PubMed Health⌕ Search

Biomedical subjects

Jianjun Liu

Publications and source records attributed to Jianjun Liu.

At least 19 recordsLinked to original sources
PubMed2026

Genome-wide DNA methylation analysis revealed epigenetic mechanism underlying end-stage renal disease.

End-stage renal disease (ESRD) remains a major clinical challenge with high morbidity and mortality, and its molecular mechanisms, particularly those shared among diverse primary kidney diseases during progression to ESRD, have not been studied. Here we conduct a large-scale two-stage epigenome-wide association study of ESRD in two independent cohorts consisting of 704 controls and 1031 ESRD cases. We identify 52 ESRD-associated differentially methylated CpG positions (ESRD DMPs) showing consistent association between the two cohorts and across diverse kidney diseases, implicating 144 candidate genes enriched in inflammatory and immune pathways. Five of the 52 DMPs are associated with ESRD complications, and seven with renal function decline in early-stage chronic kidney disease, demonstrating their potential as prognostic biomarkers for ESRD and its complications. Our findings highlight inflammation, immune dysregulation, and renal fibrosis as shared epigenetic drivers of ESRD progression, and identify biomarkers with potential utility for risk stratification and therapeutic intervention.

Humans↗
PubMed2026

The mechanism by which long-term exposure to TDCIPP promotes cognitive impairment in 3 ×Tg-AD mice: Insights from multi-omics studies.

Tri(1,3-dichloro-2-propyl) phosphate (TDCIPP) is a commonly used organophosphate ester that has the potential to adversely affect human health. Although previous studies have closely associated TDCIPP with cognitive impairment, the underlying mechanisms remain unclear. To elucidate the neurotoxic effects of TDCIPP and its mechanistic contribution to cognitive impairment in 3 ×Tg-AD mice, a multi-omics approach incorporating proteomics, untargeted metabolomics, and 16S ribosomal RNA (rRNA) gene sequencing was employed to evaluate the impact of TDCIPP exposure on neurobehavioral function. TDCIPP exposure promoted cognitive impairment in 3 ×Tg-AD mice. Proteomic analyses revealed that this promotion is associated with disturbances in the hippocampal mitochondrial autophagy pathway. Furthermore, TDCIPP may interfere with the PINK1/Parkin-mediated mitophagy pathway at the functional level, without altering PINK1 protein abundance. Untargeted metabolomic analysis of urine samples demonstrated that TDCIPP exposure altered the metabolic profile of 3 ×Tg-AD mice, with 58 metabolites upregulated and 11 downregulated. Additionally, 16S rRNA sequencing revealed substantial modifications in gut microbiome composition following exposure to TDCIPP. Notably, significant correlations were identified between the perturbed bacterial genera and the differential metabolites. In conclusion, exposure to TDCIPP promotes cognitive impairment in 3 ×Tg-AD mice, which is associated with the interference with the PINK1/Parkin-mediated mitophagy pathway, as well as alterations in the urinary metabolome and gut microbiota. These findings suggest the potential to mitigate such cognitive impairment by targeting the microbiota-gut-brain axis.

Animals↗
PubMed2025

Stratifying Lung Adenocarcinoma Risk with Multi-ancestry Polygenic Risk Scores in East Asian Never-Smokers.

