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Biomedical subjects

Li Jiang

Publications and source records attributed to Li Jiang.

At least 19 recordsLinked to original sources
PubMed2026

Discovery and validation of a multi-protein panel for predicting non-fatal major adverse cardiovascular events in diabetic kidney disease.

OBJECTIVE: To identify plasma protein biomarkers associated with incident non-fatal major adverse cardiovascular events (MACE) in diabetic kidney disease (DKD) patients. RESEARCH DESIGN AND METHODS: We analyzed 317 DKD patients from the UK Biobank. Plasma proteomics and clinical data (demographics, metabolism, renal function) were integrated. In an exploratory discovery phase, three sequential Cox regression models (crude, socio-demographic-adjusted, socio-demographic-metabolic adjusted) screened non-fatal MACE-associated proteins. To prevent information leakage, the cohort was then randomly split into training (70%) and testing (30%) sets; machine-learning feature selection, hyperparameter optimization, and final model development were performed exclusively within the training set. The associated proteins were input into the four-step machine-learning pipeline (LASSO-Cox, random survival forest, Boruta, XGBoost-Cox). Predictive performance was validated using Kaplan-Meier survival analyses, longitudinal trajectory modeling, and ROC benchmarking. An interactive web application was deployed for clinical implementation. RESULTS: Of 1,463 plasma proteins, 561 were associated with non-fatal MACE across Cox models, with 14 overlapping proteins. Nine core proteins (ANG, IL1R1, CXCL14, ESAM, PTGDS, HAVCR1, FGFR2, IGSF8, CCL3) were validated: ANG showed the strongest non-fatal MACE association (HR&#xa0;=&#xa0;3.88, 95%CI 2.33-6.48, p<0.001), and all high-expression groups had elevated non-fatal MACE risk. GO/KEGG enrichment highlighted inflammatory-immune pathways like positive regulation of MAPK cascade, Cytokine-cytokine receptor interaction and PI3K-Akt signaling pathway as key mechanisms. The model integrating proteins, demographic factors, and clinical variables achieved the highest predictive performance across non-fatal MACE (AUC&#xa0;=&#xa0;0.768), myocardial infarction (MI) (0.808), and stroke (0.816) outcomes, with superior stability in cross-validation. CoxBoost + Elastic Net framework was selected as the optimal framework via benchmarking of 101 algorithms. The model demonstrated favorable calibration in high-risk patients and yielded positive net clinical benefit across decision thresholds of 5% to 45%. The web tool (https://jiangli2941.github.io/MACE-prediction-v2/) enables input of 28 variables, outputs non-fatal MACE risk status, risk probability, and highlights abnormal indicators. CONCLUSION: Plasma proteomics combined with machine learning identifies robust non-fatal MACE predictors in DKD.

Humans↗
PubMed2026

Metagenomic next-generation sequencing for tuberculosis diagnosis: enhanced performance and cost-effectiveness.

UNLABELLED: Metagenomic next-generation sequencing (mNGS) is a promising tool for diagnosing challenging infections like tuberculosis (TB). However, previous studies largely focused on case-specific application of mNGS in TB diagnosis. Thus, we conducted a retrospective observational study to first systematically evaluate the diagnostic performance and cost-effectiveness of mNGS for TB diagnosis. We retrieved a total of 16,776 results of the seven TB diagnostic assays, including mNGS, tuberculosis IgG antibody, TB interferon-&#x3b3; release assay (TB-IGRA), TB-DNA, Xpert MTB/RIF (Xpert), culture, and acid-fast bacilli staining (AFS) from 3,757 participants with suspected TB infection at Sichuan Provincial People's Hospital from September 2021 to July 2024. Diagnostic metrics were compared against a composite reference standard. Microbial composition and a cost-utility analysis were performed. Among seven TB assays studied, the World Health Organization (WHO)-recommended assays AFS, culture, and Xpert, as well as TB-IGRA, were requested most frequently for TB diagnosis, whereas mNGS ranked last. mNGS demonstrated the highest specificity (100%), accuracy (72.3%), and area under the curve (AUC) (0.795). Its sensitivity in bronchoalveolar lavage fluid and tissue was 71.0% and 72.7%, respectively. Sequential use of mNGS after initial WHO-recommended tests (Xpert/Culture/AFS) significantly improved diagnostic performance (sensitivity, 70.4%; AUC, 0.823). Microbial analysis associated Candida albicans with TB. Cost-utility analysis showed sequential mNGS became cost-effective at higher willingness-to-pay thresholds (>200,000 RMB per correct diagnosis). mNGS offers superior specificity for TB diagnosis. A sequential strategy applying mNGS to conventional-test-negative cases provides enhanced diagnostic performance and is cost-effective at higher healthcare investment values, supporting its utility for diagnostically challenging TB. IMPORTANCE: This study systematically assesses the diagnostic performance and cost utility of metagenomic next-generation sequencing (mNGS) for tuberculosis (TB) in a large real-world cohort of 3,757 suspected patients, comparing it against six conventional assays (tuberculosis IgG antibody, TB interferon-&#x3b3; release assay, TB-DNA, Xpert, culture, and acid-fast bacilli staining). mNGS demonstrated the highest specificity (100%), accuracy (72.3%), and area under the curve (AUC) (0.795), with sensitivities of 71.0% in bronchoalveolar lavage fluid and 72.7% in tissue. Notably, sequential use of mNGS after the World Health Organization-recommended tests significantly improved sensitivity to 70.4% and AUC to 0.823. Candida albicans showed significant differences among the three groups. The sequential mNGS strategy was cost-effective compared with no mNGS, and its cost-effectiveness increased with a rising willingness-to-pay threshold. Overall, these results highlight mNGS as a valuable supplementary tool for challenging TB cases, especially when conventional tests are inconclusive, and provide strong evidence for integrating it into diagnostic algorithms to optimize clinical decision-making and resource allocation.

