin (TBIL) in the serum and liver of BDL mice with LPS. DA exerted hepatic protective effects that were also confirmed by prolonged survival of BDL mice with LPS. Liver histopathology showed reduced inflammatory cellular infiltration, bile duct proliferation, and biliary necrosis with DA treatment. Furthermore, DA reduced the expression levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in liver tissue and plasma and showed decreased NF-κB activation in BDL mice with LPS. DA could prevent LPS binding to primary Kupffer cells in the normal liver and BDL mice liver. DA also suppressed LPS-stimulated inflammatory responses by blocking the interaction between LPS and TLR4 in primary Kupffer cells and human LX-2 cells, thereby inhibiting NF-κB activation. Conclusion: DA inhibition of inflammation against liver damage following BDL with LPS may be a promising agent for the treatment of cholestatic liver injury

Protective Effect of Hydrogen on Sodium Iodate-Induced Age-Related Macular Degeneration in Mice

Oxidative stress is one of the main causes of AMD. Hydrogen has anti-oxidative stress and apoptotic effects on retinal injury. However, the effect of hydrogen on AMD is not clear. In this study, fundus radiography, OCT, and FFA demonstrated that HRW reduced the deposition of drusen-like structures in RPE layer, prevented retina from thinning and leakage of ocular fundus vasculature induced by NaIO3. ERG analysis confirmed that HRW effectively reversed the decrease of a-wave and b-wave amplitude in NaIO3-mice. Mechanistically, HRW greatly reduced the oxidative stress reaction through decreased MDA levels, increased SOD production, and decreased ROS content. The OGG1 expression was downregulated which is a marker of oxidative stress. Involvement of oxidative stress was confirmed using oxidative stress inhibitor ALCAR. Moreover, oxidative stress reaction was associated with expression of Sirt1 level and HRW significantly inhibited the downregulation of Sirt1 expression. This result was further confirmed with AICAR which restore Sirt1 expression and activity. In addition, NaIO3-induced retinal damage was related to apoptosis via caspase 8 and caspase 9, but not the caspase 3 pathways, which led to upregulation of Bax and p53, downregulation of Bcl-2, and increase in Jc-1-positive cells in mice. However, HRW effectively reversed these effects that apoptosis induced. These results suggest that HRW protects retinal functions against oxidative stress injury through inhibiting downregulation of Sirt1 and reducing retinal apoptosis. Therefore, we speculated that hydrogen administration is a promising treatment for AMD therapy

Normal-weight central obesity: implications for diabetes mellitus

BackgroundCurrent guidelines for obesity prevention and control focus on body mass index (BMI) and rarely address central obesity. Few studies have been conducted on the association between normal-weight central obesity and the risk of diabetes mellitus (DM).Methods26,825 participants from the National Health and Nutrition Examination Survey (NHANES) were included in our study. A weighted multivariate logistic regression model was used to analyze the relationship between different obesity patterns and the risk of DM.ResultsOur results suggest that normal-weight central obesity is associated with an increased risk of DM (OR: 2.37, 95% CI: 1.75–3.23) compared with normal-weight participants without central obesity. When stratified by sex, men with normal-weight central obesity, obesity and central obesity were found to have a similar risk of DM (OR: 3.83, 95% CI: 2.10–5.97; OR: 4.20, 95% CI: 3.48–5.08, respectively) and a higher risk than all other types of obesity, including men who were overweight with no central obesity (OR: 1.21, 95% CI: 0.96–1.51) and obese with no central obesity (OR: 0.53, 95% CI: 0.30–0.91).ConclusionOur results highlight the need for more attention in people with central obesity, even if they have a normal BMI

The SMAC Mimetic APG-1387 Sensitizes Immune-Mediated Cell Apoptosis in Hepatocellular Carcinoma

The inhibitor of apoptosis protein (IAP) genes are frequently overexpressed in malignancies. Second mitochondria-derived activator of caspase (SMAC) mimetics, which target IAPs, have potential to trigger cancer cell death and sensitize tumor cells to cytotoxic therapy. The aim of this study was to investigate the anti-tumor potential of a novel bivalent SMAC mimetic, APG-1387, in hepatocellular carcinoma (HCC). The mRNA and protein expressions of IAPs, including cellular IAPs (cIAP1 and cIAP2) and X chromosome-linked IAP (XIAP), were increased in HCC tumors compared with normal liver tissue. APG-1387 treatment alone significantly reduced the protein levels of IAPs, but had only a modest effect on the viability and apoptosis of HCC cells in vitro. However, APG-1387 in combination with tumor necrosis factor-alpha (TNF-α) or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) significantly reduced cell viability and proliferation, and induced apoptosis in HepG2 cells, as well as in HCCLM3 cells that harbors cancer stem cell-like properties. These synergistic killing effects were caspase-dependent and partially dependent on RIPK1 kinase activity. Furthermore, APG-1387 also promoted the killing effect of Natural Killer cells on HCC cells in vitro and the combination therapy significantly inhibited tumor growth by inducing cell apoptosis in xenograft mice model. In conclusion, our study clarified that APG-1387 could sensitize HCC cells to cytokines or immune cells mediated cell killing and implied that potential of SMAC mimetic based combination immunotherapy for HCC treatment

Downregulation of TLX induces TET3 expression and inhibits glioblastoma stem cell self-renewal and tumorigenesis

International audienceGlioblastomas have been proposed to be maintained by highly tumorigenic glioblastoma stem cells (GSCs) that are resistant to current therapy. Therefore, targeting GSCs is critical for developing effective therapies for glioblastoma. In this study, we identify the regulatory cascade of the nuclear receptor TLX and the DNA hydroxylase Ten eleven translocation 3 (TET3) as a target for human GSCs. We show that knockdown of TLX expression inhibits human GSC tumorigenicity in mice. Treatment of human GSC-grafted mice with viral vector-delivered TLX shRNA or nanovector-delivered TLX siRNA inhibits tumour development and prolongs survival. Moreover, we identify TET3 as a potent tumour suppressor downstream of TLX to regulate the growth and self-renewal in GSCs. This study identifies the TLX-TET3 axis as a potential therapeutic target for glioblastoma

Novel loci and pathways significantly associated with longevity

Only two genome-wide significant loci associated with longevity have been identified so far, probably because of insufficient sample sizes of centenarians, whose genomes may harbor genetic variants associated with health and longevity. Here we report a genome-wide association study (GWAS) of Han Chinese with a sample size 2.7 times the largest previously published GWAS on centenarians. We identified 11 independent loci associated with longevity replicated in Southern-Northern regions of China, including two novel loci (rs2069837-IL6; rs2440012-ANKRD20A9P) with genome-wide significance and the rest with suggestive significance (P < 3.65 × 10(−5)). Eight independent SNPs overlapped across Han Chinese, European and U.S. populations, and APOE and 5q33.3 were replicated as longevity loci. Integrated analysis indicates four pathways (starch, sucrose and xenobiotic metabolism; immune response and inflammation; MAPK; calcium signaling) highly associated with longevity (P ≤ 0.006) in Han Chinese. The association with longevity of three of these four pathways (MAPK; immunity; calcium signaling) is supported by findings in other human cohorts. Our novel finding on the association of starch, sucrose and xenobiotic metabolism pathway with longevity is consistent with the previous results from Drosophilia. This study suggests protective mechanisms including immunity and nutrient metabolism and their interactions with environmental stress play key roles in human longevity