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Circulating n-3 PUFA, which integrate endogenous and exogenous n-3 PUFA, can be better used to investigate the relationship between n-3 PUFA and disease. However, studies examining the associations between circulating n-3 PUFA and colorectal cancer (CRC) risk were limited, and the results remained inconclusive. This case–control study aimed to examine the association between serum n-3 PUFA and CRC risk in Chinese population. A total of 680 CRC cases and 680 sex- and age-matched (5-year interval) controls were included. Fatty acids were assayed by GC. OR and 95 % CI were calculated using multivariable logistic regression after adjustment for potential confounders. Higher level of serum α-linolenic acid (ALA), docosapentaenoic acid (DPA), DHA, long-chain n-3 PUFA and total n-3 PUFA were associated with lower odds of CRC. The adjusted OR and 95 % CI were 0·34 (0·24, 0·49, Pfor trend < 0·001) for ALA, 0·57 (0·40, 0·80, Pfor trend < 0·001) for DPA, 0·48 (0·34, 0·68, Pfor trend < 0·001) for DHA, 0·39 (0·27, 0·56, Pfor trend < 0·001) for long-chain n-3 PUFA and 0·31 (0·22, 0·45, Pfor trend < 0·001) for total n-3 PUFA comparing the highest with the lowest quartile. However, there was no statistically significant association between EPA and odds of CRC. Analysis stratified by sex showed that ALA, DHA, long-chain n-3 PUFA and total n-3 PUFA were inversely associated with odds of CRC in both sexes. This study indicated that serum ALA, DPA, DHA, long-chain n-3 PUFA and total n-3 PUFA were inversely associated with odds of having CRC in Chinese population.
In the Venus capture period, it is difficult for celestial autonomous navigation to satisfy the requirement of high precision. To improve autonomous navigation performance, a Direction, Distance and Velocity (DDV) measurements deeply integrated navigation method is proposed. The “deeply” integrated navigation reflects the fact that the direction and velocity measurements suppress the Doppler effects in the pulsar signals. In the pulsar observation period, the direction and velocity measurements are utilised to compensate for Doppler effects in the pulsar signals. By these means, the residual effects can be ignored. When the direction, distance or velocity measurements are obtained, they are fused to improve the navigation performance. Simulation results demonstrate that the DDV measurements deeply integrated navigation filter converges very well, and provides highly accurate position estimation without a high quality requirement on navigation sensors.
Introduction: The mortality of Parkinson’s disease (PD) and its associated risk factors among clinically definite PD patients in China has been rarely investigated. Our study aimed to identify the mortality rates and predictors of death in PD patients in China. Methods: 157 consecutive, clinically definite PD patients from the urban area of Shanghai were recruited from a central hospital based movement disorder clinic in 2006. All patients were regularly followed up at the clinic until December 31, 2011, or death. Mortality and associations with baseline demographics, health and medical factors were then determined within the cohort. Results: After 5 years, 11(7%) patients had died. The standardised mortality ratio was 0.62 (95% CI 0.32 to 1.07, P=0.104). The main causes of death were pneumonia (54.5%, 6/11) and digestive disorders (18.2%, 2/11), respectively. Age at onset, independent living, the mini mental state examination score, the Parkinson’s disease sleep scale score and the Epworth sleepiness scale score at baseline were statistically significantly different between the survival group and the deceased group (P<0.05). Across all participants, risk factors for death included low mini mental state examination score, and high Epworth sleepiness scale score according to a binary variable logistic regression analysis. Conclusions: This study confirms the similar survival of patients with PD to the control population up to a follow-up of 5 years. Interventions tailored to potential risk factors associated with death may offer further benefits.
Hypoxia inducible factor 1 (HIF-1) is a key transcriptional factor activated during cerebral ischemia, which regulates a great number of downstream genes, including those associated with cell death. In the present study, we aimed to test the hypothesis that post-ischemic HIF-1α up-regulation might promote autophagy activation; thereby, HIF-1α inhibitor 2ME2 might prevent neurons from ischemic injury through inhibiting autophagy.
