学会抄録

Details for the selection of physicochemical properties from AAIndex database. (DOC 31 kb

The TLR9 ligand, CpG-ODN, Induces Protection Against Cerebral Ischemia/Reperfusion Injury via Activation of pi3k/Akt Signaling.

Toll-like receptors (TLRs) have been shown to be involved in cerebral ischemia/reperfusion (I/R) injury. TLR9 is located in intracellular compartments and recognizes CpG-DNA. This study examined the effect of CpG-ODN on cerebral I/R injury. C57BL/6 mice were treated with CpG-ODN by i.p. injection 1 hour before the mice were subjected to cerebral ischemia (60 minutes) followed by reperfusion (24 hours). Scrambled-ODN served as control-ODN. Untreated mice, subjected to cerebral I/R, served as I/R control. The effect of inhibitory CpG-ODN (iCpG-ODN) on cerebral I/R injury was also examined. In addition, we examined the therapeutic effect of CpG-ODN on cerebral I/R injury by administration of CpG-ODN 15 minutes after cerebral ischemia. CpG-ODN administration significantly decreased cerebral I/R-induced infarct volume by 69.7% (6.4±1.80% vs 21.0±2.85%, P\u3c0.05), improved neurological scores, and increased survival rate, when compared with the untreated I/R group. Therapeutic administration of CpG-ODN also significantly reduced infarct volume by 44.7% (12.6±2.03% vs 22.8±2.54%, P\u3c0.05) compared with untreated I/R mice. Neither control-ODN, nor iCpG-ODN altered I/R-induced cerebral injury or neurological deficits. Nissl staining showed that CpG-ODN treatment preserved neuronal morphology in the ischemic hippocampus. Immunoblot showed that CpG-ODN administration increased Bcl-2 levels by 41% and attenuated I/R-increased levels of Bax and caspase-3 activity in ischemic brain tissues. Importantly, CpG-ODN treatment induced Akt and GSK-3β phosphorylation in brain tissue and cultured microglial cells. PI3K inhibition with LY294002 abolished CpG-ODN-induced protection. CpG-ODN significantly reduces cerebral I/R injury via a PI3K/Akt-dependent mechanism. Our data also indicate that CpG-ODN may be useful in the therapy of cerebral I/R injury

Assessing Reproducibility of Inherited Variants Detected With Short-Read Whole Genome Sequencing

Background: Reproducible detection of inherited variants with whole genome sequencing (WGS) is vital for the implementation of precision medicine and is a complicated process in which each step affects variant call quality. Systematically assessing reproducibility of inherited variants with WGS and impact of each step in the process is needed for understanding and improving quality of inherited variants from WGS. Results: To dissect the impact of factors involved in detection of inherited variants with WGS, we sequence triplicates of eight DNA samples representing two populations on three short-read sequencing platforms using three library kits in six labs and call variants with 56 combinations of aligners and callers. We find that bioinformatics pipelines (callers and aligners) have a larger impact on variant reproducibility than WGS platform or library preparation. Single-nucleotide variants (SNVs), particularly outside difficult-to-map regions, are more reproducible than small insertions and deletions (indels), which are least reproducible when \u3e 5 bp. Increasing sequencing coverage improves indel reproducibility but has limited impact on SNVs above 30×. Conclusions: Our findings highlight sources of variability in variant detection and the need for improvement of bioinformatics pipelines in the era of precision medicine with WGS

Assessing reproducibility of inherited variants detected with short-read whole genome sequencing

Background: Reproducible detection of inherited variants with whole genome sequencing (WGS) is vital for the implementation of precision medicine and is a complicated process in which each step affects variant call quality. Systematically assessing reproducibility of inherited variants with WGS and impact of each step in the process is needed for understanding and improving quality of inherited variants from WGS. Results: To dissect the impact of factors involved in detection of inherited variants with WGS, we sequence triplicates of eight DNA samples representing two populations on three short-read sequencing platforms using three library kits in six labs and call variants with 56 combinations of aligners and callers. We find that bioinformatics pipelines (callers and aligners) have a larger impact on variant reproducibility than WGS platform or library preparation. Single-nucleotide variants (SNVs), particularly outside difficult-to-map regions, are more reproducible than small insertions and deletions (indels), which are least reproducible when > 5 bp. Increasing sequencing coverage improves indel reproducibility but has limited impact on SNVs above 30x. Conclusions: Our findings highlight sources of variability in variant detection and the need for improvement of bioinformatics pipelines in the era of precision medicine with WGS.Peer reviewe

Apical-basal distribution of different subtypes of spiral ganglion neurons in the cochlea and the changes during aging.

