Multi-criteria, multi-stakeholder decision analysis on urban freight sustainability initiatives

Master'sMASTER OF ENGINEERIN

The impact of pension insurance types on the health of older adults in China: a study based on the 2018 CHARLS data

IntroductionPension insurance is an essential safeguard for the quality of life and health of older adults because it provides a stable and dependable source of income after retirement. China has constructed a multi-level social security system to accommodate the diverse needs of older adults, and offers various levels of pension insurance to maximize their interests.MethodsThis study uses propensity score matching and ordinary least squares techniques to analyze 7,359 data from the 2018 China Health and Retirement Longitudinal Study (CHARLS) in order to explore the relationship between different pension insurance categories and the health of older individuals.ResultsThe research findings reveal that advanced insurances greatly benefit the health of older adults more than basic pension insurances, and the findings pass the robustness test. In addition, the effect was found to be heterogeneous, depending on the location of retirement and the marital status of older adults.Our findings suggest that both material and non-material consumption may be potential mechanisms by which pension insurance affects the health of older adults, providing new evidence for the causal mechanism between pension insurance and the health of older adults.DiscussionThis study expands the scope of research on the health effects of pension insurance by covering a large representative sample across the country. The results show the important impact of the level of pension insurance on the health of older adults and can contribute to the development of social policies to promote the physical and mental health of older adults

Expansion of the Parkinson disease-associated SNCA-Rep1 allele upregulates human alpha-synuclein in transgenic mouse brain.

Alpha-synuclein (SNCA) gene has been implicated in the development of rare forms of familial Parkinson disease (PD). Recently, it was shown that an increase in SNCA copy numbers leads to elevated levels of wild-type SNCA-mRNA and protein and is sufficient to cause early-onset, familial PD. A critical question concerning the molecular pathogenesis of PD is what contributory role, if any, is played by the SNCA gene in sporadic PD. The expansion of SNCA-Rep1, an upstream, polymorphic microsatellite of the SNCA gene, is associated with elevated risk for sporadic PD. However, whether SNCA-Rep1 is the causal variant and the underlying mechanism with which its effect is mediated by remained elusive. We report here the effects of three distinct SNCA-Rep1 variants in the brains of 72 mice transgenic for the entire human SNCA locus. Human SNCA-mRNA and protein levels were increased 1.7- and 1.25-fold, respectively, in homozygotes for the expanded, PD risk-conferring allele compared with homozygotes for the shorter, protective allele. When adjusting for the total SNCA-protein concentration (endogenous mouse and transgenic human) expressed in each brain, the expanded risk allele contributed 2.6-fold more to the SNCA steady-state than the shorter allele. Furthermore, targeted deletion of Rep1 resulted in the lowest human SNCA-mRNA and protein concentrations in murine brain. In contrast, the Rep1 effect was not observed in blood lysates from the same mice. These results demonstrate that Rep1 regulates human SNCA expression by enhancing its transcription in the adult nervous system and suggest that homozygosity for the expanded Rep1 allele may mimic locus multiplication, thereby elevating PD risk

Linkage and linkage disequilibrium analysis of the lipoprotein lipase gene with lipid profiles in Chinese hypertensive families

