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Biomedical subjects

Rui Liu

Publications and source records attributed to Rui Liu.

At least 19 recordsLinked to original sources

Toxoplasma gondii infection disrupts secondary bile acid transformation in feline gut microbiota.

UNLABELLED: Bile acid (BA) transformation relies on gut microbiota and is vulnerable to Toxoplasma gondii infection, yet feline microbial BA-transforming capacity upon toxoplasmosis remains unclear. Here, we constructed a catalog of 2,474 nonredundant feline gut microbial genomes and integrated serum metabolomic data to verify BA transformation alterations. The results revealed that the feline gut microbiome harbored widespread genetic potential for BA transformation but lacked a complete 7α-dehydroxylation pathway due to the absence of the key gene baiE. The BA transformation-related genomes (2,045 in total) were predominantly from the phyla Bacillota_A and Actinomycetota, among which only 37 encoded baiB, all belonging to Bacillota_A. The distribution of BA transformation-related genes varied across intestinal regions: genes encoding 7α-HSDH were primarily enriched in the small intestine, whereas genes encoding 3α-HSDH, baiCD, and baiH were more abundant in the large intestine. Additionally, the abundance of genes encoding BSH and 3α-HSDH increased significantly in the small intestine on day 3 post-infection, accompanied by increases in the phylum Bacillota_C and genera such as Blautia_A, Enterococcus_E, and Ligilactobacillus. Serum metabolomics revealed a significant increase in cholesterol levels post-infection, supporting the impact of T. gondii infection on intestinal BA transformation. These findings illustrated that the feline gut microbiota played an important role in BA transformation and that T. gondii infection disrupted the microbial potential for secondary BA transformation. This study provided new insights into gut microbiota-associated metabolic perturbations during feline toxoplasmosis. IMPORTANCE: Bile acid (BA) transformation plays a critical role in host metabolism and immune regulation. Although studies on BA transformation are increasing, the capacity for BA transformation within the feline gut microbiota and the impact of Toxoplasma gondii infection on this capacity remain unclear. To bridge this gap, we constructed a catalog of 2,474 nonredundant feline gut microbial genomes and integrated serum metabolomic data to verify BA transformation alterations. Our findings revealed that the feline gut microbiome lacked a complete 7α-dehydroxylation pathway, and the specific functions involved in BA transformation may differ between the small and large intestines. Furthermore, integrated metagenomic and serum metabolomic analyses suggested that T. gondii infection disrupted BA transformation capacity in the small intestine. This study provided new insights into gut microbiota-associated metabolic perturbations during feline toxoplasmosis.

Toxoplasma gondii↗

Interkingdom remodeling of the intestinal bacteriome and virome during Toxoplasma gondii infection in rats.

Toxoplasma gondii infection is associated with intestinal microbiome disruption, but its effects on genome-resolved bacterial populations, the gut virome, and bacteriome-virome relationships remain poorly understood. Using previously generated shotgun metagenomic datasets from 36 intestinal samples collected from 18 Sprague-Dawley rats across control, acute, and chronic infection groups, we reconstructed 294 quality-filtered, non-redundant bacterial metagenome-assembled genomes (MAGs) and identified 899 medium-to-high-quality viral operational taxonomic units (vOTUs) from assembled metagenomic contigs. Infection was associated with reduced bacterial richness in the small intestine during both acute and chronic stages and lower Shannon diversity during chronic infection. In contrast, large-intestinal α-diversity remained stable despite significant compositional reorganization. Taxonomic changes included increased Lactobacillus intestinalis, Limosilactobacillus reuteri, and Prevotella sp900547005, together with decreased Rothia sp002492045 and Akkermansia muciniphila. Functional profiling revealed region- and stage-specific changes in predicted bacterial metabolic potential, including reduced energy-related pathways and carbohydrate-active enzyme abundance. The virome also showed significant compositional changes in both intestinal regions. Quimbyviridae and Podoviridae_crAss-like viruses decreased in the small intestine during chronic infection, while Quimbyviridae, Flandersviridae, and Podoviridae_crAss-like viruses showed stage-specific decreases in the large intestine. Predicted bacterial hosts were assigned to 48.39% of vOTUs, with Lachnospiraceae and Ruminococcaceae being the most frequently linked families. Trans-kingdom networks further revealed region-specific positive and negative abundance correlations between bacterial and viral taxa. These findings extend previous microbiota-metabolome observations by integrating genome-resolved bacteriome analysis with contig-based virome profiling, providing a foundation for future mechanistic studies of toxoplasmosis-associated microbiome remodeling.