BACKGROUND: Lung adenocarcinoma (LUAD) in never-smokers is a major public health burden, especially among East Asian women. Polygenic risk scores (PRSs) are promising for risk stratification but are primarily developed in European-ancestry populations. We aimed to develop and validate single- and multi-ancestry PRSs for East Asian never-smokers to improve LUAD risk prediction. METHODS: PRSs were developed using genome-wide association study summary statistics from East Asian (8,002 cases; 20,782 controls) and European (2,058 cases; 5,575 controls) populations. Single-ancestry models included PRS-25, PRS-CT, and LDpred2; multi-ancestry models included LDpred2+PRS-EUR128, PRS-CSx, and CT-SLEB. Performance was evaluated in independent East Asian data from the Female Lung Cancer Consortium (FLCCA) and externally validated in the Nanjing Lung Cancer Cohort (NJLCC). We assessed predictive accuracy via AUC, with 10-year and (age 30-80) absolute risks estimates. RESULTS: The best multi-ancestry PRS, using East Asian and European data via CT-SLEB (clumping and thresholding, super learning, empirical Bayes), outperformed the best East Asian-only PRS (LDpred2; AUC=0.629, 95% CI:0.618,0.641), achieving an AUC of 0.640 (95% CI:0.629,0.653) and odds ratio of 1.71 (95% CI:1.61,1.82) per SD increase. NJLCC Validation confirmed robust performance (AUC =0.649, 95% CI: 0.623, 0.676). The top 20% PRS group had a 3.92-fold higher LUAD risk than the bottom 20%. Further, the top 5% PRS group reached a 6.69% lifetime absolute risk. Notably, this group reached the average population 10-year LUAD risk at age 50 (0.42%) by age 41, nine years earlier. CONCLUSIONS: Multi-ancestry PRS approaches enhance LUAD risk stratification in East Asian never-smokers, with consistent external validation, suggesting future clinical utility.

East Asian never smokers↗
PubMed2006

A first-principles analysis of hydrogen interaction in Ti-doped NaAlH4 surfaces: structure and energetics.

First principles density functional theory studies have been carried out to investigate the hydrogen interactions in Ti-doped NaAlH4 (001) and (100) surfaces. In both surfaces, Ti was found to energetically favor the interstitial sites formed by three neighboring AlH4- units and interact directly with them. The resulting local structure corresponds to a formula of TiAl3Hx with x = 12 before hydrogen desorption starts. The hydrogen desorption energies from many positions of TiAl3Hx are reduced considerably as compared with that from the corresponding clean, undoped NaAlH4 surfaces. The almost invariant local environment surrounding Ti during dehydrogenation makes the TiAl3Hx complex a precursor state for the formation of experimentally observed TiAl3. The importance of the complex has been explored by analyzing the structures and energetics accompanying hydrogen desorption from the complex and from the neighboring AlH4- units. The TiAl3Hx has extended effects beyond the locally reducing hydrogen desorption energy. It facilitates low-energy hydrogen desorption by either transferring hydrogen to the TiAl3Hx complex or reducing hydrogen desorption energy in the neighboring AlH4- by linking these AlH4- units with the complex structure. The possible mechanisms for forming octahedral AlH6(3-) were also identified in the vicinity of TiAl3Hx. Desorbing hydrogen atoms between Ti and Al atoms causes a symmetrical expansion of Ti-Al bonds and leads to the formation of octahedral AlH6(3-).

Journal Article↗
PubMed2006

Effect of ATM, CHEK2 and ERBB2 TAGSNPs and haplotypes on endometrial cancer risk.

Family history of endometrial cancer increases the risk of developing the disease, but it is still largely unknown which germ-line genetic factors are involved in the aetiology of endometrial cancer. In a Swedish population-based case-control study including 705 cases and 1565 controls, we examined common variation in the ATM, CHEK2 and ERBB2 genes in relation to endometrial cancer risk overall, restricted to tumours of certain characteristics or stratified by various endometrial cancer risk factors. We genotyped a large number of single-nucleotide polymorphisms (SNPs) in the genes and selected seven haplotype-tagging SNPs (tagSNPs) in ATM, six tagSNPs in CHEK2 and seven tagSNPs in ERBB2 that could predict common variants and haplotypes (frequency > or =0.03) in each gene with R(2) > or = 0.8. We included the tagSNPs or their haplotypes as explanatory variables in unconditional logistic regression models adjusted for age. Our results indicated an increased risk of developing endometroid endometrial cancer for homozygous carriers of the rare allele (AA) of a tagSNP (rs4987886) in CHEK2 (P = 0.005) when contrasted with GG carriers. We also found a decreased endometrial cancer risk among non-smoking carriers of a haplotype in ATM (P = 0.0007) and among carriers of a haplotype in CHEK2, who had experienced menopause below 49 years of age (P = 0.0009) compared with non-carriers of these haplotypes. We found no effect of genetic variation in ERBB2 on endometrial cancer risk. In conclusion, it is possible that common variants in the ATM and CHEK2 genes, in interaction with oestrogen-related exposures, are involved in endometrial cancer aetiology.

