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Biomedical subjects

Yi Ding

Publications and source records attributed to Yi Ding.

At least 19 recordsLinked to original sources

All of Us diversity and scale yield context-dependent improvements in polygenic prediction.

Polygenic risk scores (PRSs) trained on multiancestry data can improve prediction in under-represented groups, but large linked genetic and health datasets capturing broad human diversity remain limited. Using 245,388 whole-genome sequences from the All of Us research program (AoU) together with UK Biobank data, we developed multiancestry PRSs for 32 traits and diseases. We evaluated how ancestry, methodology and genetic architecture influenced PRS performance across ancestrally diverse AoU participants. Increased diversity in the AoU improved PRS accuracy for several traits, especially in under-represented populations. However, maximizing sample size by meta-analyzing AoU and UK Biobank was not universally optimal: for less polygenic traits, AoU-only training performed best in African ancestry participants, consistent with ancestry-enriched effects. Individual PRS accuracy declined linearly with increasing ancestry divergence from the discovery GWAS, but this decay was attenuated using multiancestry training data. These findings underscore the value of more representative biobanks for equitable PRS performance.

Journal Article↗

Comparative genomics reveals lineage-associated structural variation and diversification in a barley fungal pathogen.

Leaf rust, caused by Puccinia hordei, is a major barley disease worldwide. Despite repeated shifts in virulence, contrasting reproductive histories, and emerging fungicide insensitivity, the genomic basis of its diversification and adaptation remains poorly understood. In this study, we generated haplotype-resolved, chromosome-level genome assemblies for two isolates with contrasting virulence and analyzed 41 Australian isolates collected over 54 yr (1966-2020), integrating comparative and population genomics, mating-type gene phylogenies, chromosome-specific k-mer profiling, genome-wide copy-number variation (CNV) analysis, and gene-expression analysis. We identified a structurally dynamic chromosome characterized by repeat-associated rearrangements, structural variation, and lineage-associated CNV, representing the first evidence in a rust fungus of chromosome-scale structural diversification of this extent. Population analyses distinguished clonally expanded lineages from recombination-associated lineages, with mating-type gene phylogenies providing further support for lineage differentiation. More recently collected isolates showed increased duplication-associated variation, and CNV boundaries were associated with structural-variant breakpoints. We also identified lineage-associated amplification of Cyp51, with increased copy number associated with higher transcript abundance, supporting a potential role in fungicide adaptation. Overall, our findings highlight structural variation, contrasting reproductive histories, and lineage-associated CNV as important contributors to diversification in P. hordei, providing insights for future rust pathogen surveillance and management strategies.

Cyp51 gene↗

Oral and gut microbiota profiles in patients with locally advanced rectal cancer with varying responses to neoadjuvant chemoradiotherapy.

Recent research has focused on gut bacteria in colorectal cancer, but the influence of other microbiota, including oral and nonbacterial gut microbiota, on treatment efficacy remains insufficiently explored. This study aimed to investigate their relationship with the efficacy of neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC). Saliva and fecal samples were collected from patients with LARC before treatment. Shotgun metagenomic sequencing was used to profile bacterial, archaeal, eukaryotic, and viral taxonomic groups and to examine oral and gut microbial functions. An artificial intelligence-based prediction model was developed by integrating oral and gut microbiome data with clinical information. Statistical analyses compared diversity and response-associated microbial features between responders and non-responders to nCRT. Response-associated differences were observed in bacterial and nonbacterial taxonomic profiles and in oral and gut microbial functional profiles. In the internal test subset, the integrated analysis yielded an observed AUC of 0.917. Given the small cohort and the exploratory comparison of candidate classifiers, this estimate requires confirmation in larger, independent cohorts. Baseline oral and gut microbiome profiles were associated with response to nCRT. Integrating microbiome and clinical features showed potential for response prediction, but the model remains exploratory and requires validation in larger, independent cohorts before clinical application. Retrospectively registered on 01/08/2026, NCT07346729.

Aged↗

Large-Scale Plasma Proteomics Enhances Prediction of Liver-Related Events Among Individuals With Prediabetes and Type 2 Diabetes: A Prospective Cohort Study in the UK Biobank.