Adult↗
PubMed2007

The repairing effect of a recombinant human connective-tissue growth factor in a burn-wounded rhesus-monkey (Macaca mulatta) model.

CTGF (connective-tissue growth factor) has been characterized as an extracellular-matrix-associated protein that modulates basic-fibroblast-growth-factor signalling and angiogenesis. In the present paper, the cloning of the ctgf gene from human umbilical-vein endothelial cells and expression of the protein in Escherichia coli as an N-terminal hexahistidine fusion protein is described. Recombinant human CTGF (rhCTGF) was expressed and purified so that we could investigate its effect on the proliferation of human embryo fibroblast KMB-17 and NIH3T3 cells. The results indicated not only that the protein was properly folded, but also that it had the same specific activity and stability as the native protein. Furthermore, we administered this recombinant protein in a non-human primate [rhesus monkey (Macaca mulatta)] burn-wound model and report the clinical findings and structural effects. Epitheliotrophic effects were conspicuous in wounded tissues at 10-100 ng of CTGF/cm(2), suggesting that administered rhCTGF can play a normal physiological role in wound repairing in a non-human primate model.

Animals↗
PubMed2006

The eukaryotic initiation factor-2 kinase pathway facilitates differential GADD45a expression in response to environmental stress.

Phosphorylation of eukaryotic initiation factor-2 (eIF2) regulates general and gene-specific translation in response to diverse environmental stresses. Central to gene expression induced by eIF2 phosphorylation is the preferential translation of ATF4, a basic zipper transcription activator. Phosphorylation of eIF2 and its attendant induction of ATF4 can lead to different patterns of gene expression depending on the environmental stress. This is of fundamental importance because eIF2 kinases can induce the expression of genes involved in survival as well as in apoptosis. In this report, we explore the molecular basis for why there can be differential expression of GADD45a, a stress-responsive protein that regulates genome stability, apoptosis, and immune responses. We find that whereas ATF4 is required for GADD45a transcription during many different environmental stresses, GADD45a protein accumulates only during a limited number of stress arrangements. The basis for this difference between measurable GADD45a mRNA and protein lies in the observation that GADD45a protein is labile. Those stress agents that enhance ATF4-directed GADD45a transcription and impede the turnover of GADD45a protein by blocking ubiquitin/proteasome-mediated degradation elevate GADD45a protein levels. By comparison, those stress arrangements that trigger ATF4 levels and GADD45a transcription, but do not perturb the proteasome pathway, only elevate GADD45a mRNA levels. This study highlights the molecular mechanisms by which environmental stresses can differentially control central regulatory proteins targeted by the eIF2 kinase pathway.

Activating Transcription Factor 4↗
PubMed2006

Molybdenum trioxide nanostructures: the evolution from helical nanosheets to crosslike nanoflowers to nanobelts.

MoO(3) nanostructures with different morphologies, such as helical nanosheets, crosslike nanoflowers, and nanobelts, have been synthesized on a large scale by an environmentally friendly chemical route. The evolution process from helical nanosheets to crosslike nanoflowers to nanobelts is observed for the first time. The influences of reaction time and the molar ratio of molybdenum and H(2)O(2) on the morphologies of MoO(3) nanostructures have been investigated. The synthetic process is environmentally friendly and may be extended to synthesize nanostructures of other metal (W, Ti, and Cr) oxides.