Age Factors↗
PubMed2006

Structural and electronic properties of fluorinated boron nitride nanotubes.

The effects of F doping on the structural and electronic properties of the (5, 5) single-walled boron nitride nanotube (BNNT) are investigated by using the density functional theory method. The chemiadsorption of F maintains the hexagonal BN network, increases the lattice constant, and introduces acceptor impurity states. On the other hand, substitutional doping of F destroys the hexagonal BN network, decreases the lattice constant, but does not alter the insulating feature of the BNNT. The observed insulator-to-semiconducting transition, a lattice contraction, and a highly disordered atom arrangement in the sidewall of BNNTs upon F doping appear to be most reasonably attributed to a codoping of dominating substitutional F over chemiabsorbed F, which can induce deep donor impurity states, a lattice contraction, and a destruction of the hexagonal BN network simultaneously.

Journal Article↗
PubMed2006

High-throughput genomic technology in research and clinical management of breast cancer. Evolving landscape of genetic epidemiological studies.

Candidate polymorphism-based genetic epidemiological studies have yielded little success in the search for low-penetrance breast cancer susceptibility genes. The lack of progress is partially due to insufficient coverage of genomic regions with genetic markers, as well as economic constraints, limiting both the number of genetic targets and the number of individuals being studied. Recent rapid advances in high-throughput genotyping technology and our understanding of genetic variation patterns across the human genome are now revolutionizing the way in which genetic epidemiological studies are being designed and conducted. Genetic epidemiological studies are quickly progressing from candidate gene studies to comprehensive pathway investigation and, further, to genomic epidemiological studies where the whole human genome is being interrogated to identify susceptibility alleles. This paper reviews the evolving approaches in the search for low-penetrance breast cancer susceptibility gene variants and discusses their potential promises and pitfalls.

Breast Neoplasms↗
PubMed2006

Linkage disequilibrium mapping of CHEK2: common variation and breast cancer risk.

BACKGROUND: Checkpoint kinase 2 (CHEK2) averts cancer development by promoting cell cycle arrest and activating DNA repair in genetically damaged cells. Previous investigation has established a role for the CHEK2 gene in breast cancer aetiology, but studies have largely been limited to the rare 1100delC mutation. Whether common polymorphisms in this gene influence breast cancer risk remains unknown. In this study, we aimed to assess the importance of common CHEK2 variants on population risk for breast cancer by capturing the majority of diversity in the gene using haplotype tagging single nucleotide polymorphisms (tagSNPs). METHODS AND FINDINGS: We analyzed 14 common SNPs spanning 52 kilobases (kb) of the CHEK2 gene in 92 Swedish women. Coverage evaluation indicated that these typed SNPs would efficiently convey association signal also from untyped SNPs in the same region. Six of the 14 SNPs predicted well both the haplotypic and single SNP variations within CHEK2. We genotyped these six tagSNPs in 1,577 postmenopausal breast cancer cases and 1,513 population controls, but found no convincing association between any common CHEK2 haplotype and breast cancer risk. The 1100delC mutation was rare in our Swedish population--0.7% in cases and 0.4% in controls--with a corresponding odds ratio for carriers versus noncarriers of 2.26 (95% confidence interval, 0.99-5.15). Estimates of the population frequency and the odds ratio of 1100delC indicate that our sample is representative of a Northern European population. CONCLUSIONS: Notwithstanding the involvement of the CHEK2 gene in breast cancer aetiology, we show that common polymorphisms do not influence postmenopausal breast cancer risk.

