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Rui Li

Publications and source records attributed to Rui Li.

13 recordsLinked to original sources
PubMed2026

Transposable Element Dynamics Drive the Genomic Evolution and Phenotypic Diversification of Allotetraploid Common Carp.

An important question in evolutionary biology is how polyploidization generates raw material for phenotypic diversification. Transposable elements (TEs) represent an underestimated source of genetic variation in eukaryotic genomes. By integrating 516 whole-genome resequencing datasets and 236 transcriptomes from common carp (Cyprinus carpio), a representative allotetraploid fish, we constructed the first population-scale landscape of TE insertions in teleosts. TE insertions are widespread in the carp genome and preferentially associated with stress-responsive genes, with DNA transposons as major contributors. Relaxed purifying selection and TE burst events coexist, generating abundant variation for subsequent subspecies differentiation. Compared with a closely related diploid species, carp exhibits more exonic TE insertions and shorter TE-gene distances, and multiple TE superfamilies expanded during tetraploidization. Genome-wide association analyses uncovered intragenic TE variants underlying domesticated traits missed by SNPs, including DNA transposon deletions associated with scale reduction and altered body shape. Notably, lighter-colored individuals harbor homozygous deletions of LTR and DNA transposons within mdfic2, whose knockout in zebrafish reduces pigmentation. Most trait-associated variants reflect lineage-specific loss of ancient TE insertions rather than recent transposition. Overall, these findings highlight the distinct role of TEs in polyploid genome evolution and phenotypic diversification, providing new insights into TE dynamics in vertebrates.

allotetraploidization↗
PubMed2026

The emerging landscape of polymerase θ in tumor pathogenesis and precision treatment.

DNA polymerase θ (Polθ) has emerged as a central yet paradoxical regulator of genome stability and tumor progression. Unlike conventional DNA repair factors, Polθ governs an error-prone double-strand break repair pathway-termed theta-mediated end joining (TMEJ)-which becomes essential for survival in homologous recombination (HR)-deficient cancers while simultaneously fueling genomic instability. This review presents a comprehensive and updated synthesis of Polθ's structural architecture, regulatory networks, and context-dependent functions across major malignancies, including ovarian, breast, lung, and colorectal cancers. We highlight recently uncovered mechanisms, such as the iron-FTH1/FTL-POLQ-RAD51 axis in platinum-resistant ovarian cancer, the differential POLQ regulation under methionine restriction in BRCA1-mutant breast cancer, and the identification of germline POLQ mutations defining a novel hereditary colorectal cancer subtype. Beyond DNA repair, we integrate emerging evidence linking Polθ to replication stress tolerance, base excision repair, and immune modulation via type I interferon activation and macrophage polarization. The review also provides a critical evaluation of current Polθ inhibitors-including ART558, RP-6685, novobiocin, and AB25583-focusing on their mechanisms, synthetic lethality profiles, and ability to overcome PARP inhibitor resistance. By bridging molecular mechanisms with tumor biology and therapeutic translation, this review offers a unique framework for understanding Polθ as both a prognostic biomarker and a precision oncology target, with implications for combination therapies involving radiotherapy, immunotherapy, and chemotherapy.

Cancer therapy↗
PubMed2026

Discovery and validation of novel plasma protein biomarkers for severe tuberculosis patients.

OBJECTIVE: Severe tuberculosis (STB) imposes a substantial disease burden, yet reliable biomarkers for distinguishing STB from mild/moderate tuberculosis (MTB) remain scarce. This study aimed to identify and independently validate plasma protein biomarkers associated with tuberculosis severity. METHODS: In this multicenter prospective study, 298 adults with confirmed pulmonary tuberculosis were enrolled into screening (n = 128) and independent validation (n = 170) cohorts. Plasma samples were analysed using data-independent acquisition proteomics. Differentially expressed proteins were screened via Limma and four machine-learning algorithms, with candidate proteins measured by enzyme-linked immunosorbent assays. Receiver operating characteristic analysis assessed individual and combined diagnostic performance. RESULTS: STB patients were older and presented with lymphopenia, hypoalbuminemia, neutrophilia, and elevated lactate dehydrogenase. Among 166 differentially expressed proteins, HSPA5, HSP90B1, EEF1D, and SULT1A1 were selected for validation. In STB patients, HSPA5, HSP90B1, and EEF1D were upregulated, whereas SULT1A1 was downregulated. The four-protein panel achieved an AUC of 0.908 (95% CI 0.864-0.952), with 87.5% sensitivity and 83.8% specificity, modestly outperforming HSPA5 alone (AUC = 0.894). Functional enrichment implicated cholesterol metabolism, immune-inflammatory pathways, and endoplasmic reticulum stress. CONCLUSIONS: The four-protein panel effectively discriminated STB from MTB; however, its marginal improvement over HSPA5 alone suggests that an HSPA5-based assay may offer a simpler, more practical, and potentially cost-effective strategy for severity stratification.