Journal Article↗
PubMed2006

A paracentric inversion suppresses genetic recombination at the FON3 locus with breakpoints corresponding to sequence gaps on rice chromosome 11L.

Paracentric inversion is known to inhibit genetic recombination between normal and inverted chromosomal segments in heterozygous arrangements. Insect inversion polymorphisms have been studied to reveal adaptive processes for maintaining genetic variation. We report the first paracentric inversion in rice (Oryza sativa), which was discovered in our effort to clone the floral organ number gene FON3. Recombination at the FON3 locus on the long arm of chromosome 11 was severely suppressed over a distance of more than 36 cM. An extensive screening among 8,242 F(2) progeny failed to detect any recombinants. Cytological analysis revealed a loop-like structure on pachytene chromosomes, whereas FISH analysis showed the migration of a BAC clone from a distal location to a position closer to the centromere. Interestingly, the locations where the genetic recombination suppression began were coincided with the positions of two physical gaps on the chromosome 11, suggesting a correlation between the physical gaps, the inversion breakpoints. Transposons and retrotransposons, and tandemly arranged members of gene families were among the sequences immediately flanking the gaps. Taken together, we propose that the genetic suppression at the FON3 locus was caused by a paracentric inversion. The possible genetic mechanism causing such a spontaneous inversion was proposed.

Base Sequence↗
PubMed2006

Voltammetric sizing of a sphere.

The size of a glass sphere positioned in the center of a microdisk electrode is determined by using a simple electrochemical procedure and is confirmed, additionally, by a microscopical measurement of the sphere at the time of the electrochemical measurement. The cyclic voltammetric response of the naked electrode and of the electrode with the sphere positioned in its center is recorded over a wide range of scan rates (0.002-1.5 V s(-1)). The size of the sphere is then determined by comparison of the experimental voltammogram with simulations for each individual scan rate.

Journal Article↗
PubMed2006

AtGRP7 is involved in the regulation of abscisic acid and stress responses in Arabidopsis.

The Arabidopsis AtGRP7 gene, encoding a glycine-rich RNA-binding protein, has been shown to be involved in the regulation of a circadian-regulated negative feedback loop. However, little is known about the role of AtGRP7 in mediating abscisic acid (ABA) and stress responses. Here, we show that AtGRP7 plays a role in both. AtGRP7 was repressed by ABA, high salt and mannitol. Disruption of AtGRP7 by T-DNA insertion led to hypersensitive responses to ABA in both seed germination and root growth assays. The atgrp7-1 mutant was also hypersensitive to osmotic stress conditions, such as high salt and high concentrations of mannitol. In addition, the atgrp7-1 mutant plants accumulated significantly higher transcript levels of two ABA-and stress-inducible genes, RD29A and RAB18, compared with the wild-type plants. Taken together, these results suggest that AtGRP7 is involved in the regulation of ABA and stress responses.

Abscisic Acid↗
PubMed2006

Deletion and single nucleotide substitution at G:C in the kidney of gpt delta transgenic mice after ferric nitrilotriacetate treatment.

An iron chelate, ferric nitrilotriacetate (Fe-NTA), induces oxidative renal proximal tubular damage that subsequently leads to a high incidence of renal cell carcinoma in rodents, presenting an intriguing model of free radical-induced carcinogenesis. In the present study, we used gpt delta transgenic mice, which allow efficient detection of point mutations and deletions in vivo, to evaluate the mutation spectra, in association with the formation of 8-oxoguanine and acrolein-modified adenine during the first 3 weeks of carcinogenesis. Immunohistochemical analysis revealed the highest levels of 8-oxoguanine and acrolein-modifed adenine in the renal proximal tubules after 1 week of repeated administration. DNA immunoprecipitation and quantitative polymerase chain reaction analysis showed that the relative abundance of 8-oxoguanine and acrolein-modified adenine at the gpt reporter gene were increased at the first week in the kidney. Similarly, in both 6-thioguanine and Spi(-) selections performed on the renal specimens after Fe-NTA administration, the mutant frequencies were increased in the Fe-NTA-treated mice at the first week. Further analyzes of 79 mutant clones and 93 positive plaques showed a high frequency of G:C pairs as preferred targets for point mutation, notably G:C to C:G transversion-type mutation followed by deletion, and of large-size (>1 kilobase) deletions with short homologous sequences in proximity to repeated sequences at the junctions. The results demonstrate that the iron-based Fenton reaction is mutagenic in vivo in the renal tubular cells and induces characteristic mutations.

