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Biomedical subjects

Di Liu

Publications and source records attributed to Di Liu.

At least 19 recordsLinked to original sources

Longitudinal analysis of circulating tumor DNA and CA19-9 dynamics in predicting disease relapse and monitoring treatment response in stage I-III pancreatic ductal adenocarcinoma: An interim analysis of a prospective observational study.

INTRODUCTION: Postoperative recurrence is the leading cause of mortality in resected pancreatic ductal adenocarcinoma (PDAC), yet reliable tools for early relapse detection and treatment response assessment remain lacking. METHODS: In a prospective cohort of 136 patients with resected stage I-III PDAC receiving adjuvant chemotherapy, we evaluated circulating tumor DNA (ctDNA) and CA19-9 as longitudinal biomarkers across multiple postoperative time windows. RESULTS: ctDNA consistently outperformed CA19-9 as an independent prognostic factor; ctDNA positivity at on-treatment and surveillance assessments achieved a positive predictive value of 91.7%, while persistent negativity identified the lowest-risk patients. Integrating CA19-9 with ctDNA resolved the ctDNA-alone gap in distinguishing treatment clearance from conversion, improving discrimination of responders from non-responders (HR 3.72; P = .008). A time-weighted dynamic ctDNA risk score (MinerVa-dynamic) further stratified ctDNA-negative patients into clinically distinct prognostic subgroups, achieving an area under the curve of 0.87 and 0.82 for one- and two-year disease-free survival prediction, respectively. CONCLUSIONS: These findings support a dual-biomarker longitudinal monitoring framework as a practical, individualized approach to postoperative surveillance and early therapeutic decision-making in PDAC.

CA19-9↗

Genetic Association of the Transcriptome and Immunoglobulin G N-glycome with Cognitive Function.

OBJECTIVE: Immunoglobulin G (IgG) N-glycosylation is associated with mild cognitive impairment through the regulation of inflammatory balance; however, the underlying mechanisms remain unclear. METHODS: Our study utilized a post-genome-wide association studies (GWAS) method that integrated GWAS data for cognitive function with gene expression quantitative trait loci (eQTL), protein QTL (pQTL), and IgG N-glycan-QTL data. RESULTS: Mendelian randomization (MR) analyses suggested bidirectional causalities between glycan peaks (GPs) and cognitive function, with GP7, GP12, and GP19 showing a causal effect on cognitive function, while cognitive function conversely showed a causal effect on GP1 and GP8. Two proteins and 10 genes were implicated in the regulation of IgG N-glycosylation. Furthermore, multivariable MR results suggested complex causalities between genes/proteins and IgG N-glycans, which jointly promote or independently affect cognitive function. CONCLUSION: Our study reveals a novel mechanism by which genes, proteins, and modified IgG N-glycans converge to pathologically affect cognitive function.

Immunoglobulin G↗

Genomic insights into the demographic history and local adaptation of wild boars across Eurasia.

Wild boars exhibit genetic and phenotypic diversity shaped by migrations and local adaptations. Their expansion across Eurasia, especially in Central Asia, remains underexplored. Here, we present newly sequenced whole-genome data of 47 wild boars from Eastern Asia, Central Asia, and Europe, combined with 49 existing genomes, creating a comprehensive dataset of 96 individuals. Our analyses show that Asian wild boars and Southeast Asian Suids split ∼3.6 million years ago (mya), with Central Asian and Southern Chinese ancestors diverging ∼1.8 mya. The split between Central Asian and European-Near East ancestors occurred ∼0.9 mya, followed by a European-Near East divergence ∼0.6 mya. We identify signatures of local adaptation in Central Asian populations, including two positively selected variants in LPIN1, associated with lipid metabolism, and a missense mutation in ALPK2, linked to meat traits. These findings provide insights into wild boar dispersal and adaptation and shed light on domestic pig breeding.

Animals↗

Renaturation and purification of ApxII toxin of Actinobacillus pleuropneumoniae.