Humans↗
PubMed2026

Skin barrier repairing and anti-aging effects evaluation of a comprehensive topical regimen incorporating niacinamide, Pro-Xylane, and panthenol after PicoWay laser: a randomized controlled study.

Pro-Xylane is a potent anti-aging ingredient; however, there is limited knowledge regarding whether a comprehensive post-procedure regimen incorporating a combination of Pro-Xylane, niacinamide, and panthenol alongside other active agents can deliver synergistic benefits for both skin barrier repair and anti-aging. This study assesses the effectiveness of the REGENMEDIC cream (anti-aging cream) and REGENMEDIC serum (anti-aging serum) in promoting skin barrier recovery and enhancing anti-aging effects following PicoWay laser treatment. A 112-day randomized controlled trial was conducted with 88 Chinese females, who were divided into two groups: the test group, using REGENMEDIC cream and Serum following PicoWay laser treatment, and the control group, using standard care regimen consisting of a standard cream. Skin barrier-repairing effects were assessed during the initial 14 days following a single use of REGENMEDIC cream, while skin elasticity, firmness, wrinkles and skin tone were evaluated over the 112-day study period after the combined use of REGENMEDIC cream and Serum. The test group exhibited lower transepidermal water loss (TEWL) and higher hydration after 14 days compared to the control group, along with a more significant reduction in skin redness. After 112-day use of REGENMEDIC cream and serum, test group showed increased skin elasticity and firmness, reduced wrinkles, and an overall improvement in skin tone and texture. Dermatologists reported excellent tolerability, with minimal adverse events. Initial application of the REGENMEDIC cream facilitated rapid skin barrier repair, while the subsequent sequential regimen incorporating the serum yielded significant long-term anti-aging benefits following PicoWay laser treatment. This study demonstrates that targeting multiple physiological pathways-specifically hydration, barrier integrity, and cellular senescence-provides a robust therapeutic option for amplifying the anti-aging outcomes of aesthetic procedures.

Humans↗
PubMed2026

Spatially resolved single-cell atlas reveals the macroevolutionary trajectory of animal hearts.

Animal hearts display diverse anatomical structures during adaptive evolution. Here, we present a multiomics atlas of adult hearts from 27 species across chordates, arthropods, and mollusks. Joint analysis indicates that Bilateria hearts share a core gene repertoire, taking a stepwise "add-on" approach as a universal evolutionary strategy. The "proto-heart" is populated by key cell types, including cardiomyocytes, fibroblasts, endothelial cells, and neural cells, which maintained core signatures while evolving with shifts in living environments and corresponding adaptations in the cardiovascular system. Additionally, we reveal an evolutionarily conserved cardiomyocyte state dynamic potentially linked to cardiac development and stress responses. Finally, we identify a common molecular program underpinning chamber evolution from a ventricular foundation. This work establishes a resource for understanding the intrinsic mechanisms of heart evolution.

Animals↗
PubMed2026

PepGen: conditional generation of peptides for MHC binding.