Animals↗
PubMed2006

Alpha-tocopherol induces calnexin in renal tubular cells: another protective mechanism against free radical-induced cellular damage.

Pre-administration of alpha-tocopherol is protective against oxidative renal tubular damage and subsequent carcinogenesis by ferric nitrilotriacetate (Fe-NTA) in rats. We searched for mechanisms other than the scavenging effect of alpha-tocopherol with microarray analyses, which implicated calnexin, a chaperone for glycoproteins. Renal mRNA levels of calnexin significantly increased 3h after an injection of Fe-NTA in rats fed a standard diet whereas those fed an alpha-tocopherol-supplemented diet showed an increase prior to injection, but after injection showed a decrease in renal calnexin mRNA levels, with unaltered protein levels. In experiments using LLC-PK1 cells, addition of alpha-tocopherol was protective against oxidative stress by H2O2, concomitant with calnexin induction. Knockdown of calnexin by siRNA significantly reduced this protection. Furthermore, COS-7 cells transfected with the calnexin gene were more resistant to H2O2. Together with the fact that alpha-tocopherol induced N-acetylglucosaminyltransferase 3, our data suggest that alpha-tocopherol modifies glycoprotein metabolism partially by conferring mild ER stress. This adds another molecular mechanism of alpha-tocopherol toward cancer prevention.

Animals↗
PubMed2006

MHC-BPS: MHC-binder prediction server for identifying peptides of flexible lengths from sequence-derived physicochemical properties.

Major histocompatibility complex (MHC)-binding peptides are essential for antigen recognition by T-cell receptors and are being explored for vaccine design. Computational methods have been developed for predicting MHC-binding peptides of fixed lengths, based on the training of relatively few non-binders. It is desirable to introduce methods applicable for peptides of flexible lengths and trained by using more diverse sets of non-binders. MHC-BPS is a web-based MHC-binder prediction server that uses support vector machines for predicting peptide binders of flexible lengths for 18 MHC class I and 12 class II alleles from sequence-derived physicochemical properties, which were trained by using 4,208 approximately 3,252 binders and 234,333 approximately 168,793 non-binders, and evaluated by an independent set of 545 approximately 476 binders and 110,564 approximately 84,430 non-binders. The binder prediction accuracies are 86 approximately 99% for 25 and 70 approximately 80% for five alleles, and the non-binder accuracies are 96 approximately 99% for 30 alleles. A screening of HIV-1 genome identifies 0.01 approximately 5% and 5 approximately 8% of the constituent peptides as binders for 24 and 6 alleles, respectively, including 75 approximately 100% of the known epitopes. This method correctly predicts 73.3% of the 15 newly published epitopes in the last 4 months of 2005. MHC-BPS is available at http://bidd.cz3.nus.edu.sg/mhc/ .

Algorithms↗
PubMed2006

Functionalized carbon nanotubes as sensitive materials for electrochemical detection of ultra-trace 2,4,6-trinitrotoluene.

This report demonstrates a novel electrochemical method for fast and sensitive detection of ultra-trace 2,4,6-trinitrotoluene (TNT) based on modified electrodes by functionalized MWCNTs. To fabricate new kind of functionalized MWCNTs material sensitive to TNT, our work first theoretically investigated the interaction between triphenylene (TP) and TNT by calculating their electrostatic potentials, and secondly characterized this interaction by the fluorescence spectra. The functionalized MWCNTs of TP-MWCNTs were thoroughly characterized by fluorescence and UV-visible spectra, and by analysing these results, the interaction between TP and MWCNTs was also examined. Electrochemical experiment suggests, compared to MWCNTs- and TP- modified electrodes, TP-MWCNTs-modified electrodes result in both fast response and enhanced sensitivity to TNT detection. These results show the attachment of TP on MWCNTs leads to better sensing unit with more receptor site to TNT, associated with the coordinative recognition of TP and MWCNTs to TNT, finally result in the improvement of response and sensitivity. And this improved recognition process is attributed to the geometric and electrostatic complementarity between TP and TNT. The present study demonstrates TP-MWCNTs-modified electrode holds promising and important implications for the detection of ultra-trace TNT.

Electrochemistry↗
PubMed2006

Environmentally friendly chemical route to vanadium oxide single-crystalline nanobelts as a cathode material for lithium-ion batteries.