ApxII toxin is the only Apx toxin that is produced by Actinobacillus pleuropneumoniae serotype 7. In order to determine whether the recombinant ApxII that derived from Escherichia coli (E. coli) expression is faithful to the natural ApxII so that can be used as additional component in vaccine preparation, the structure gene apxIIA of ApxII toxin was expressed in E. coli with prokaryotic expression vector pGEX-6p-1 (formed pGEX-6p-A). pGZRS-C which is A. pleuropneumoniae-E. coli shuttle vector pGZRS-38 expressing the post-transcriptional activation gene apxII C was co-expressed with pGEX-6p-A. The expression product of rApxII A formed inclusion. The inclusion protein was oxidized, refolded and restored hemolytic activity after denaturation, renaturation and purification. The result indicated that E. coli expressed recombinant ApxII toxin has good fidelity, which makes it possible to produce this valuable antigen for vaccine preparation or diagnosis.

Actinobacillus pleuropneumoniae↗

Optimal transition paths of stochastic chemical kinetic systems.

We present a new framework for finding the optimal transition paths of metastable stochastic chemical kinetic systems with large system sizes. The optimal transition paths are identified, in terms of reaction advancement coordinates, to be the most probable paths according to large deviation theory for the limiting dynamics governed by stochastic differential equations. Dynamical equations for the optimal transition paths are obtained using the variational principle. A multiscale minimum action method is proposed as a numerical scheme to solve the optimal transition paths. Applications to the toggle switch model are presented.

Journal Article↗

[A new polymorphic site of ESR gene in pigs].

ESR (Estrogen Receptor) gene has been determined to be one of the major genes affecting phenotype of litter size without any genetic negative correlation to growth and carcass trait. Recent studies mainly focused on the PvuII enzyme site found by Rothschild in 1996. An optimized standard PCR-SSCP protocol was employed to detect the exon 7 of ESR gene. The results showed that there were a new mutation site and three genotypes, which may be used as a new DNA marker site to further research.

Animals↗

[Analysis of SNPs in exons 2 and 3 of the leptin gene in wild boar, swine and hybrid swine].

Leptin is a 167-amino acid hormone mainly expressed in the fat tissue. It serves as an important regulator of energy uptake and consumption through action on the hypothalamus. Herein single nucleotide polymorphisms (SNPs) were detected in exons 2 and 3 of the Leptin gene in wild boar, swine and half-bred swine by PCR-SSCP. Cloning and sequencing of homozygous fragments revealed the following variations in the coding region: a silent T to C transversion at nucleotide 214; CG to GC at nucleotides 364 and 365, which converts Arg to Ala; a silent G to A transversion at nucleotide 426; a T insertion at nucleotide 451 resulting in frameshift; and a G to T transversion at nucleotide 462.

Amino Acid Substitution↗

Nested stochastic simulation algorithm for chemical kinetic systems with disparate rates.

An efficient simulation algorithm for chemical kinetic systems with disparate rates is proposed. This new algorithm is quite general, and it amounts to a simple and seamless modification of the classical stochastic simulation algorithm (SSA), also known as the Gillespie [J. Comput. Phys. 22, 403 (1976); J. Phys. Chem. 81, 2340 (1977)] algorithm. The basic idea is to use an outer SSA to simulate the slow processes with rates computed from an inner SSA which simulates the fast reactions. Averaging theorems for Markov processes can be used to identify the fast and slow variables in the system as well as the effective dynamics over the slow time scale, even though the algorithm itself does not rely on such information. This nested SSA can be easily generalized to systems with more than two separated time scales. Convergence and efficiency of the algorithm are discussed using the established error estimates and illustrated through examples.

Journal Article↗

DATF: a database of Arabidopsis transcription factors.

UNLABELLED: We have probably developed the most comprehensive database of Arabidopsis transcription factors (DATF). The DATF contains known and predicted Arabidopsis transcription factors (1827 genes in 56 families) with the unique information of 1177 cloned sequences and many other features including 3D structure templates, EST expression information, transcription factor binding sites and nuclear location signals. AVAILABILITY: DATF is freely available at http://datf.cbi.pku.edu.cn

Amino Acid Sequence↗

An annotation update via cDNA sequence analysis and comprehensive profiling of developmental, hormonal or environmental responsiveness of the Arabidopsis AP2/EREBP transcription factor gene family.