Sound information is transmitted from the cochlea to the brain mainly by type I spiral ganglion neurons (SGNs), which consist of different subtypes with distinct physiological properties and selective expression of molecular markers. It remains unclear how these SGN subtypes distribute along the tonotopic axis, and whether the distribution pattern changes during aging that might underlie age-related hearing loss (ARHL). We investigated these questions using immunohistochemistry in three age groups of CBA/CaJ mice of either sex, including 2-5 months (young), 17-19 months (middle-age), and 28-32 months (old). Mouse cochleae were cryo-sectioned and triple-stained using antibodies against Tuj1, calretinin (CR) and calbindin (CB), which are reportedly expressed in all type I, subtype Ia, and subtype Ib SGNs, respectively. Labeled SGNs were classified into four groups based on the expression pattern of stained markers, including CR+ (subtype Ia), CB+ (subtype Ib), CR+CB+ (dual-labeled Ia/Ib), and CR-CB- (subtype Ic) neurons. The distribution of these SGN groups was analyzed in the apex, middle, and base regions of the cochleae. It showed that the prevalence of subtype Ia, Ib and dual-labeled Ia/Ib SGNs are high in the apex and low in the base. In contrast, the distribution pattern is reversed in Ic SGNs. Such frequency-dependent distribution is largely maintained during aging except for a preferential reduction of Ic SGNs, especially in the base. These findings corroborate the prior study based on RNAscope that SGN subtypes show differential vulnerability during aging. It suggests that sound processing of different frequencies involves distinct combinations of SGN subtypes, and the age-dependent loss of Ic SGNs in the base may especially impact high-frequency hearing during ARHL

Serum lipid and lipoprotein levels of middle-aged and elderly Chinese men and women in Shandong Province

Abstract Background Cardiovascular and cerebrovascular diseases have become leading causes of death in China as the economy develop and lifestyles change. This study aimed to estimate the relationship of the age, gender, and glucose metabolism with the serum lipid and lipoprotein levels of middle-aged and elderly Chinese men and women in Shandong Province. Methods We conducted a cross-sectional study in Shandong Province that included 10,028 adults aged ≥40 years. Fasting serum total, low-density lipoprotein (LDL), high-density lipoprotein (HDL) cholesterol and triglycerides were measured by standard methods. Results The estimates of total, LDL, and HDL cholesterol and triglycerides were as follows: 5.35, 3.18, 1.51, and 1.34 mmol/L in the middle-aged and elderly Chinese adult population; 5.14, 3.08, 1.42, and 1.33 mmol/L in male subjects; 5.46, 3.24, 1.56, and 1.34 mmol/L in females; 5.27, 3.11, 1.54, and 1.24 mmol/L in the normal glucose tolerance population, 5.49, 3.27, 1.50, and 1.41 mmol/L in the population with pre-diabetes, and 5.39, 3.23, 1.43, and 1.58 mmol/L in the population with diabetes, respectively. Moreover, 36.92 and 19.10% of the adults had borderline-high and high total cholesterol. The population estimates for borderline-high, high LDL and low HDL cholesterol levels were 25.24, 13.39, and 5.64%, respectively. Meanwhile, borderline high and high triglyceride levels accounted for 16.7 and 17.47% of the population, respectively. Conclusions Serum total and LDL cholesterol levels were high in the ≥40 years old population of Shandong Province. Age, gender, glucose metabolism status, body mass index (BMI) and glycosylated hemoglobin (HbA1c) can affect serum lipid and lipoprotein levels

Optimizing the planting structure in Daxing District in 2020 based on inaccurate two-stage planning model and grey model

In order to optimize the planting structure and use water more efficiently, an inaccurate two-stage planning model is proposed in this paper. This model can not only reflect uncertainty of the probability distribution in the form of the possible distribution interval, but also build a recourse relationship between expected benefits and penalties for failing to achieve target goals. The two-stage planning model, combined with the gray GM (1.1) model, is applied to Daxing district of Beijing to optimize and adjust planting areas of the grain crops, fruits and vegetables, and garden plots in 2020. In the meantime, three scenarios were established for comparative analysis. Results show that after optimization, the economic benefits of above-mentioned three planting areas in Daxing district in 2020 is 3.71 billion CNY, an increase of 348 million from 2016 CNY; the total water consumption is 64.17 million cubic meters, a decrease of 62.79 million cubic meters from 2016. Results indicate that this model method is feasible for optimizing planting structure, and to some extent, can provide decision-making support and a theoretical basis for planting structure optimization and prediction in similar areas to Daxing district

Optimizing the planting structure in Daxing District in 2020 based on inaccurate two-stage planning model and grey model

In order to optimize the planting structure and use water more efficiently, an inaccurate two-stage planning model is proposed in this paper. This model can not only reflect uncertainty of the probability distribution in the form of the possible distribution interval, but also build a recourse relationship between expected benefits and penalties for failing to achieve target goals. The two-stage planning model, combined with the gray GM (1.1) model, is applied to Daxing district of Beijing to optimize and adjust planting areas of the grain crops, fruits and vegetables, and garden plots in 2020. In the meantime, three scenarios were established for comparative analysis. Results show that after optimization, the economic benefits of above-mentioned three planting areas in Daxing district in 2020 is 3.71 billion CNY, an increase of 348 million from 2016 CNY; the total water consumption is 64.17 million cubic meters, a decrease of 62.79 million cubic meters from 2016. Results indicate that this model method is feasible for optimizing planting structure, and to some extent, can provide decision-making support and a theoretical basis for planting structure optimization and prediction in similar areas to Daxing district