OBJECTIVE: To develop a protein risk score (ProRS) for predicting liver-related events (LREs) in patients with diabetes and compare its predictive performance with the Fibrosis-4 Index (FIB-4) and an established polygenic risk score. RESEARCH DESIGN AND METHODS: This prospective cohort study included 13 516 individuals with prediabetes and type 2 diabetes (T2D) from the UK Biobank. Cox proportional hazards models and LASSO regression were applied to identify proteins associated with incident LREs and construct the ProRS. Predictive performance was assessed using Harrell's C-index, time-dependent area under the receiver operating characteristic curve, net reclassification improvement and integrated discrimination improvement. RESULTS: Over a median follow-up of 13.5 years, 171 (1.3%) incident LREs occurred. We identified 877 proteins associated with LRE risk, primarily enriched in inflammatory signalling, extracellular matrix remodelling and complement/coagulation cascades. In the training set, we developed a 24-protein ProRS (C-index, 0.842; 95% CI 0.797-0.884) that stratified individuals into low-, medium- and high-risk groups, with 10-year cumulative incidences of LREs of 0.2%, 1.2% and 14.2%, respectively. Compared with the low-risk group, the hazard ratio for LREs was 57.1 (95% CI 31.9-102) in the high-risk group. In the internal validation set, the ProRS model (C-index, 0.876; 95% CI 0.827-0.920) accurately predicted both short- and long-term LREs and outperformed FIB-4 index (C-index, 0.733; 95% CI 0.657-0.807) and polygenic risk score (C-index, 0.636; 95% CI 0.564-0.706). CONCLUSIONS: The protein risk score demonstrated superior performance compared with the FIB-4 index and the polygenic risk score in predicting incident LREs among individuals with prediabetes and T2D. The score allows stratification of individuals according to liver-related risk, though external validation in multi-ethnic cohorts is warranted.

Humans↗

Multi-trait polygenic scores for COPD and COPD exacerbations implicate druggable proteins.

BACKGROUNDWe constructed multi-trait polygenic risk scores (PRSs) predicting chronic obstructive pulmonary disease (COPD) and exacerbations, validated their performance in diverse cohorts, and identified PRS-related proteins for potential therapeutic targeting.METHODSPRSmix+, a multi-trait PRS framework, is used to train a composite PRS (PRSmulti) in COPDGene non-Hispanic White participants (n = 6,647). Associations of PRSmulti with COPD status (GOLD 2-4 vs. GOLD 0 or ICD) and exacerbation frequency were tested in COPDGene African American (n = 2,466), ECLIPSE (n = 1,858), Mass General Brigham Biobank (n = 15,152), and All of Us (n = 118,566). Protein prediction models were applied to GWAS summary statistics from traits contributing to PRSmulti and were validated with proteomic data in COPDGene (n = 5,173) and UK Biobank (n = 5,012).RESULTSPRSmix+ selected 7 traits for PRSmulti. In multivariable models, PRSmulti was associated with COPD status (meta-analysis random effects [RE] OR 1.58 [95% CI: 1.28-1.94]) and exacerbation frequency (meta-analysis RE β 0.21 [95% CI: 0.11-0.31]), with higher effect sizes observed in smoking-enriched cohorts. PRSmulti outperformed traditional single-trait PRS in all tested cohorts. Using protein prediction models, we identified 73 proteins associated with the PRSs that were also validated with measured protein levels in COPDGene and UK Biobank. Of these proteins, 25 were linked to approved or investigational drugs. Notable targets include RAGE/sRAGE, IL1RL1, and SCARF2, all implicated in COPD pathogenesis and exacerbations.CONCLUSIONSMulti-trait PRS improves prediction of COPD and exacerbation risk. Integration with proteomic data identifies druggable protein targets, offering a promising avenue for precision medicine in COPD management.TRIAL REGISTRATIONCOPDGene: ClinicalTrials.gov NCT00608764; ECLIPSE: ClinicalTrials.gov NCT00292552.

Humans↗

Integrated multi-omics analysis reveals TMEM147 as an immunosuppressive prognostic biomarker in LUAD.

TMEM147, an endoplasmic reticulum (ER) membrane protein, is implicated in lung adenocarcinoma (LUAD) progression, although its precise role remains unclear. To elucidate its function, this study integrated bioinformatics analyses with experimental validation. First, TMEM147 expression was assessed using TCGA and GEO datasets, with validation performed in LUAD cell lines. Survival analysis evaluated its prognostic significance. Subsequently, Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses and single-sample gene set enrichment analysis (ssGSEA) were employed to identify associated functional pathways and interactions within the tumor immune microenvironment. Transcription factor binding predictions and in vitro functional assays (migration, invasion, proliferation) further characterized TMEM147's role. Results indicated that TMEM147 was significantly upregulated in LUAD and correlated with poor outcomes in patients. FLI1 was predicted as a key transcriptional regulator of TMEM147. Furthermore, TMEM147 expression influenced immune cell infiltration profiles and was associated with pathways involved in ribonucleoprotein biogenesis and oxidative phosphorylation (OXPHOS). Importantly, silencing TMEM147 significantly reduced cancer cell migration, invasion, and proliferation. These findings collectively suggest that TMEM147 promotes LUAD progression and holds potential as both a prognostic biomarker and a therapeutic target.