AP2/EREBP transcription factors (TFs) play functionally important roles in plant growth and development, especially in hormonal regulation and in response to environmental stress. Here we reported verification and correction of annotation through an exhaustive cDNA cloning and sequence analysis performed on 145 of 147 gene family members. A RACE analysis performed on genes with potential in-frame up-stream ATG codon resulted in identification of At2g28520 as an authentic AP2/EREBP member and corrected ORF annotations for three other members. A further phylogenetic analysis of this updated and likely complete family divided it into three major subfamilies. The expression patterns of the AP2/EREBP family members among the 11 organ or tissue types were examined using an oligo microarray and their hormonal and environmental responsiveness were further characterized using cDNA custom macroarrays. These detailed expression profile results provide strong support for a role for AP2/EREBP family members in development and in response to environmental stimuli, and a foundation for future functional analysis of this gene family.

Algorithms↗

Control of spontaneous B lymphocyte autoimmunity with adenovirus-encoded soluble TACI.

OBJECTIVE: Serum B lymphocyte stimulator (BLyS) is increased in autoimmune diseases, both in animal models and in humans. This study examined the effect of BLyS blockade in 3 animal models of lupus. METHODS: Antibodies and lupus-like disease manifestations were examined in mice after administration of a single injection of an adenoviral construct for the transmembrane activator and CAML interactor receptor (AdTACI) that produces high serum levels of TACI-Fc fusion protein. RESULTS: In C57BL/6 (B6) lpr/lpr mice (B6.lpr/lpr), which were used to model autoimmunity in the absence of severe disease, treatment of younger mice with AdTACI prevented the development of hypergammaglobulinemia. In contrast, use of AdTACI for BLyS blockade had only transient effects on the levels of IgG in normal B6 mice. AdTACI blocked the development of autoantibodies in younger B6.lpr/lpr mice and reversed the production of autoantibodies in older B6.lpr/lpr mice, and also reduced the numbers of splenic plasma cells. In MRL.lpr/lpr mice, which were used to examine disease manifestations, AdTACI reduced the extent of glomerulonephritis and proteinuria and improved survival, but had little effect on T cell infiltration and interstitial nephritis. However, in (NZB x NZW)F(1) mice, AdTACI induced neutralizing anti-TACI antibodies and failed to reduce the numbers of B cells. CONCLUSION: BLyS blockade has little effect on IgG levels in normal mice, but reverses the production of spontaneously produced IgM and IgG autoantibodies in the setting of established autoimmunity. Blockade of BLyS ameliorates B cell-dependent disease manifestations even in the MRL.lpr/lpr model, but its effectiveness on autonomous T cell aspects of the disease is limited. Moreover, its effectiveness is neutralized by anti-TACI antibodies when present. These results provide a basis for understanding the potential effects of BLyS blockade in human disease.

Adenoviridae↗

The effect of the PREMIER interventions on insulin sensitivity.

OBJECTIVE: This ancillary study of PREMIER sought to determine the effects on insulin sensitivity of a comprehensive behavioral intervention for hypertension with and without the Dietary Approaches to Stop Hypertension (DASH) dietary pattern. RESEARCH DESIGN AND METHODS: Participants were assigned to one of three nonpharmacologic interventions for blood pressure (group A, advice only; group B, established; and group C, established plus DASH). The established intervention included weight loss, reduced sodium intake, increased physical activity, and moderate alcohol intake; the DASH dietary pattern was added to the established intervention for those in group C. The DASH dietary pattern is high in fruits, vegetables, and low-fat dairy products while being lower in total fat, saturated fat, and cholesterol. It is abundant in nutrients such as magnesium, calcium, and protein, which have been associated with improved insulin sensitivity. Insulin sensitivity was measured at baseline and at 6 months using the frequently sampled intravenous glucose tolerance test with minimal model analysis. RESULTS: Both intervention groups decreased total calories, percentage of calories from fat, and sodium intake to similar levels, with similar amounts of energy expenditure and weight loss. Covariate differences seen only in group C included increased intake of protein, potassium, calcium, and magnesium. Compared with control subjects, insulin sensitivity improved significantly only in group C, from 1.96 to 2.95 (P = 0.047). Group B did have a significant decrease in fasting insulin and glucose, but the changes in insulin sensitivity did not reach statistical significance when compared with control subjects. CONCLUSIONS: These results suggest that including the DASH dietary pattern as part of a comprehensive intervention for blood pressure control enhances insulin action beyond the effects of a comprehensive intervention that does not include DASH.

Adult↗

TRAIL-R2 (DR5) mediates apoptosis of synovial fibroblasts in rheumatoid arthritis.