Gut virome↗

Genome-resolved analysis reveals disruption of gut microbial vitamin B and K2 biosynthesis during Toxoplasma gondii infection in mice.

UNLABELLED: Toxoplasma gondii infection remodels the gut microbiome, yet its impact on microbial vitamin biosynthetic potential and host redox metabolism remains unclear. Here, we integrated mouse gut metagenomes with publicly available metagenome-assembled genomes (MAGs) to construct a genome-resolved atlas of B-vitamin and vitamin K2 biosynthesis. From 45,697 MAGs, we curated 4,771 representative genomes, of which 2,682 met high-quality criteria (completeness &#x2265;90%, contamination <5%). Functional annotation identified 229,717 vitamin-related genes corresponding to 177 Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologs across de novo pathways for eight B vitamins, thiamine (B1), riboflavin (B2), niacin (B3), pantothenate (B5), pyridoxine (B6), biotin (B7), folate (B9), cobalamin (B12), and vitamin K2. Among the high-quality genomes, 1,665 encoded complete de novo pathways for at least one vitamin, highlighting functional specialization and community-level complementarity. Transcripts per million-normalized metagenomic read counts revealed significant differences in KEGG ortholog abundances across six of the nine vitamin pathways. Reanalysis of metagenomic data from infected mice (acute, chronic, and control; n = 10 per group) revealed a stage-dependent reduction in &#x3b1;-diversity of vitamin biosynthesis pathways during acute infection, and a clear &#x3b2;-diversity separation from chronic and control groups. Core niacin biosynthesis genes (nadB, nadA, nadC) displayed phylum-specific redistribution, indicating selective remodeling of microbial NAD+ precursor production under infection-induced metabolic stress. These results suggest that T. gondii infection disrupts cooperative vitamin biosynthetic networks while specifically modulating niacin pathways linked to host NAD+ metabolism. IMPORTANCE: Gut microbes can synthesize essential vitamins, but how infection alters this function is poorly understood. By integrating mouse gut metagenomes with genome-resolved microbial data, we show that Toxoplasma gondii infection reshapes the vitamin biosynthetic potential of the gut microbiome in a stage-dependent manner. Acute infection reduces the diversity of vitamin biosynthesis pathways and shifts the taxonomic distribution of key niacin biosynthesis genes involved in microbial NAD+ precursor production. These findings identify vitamin metabolism, especially niacin-related pathways, as a sensitive functional axis of microbiome remodeling during infection. Our work links microbial taxonomic changes to functional metabolic consequences and suggests that microbiome-mediated regulation of NAD+-related metabolism may contribute to host redox adaptation during T. gondii infection.

B vitamins↗

Chromosome-Scale Genome Analysis Reveals Locus-Specific Disruption of the Citrinin-Associated Region in a Furu-Derived Monascus ruber Strain BC20.

Monascus species are widely used in traditional fermented foods for pigment and flavor formation, but citrinin contamination remains a major safety concern that limits broader food applications. Therefore, this study aimed to evaluate the citrinin risk of a furu-derived Monascus ruber strain, BC20, by integrating phenotypic screening across food-relevant matrices with genome-resolved analysis. After 14 days of cultivation across eight matrices, including fungal media as well as dairy-, cereal-, and bran-based substrates, citrinin was not detected by immunoaffinity cleanup combined with HPLC-FLD (LOD, 4 &#x3bc;g/kg; LOQ, 12 &#x3bc;g/kg). To investigate the genetic basis of this phenotype, we generated a chromosome-scale genome assembly for BC20 and conducted comparative analyses across a total of 19 Monascus genomes. ANI analysis and phylogenomic inference consistently placed BC20 within the ruber-pilosus clade. Comparative synteny analysis showed that the citrinin-associated locus in BC20 no longer retained an intact cluster configuration but instead exhibited a remnant-locus architecture, and similar patterns were also observed in several related genomes from the same clade. By contrast, the monacolin K (mk) locus remained syntenically conserved in BC20, supporting locus-specific structural disturbance rather than assembly-derived pseudo-absence. Additionally, its antifungal susceptibility was determined. Overall, BC20 represents a M. ruber candidate strain with undetectable citrinin, and this study provides a practical analytical framework for citrinin risk screening in food-related Monascus isolates.

biosynthetic gene cluster↗

Polygenic risk scores in major depressive disorder: A systematic review across diagnostic, treatment, course/severity, and subtype domains.

