Biomedical subjects

Yang Liu

Publications and source records attributed to Yang Liu.

At least 37 records · Page 2Linked to original sources

PubMed2026

In silico analysis based on network pharmacology and biomolecular informatics to explore the mechanism of action of Erjing Pills (from Shengji Zonglu) in the treatment of leukotrichia.

This study aimed to explore the core active ingredients and potential molecular mechanisms of Erjing Pills, a prescription in the classic work of Traditional Chinese Medicine, "Shengji Zonglu," in the treatment of leukotrichia by utilizing network pharmacology and biomolecular docking techniques. The chemical components and potential targets of Chinese herbal medicines were analyzed through databases such as the Traditional Chinese Medicine Systems Pharmacology Database. The targets related to leukotrichia were collected using GeneCards. The intersection targets were obtained using RStudio. The protein-protein interaction (PPI) network map and the "drug-component-target-disease" visualization network were generated using Cytoscape and STRING to screen the core components and key targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were carried out using the Database for Annotation, Visualization and Integrated Discovery and RStudio. Finally, molecular docking verification was performed by AutoDock and PyMOL (Schrödinger LLC). The key active ingredients of Erjing Pills in the treatment of leukotrichia are β-sitosterol, quercetin, baicalein, and stigmasterol. The top 5 PPI core target proteins, in order, are AKT serine/threonine kinase 1, interleukin 6, tumor protein p53, cysteine-aspartic acid protease 3, and interleukin 1 beta. The Gene Ontology enrichment analysis suggests that the biological processes mainly include responses to exogenous stimuli, membrane rafts, and DNA-binding transcription factor binding. The Kyoto Encyclopedia of Genes and Genomes pathways involve signal pathways such as lipid and atherosclerosis, hepatitis B, Kaposi sarcoma virus infection, chemical carcinogenesis, and human cytomegalovirus infection. The molecular docking results indicate that most of the main active ingredients in Erjing Pills have relatively stable binding activities with the key targets, such as AKT serine/threonine kinase 1, interleukin 6, tumor protein p53, cysteine-aspartic acid protease 3, and interleukin 1 beta, in the PPI network. The active ingredients of Erjing Pills may interfere with the pathological process of leukotrichia by regulating key targets and signal pathways. This study provides a theoretical basis for the clinical application of Erjing Pills and indicates the direction for subsequent experimental research.

Drugs, Chinese Herbal↗

PubMed2026

Emergence of two novel HIV-1 Circulating Recombinant Forms (CRF190_0708 and CRF191_0708): molecular characterization and clinical insights from a five-year study in Yunnan, China.

BACKGROUND: To characterize HIV-1 molecular epidemiology and identify novel circulating recombinant forms (CRFs) among antiretroviral therapy (ART)-naïve heterosexuals in Yunnan, China, and evaluate their clinical impact. METHODS: This study examined 636 HIV-1 pol sequences to analyze genetic diversity, pretreatment drug resistance (PDR), and transmission networks. Near full-length genomes were obtained to identify and characterize novel recombinants, with their evolutionary history inferred by Bayesian analysis. Co-receptor tropism was predicted, and the five-year clinical outcomes (including immune reconstitution and virologic response) of patients infected with the novel CRFs were compared. RESULTS: The most prevalent type identified was CRF08_BC, accounting for 50.16% of cases. The prevalence of drug resistance was 5.97% (38/636), with the K103N mutation being the most common. An analysis of transmission networks revealed that 52.2% (272/521) of clusters were associated with CRF07_BC and CRF08_BC. Two novel second-generation CRFs were identified: CRF190_0708, with an estimated time to the most recent common ancestor (tMRCA) of 1998.9, and CRF191_0708, with a more recent tMRCA ranging from 2009.5 to 2011.6. During the five-year follow-up period, viral rebound was observed in 7 patients in the CRF190_0708 group and in 1 patient in the CRF191_0708 group. Drug-resistance mutations (M184V and K103N) were detected in a subset of rebound cases in the CRF190_0708 group. CONCLUSIONS: This study identifies two novel HIV-1 recombinants, CRF190_0708 and CRF191_0708, highlighting ongoing viral evolution in Yunnan. Preliminary findings suggest possible clinical differences, warranting further investigation. Continued molecular surveillance is needed. TRIAL REGISTRATION: The clinical study was registered at ClinicalTrials.gov under the identifier NCT03852849. The date of registration was March 22, 2019.

Adult↗

PubMed2026

A TIGIT nanotrapping-guided STING-activatable immunometabolic strategy overcomes innate immune silence and T cell exhaustion in breast cancer.