Bioinformatics analysis↗

Exploring depression treatment response by using polygenic risk scoring across diverse populations.

Treatment-resistant depression (TRD), usually defined as limited or no response to at least two antidepressants, occurs in approximately one-third of individuals diagnosed with major depressive disorder (MDD). Studies of individuals of European ancestry highlight a genetic overlap between TRD and MDD. We analyzed two large and diverse biobanks, the UCLA ATLAS Community Health Study (ATLAS) and the All of Us Research Program (AoU), to test for associations between a polygenic score for major depression (MDD-PGS) and TRD. Compared to treatment responders, TRD individuals have higher MDD-PGS across all ancestries. MDD-PGS was significantly associated with response to selective serotonin reuptake inhibitors in individuals of European and Hispanic/Latin American genetic ancestries in both biobanks. In AoU, a decreased MDD-PGS was observed in response to tricyclics or serotonin modulators in individuals of European American ancestry and in response to serotonin and norepinephrine reuptake inhibitors in individuals of African American ancestry. ATLAS found that MDD-PGS showed lower odds of responding to atypical agents than did TRD in MDD-affected individuals belonging to the Hispanic/Latin American group, MDD-PGS was associated with atypical agents. Overall, by leveraging larger sample sizes from two diverse biobanks, we provide new insights into antidepressant response and treatment specificity for MDD in individuals of diverse genetic ancestries.

Adult↗

Low temperature CO oxidation over unsupported nanoporous gold.

Supported Au nanoclusters are well-known for their unusual properties in catalysis. We describe here that nanostructured porous Au made via dealloying represents a new class of unsupported catalysts with extraordinary activities in important reactions such as CO oxidation. Although nanoporous Au may contain some oxides on the surface, our results demonstrate that it is metallic Au that plays the main role in this catalytic reaction. Furthermore, this material has good low-temperature catalytic stability and is extremely CO tolerant.

Journal Article↗

3D architectures of iron molybdate: phase selective synthesis, growth mechanism, and magnetic properties.

Monoclinic and orthorhombic Fe(2)(MoO(4))(3) microsized particles with complex 3D architectures have been selectively prepared by a template-free hydrothermal process. The pH value, reaction time, temperature, and molybdenian source have crucial influence on the phase formation, shape evolution, and microstructures. Monoclinic Fe(2)(MoO(4))(3) particles obtained at pH 1 and pH 1.65 display ferromagnetic ordering at 10.4 K and 10.5 K, respectively, and the ferromagnetic component is determined to be 0.0458 mu(B) and 0.0349 mu(B) per Fe-ion at 10 K, respectively. For orthorhombic beta-Fe(2)(MoO(4))(3), antiferromagnetic ordering was observed about 12 K. At higher temperatures, beta-Fe(2)(MoO(4))(3) began to follow the Curie-Weiss law with theta=-70 K. Such 3D architectures of monoclinic and orthorhombic beta-Fe(2)(MoO(4))(3) microparticles with unique shapes and structural characteristics may find applications as catalysts and as well as in other fields.

Crystallization↗

Cerebellar modulation of feeding-related neurons in rat dorsomedial hypothalamic nucleus.

Cerebellum has newly been implicated in many more nonsomatic functions other than motor control. Previous studies indicate that the cerebellum is involved in feeding regulation and that the gastric vagal nerves transmit short-term meal-related visceral signals, including cholecystokinin (CCK), into the hypothalamus. Recently, the dorsomedial hypothalamic nucleus (DMN) has been thought to play an important role in feeding control. Here we investigate whether the inputs from cerebellar interpositus nucleus (IN) can reach and converge onto single DMN neurons with some feeding-related visceral signals, including gastric vagal inputs, CCK, and blood glucose, whose concentration is closely linked to food intake. Among the 259 DMN neurons recorded, 120 (46.3%) and 169 (65.3%) responded to the cerebellar IN and gastric vagal stimulations, respectively. Within the 120 DMN neurons responsive to the cerebellar IN stimulation, 98 (81.7%) also responded to the gastric vagal stimulus, and a summation of the responses was observed further (n = 20), suggesting a convergence and interaction of cerebellar and gastric vagal inputs on the cells. Moreover, among the 98 cells receiving convergent inputs from cerebellar IN and gastric vagal nerves, 69 (70.4%) were identified to be glycemia sensitive, and 22 (68.8%) of the 32 tested neurons were also sensitive to systemic CCK. These results demonstrate that the DMN integrates somatic information forwarded by the cerebellar IN and visceral signals related to food intake, including gastric vagal, CCK and glycemia, and electrophysiologically reveal a novel cerebellohypothalamic IN-DMN pathway through which the cerebellum may actively participate in short-term feeding regulation.