A B S T R A C T Elevated TG [triacylglycerol (triglyceride)] is a significant independent risk factor for cardiovascular disease. LPL (lipoprotein lipase) is one of the key enzymes in the metabolism of the TG-rich lipoproteins which hydrolyses TG from the chylomicrons and very-LDL (low-density lipoprotein). To investigate the relationship between the LPL gene and lipid profiles, especially TG, in 148 hypertensive families, we have chosen seven flanking microsatellite markers and four internal markers of the LPL gene and conducted linkage analysis by SOLAR and S.A.G.E. (statistical analysis for genetic epidemiology)/SIBPAL 2 programs, and linkage disequilibrium analysis by QTDT (quantitative transmission/disequilibrium test) and GOLD (graphical overview of linkage disequilibrium). There were statistically significant differences in lipid levels between subjects without and with hypertension within families. A maximum LOD score of 1.3 with TG at the marker D8S261 was observed by SOLAR. Using S.A.G.E./SIBPAL 2, we identified a linkage with TG at the marker 'ATTT' located within intron 6 of the LPL gene (P = 0.0095). Two SNPs (single nucleotide polymorphisms), HindIII and HinfI, were found in linkage disequilibrium with LDLcholesterol levels (P = 0.0178 and P = 0.0088 respectively). A strong linkage disequilibrium was observed between the HindIII in intron 8 and HinfI in the exon 9 (P < 0.00001, D = 0.895). Linkage disequilibrium was also found between the 'ATTT' polymorphism in intron 6 and two SNPs (P = 0.0021 and D = 0.611 for HindIII; and P = 0.00004, D = 0.459 for HinfI). The present study in the Chinese families with hypertension suggested that the LPL gene might influence lipid levels, especially TG metabolism. Replication studies both in Chinese and other populations are warranted to confirm these results

Comprehensive transcriptome analysis of peripheral blood unravels key lncRNAs implicated in ABPA and asthma

Allergic bronchopulmonary aspergillosis (ABPA) is a complex hypersensitivity lung disease caused by a fungus known as Aspergillus fumigatus. It complicates and aggravates asthma. Despite their potential associations, the underlying mechanisms of asthma developing into ABPA remain obscure. Here we performed an integrative transcriptome analysis based on three types of human peripheral blood, which derived from ABPA patients, asthmatic patients and health controls, aiming to identify crucial lncRNAs implicated in ABPA and asthma. Initially, a high-confidence dataset of lncRNAs was identified using a stringent filtering pipeline. A comparative mutational analysis revealed no significant difference among these samples. Differential expression analysis disclosed several immune-related mRNAs and lncRNAs differentially expressed in ABPA and asthma. For each disease, three sub-networks were established using differential network analysis. Many key lncRNAs implicated in ABPA and asthma were identified, respectively, i.e., AL139423.1-201, AC106028.4-201, HNRNPUL1-210, PUF60-218 and SREBF1-208. Our analysis indicated that these lncRNAs exhibits in the loss-of-function networks, and the expression of which were repressed in the occurrences of both diseases, implying their important roles in the immune-related processes in response to the occurrence of both diseases. Above all, our analysis proposed a new point of view to explore the relationship between ABPA and asthma, which might provide new clues to unveil the pathogenic mechanisms for both diseases

The Inheritance of Peripapillary Atrophy

PURPOSE. To estimate the relative importance of genes and environment in peripapillary atrophy type beta (␤-PPA) in a classic twin study. METHODS. Female twin pairs (n ϭ 506) aged 49 to 79 years were recruited from the St. Thomas' UK Adult Twin Registry. Peripapillary atrophy was identified from masked grading of stereoscopic optic disc photographs. Structural equation modeling was performed using Mx with polychoric correlations of ␤-PPA and refractive error (divided into deciles). RESULTS. ␤-PPA prevalence was 25.1% and did not vary with zygosity. Case-wise concordance for right eyes was 0.76 (95% CI, 0.57-0.88) for monozygotic (MZ) and 0.37 (95% CI, 0.15-0.56) for dizygotic (DZ) pairs. Multivariate modeling suggested additive genetic effects and individual environment, with no shared environment or dominant genetic effect. ␤-PPA heritability was 0.70 (95% CI, 0.54 -0.83), and spherical equivalent 0.88 (95% CI, 0.85-0.91); age had no significant effect on variance. The genetic correlation between ␤-PPA and spherical equivalent was Ϫ0.21. However, only 3% of the genetic variance of ␤-PPA was explained by genetic factors in common with refractive error, with 67% explained by specific genetic factors for ␤-PPA. Of the 30% of variance explained by unique environmental factors, only 3% was explained by these factors in common with environmental factors involved in refractive error. CONCLUSIONS. The presence of ␤-PPA, a frequent ocular finding known to be associated with open-angle glaucoma, appears to be under strong genetic control, with only a small amount of this genetic effect shared with genes involved in myopia. (Invest Ophthalmol Vis Sci