Breast cancer exhibits a profoundly immunosuppressive tumor microenvironment (TME), where innate immune silence prevents antigen sensing and persistent T cell exhaustion limits effector responses, rendering most immunotherapies ineffective. Clinical profiling of 1093 The Cancer Genome Atlas (TCGA) cases identified a glucose-fueled glutathione (GSH)-glutathione peroxidase 4 (GPX4)-dihydrolipoamide S-acetyltransferase (DLAT) axis as a dominant metabolic shield that suppresses oxidative stress, and thereby enforces both stimulator of interferon genes (STING) silence and CD8+ T cell exclusion. To dismantle this barrier, we developed an immunometabolic nanotherapy, GOx/ES-CO-LDH@TIGIT-Nanotrap (TNT). In acidic tumors, proton-driven layered double hydroxide (LDH) disassembly releases glucose oxidase (GOx) and extremely small cuprous oxide (ES-CO). GOx depletes glucose and nicotinamide adenine dinucleotide phosphate (NADPH) to induce disulfidptosis, while ES-CO releases cuprous ions (Cu+) that trigger cuproptosis via binding to lipoylated mitochondrial proteins. Their mutual biochemical amplification produces a cycloacclerated disulfidptosis-cuproptosis cascade that collapses the GSH-GPX4-DLAT axis and restores STING activation. Meanwhile, the macrophage-derived T cell immunoreceptor with Ig and ITIM domains (TIGIT) Nanotrap sequesters CD155 to prevent T cell suppression. Together, this coordinated innate reactivation and adaptive rescue converts immune-cold tumors into STING-inflamed and T cell responsive lesions.

Female↗

PubMed2026

Oro-esophageal feeding for tracheostomized patients with severe traumatic brain injury: a randomized controlled trial.

BACKGROUND: This study reports the clinical effects of intermittent oro-esophageal tube feeding (IOE) versus nasogastric tube feeding (NGT) on nutritional status, aspiration pneumonia, decannulation, and level of consciousness in tracheostomized patients with severe traumatic brain injury (sTBI). METHODS: A randomized controlled trial was conducted between March 2024 and October 2025 in China and included tracheostomized patients with sTBI. Participants were randomized 1:1 to the intervention and control groups for 28-day interventions. IOE or NGT was used for nutritional supports, respectively. The primary outcome was nutritional status, including hemoglobin, albumin, prealbumin and body mass index. The secondary outcomes included aspiration pneumonia, decannulation, and level of consciousness assessed using the Glasgow Coma Scale (GCS). Generalized linear mixed-effects models, generalized estimating equations, and Cox regression were used for data analyze. RESULTS: A total of 104 participants were included in the analysis. After intervention, significant interaction effects were observed in hemoglobin (β = 5.272, 95% CI: 2.707, 7.837), albumin (β = 3.675, 95% CI: 1.854, 5.496), prealbumin (β = 11.835, 95% CI: 6.623, 17.047), body mass index (β = 1.719, 95% CI: 0.868, 2.569), the GCS (β = 0.981, 95% CI: 0.572, 1.390), and aspiration pneumonia (OR= 0.304, 95% CI: 0.133, 0.693). The Cox model revealed that group significantly influenced the decannulation outcomes [HR (95% CI) =5.556 (3.197, 9.657), p < 0.001]. CONCLUSIONS: In tracheostomized patients with sTBI who received routine treatment, IOE is more conducive to decannulation and the improvement in nutritional status, aspiration pneumonia, and level of consciousness than NGT. CLINICAL TRIAL REGISTRATION: Prospectively registered at ClinicalTrials.gov (NCT06328985, 03/18/2024, clinicaltrials.gov/study/NCT06328985).

Humans↗

PubMed2026

Targeting cancer-specific mutations with RNA-triggered chromatin shredding.

Genetic mutations that drive cancer often occur in tumour-suppressor proteins such as the p53 transcription factor, which is altered in 40-50% of cases1,2. However, current therapies often fail to target these mutations because the mutant proteins typically lack defined drug-binding pockets and restoring their endogenous function has proven challenging. Here we program Cas12a2, an RNA-guided CRISPR nuclease with trans-nucleolytic cleavage activity3,4, to kill cancer cells selectively by targeting cancer-specific transcripts. This approach limited cell growth by inducing trans shredding of chromatin and triggering DNA-damage responses and cell death. In contrast to existing methods, RNA-guided Cas12a2 senses cellular RNA signatures, enabling precise targeting of undruggable mutations. Transcript-activated chromatin shredding provides an innovative approach to precision disease treatments for undruggable targets.

Animals↗

PubMed2026

MYC-bound enhancer RNAs in cis regulate gene transcription and tumorigenesis.

Emerging evidence suggests that MYC binds RNAs, but its functional consequences remain unclear. Here, we integrate multiomics data and reveal that MYC broadly binds enhancer RNAs (eRNAs), which exhibit high cancer- and tissue-specific expression in cancer cell lines and patient tumors. Moreover, we developed a computational pipeline to identify potential cis-regulatory MYC-eRNA target genes, with most predicted eRNA-target pairs supported by RNA polymerase II-mediated chromatin interaction data. Among these, we functionally characterized MERG1 as an oncogenic eRNA that promotes breast cancer tumorigenesis. Mechanistically, MERG1 interacts with MYC to enhance its occupancy at the GREB1 promoter, driving chromatin remodeling and epigenetic activation. This process specifically amplifies GREB1 expression and promotes tumor progression. Last, nanoparticle-mediated delivery of antisense oligonucleotides targeting MERG1 suppresses MYC-mediated breast cancer growth. These results advance our understanding of the enhancer-driven regulation of gene expression and tumorigenesis and provide insights into the regulatory landscape of MYC in cancer.