TRAIL has been proposed as an anti-inflammatory cytokine in animal models of rheumatoid arthritis (RA). Using two agonistic mAbs specific for TRAIL-R1 (DR4) and TRAIL-R2 (DR5), we examined the expression and function of these death receptors in RA synovial fibroblast cells. The synovial tissues and primary synovial fibroblast cells isolated from patients with RA, but not those isolated from patients with osteoarthritis, selectively expressed high levels of cell surface DR5 and were highly susceptible to anti-DR5 Ab (TRA-8)-mediated apoptosis. In contrast, RA synoviocytes did not show increased expression of TRAIL-R1 (DR4), nor was there any difference in expression of Fas between RA and osteoarthritis synovial cells. In vitro TRA-8 induced apoptosis of RA synovial cells and inhibited production of matrix metalloproteinases induced by pro-inflammatory cytokines. In vivo TRA-8 effectively inhibited hypercellularity of a SV40-transformed RA synovial cell line and completely prevented bone erosion and cartilage destruction induced by these cells. These results indicate that increased DR5 expression and susceptibility to DR5-mediated apoptosis are characteristic of the proliferating synovial cells in RA. As highly proliferative transformed-appearing RA synovial cells play a crucial role in bone erosion and cartilage destruction in RA, the specific targeting of DR5 on RA synovial cells with an agonistic anti-DR5 Ab may be a potential therapy for RA.

Adult↗

Isolation and analyses of genes preferentially expressed during early cotton fiber development by subtractive PCR and cDNA array.

Cotton fibers are differentiated epidermal cells originating from the outer integuments of the ovule. To identify genes involved in cotton fiber elongation, we performed subtractive PCR using cDNA prepared from 10 days post anthesis (d.p.a.) wild-type cotton fiber as tester and cDNA from a fuzzless-lintless (fl) mutant as driver. We recovered 280 independent cDNA fragments including most of the previously published cotton fiber-related genes. cDNA macroarrays showed that 172 genes were significantly up-regulated in elongating cotton fibers as confirmed by in situ hybridization in representative cases. Twenty-nine cDNAs, including a putative vacuolar (H+)-ATPase catalytic subunit, a kinesin-like calmodulin binding protein, several arabinogalactan proteins and key enzymes involved in long chain fatty acid biosynthesis, accumulated to greater than 50-fold in 10 d.p.a. fiber cells when compared to that in 0 d.p.a. ovules. Various upstream pathways, such as auxin signal transduction, the MAPK pathway and profilin- and expansin-induced cell wall loosening, were also activated during the fast fiber elongation period. This report constitutes the first systematic analysis of genes involved in cotton fiber development. Our results suggest that a concerted mechanism involving multiple cellular pathways is responsible for cotton fiber elongation.

Cell Division↗

[Introduction to genome databases].

A brief introduction to the genome databases GDB, GenoList and Ensembl is given. These databases, mirrored and maintained at the Centre of Bioinformatics, Peking University, provide useful information for genome research.

English Abstract↗

[Studies on the karyotype and bands of hybrid pig].

Using usual method, we got karyotype of hybrid pig (wild soar (male symbol) x domestic pig (female symbol)), C-band and approximate 174 bands of G-band, and we also obtained approximate 258 bands of high resolution G-band by micro-Colchicin method. The result indicate that the diploid chromosome number is 2n=38; there is polymorphism in C-band,and compared with domestic pig in G-band and high resolution G-band there is no distinguish difference. They belong to the same seed.

English Abstract↗

Simplified amino acid alphabets based on deviation of conditional probability from random background.

The primitive data for deducing the Miyazawa-Jernigan contact energy or blocks substitution matrix (BLOSUM) consists of pair frequency counts. Each amino acid corresponds to a conditional probability distribution. Based on the deviation of such a conditional probability from random background, a scheme for the reduction of the amino acid alphabet is proposed. It is observed that an evident discrepancy exists between the reduced alphabets obtained from the raw data of the Miyazawa-Jernigan's and BLOSUM's residue pair counts. Taking a homologous sequence database SCOP40 as a test set, we detect homology with the obtained coarse-grained substitution matrices. It is verified that the reduced alphabets obtained well preserve information contained in the original 20-letter alphabet.

Algorithms↗