Orthorhombic V(2)O(5) single-crystalline nanobelts with widths of 100-300 nm, thicknesses of 30-40 nm, and lengths up to tens of micrometers have been synthesized on a large scale in a hydrogen peroxide aqueous solution by an environmentally friendly chemical route. Such nanobelts grow along the direction of [010]. The influence of the reaction time on the crystal structures and morphologies of the resulting products are investigated. A probable dehydration-recrystallization-cleavage mechanism for the formation of V(2)O(5) nanobelts is proposed. The experiments demonstrate that the use of a nanosized belt-like structure can considerably enhance the specific discharge capacity in lithium-ion batteries.

Journal Article↗
PubMed2006

The di-leucine motif contributes to class a scavenger receptor-mediated internalization of acetylated lipoproteins.

OBJECTIVE: The di-leucine motif exists in the intracellular domains of certain cell surface receptors, participating in the receptor-mediated endocytosis. The present study was aimed at determining the role of the di-leucine motif in class A scavenger receptor (SR-A)-mediated ligand endocytosis. METHODS AND RESULTS: cDNA coding for a mutant (SR-A mutant N3132LM) with deletion of the di-leucine structure was transfected into Chinese hamster ovary (CHO) cells. Compared with wild-type SR-A-expressing cells, the cells expressing the SR-A mutant N3132LM showed a significant decrease in uptake but almost no change in binding of the SR-A ligand acetylated low-density lipoprotein (AcLDL). Western blot analysis revealed coimmunoprecipitation of SR-A mutant and clathrin from the lysates of the mutant but not wild-type CHO cells, suggesting that AcLDL-bound SR-A mutant N3132LM is associated with the clathrin-coated pit of cellular membrane. Removal of the first 27 amino acid residues from the SR-A N-terminus further reduced AcLDL uptake by the cells with the di-leucine motif mutation. CONCLUSIONS: The di-leucine motif of SR-A intracellular domain contributes to the SR-A-mediated cellular internalization of AcLDL. Di-leucine pair exists in the cytoplasmic domain of class A scavenger receptor. The cells expressing di-leucine mutants showed decreased uptake and unchanged binding of AcLDL. The di-leucine pair was not associated to coated pits. It suggests that di-leucine motif acts as a signal sequence to mediate SR-A into cell.

Amino Acid Motifs↗
PubMed2006

Mathematical modelling and simulation of adsorption processes at spherical microparticles.

A model for the adsorption process at spherical microparticles under transient diffusion conditions has been developed and solved using numerical simulation. This model allowed us to demonstrate that the system is controlled by two main dimensionless parameters: the adsorption rate constant ka' and the saturation parameter beta. Analytical models for the adsorption process at spherical microparticles under steady-state mass transport conditions have been derived. These models use previously developed empirical relationships for the calculation of the mass transfer coefficient (kc). The properties of the system were studied for both the case where mass transport is described by diffusion only and the case where it is the result of a coupled diffusion/convection process. These mathematical tools were then used to analyse the results obtained for the uptake of CuII by glassy carbon powder modified with the monomer L-cysteine methyl ester and to extract a minimum value for the adsorption rate constant which was found to be of the order of 10(-4) cm s(-1).

Journal Article↗
PubMed2006

Particularly interesting new cysteine-histidine rich protein expression in colorectal adenocarcinomas.

AIM: To study the relationship between particularly interesting new cysteine-histidine rich protein (PINCH) expression and clinicopathological factors in Chinese colorectal cancer patients. METHODS: The expression of PINCH was examined by immumohistochemistry in 141 samples of primary colorectal adenocarcinoma and 92 normal samples of colorectal mucosa. Eighty of the cases had both primary tumour and normal mucosa from the same patients. RESULTS: PINCH was expressed in the stroma of normal mucosa and tumours. PINCH expression in tumour-associated stroma was increased compared to normal mucosa in both unmatched cases (n = 141, c2 = 85.79, df = 3, P < 0.0001) and matched cases (n = 80, c2 = 45.86, df = 3, P < 0.0001). Among 135 tumours with visible invasive margin, 86 (64%) showed stronger PINCH expression at the invasive margin than in the intratumoural stroma. The frequency of PINCH strong expression in mucinous and signet-ring cell carcinomas was higher (52%) compared to non-mucinous carcinomas (29%, c2 = 5.13, P = 0.02). We did not find that PINCH expression was related to patient's gender, age, tumour location, tumour size, gross status, histological type, differentiation, invasion depth, lymph node status and Dukes'stage (P > 0.05). CONCLUSION: The expression of PINCH was upregulated in colorectal cancers, and especially at the margin of tumours, and further was related to mucinous and signet-ring cell carcinomas. The results suggest that expression of PINCH may be involved in the tumourigenesis and aggressiveness of colorectal cancers.

Adaptor Proteins, Signal Transducing↗