Development and verification of a combined immune- and cancer-associated fibroblast related prognostic signature for colon adenocarcinoma

IntroductionTo better understand the role of immune escape and cancer-associated fibroblasts (CAFs) in colon adenocarcinoma (COAD), an integrative analysis of the tumor microenvironment was performed using a set of 12 immune- and CAF-related genes (ICRGs).MethodsUnivariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses were used to establish a prognostic signature based on the expression of these 12 genes (S1PR5, AEN, IL20RB, FGF9, OSBPL1A, HSF4, PCAT6, FABP4, KIF15, ZNF792, CD1B and GLP2R). This signature was validated in both internal and external cohorts and was found to have a higher C-index than previous COAD signatures, confirming its robustness and reliability. To make use of this signature in clinical settings, a nomogram incorporating ICRG signatures and key clinical parameters, such as age and T stage, was developed. Finally, the role of S1PR5 in the immune response of COAD was validated through in vitro cytotoxicity experiments.ResultsThe developed nomogram exhibited slightly improved predictive accuracy compared to the ICRG signature alone, as indicated by the areas under the receiver operating characteristic curves (AUC, nomogram:0.838; ICRGs:0.807). The study also evaluated the relationships between risk scores (RS) based on the expression of the ICRGs and other key immunotherapy variables, including immune checkpoint expression, immunophenoscore (IPS), and microsatellite instability (MSI). Integration of these variables led to more precise prediction of treatment efficacy, enabling personalized immunotherapy for COAD patients. Knocking down S1PR5 can enhance the efficacy of PD-1 monoclonal antibody, promoting the cytotoxicity of T cells against HCT116 cells ((p<0.05).DiscussionThese findings indicate that the ICRG signature may be a valuable tool for predicting prognostic risk, evaluating the efficacy of immunotherapy, and tailoring personalized treatment options for patients with COAD

A Genome-Wide Association Study in Chronic Obstructive Pulmonary Disease (COPD): Identification of Two Major Susceptibility Loci

There is considerable variability in the susceptibility of smokers to develop chronic obstructive pulmonary disease (COPD). The only known genetic risk factor is severe deficiency of α1-antitrypsin, which is present in 1–2% of individuals with COPD. We conducted a genome-wide association study (GWAS) in a homogenous case-control cohort from Bergen, Norway (823 COPD cases and 810 smoking controls) and evaluated the top 100 single nucleotide polymorphisms (SNPs) in the family-based International COPD Genetics Network (ICGN; 1891 Caucasian individuals from 606 pedigrees) study. The polymorphisms that showed replication were further evaluated in 389 subjects from the US National Emphysema Treatment Trial (NETT) and 472 controls from the Normative Aging Study (NAS) and then in a fourth cohort of 949 individuals from 127 extended pedigrees from the Boston Early-Onset COPD population. Logistic regression models with adjustments of covariates were used to analyze the case-control populations. Family-based association analyses were conducted for a diagnosis of COPD and lung function in the family populations. Two SNPs at the α-nicotinic acetylcholine receptor (CHRNA 3/5) locus were identified in the genome-wide association study. They showed unambiguous replication in the ICGN family-based analysis and in the NETT case-control analysis with combined p-values of 1.48×10−10, (rs8034191) and 5.74×10−10 (rs1051730). Furthermore, these SNPs were significantly associated with lung function in both the ICGN and Boston Early-Onset COPD populations. The C allele of the rs8034191 SNP was estimated to have a population attributable risk for COPD of 12.2%. The association of hedgehog interacting protein (HHIP) locus on chromosome 4 was also consistently replicated, but did not reach genome-wide significance levels. Genome-wide significant association of the HHIP locus with lung function was identified in the Framingham Heart study (Wilk et al., companion article in this issue of PLoS Genetics; doi:10.1371/journal.pgen.1000429). The CHRNA 3/5 and the HHIP loci make a significant contribution to the risk of COPD. CHRNA3/5 is the same locus that has been implicated in the risk of lung cancer