Explore the vast range of titles available.

The genetic basis of colorectal cancer (CRC) and its clinical associations remain poorly understood due to limited samples or targeted genes in current studies. Here, we perform ultradeep whole-exome sequencing on 1015 patients with CRC as part of the ChangKang Project. We identify 46 high-confident significantly mutated genes, 8 of which mutate in 14.9% of patients: LYST , DAPK1 , CR2 , KIF16B , NPIPB15 , SYTL2 , ZNF91 , and KIAA0586 . With an unsupervised clustering algorithm, we propose a subtyping strategy that classisfies CRC patients into four genomic subtypes with distinct clinical characteristics, including hypermutated, chromosome instability with high risk, chromosome instability with low risk, and genome stability. Analysis of immunogenicity uncover the association of immunogenicity reduction with genomic subtypes and poor prognosis in CRC. Moreover, we find that mitochondrial DNA copy number is an independent factor for predicting the survival outcome of CRCs. Overall, our results provide CRC-related molecular features for clinical practice and a valuable resource for translational research. The ChangKang (Heathy Bowel) project was established to collect molecular and clinical information of a thousand Chinese colorectal cancer patients. Here, the authors present the genomic landscape of the ChangKang cohort and find a subgroup of patients defined by abnormal mitochondrial copy numbers.

[ Objectives] The paper aimed to select drugs reasonably for treatment of rex rabbit colibacillosis, and to isolate the pathogenicity of Escherichia coll. [ Methods ] Pathogen isolation, drug sensitivity test and pathogen regression test were performed with rex rabbits killed by E. coli in clinic. [ Results] The isolate was E. coli 0-23, susceptible to amikacin and cefotaxime sodium; when the challenge dose was 1.0 mL/rabbit （about one billion E. coli）, the test animal would discharge mucous feces. [ Conclusions] The results provided model support for clinical medicine selection against rex rabbit colibacillosis.

Aim： To examine whether β-adrenoceptor （β-AR） agonists can induce hypoxia-inducible factor （HIF）-1α accumulation which then upregulate the expression of its target genes in pancreatic cancer cells at normoxia, and to further elucidate the mechanism involved. Methods： Pulse-chase assay, RT-PCR, and Western blot were employed to detect the effects of β-AR agonists and antagonists, siRNA as well as several inhibitors of signal transduction pathways on MIA PaCa2 and BxPC-3 pancreatic cancer cells. Results： Treatment of pancreatic cancer cell lines with β-AR agonists led to accumulation of HIF-1α and then up-regulated expression of its target genes independently of oxygen levels. The induction was partly or completely inhibited not only by β-AR antagonists but also by inhibitors of PKA transduction pathways and by siHIF-1α. Both β1-AR and β2-AR agonists produced the above-mentioned effects, but β2-AR agonist was more potent. Conclusion： Activation of β-AR receptor transactivates epidermal growth factor receptor （EGFR） and then elicites Akt and ERK1/2 in a PKA-dependent manner, which together up-regulate levels of HIF-1α and downstream target genes independently of oxygen level. Our data suggest a novel mechanism in pancreatic cancer cells that links β-AR and HIF-1α signaling under normoxic conditions, with impli- cations for the control of glucose transport, angiogenesis and metastasis.

In this study, Pearl oyster mantle type V collagen (POMC) and tilapia scale type I collagen (TSC) were extracted and hydrolyzed by various proteases in order to obtain peptides. The antioxidant activity of the peptides was investigated by DPPH, hydroxyl radical scavenging experiments and a dynamic digestion model in vitro. The results show that there are significant differences in amino acid composition between POMC and TSC. The collagen peptides obtained from pearl oyster mantle (POMCP) by treating with alkaline protease exhibited higher antioxidant activity than that from tilapia scale (TSCP) treated with papaya protease, and both of them showed greater DPPH and hydroxyl radical scavenging activity than other peptides. After being separated via Sephadex G-25 chromatography, the M1 fraction isolated from POMCP, and the S1 fraction from TSCP with which both had higher molecular weights showed the strongest antioxidant activity than other fractions, and the M1 fraction exhibited stronger antioxidant activity than the S1 fraction in scavenging free-radicals and protecting cells from the oxidation damage. Furthermore, after treating the dynamic digestion system model in vitro, the DPPH and hydroxyl radical scavenging activity of the M1 fraction increased slightly.These results suggest that POMCP exhibits stronger antioxidant activity than TSCP, which means that PMOP may be a good candidate to be a potential natural antioxidant in the food-processing industry.