BACKGROUND: Major depressive disorder (MDD) is heterogeneous across diagnostic, treatment-related, course/severity, and subtype domains. Polygenic risk score (PRS) studies have examined these domains, but differences in PRS sources, samples, methods, and endpoint definitions have fragmented the evidence. We synthesised findings and examined potential contributors to heterogeneity. METHODS: PubMed/MEDLINE, Embase, PsycINFO, and Web of Science were searched for studies published from January 2016 through 25 November 2025. Result records were synthesised using SWiM, and certainty was assessed with an adapted GRADE framework. RESULTS: Sixty studies contributed 493 retained records; 450 were descriptively classified as positive, null, or reverse, although records were not independent. Positive findings accounted for 44/56 diagnostic, 61/273 treatment-related, 64/100 course/severity, and 14/21 subtype records. For MDD/depression-derived PRSs and case-control MDD status, all 10 contributing studies showed higher liability in cases (exploratory exact sign test p&#xa0;=&#xa0;0.002; FDR q&#xa0;=&#xa0;0.004). The same PRS group showed positive findings for overall depressive symptom severity (14/18), although the study-level test was imprecise (5/5 studies; p&#xa0;=&#xa0;0.063). Pharmacological response/remission findings for these PRSs were mostly null or directionally mixed (10 positive, 18 null, and 9 reverse). Treatment-resistant depression (TRD) findings differed by operational definition. Atypical and psychotic subtype signals arose mainly from single-study PRS and endpoint contrasts. CONCLUSIONS: PRS evidence was clearest for MDD diagnostic status and showed a tentative pattern for overall symptom burden. Treatment and subtype findings were less consistent or less replicated. Larger, ancestrally diverse studies with standardised endpoints and transparent PRS methods are needed.

Humans↗

CTRP9 ameliorates heart failure with preserved ejection fraction by regulating lipid metabolism.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a major clinical challenge, with cardiac lipotoxicity emerging as a key driver of disease progression. Despite CTRP9&#x2019;s role in lipid metabolism and cardioprotective properties, its therapeutic potential in HFpEF remains unexplored. This study aimed to investigate whether CTRP9 ameliorates HFpEF by regulating cardiac lipid metabolism and to identify the underlying molecular mechanisms. METHODS: In the established two-hit HFpEF mouse model (induced by a high-fat diet and L-NAME), the mice were treated with either CTRP9 or saline. Cardiac function was evaluated by echocardiography, while hypertrophy, fibrosis, and lipid accumulation were assessed using histology and molecular assays. Proteomic sequencing was further employed to identify downstream targets of CTRP9. RESULTS: CTRP9 treatment significantly improved diastolic function and attenuated cardiac hypertrophy and fibrosis in HFpEF mice. Myocardial lipid accumulation was substantially reduced, accompanied by enhanced fatty acid oxidation. Proteomic analysis identified GPD1 as a key downstream target upregulated by CTRP9. Cardiac-specific knockdown of GPD1 partly abolished the therapeutic benefits of CTRP9. CONCLUSION: Our data suggest that CTRP9 ameliorates HFpEF through GPD1-mediated regulation of cardiac lipid metabolism, identifying the CTRP9-GPD1 axis as a promising therapeutic target for HFpEF.

Animals↗

Significance in scale space for Hi-C data.

MOTIVATION: Hi-C technology has been developed to profile genome-wide chromosome conformation. So far Hi-C data have been generated from a large compendium of different cell types and different tissue types. Among different chromatin conformation units, chromatin loops were found to play a key role in gene regulation across different cell types. While many different loop calling algorithms have been developed, most loop callers identified shared loops as opposed to cell-type-specific loops. RESULTS: We propose SSSHiC, a new loop calling algorithm based on significance in scale space, which can be used to understand data at different levels of resolution. By applying SSSHiC to neuronal and glial Hi-C data, we detected more loops that are potentially engaged in cell-type-specific gene regulation. Compared with other loop callers, such as Mustache, these loops were more frequently anchored to gene promoters of cellular marker genes and had better APA scores. Therefore, our results suggest that SSSHiC can effectively capture loops that contain more gene regulatory information. AVAILABILITY AND IMPLEMENTATION: The Hi-C data used in this study can be accessed through the PsychENCODE Knowledge Portal at https://www.synapse.org/#! Synapse: syn21760712. The code utilized for Curvature SSS cited in this study is available at https://github.com/jsmarron/MarronMatlabSoftware/blob/master/Matlab9/Matlab9Combined.zip. All custom code used in this research can be found in the GitHub repository: https://github.com/jerryliu01998/HiC. The code has also been submitted to Code Ocean with the doi: 10.24433/CO.1912913.v1.

Algorithms↗

ESMpHLA: Evolutionary Scale Model-Based Deep Learning Prediction of HLA Class I Binding Peptides.