MOTIVATION: Peptide-MHC II binding drives adaptive immunity, yet discovery of novel binder peptides remains challenging due to open binding grooves of MHC-II that accommodate variable-length peptides. While discriminative models perform well, they are unfeasible for generation via enumeration due to vast peptide space (2013≈8×1016 for peptides of length 13 amino acids). Generative AI approaches could accelerate binder design to enable vaccines targeted to particular MHC-II alleles or optimize other peptide chemical properties. RESULTS: We introduce PepGen, the first protein language model for MHC II peptide generation building on Generalized Language Modeling. PepGen conditions on alleles, arbitrary partial peptides including putative TCR-interacting motifs, and continuous binding affinity. Across multiple benchmarks including infilling and de novo generation, PepGen outperformed frequency sampling, Gibbs clustering, and autoregressive baselines. Adjusted log-probabilities enable good classification performance. Experimental validation confirmed that the SARS-CoV-2 peptide TEGALNTPKDHIGTR binding the HLA-DQA101:03-DQB106:03 allele can be redesigned to bind the HLA-DQA101:02-DQB105:02 allele. PepGen generated three putative TCR-motif-preserving binders gaining up to 70% of original MFI. Overall, PepGen provides scalable, motif-constrained MHC II peptide redesign and de novo generation, validated through thorough benchmarks and functional assays. AVAILABILITY AND IMPLEMENTATION: Code and Data are available at https://github.com/DaniTheOrange/PepGen.

Peptides↗
PubMed2026

Exploring the mechanism of aroma production in fermented cherry juice by L. brevis LD1.0600 using flavomics and whole genome analysis.

This study focused on L.brevis LD1.0600 with excellent fermentation traits: it analyzed genome-wide key regulatory genes for micro-metabolites, combined with fermented cherry juice flavor metabolomics data, and used machine learning to explore correlations between gene regulation, metabolite production, and flavor formation. The SVM model screened and verified fermented cherry juice VOCs; through OAV and flavor wheel analysis, LD1.0600 emerged as the top-performing strain, with a sweet, fruity dominant aroma. Key aroma-active components (OAV > 100) included 2-methoxy-4-vinylphenol, benzaldehyde, 2-methyl-butanoic acid and hexanoic acid, and 2-methoxy-4-vinylphenol and hexanoic acid elevated by LD1.0600-regulated genes (Chrom1-001884, Chrom1-000925, fabF and Chrom1-000199). At the same time, through research, a "strain screening-SVM screening of DVCs-OAV screening of key aroma components-whole genome sequencing of flavor regulatory genes" system was established. This system can not only be applied to the screen fermentation strains, but also can be extended to the application of other fermentation products.

Fermentation↗
PubMed2026

AP2: an indispensable host factor in virus infection.

Adaptor protein complex 2 (AP2), a central regulator of clathrin-mediated endocytosis and intracellular cargo trafficking, is hijacked by numerous viruses to complete their infectious cycles. This review systematically synthesizes the multifaceted roles of AP2 across the entire viral life cycle, from entry and replication to assembly and release, as well as in immune evasion. By delineating how diverse viruses exploit this key host machinery, we further consolidate the rationale and current progress in developing broad-spectrum antiviral strategies that target AP2 and its regulatory pathways. This work aims to provide a unified perspective on AP2 as a critical host-pathogen interface, offering new insights into viral pathogenesis and antiviral drug discovery.

Humans↗
PubMed2025

Dynamic phosphorylation of Hcm1 promotes fitness in chronic stress.

Cell survival depends upon the ability to adapt to changing environments. Environmental stressors trigger an acute stress response program that rewires cell physiology, downregulates proliferation genes and pauses the cell cycle until the cell adapts. After the acute response is resolved, cells resume cycling but at a reduced rate. The importance of cell cycle changes for survival in chronic stress is not clear. Here, we show that dynamic phosphorylation of the yeast cell cycle-regulatory transcription factor Hcm1 is required to maintain fitness in chronic stress. Hcm1 is activated by cyclin dependent kinase (CDK) during S-phase and is inactivated by the phosphatase calcineurin (CN) in response to stressors that signal through increases in cytosolic Ca2+. Cells expressing a constitutively active, phosphomimetic Hcm1 mutant exhibit a reduction in fitness in stress, suggesting Hcm1 inactivation promotes survival. However, a comprehensive analysis of Hcm1 phosphomutants revealed that Hcm1 activity is also important to survive stress, and that all mutants with fixed phosphorylation states are less fit in stress. Moreover, our data suggests that pulses of Hcm1 activity are necessary to maximize target gene expression in stress. These findings demonstrate that expression levels of Hcm1 target genes influence fitness in stress and suggest that the dynamic phosphorylation of cell cycle regulators plays a crucial role in promoting survival in stressful environments.

Phosphorylation↗
PubMed2025

Enhancer activation from transposable elements in extrachromosomal DNA.