Aged↗
PubMed2006

Colloidal interactions between asphaltene surfaces in aqueous solutions.

Asphaltene at oil/water interfaces plays a dominant role in the recovery of crude oil. In this study, asphaltene monolayer films were deposited on hydrophobic silicon wafers and silica spheres from oil-water interfaces using a Langmuir interfacial trough. The morphology of the deposited asphaltene films was characterized with an atomic force microscope (AFM). The colloidal forces between the prepared asphaltene films in aqueous solutions were measured with AFM to shed light on the stabilization of water or oil droplets coated with asphaltene films. Factors such as solution pH, KCl concentration, calcium addition, and temperature all showed a strong impact on colloidal forces between the prepared asphaltene films. The findings provided a better understanding of asphaltene interfacial films at an oil/water interface in stabilizing bitumen-in-water and water-in-bitumen emulsions.

Journal Article↗
PubMed2006

Diverse phenotype of Brooke-Spiegler syndrome associated with a nonsense mutation in the CYLD tumor suppressor gene.

Brooke-Spiegler syndrome (BSS) is an autosomal dominant disease characterized by cylindromas, trichoepitheliomas and occasionally spiradenomas. The disease gene was mapped to 16q12-13, and mutations in the CYLD gene were identified in families with BSS. In the present report, we describe a large consanguineous Chinese family with BSS showing an intra-family phenotypic variability. Clinically, some affected individuals only revealed discrete small skin-coloured tumors whereas the proband showed an expansion of multiple large tumors on the back of nose and numerous dome-shaped papules on her scalp. Histologically, both trichoepitheliomas and cylindromas were found in the affected individuals. By sequence analysis, we identified a recurrent mutation 2272C>T (R758X) of the CYLD gene in the affected individuals of this family, which was previously identified in other ethnic families with familial cylindromatosis. Our result provided additional information for phenotype-genotype correlation in BSS.

Adult↗
PubMed2006

Comprehensive analysis of the ATM, CHEK2 and ERBB2 genes in relation to breast tumour characteristics and survival: a population-based case-control and follow-up study.

BACKGROUND: Mutations in the ataxia-telangiectasia mutated (ATM) and checkpoint kinase 2 (CHEK2) genes and amplification of the v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (ERBB2) gene have been suggested to have an important role in breast cancer aetiology. However, whether common variation in these genes has a role in the development of breast cancer or breast cancer survival in humans is still not clear. METHODS: We performed a comprehensive haplotype analysis of the ATM, CHEK2 and ERBB2 genes in a Swedish population-based study, which included 1,579 breast cancer cases and 1,516 controls. We followed the cases for 8.5 years, on average, and retrieved information on the date and cause of death during that period from the nationwide Swedish causes of death registry. We selected seven haplotype-tagging SNPs (tagSNPs) in the ATM gene, six tagSNPs in the CHEK2 gene and seven tagSNPs in the ERBB2 gene that predicted both haplotypic and single locus variations in the respective genes with R2 values > or = 0.8. These tagSNPs were genotyped in the complete set of cases and controls. We computed expected haplotype dosages of the tagSNP haplotypes and included the dosages as explanatory variables in Cox proportional hazards or logistic regression models. RESULTS: We found no association between any genetic variation in the ATM, CHEK2 or ERBB2 genes and breast cancer survival or the risk of developing tumours with certain characteristics. CONCLUSION: Our results indicate that common variants in the ATM, CHEK2 or ERBB2 genes are not involved in modifying breast cancer survival or the risk of tumour-characteristic-defined breast cancer.

Aged↗
PubMed2006

[Soil carbon cycle of Pinus tabulaeformis forest in Huoditang forest region of Qinling Mountains].