Global ischemia was induced using the four-vessel occlusion model (4-VO) in Sprague-Dawley rats (male, 250-280g). 2-Methoxyestradiol (2ME2, 5mg/kg, i.p.) was administrated to down-regulate HIF-1α expression. Post-ischemic beclin-1 and LC3 protein expression was determined at different time points through Western blot assay. Neuronal injury was determined by cresyl violet staining and TUNEL staining in coronal histological sections.
The expression of beclin-1 and the ratio of LC3-II/LC3-I increased significantly at 12 and 24 h after ischemia. 2ME2 could remarkably inhibit the up-regulation of beclin-1 and the increase of LC3-II/LC3-I ratio during reperfusion. Moreover, 2ME2 and 3-MA exhibited powerful protective effects against ischemic/reperfusion induced neuronal injury.
This study confirmed that autophagy participated in post-ischemic neuronal injury. 2ME2, a HIF-1α inhibitor, might significantly decrease autophagy activation after cerebral ischemia and relieve post-ischemic neuronal injury. Our findings demonstrate that autophagy could be a potential target for neuronal protection after cerebral ischemia.
High-throughput gene profiling studies have been extensively conducted, searching for markers associated with cancer development and progression. In this study, we analyse cancer prognosis studies with right censored survival responses. With gene expression data, we adopt the weighted gene co-expression network analysis (WGCNA) to describe the interplay among genes. In network analysis, nodes represent genes. There are subsets of nodes, called modules, which are tightly connected to each other. Genes within the same modules tend to have co-regulated biological functions. For cancer prognosis data with gene expression measurements, our goal is to identify cancer markers, while properly accounting for the network module structure. A two-step sparse boosting approach, called Network Sparse Boosting (NSBoost), is proposed for marker selection. In the first step, for each module separately, we use a sparse boosting approach for within-module marker selection and construct module-level ‘super markers’. In the second step, we use the super markers to represent the effects of all genes within the same modules and conduct module-level selection using a sparse boosting approach. Simulation study shows that NSBoost can more accurately identify cancer-associated genes and modules than alternatives. In the analysis of breast cancer and lymphoma prognosis studies, NSBoost identifies genes with important biological implications. It outperforms alternatives including the boosting and penalization approaches by identifying a smaller number of genes/modules and/or having better prediction performance.
The present study was conducted in a one-factorial arrangement to determine the effects of dl-2-hydroxy-4-methylthiobutyrate (dl-HMTB) on the first-pass intestinal metabolism of dietary methionine and its extra-intestinal availability. Barrows (n 6; aged 35 d; weight 8·6 kg), implanted with arterial, portal, mesenteric and gastric catheters, were fed a diet containing dl-methionine (dl-MET) or dl-HMTB once hourly and infused intramesenterically with 1 % p-aminohippurate and intragastrically with [1-13C]methionine at 7·0 μmol/kg body weight per h. Arterial and portal blood samples were taken at hourly intervals until 6 h of tracer infusion and pigs was then killed for collection of muscle, intestine, liver and kidney samples. The net portal appearance of methionine, expressed as the fraction of ingested directly available l-methionine, was higher (P < 0·05) in the dl-HMTB than in the dl-MET diet, and there was no difference (P = 0·26) in the fractional portal balance of [1-13C]methionine between the diets. [1-13C]methionine enrichment (tracer:tracee ratio; mol/100 mol amino acid) in the jejunum, arterial and portal plasma, liver, kidney and muscle was also not different (P>0·05) between the groups. Over the 6 h period after the start of feeding, the average concentration of citrulline both in the arterial and portal plasma was higher (P < 0·05) in the dl-HMTB than in the dl-MET group, and arterial plasma ornithine and taurine concentration was also higher (P < 0·05) in the dl-HMTB than in the dl-MET group. However, plasma urea concentration both in the arterial and portal vein was lower (P < 0·05) in the dl-HMTB than in the dl-MET group. These results suggested that the potential difference in the first-pass use of methionine by the intestine between the dl-HMTB and dl-MET diets might affect intestinal and systemic metabolism of other amino acids, which may provide new important insights into nutritional efficiency of different methionine sources.
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