Extrachromosomal DNA (ecDNA) drives oncogene amplification and intratumoral heterogeneity in aggressive cancers. While transposable element (TE) reactivation is common in cancer, its role on ecDNA remains unexplored. Here, we map the 3D architecture of MYC-amplified ecDNA in colorectal cancer cells and identify 68 ecDNA-interacting elements (EIEs)-genomic loci enriched for TEs that are frequently integrated onto ecDNA. We focus on an L1M4a1#LINE/L1 fragment co-amplified with MYC, which functions only in the ecDNA amplified context. Using CRISPR-CATCH, CRISPR interference, and reporter assays, we confirm its presence on ecDNA, enhancer activity, and essentiality for cancer cell fitness. These findings reveal that repetitive elements can be reactivated and co-opted as functional rather than inactive sequences on ecDNA, potentially driving oncogene expression and tumor evolution. Our study uncovers a mechanism by which ecDNA harnesses repetitive elements to shape cancer phenotypes, with implications for diagnosis and therapy.

Journal Article↗
PubMed2025

Adaptive laboratory evolution of Micrococcus luteus and identification of genes associated with radioresistance through genome-wide association study.

Micrococcus luteus (V017) is a Gram-positive bacterium that was isolated from a sterilization area exposed to 60Co radiation. In this study, we performed an adaptive laboratory evolution experiment with M. luteus, exposing it to 24 continuous cycles of gamma irradiation at four different doses (1.5 kGy, 3.5 kGy, 5.5 kGy, and 7.5 kGy). This led to the creation of four evolved populations with different levels of radioresistance, which were positively correlated with the radiation dose applied. The survival rate of the evolved population that underwent adaptive treatment at the highest dose (7.5 kGy) was 0.69% after exposure to 5.5 kGy, which is about five orders of magnitude higher than that of the original strain V017. Furthermore, 76 evolved strains were selected from these populations, and their genomes were re-sequenced, uncovering a total of 3072 mutations. A genome-wide association study identified 56 single nucleotide polymorphisms (SNPs) significantly associated with radioresistance, linked to 62 candidate genes. Ultimately, 9 genes were selected for functional validation. Inactivating 6 of these genes, including H0H31_RS03855 (SMC family ATPase, SbcC), H0H31_RS04250 (ribonuclease HII), H0H31_RS04570 (endonuclease VIII), H0H31_RS07595 (bifunctional 3'-5' exonuclease/DNA polymerase I), H0H31_RS00170 (serine/threonine phosphatase PPP), and H0H31_RS05860 (CBS-domain-containing protein), significantly increased sensitivity to gamma radiation, underscoring their importance in radioresistance.

Micrococcus luteus↗
PubMed2024

Exploring the prognostic landscape of oral squamous cell carcinoma through mitochondrial damage-related genes.

Oral squamous cell carcinoma (OSCC), the most prevalent form of oral cancer, poses significant challenges to the medical community due to its high recurrence rate and low survival rate. Mitochondrial Damage-Related Genes (MDGs) have been closely associated with the occurrence, metastasis, and progression of OSCC. Consequently, we constructed a prognostic model for OSCC based on MDGs and identified potential mitochondrial damage-related biomarkers. Gene expression profiles and relevant clinical information were obtained from The Cancer Genome Atlas (TCGA) database. Differential analysis was conducted to identify MDGs associated with OSCC. COX analysis was employed to screen seven prognosis-related MDGs and build a prognostic prediction model for OSCC. Cases were categorized into low-risk or high-risk groups based on the optimal risk score threshold. Kaplan-Meier (KM) analysis revealed significant survival differences (P&#x2009;<&#x2009;0.05). Additionally, the area under the ROC curve (AUC) for patient survival at 1 year, 3 years, and 5 years were 0.687, 0.704, and 0.70, respectively, indicating a high long-term predictive accuracy of the prognostic model. To enhance predictive accuracy, age, gender, risk score, and TN staging were incorporated into a nomogram and verified using calibration curves. Risk scoring based on MDGs was identified as a potential independent prognostic biomarker. Furthermore, BID and SLC25A20 were identified as two potential independent mitochondrial damage-related prognostic biomarkers, offering new therapeutic targets for OSCC.

Humans↗