The structure and decay properties of d＊ have been detailedly investigated in both the chiral SU（3） quark model and the extended chiral SU（3） quark model that describe the energies of baryon ground states and the nucleon-nucleon （NN） scattering data satisfactorily. By performing a dynamical coupled-channels study of the system of △△ and hidden-color channel （CC） with quantum numbers l（JP） = 0（3^＋） in the framework of the resonating group method （RGM）, we find that the d＊ has a mass of about 2.38-2.42 GeV and a root-mean-square radius （RMS） of about 0.76-0.88 fm. The channel wave function is extracted by a projection of the RGM wave function onto the physical basis, and the fraction of CC component in the d＊ is found to be about 66%-68%, which indicates that the d＊ is a hexaquark-dominated exotic state. Based on this scenario the partial decay widths of d＊ → dπ^0π^0 and d＊ → dn^＋n^- are further explicitly evaluated and the total width is then obtained by use of the branching ratios extracted from the measured cross sections of other possible decay channels. Both the mass and the decay width of d＊ calculated in this work are compatible with the data （M ≈ 2380 MeV, F ≈ 70 MeV） reported by WASA-at-COSY Collaboration.

Introduction Colorectal cancer (CRC) is the third most common cancer in China. The incidence of CRC has been increasing in recent years. The aim of this study was to explore the incidence trends and the age distribution of CRC by subsite in Guangzhou between 2000 and 2011. Methods A total of 22,432 incident cases of CRC between 2000 and 2011 from Guangzhou Cancer Registry were identified. Crude incidence and age‐standardized rates (ASRs), using the Segi's world standard population, were calculated for CRC and CRC subsites. The incidence trend was analyzed and the annual percentage change (APC) in incidence was calculated by using JoinPoint software. Results The crude incidence increased significantly from 23.4/105 in 2000 to 37.4/105 in 2011 for males and from 20.9/105 to 30.5/105 for females. The ASRs of CRC incidence stabilized during the period of 2000–2011 for both males and females. The ages at the onset of CRC for both males and females during 2010–2011 were significantly higher compared with those during 2000–2002 (males: t = 1.95, P = 0.05; females: t = 6.03, P < 0.01). For males aged 50–64 years, the CRC incidence increased by 8.50% annually (P = 0.04) during 2000–2004 and by 1.68% annually (P = 0.03) during 2005–2011. For females aged 65 years and older, the CRC incidence increased by 5.77% annually (P = 0.03) during 2000–2004. There were no significant changes for the CRC incidences in males aged 49 and younger and 65 years and older and females aged 64 years and younger during 2000–2004, or for those in all females as well as males aged 49 years and younger and 65 years and older during 2005–2011. The percentage of colon cancer in all CRCs increased significantly for both males and females between the periods of 2000–2002 and 2010–2011. The ASRs of descending colon and sigmoid colon cancer incidences increased significantly for females during 2005–2011 (APC, 5.51% and 1.08%, respectively, both P < 0.05). Conclusions The crude incidence of CRC increased significantly between 2000 and 2011 because of the aging, whereas the ASRs kept stable. The percentage of colon cancer in all CRCs increased significantly. Further surveillance, research, and intervention are needed to identify the causes of these changes and to reduce the incidence and mortality of CRC.