With soil carbon cycle compartment model,this paper studied the carbon storage and flux of each carbon compartment of soil under Pinus tabulaeformis, a main forest type in the Huoditang forest region of Qinling Mountain. The results showed that the storage of soil organic carbon was 146.071 t x hm(-2), with 130.366 t x hm(-2) in mineral soil layer and 12.626 t x hm(-2) in litter layer. The storage was lower than the average value of forest soils in China and of oak Sharptooth forest soil in Huoditang, but higher than that of the soils under temperate coniferous forest and tropical forest. The annual carbon input into litter layer was 5.939 t x hm(-2), with 56.9% from above-ground litter and 43.1% from underground dead roots, while that into mineral soil layer via humic acid was 2. 034 t x hm(-2). The annual amount of carbon released from the respiration of P. zabulaeformis forest-soil system was 14. 012 t x hm(-2), with litter layer, mineral soil layer, dead root system, and live root system occupied 15.7%, 14.5%, 11.7% and 58.1%, respectively.

Carbon↗
PubMed2005

Ab initio potential-energy surfaces of O2(X3Sigmag -, a1Deltag, b1Sigmag +) +O2 (X3Sigmag -, a1Deltag, b1Sigmag +): mechanism of quenching of O2 (a 1Deltag).

Ab initio computational studies were carried out in order to explore the possible mechanisms of quenching of O(2)(a (1)Delta(g)) by O(2)(X (3)Sigma(g) (-)): the self-quenching of O(2)(a (1)Delta(g)) and other energy-transfer processes involving two O(2) molecules. All eighteen states arising from two O(2) molecules in the X (3)Sigma(g) (-), a (1)Delta(g), and b (1)Sigma(g) (+) states are considered. After scans at the state-averaged complete active space self-consistent field method to identify possible regions of crossing between states belonging to different asymptotes, complete active state second-order perturbation theory high-symmetry optimization and low-symmetry scans established that four different minima on the seams of crossing (MSXs), arising between the a+a manifold and the X+b manifold and responsible for self-quenching: O(2)(a (1)Delta(g))+O(2)(a (1)Delta(g))-->O(2)(X (3)Sigma(g) (-))+O(2)(b (1)Sigma(g) (+)), have coplanar C(2h) or C(2v) symmetries and are only 0.45 eV barrier relative to the a+a asymptote and energetically easily accessible. The rate constant for this process was estimated based on the Landau-Zener formalism. The MSXs for quenching of O(2)(a (1)Delta(g)) by the ground state O(2)(X (3)Sigma(g) (-)):O(2)(a (1)Delta(g))+O(2)(X (3)Sigma(g) (-))-->O(2)(X (3)Sigma(g) (-))+O(2)(X (3)Sigma(g) (-)) require higher energies and the process is not likely to be important.

Journal Article↗
PubMed2005

Comprehensive evaluation of common genetic variation within LRRK2 reveals evidence for association with sporadic Parkinson's disease.

Parkinson's disease (PD) is a complex neurodegenerative disorder whose aetiologies are largely unknown. To date, mutations in six genes have been found causal for some rare familial forms of the disease and common variation within at least three of these is associated with the more common sporadic forms of PD. LRRK2 is the most recently identified familial PD gene, although its role in sporadic disease is unknown. In this study, we have performed the first comprehensive evaluation of common genetic variation within LRRK2 and investigated its contribution to risk of sporadic PD. We first characterized the linkage disequilibrium within LRRK2 using a panel of densely spaced SNPs across the gene. We then identified a subset of tagging-SNPs (tSNP) that capture the majority of common variation within LRRK2. Both single tSNP and tSNP haplotype analyses, using a large epidemiologically matched sporadic case-control series comprising 932 individuals, yielded significant evidence for disease association. We identified a haplotype that dramatically increases disease risk when present in two copies (OR=5.5, 95%CI=2.1-14.0, P=0.0001). Thus, we provide the first evidence that common genetic variation within LRRK2 contributes to the risk of sporadic PD in the Chinese population.