The recognition of endogenous peptides by HLA class I plays a crucial role in CD8+ T cell immune responses and human adaptive cell immune. Thus, the prediction of HLA class I-peptide binding affinities is always the core issue for the research of immune recognition and vaccine development. In this study, an evolutionary scale model (ESM) combined with parallel CNN blocks and a cross attention mechanism was used to construct a novel ESMpHLA model for predicting HLA class I binding peptides. Based on the 91,560 binding peptides of 41 HLA-A alleles, 56,731 of 50 HLA-B alleles and 2444 of 10 HLA-C alleles, the ESMpHLA model was successfully established and achieved satisfying prediction performances with the overall accuracy and AUC values of 0.874 and 0.938 for the test dataset. The results indicate that the ESMpHLA model performs well in dealing with different HLA class I 2-field alleles as well as the peptides with different lengths. Then, the generalisation ability of the ESMpHLA model was validated by an independent test dataset compiled from recent IEDB weekly benchmark datasets. The results showed that the ESMpHLA model achieved the highest ROC-AUC and PR-AUC values when compared with the latest BVMHC, CapsNet-MHC, STMHCpan and BVLSTM models. In addition, two ensemble models were also established by integrating the above 5 deep learning models using soft-voting and hard-voting strategies.

Humans↗

The prognostic role of a gene signature from tumorigenic breast-cancer cells.

BACKGROUND: Breast cancers contain a minority population of cancer cells characterized by CD44 expression but low or undetectable levels of CD24 (CD44+CD24-/low) that have higher tumorigenic capacity than other subtypes of cancer cells. METHODS: We compared the gene-expression profile of CD44+CD24-/low tumorigenic breast-cancer cells with that of normal breast epithelium. Differentially expressed genes were used to generate a 186-gene "invasiveness" gene signature (IGS), which was evaluated for its association with overall survival and metastasis-free survival in patients with breast cancer or other types of cancer. RESULTS: There was a significant association between the IGS and both overall and metastasis-free survival (P<0.001, for both) in patients with breast cancer, which was independent of established clinical and pathological variables. When combined with the prognostic criteria of the National Institutes of Health, the IGS was used to stratify patients with high-risk early breast cancer into prognostic categories (good or poor); among patients with a good prognosis, the 10-year rate of metastasis-free survival was 81%, and among those with a poor prognosis, it was 57%. The IGS was also associated with the prognosis in medulloblastoma (P=0.004), lung cancer (P=0.03), and prostate cancer (P=0.01). The prognostic power of the IGS was increased when combined with the wound-response (WR) signature. CONCLUSIONS: The IGS is strongly associated with metastasis-free survival and overall survival for four different types of tumors. This genetic signature of tumorigenic breast-cancer cells was even more strongly associated with clinical outcomes when combined with the WR signature in breast cancer.

Breast↗

Application of a larval medaka assay to evaluate the fish safety level in Sagami River, Japan.

Despite of the increasing concern on aquatic life preservation from water pollution, few methods are available to evaluate the fish safety level of river water. In this study, a principal urban river of Japan, Sagami River, was investigated the geographical and seasonal changes in the fish safety level using an efficient larval medaka (Oryzias latipes) assay. Then combined with topography and land-use character of the catchment, the influence of human activity was discussed. The results revealed the highest fish safety levels and the lowest dissolved organic carbon (DOC) concentrations in the preserved region of the upstream. In the lower mainstream and the west tributaries, catchments of which were developed regions with high sewerage diffusion rates, the fish safety levels slightly decreased although the DOC concentrations were low. By comparison, the east tributaries, which were allocated in highly developed regions without sufficient sewerage service, showed not only high DOC concentrations but also greatly decreased fish safety levels. Two small east tributaries showed three to four times increase in the toxicity in winter, as influenced by the irrigation activity on the bank. The safety level did not closely depend on the common water quality indicator of DOC, although extremely high DOC concentrations tended to relate to low safety levels. The data is useful for better management of the river studied, and the approaches used in this paper will give a hint to the management of other rivers.

Animals↗

pEGFP-T, a novel T-vector for the direct, unidirectional cloning and analysis of PCR-amplified promoters.

A novel T-vector, designated as pEGFP-T, was constructed which could be used for direct and unidirectional cloning and analysis of promoters. The method involves minimizing the non-recombinant background of the T-vector when used to clone PCR products, and maintaining only the forward orientation of the PCR products prior to transformation. The usefulness of this vector is demonstrated in cloning and analyzing promoters.

Base Sequence↗

Evaluating the fish safety level of river water and wastewater with a larval medaka assay.