Background： Amyloid β （Aβ） deposits and the endoplasmic reticulum stress （ERS） are both well established in the development and progression of Alzheimer＇s disease （AD）. However, the mechanism and role of Aβ-induced ERS in AD-associated pathological progression remain to be elucidated. Methods： The five familial AD （5×FAD） mice and wild-type （WT） mice aged 2, 7, and 12 months were used in the present study. Monis water maze test was used to evaluate their cognitive performance, lmmunofluorescence and Western blot analyses were used to examine the dynamic changes of pro-apoptotic （CCAAT/enhancer-binding protein homologous protein [CHOP] and cleaved caspase-12） and anti-apoptotic factors （chaperone glucose-regulated protein [GRP] 78 and endoplasmic reticulum-associated protein degradation-associated ubiquitin ligase synovial apoptosis inhibitor 1 [SYVN 1]） in the ERS-associated unfolded protein response （UPR） pathway. Results： Compared with age-matched WT mice, 5 xFAD mice showed higher cleaved caspase-3, lower neuron-positive staining at the age of 12 months, but earlier cognitive deficit at the age of 7 months （all P 〈 0.05）. Interestingly, for 2-month-old 5×FAD mice, the related proteins involved in the ERS-associated UPR pathway, including CHOP, cleaved caspase-12, GRP 78, and SYVN 1, were significantly increased when compared with those in age-matched WT mice （all P 〈 0.05）. Moreover, ERS occurred mainly in neurons, not in astrocytes. Conclusions： These findings suggest that compared with those of age-matched WT mice, ERS-associated pro-apoptotic and anti-apoptotic proteins are upregulated in 2-month-old 5×FAD mice, consistent with intracellular Aβ aggregation in neurons.

We previously found that oxygen-glucose-serum deprivation/restoration（OGSD/R） induces apoptosis of spinal cord astrocytes, possibly via caspase-12 and the integrated stress response, which involves protein kinase R-like endoplasmic reticulum kinase（PERK）, eukaryotic initiation factor 2-alpha（eIF2α） and activating transcription factor 4（ATF4）. We hypothesized that edaravone, a low molecular weight, lipophilic free radical scavenger, would reduce OGSD/R-induced apoptosis of spinal cord astrocytes. To test this, we established primary cultures of rat astrocytes, and exposed them to 8 hours/6 hours of OGSD/R with or without edaravone（0.1, 1, 10, 100 μM） treatment. We found that 100 μM of edaravone significantly suppressed astrocyte apoptosis and inhibited the release of reactive oxygen species. It also inhibited the activation of caspase-12 and caspase-3, and reduced the expression of homologous CCAAT/enhancer binding protein, phosphorylated（p）-PERK, p-eIF2α, and ATF4. These results point to a new use of an established drug in the prevention of OGSD/R-mediated spinal cord astrocyte apoptosis via the integrated stress response.

There were two strategies for the data forwarding in the content-centric networking （CCN）： forwardingstrategy and routing strategy. Forwarding strategy only considered a separated node rather than the whole networkperformance, and Interest flooding led to the network overhead and redundancy as well. As for routing strategy inCCN, each node was required to run the protocol. It was a waste of routing cost and unfit for large-scale deployment.This paper presents the super node routing strategy in CCN. Some super nodes selected from the peer nodes in CCNwere used to receive the routing information from their slave nodes and compute the face-to-path to establish forwardinginformation base （FIB）. Then FIB was sent to slave nodes to control and manage the slave nodes. The theoreticalanalysis showed that the super node routing strategy possessed robustness and scalability, achieved load balancing,reduced the redundancy and improved the network performance. In three topologies, three experiments were carriedout to test the super node routing strategy. Network performance results showed that the proposed strategy had ashorter delay, lower CPU utilization and less redundancy compared with CCN.

Autophagy is involved in neural cell death after cerebral ischemia. Our previous studies showed that rapamycin-induced autophagy decreased the rate of apoptosis, but the rate of apoptosis was in- creased after the autophagy inhibitor, 3-methyladenine, was used. In this study, a suture-occluded method was performed to generate a rat model of brain ischemia. Under a transmission electron microscope, autophagic bodies and autophagy lysosomes were markedly accumulated in neurons at 4 hours post brain ischemic injury, with their numbers gradually reducing over time. Western blotting demonstrated that protein levels of light chain 3-11 and cathepsin B were significantly in- creased within 4 hours of ischemic injury, but these levels were not persistently upregulated over time. Confocal microscopy showed that autophagy was mainly found in neurons with positive light chain 3 signal. Injection of rapamycin via tail vein promoted the occurrence of autophagy in rat brain tissue after cerebral ischemia and elevated light chain 3 and cathepsin B expression. However, in- jection of 3-methyladenine significantly diminished light chain 3-11 and cathepsin B expression. Results verified that autophagic and lysosomal activity is increased in ischemic neurons. Abnormal components in cells can be eliminated through upregulating cell autophagy or inhibiting autophagy after ischemic brain injury, resulting in a dynamic balance of substances in cells. Moreover, drugs that interfere with autophagy may be potential therapies for the treatment of brain injury.