Adult↗
PubMed2005

CYP17 gene polymorphism in relation to breast cancer risk: a case-control study.

INTRODUCTION: The c.1-34T>C 5' promoter region polymorphism in cytochrome P450c17 (CYP17), a key enzyme in the biosynthesis of estrogen, has been associated with breast cancer risk, but most previous studies have been relatively small. METHODS: We genotyped 1,544 incident cases of primary breast cancer and 1,502 population controls, all postmenopausal Swedish women, for the CYP17 c.1-34T>C polymorphism and calculated odds ratios (ORs) and 95% confidence intervals (CIs) from logistic regression models. RESULTS: No overall association was found between CYP17 c.1-34T>C and breast cancer risk, OR 1.0 (95% CI 0.8-1.3) for the A2/A2 (CC) carriers compared to the A1/A1 (TT) carriers, regardless of histopathology. We detected an interaction between CYP17 c.1-34T>C and age at menarche (P = 0.026) but regarded that as a chance finding as no dose-response pattern was evident. Other breast cancer risk factors, including menopausal hormone use and diabetes mellitus, did not modify the overall results. CONCLUSION: It is unlikely that CYP17 c.1-34T>C has a role in breast cancer etiology, overall or in combination with established non-genetic breast cancer risk factors.

Aged↗
PubMed2005

Combined analysis from eleven linkage studies of bipolar disorder provides strong evidence of susceptibility loci on chromosomes 6q and 8q.

Several independent studies and meta-analyses aimed at identifying genomic regions linked to bipolar disorder (BP) have failed to find clear and consistent evidence of linkage regions. Our hypothesis is that combining the original genotype data provides benefits of increased power and control over sources of heterogeneity that outweigh the difficulty and potential pitfalls of the implementation. We conducted a combined analysis using the original genotype data from 11 BP genomewide linkage scans comprising 5,179 individuals from 1,067 families. Heterogeneity among studies was minimized in our analyses by using uniform methods of analysis and a common, standardized marker map and was assessed using novel methods developed for meta-analysis of genome scans. To date, this collaboration is the largest and most comprehensive analysis of linkage samples involving a psychiatric disorder. We demonstrate that combining original genome-scan data is a powerful approach for the elucidation of linkage regions underlying complex disease. Our results establish genomewide significant linkage to BP on chromosomes 6q and 8q, which provides solid information to guide future gene-finding efforts that rely on fine-mapping and association approaches.

Bipolar Disorder↗
PubMed2005

Interaction forces in bitumen extraction from oil sands.

Water-based extraction process (WBEP) has been successfully applied to bitumen recovery from Athabasca oil sand ore deposits in Alberta. In this process, two essential steps are involved. The bitumen first needs to be "liberated" from sand grains, followed by "aeration" with air bubbles. Bitumen "liberation" from the sand grains is controlled by the interaction between the bitumen and sand grains. Bitumen "aeration" is dependent, among other mechanical and hydrodynamic variables, on the hydrophobicity of the bitumen surface, which is controlled by water chemistry and interactions between bitumen and fine solids. In this paper, the interaction force measured with an atomic force microscope (AFM) between bitumen-bitumen, bitumen-silica, bitumen-clays and bitumen-fines is summarized. The measured interaction force barrier coupled with the contacted adhesion force allows us to predict the coagulative state of colloidal systems. Zeta potential distribution measurements, in terms of heterocoagulation, confirmed the prediction of the measured force profiles using AFM. The results show that solution pH and calcium addition can significantly affect the colloidal interactions of various components in oil sand extraction systems. The strong attachment of fines from a poor processing ore on bitumen is responsible for the corresponding low bitumen flotation recovery. The identification of the dominant non-contact forces by fitting with the classical DLVO or extended DLVO theory provides guidance for controlling the interaction behavior of the oil sand components through monitoring the factors that could affect the non-contact forces. The findings provide insights into megascale industrial operations of oil sand extraction.

Journal Article↗