A larval medaka (Oryzias latipes) assay was proposed to evaluate the fish safety level of river waters and wastewaters. Organic toxicants were 10-100 times concentrated with adsorption cartridges from 4 l of river water or 1-10 times concentrated from 400 ml of wastewater. Toxicity of these concentrated solutions was determined by exposing 48-72 h post-hatch age larvae for 48 h. The method effectively revealed a variation of the median lethal concentration ratio (LCR50) from 13 to >100 in 125 river water samples, and from <1 to >10 in five typical wastewater samples. Ayase River, which takes water mostly from agricultural or household discharge, showed significantly (P<0.001) lower LCR50 than Sagami River that takes natural water as the source. Safety Levels in both Sagami River and Ayase River were influenced by the irrigation activity, LCR50 at some sites showing a seasonal-specific decrease in winter. Pollution from pulp and paper industries contributed to the low LCR50 in several tributaries of Ayase River. Required little manpower in sampling, pretreatment and testing, the proposed larval medaka assay was proved as an efficient tool for screening those high risk sites for priority management.

Animals↗

Left ventricular systolic dysfunction and the risk of ischemic stroke in a multiethnic population.

BACKGROUND AND PURPOSE: Left ventricular dysfunction (LVD) is associated with cardiovascular mortality. Its association with ischemic stroke has been mainly documented after myocardial infarction. The stroke risk associated with LVD, especially of mild degree, in the general population is unclear. The purpose of this study was to evaluate the relationship between LVD and ischemic stroke in a multiethnic cohort. METHODS: LV systolic function was assessed by transthoracic 2-dimensional echocardiography in a subset of subjects from the Northern Manhattan Study (NOMAS), 270 patients with first ischemic stroke and 288 age-, gender- and race-matched community controls. LV ejection fraction was measured by a simplified cylinder-hemiellipsoid formula, and categorized as normal (>50%), mildly (41% to 50%), moderately (31% to 40%) or severely (< or =30%) decreased. The association between impaired ejection fraction and ischemic stroke was evaluated by logistic regression analysis after adjustment for established stroke risk factors. RESULTS: LVD of any degree was more frequent in stroke patients (24.1%) than in controls (4.9%; P<0.0001), as was moderate/severe LVD (13.3% versus 2.4%; P<0.001). A decreased ejection fraction was associated with ischemic stroke even after adjusting for other stroke risk factors. The adjusted odds ratio for any degree of LVD was 3.92 (95% CI, 1.93 to 7.97). The adjusted odds ratio for mild LVD was 3.96 (95% CI, 1.56 to 10.01) and for moderate/severe LVD 3.88 (95% CI, 1.45 to 10.39). The association between LVD of any degree and stroke was present in all age, gender and race-ethnicity subgroups. CONCLUSIONS: LVD, even of mild degree, is independently associated with an increased risk of ischemic stroke. The assessment of LV function should be considered in the assessment of the stroke risk.

Adult↗

Organometallic molecular rectification.

We study the rectification of current through a single molecule with an intrinsic spatial asymmetry. The molecule contains a cobaltocene moiety in order to take advantage of its relatively localized and high-energy d states. A rectifier with large voltage range, high current, and low threshold can be realized. The evolution of molecular orbitals under both forward and reverse biases is captured in a self-consistent nonequilibrium Green function plus density functional theory description. Our calculations demonstrate the plausibility of making excellent molecular diodes by using metallocenes, pointing to a fruitful class of molecules.

Journal Article↗

10-Phenyl-[12]-cytochalasins Z7, Z8, and Z9 from the marine-derived fungus Spicaria elegans.

The three new 10-phenyl-[12]-cytochalasins Z7, Z8, and Z9 (1-3), together with two known analogues, cytochalasins E (4) and K (5), were isolated from the marine-derived fungus Spicaria elegans. This is only the second report to date that cytochalasins contain a 12-membered macrocyclic ring. The structures of the three new cytochalasins were elucidated by spectroscopic methods, and their absolute configurations were determined for the first time by the modified Mosher's method. All five cytochalasins were evaluated for their cytotoxic effects on P388 and A-549 cell lines by the MTT method.

Animals↗

A new diphenyl ether from marine-derived fungus Aspergillus sp. B-F-2.

A new diphenyl ether dimethyl 2,3'-dimethylosoate (1) together with three known compounds monomethylsulochrin (2), emodin (3), and questin (4) were isolated through bioassay-guided fractionations from the culture of a marine-derived fungus Aspergillus sp. B-F-2. The structures of these compounds were determined by spectroscopic methods. Cytotoxicities of compounds 1 and 2 against K562 cell line were preliminarily evaluated by the MTT method and flow cytometry.

Antibiotics, Antineoplastic↗