Action Potentials↗

Constituents of the flowers of Punica granatum.

A new polyphenol compound named pomegranatate (1), together with, ellagic acid, 3,3',4'-tri-O-methylellagic acid, ethyl brevifolincarboxylate, urolic and maslinic acids, and daucosterol were isolated from the ethanolic extract of the flowers of Punica granatum. The structure of compound 1 was determined by spectroscopic analysis. Maslinic acid exhibited antioxidant activity, evaluated by measurement of LDL susceptibility to oxidation.

Animals↗

[The study of relationship between nuclear metrix protein 22 urinary level and the grade and stage of bladder transitional cell carcinoma].

OBJECTIVE: To assess the relationship between nuclear matrix protein (NMP) 22 urinary level and the grade and stage of bladder transitional cell carcinoma. METHODS: From June 1999 to March 2005 642 patients underwent NMP22 test, and then the test by cystoscope and pathology were performed in 1 week to 1 month. According to the pathological grade, the patients were divided into 3 groups: group G(1): 69 cases, male 58 and female 11; group G(2): 375 cases, male 255 and female 120; group G(3): 198 cases, male 143 and female 55. And the difference of NMP22 between each group were compared. Meanwhile, according to pathological stage, 239 patients were divided into 3 groups: group PT(1): 121 cases, male 76 and female 45; group PT(2): 65 cases, male 37 and female 28; group PT(3): 53 cases, male 29 and female 24. And the difference of NMP22 between each group were compared. RESULTS: The concentrations of NMP22 had significant difference between the 3 groups which divided according to pathological grade (Kruskal-Wallis test chi(2) = 67.547, P < 0.001); The concentrations of NMP22 had significant difference between the 3 groups which divided according to pathological stage (Kruskal-Wallis test chi(2) = 20.629, P < 0.001). CONCLUSIONS: There is a relation between NMP22 urinary level and the grade and stage of bladder transitional cell carcinoma.

Adolescent↗

Regulatory T cells inhibit stable contacts between CD4+ T cells and dendritic cells in vivo.

Regulatory T (T reg) cells exert powerful down-modulatory effects on immune responses, but it is not known how they act in vivo. Using intravital two-photon laser scanning microscopy we determined that, in the absence of T reg cells, the locomotion of autoantigen-specific T cells inside lymph nodes is decreased, and the contacts between T cells and antigen-loaded dendritic cells (DCs) are of longer duration. Thus, T reg cells can exert an early effect on immune responses by attenuating the establishment of stable contacts during priming of naive T cells by DCs.

Animals↗

Interferon-inducible protein IFIXalpha1 functions as a negative regulator of HDM2.

The 200-amino-acid repeat (HIN-200) gene family with the hematopoietic interferon (IFN)-inducible nuclear protein encodes highly homologous proteins involved in cell growth, differentiation, autoimmunity, and tumor suppression. IFIX is the newest member of the human HIN-200 family and is often downregulated in breast tumors and breast cancer cell lines. The expression of the longest isoform of IFIX gene products, IFIXalpha1, is associated with growth inhibition, suppression of transformation, and tumorigenesis. However, the mechanism underlying the tumor suppression activity of IFIXalpha1 is not well understood. Here, we show that IFIXalpha1 downregulates HDM2, a principal negative regulator of p53, at the posttranslational level. IFIXalpha1 destabilizes HDM2 protein and promotes its ubiquitination. The E3 ligase activity of HDM2 appears to be required for this IFIXalpha1 effect. Importantly, HDM2 downregulation is required for the IFIXalpha1-mediated increase of p53 protein levels, transcriptional activity, and nuclear localization, suggesting that IFIXalpha1 positively regulates p53 by acting as a negative regulator of HDM2. We found that IFIXalpha1 interacts with HDM2. Interestingly, the signature motif of the HIN-200 gene family, i.e., the 200-amino-acid HIN domain of IFIXalpha1, is sufficient not only for binding HDM2 but also for downregulating it, leading to p53 activation. Finally, we show that IFIX mediates HDM2 downregulation in an IFN-inducible system. Together, these results suggest that IFIXalpha1 functions as a tumor suppressor by repressing HDM2 function.

Amino Acid Sequence↗

Invasion and control of water hyacinth (Eichhornia crassipes) in China.

By the time of primary 21st century, water hyacinth had become a serious environmental problem in China. Water hyacinth contributes to the major part of ecological hazards from the invasion of foreign plant species, which is estimated about USD 7 billion a year in values. In the past 10 years, herbicides glyphosate, 2,4-D and paraquat have been used in controlling water hyacinth in China. Although the herbicides provided effective control on the weed in some areas, they could not provide the sustainable inhibition on the weed population, while would lead to pollution of water at various levels. At present, the herbicide application on water hyacinth is forbidden in many areas of China such as Shanghai. In this situation, the asexual reproduction inhibitor, KWH02, was invented for controlling water hyacinth and it provided about 70% of growth inhibition without any risk of dead plant pollution. It has been about 10 years for bio-control of water hyacinth in China. Works focused on mainly the efficacy and safety of the utilization of foreign insects. Researches on microorganism herbicides to control water hyacinth were started and obtained primary achievements in recent years. Although there are different opinion on how to face the water hyacinth problem in China, it is accepted widely that the control methods should be high efficient and safe with low cost. Some practical measures for integrated management of water hyacinth are suggested.

Animals↗

[High-throughput screening assay for groups of effective components extracted from Xiaoxuming Recipe].

OBJECTIVE: To present a new approach for the research of effective components extracted from compounds of traditional Chinese medicine and their action mechanisms by high-throughput screening assay. METHODS: We observed the anti-oxidation activities of 240 sequential components (L1-L120 and A1-A120) extracted from Xiaoxuming Recipe, the effects of these components on SH-SY5Y cells with H(2)O(2)-induced and L-glutamic acid-induced damages and the levels of resting calcium ion in neurocytes of rats. RESULTS: Some components (L1-L40, A100-A120) extracted from Xiaoxuming Recipe had the corresponding effects listed above. The combination of these components was regarded as the groups of effective components of Xiaoxuming Recipe in treating sequelae resulting from brain ischemia. CONCLUSION: Xiaoxuming Recipe has protective effect on brain-ischemia-induced damages through the actions of multiple components with multiple targets.

Animals↗

Significance of Id-1 up-regulation and its association with EGFR in bladder cancer cell invasion.

Epidermal growth factor receptor (EGFR) is suggested to be one of the positive factors in the invasive progression of bladder cancer. Id-1 (inhibitor of differentiation or DNA binding), a helix-loop-helix (HLH) transcription factor, was recently identified as a key factor in the EGFR signalling pathway. The aim of this study was to investigate the role of Id-1 in bladder cancer progression and its relation-ship with EGFR. Using clinical specimens from different stages of bladder cancer, immunohistochemical staining was performed to determine if Id-1 expression was positively associated with tumour staging and EGFR expression. The direct role of Id-1 in cancer cell invasion was also investigated through ectopically expressing the Id-1 gene in a RT112 bladder cancer cell line by wound closure and collagen invasion assays. To explore the therapeutic potential of targeting the Id-1 gene in the treatment of invasive bladder cancer, we studied if inactivation of the Id-1 gene through small RNA interference could lead to the suppression of invasion in a MGHU1 bladder cancer cell line. Our results showed that the up-regulation of Id-1 was associated with increased EGFR expression, clinical staging and the invasion ability of bladder cancer cells. Inactivation of Id-1 may be a potential therapeutic target to inhibit the invasion by bladder cancer cells.

Blotting, Western↗

[Analysis of the volatile components of YL2000 decoction by GC-MS].

OBJECTIVE: To analyze the volatile components of YL2000 decoction, which contain four herbs: rhizome and root of the Notopterygium incisum, the root of the Angelica pubescens f. biserrata, Scutellaria baicalensis and Coptis chinensis and investigate the changes of volatile constituents from those four herbs before and after compatibility of the herbal medicines. METHOD: The volatile components of YL2000 decoction were extracted by water-steam distillation, separated and identified by GC-MS. The relative percent content of each volatile component was quantified by area normalization method. The volatile components of YL2000 decoction were compared with the composition of the volatile oil from individual herb respectively. RESULT: 39 of the 146 separated constituents in volatile oil of YL2000 decoction, accounting for 85.66%, were identified and quantified. After compatibility of the herbal medicines, most volatile oil components reported by high proportion in individual herb were not detected, in the mean time, some components in volatile oil of YL2000 decoction have never been reported before in those of all four herbs. CONCLUSION: The changes of volatile oil from those four herbs before and after compatibility of the herbal medicines indicate that solubilization, chemical reactions and evaporation of some volatile components during decocting may induce changes of several components.

Angelica↗