Humans↗

PubMed2026

Classification and sequencing of hepatitis D virus from a large cohort of chronically infected individuals paired with co-infecting hepatitis B virus sequencing: a genomic characterisation study.

BACKGROUND: The most severe form of viral hepatitis is caused by co-infection of hepatitis D virus (HDV) and hepatitis B virus (HBV). Phylogenetic analyses classify HBV and HDV into eight major genotypes: HBV GTA to GTH and HDV GT1 to GT8. Paired HBV and HDV sequencing data from participants with chronic hepatitis delta are scarce. We aimed to sequence and genotype HDV and HBV from a large cohort of participants from clinical studies and diverse countries of origin. METHODS: 407 participants with chronic hepatitis D from 24 countries were characterised (124 participants from MYR301 clinical trial, 93 from MYR204, 114 from MYR202, and an additional 76 participants from diverse geographical locations). HBV and HDV from participants were analysed using sequencing, enzyme immunoassay, or both to determine HBV and HDV genotypes. BLAST analysis and phylogenetics were used to determine HBV and HDV genotypes with reference sequence libraries. Bulevirtide treatment response (measured by HDV RNA decline and normalisation of alanine aminotransferase) was compared by genotype for MYR trial participants. FINDINGS: HDV sequencing assays were successful for 386 (95%) of 407 participants and HBV sequencing or serology-based HBV genotyping assays were successful for genotyping 395 (97%) participants. For individual genotypes, HBV GTD (336 [83%] participants) and HDV GT1 (364 [89%]) were the most prevalent. For paired HBV-HDV genotypes, HBV-HDV D/1 was most common (320 [79%] of 407) followed by A/1 (30 [7%]). Phylogenetic analyses of HDV full-genome sequences showed distinct clusters of sequences within HDV GT1, and four novel provisional HDV GT1 subgenotypes, HDV GT1fp to HDVGT1ip, were identified. For 218 MYR clinical trial participants, bulevirtide treatment response was similar across HDV GT1 subgenotypes (both established and newly identified). INTERPRETATION: Novel HDV subgenotypes identified in this study indicate a greater genetic diversity of HDV GT1 than previously recognised. This knowledge will be important for developing better diagnostics, and in understanding HDV genotype-specific biology and response to treatment. More extensive HDV sequencing from under-sampled regions, such as Africa, is needed to determine the true breadth of HDV sequence and genotype diversity. FUNDING: Gilead Sciences.

Hepatitis Delta Virus↗

PubMed2026

Glycolysis-dependent reactive oxygen species mediate desmopressin acetate-induced rescue of platelet dysfunction caused by antiplatelet therapy.

Antiplatelet therapy is extensively used in the prevention and treatment of cardiovascular and cerebrovascular diseases; however, life-threatening hemorrhage requires urgent reversal of platelet dysfunction. Desmopressin acetate has been proposed as a rescue strategy, yet its efficacy and underlying mechanisms remain incompletely understood, particularly regarding redox regulation. A mouse carotid artery blood flow injury model was employed to evaluate the effects of desmopressin acetate on platelet and coagulation dysfunction induced by antiplatelet therapy. Proteomic analyses were performed in both patients and mice to identify differentially expressed proteins. Genetic knockout and pharmacological inhibition approaches were used to investigate the mechanistic pathways involved. Desmopressin acetate effectively restored platelet function and coagulation capacity in antiplatelet-treated mice. Proteomic profiling identified peroxiredoxin-5, a key antioxidant enzyme, as significantly upregulated following antiplatelet therapy but markedly downregulated after desmopressin acetate administration; these findings were validated in plasma samples from 10 patients who received dual antiplatelet therapy for unruptured intracranial aneurysms. Functional studies demonstrated that proteomic profiling identified peroxiredoxin-5 supplementation impaired platelet function, whereas proteomic profiling identified peroxiredoxin-5 knockout or inhibition significantly improved platelet activity. Notably, desmopressin acetate primarily suppressed liver-derived proteomic profiling identified peroxiredoxin-5 expression. Mechanistically, desmopressin acetate enhanced platelet glycolysis via phosphofructokinase-2/fructose-2,6-bisphosphatase 3 activation, leading to increased intracellular reactive oxygen species levels. Inhibition of phosphofructokinase-2/fructose-2,6-bisphosphatase 3 attenuated glycolysis, reduced reactive oxygen species generation, and restored proteomic profiling identified peroxiredoxin-5 expression, thereby abolishing the platelet-rescuing effects of desmopressin acetate. Desmopressin acetate rescued platelet dysfunction induced by antiplatelet therapy through a glycolysis-reactive oxygen species-proteomic profiling identified peroxiredoxin-5 axis, in which glycolysis-driven reactive oxygen species generation plays a central regulatory role. These findings indicate redox modulation as a critical mechanism underlying desmopressin acetate-mediated platelet rescue and suggest a potential therapeutic strategy for managing severe bleeding associated with antiplatelet therapy.

Animals↗

PubMed2026

Accessing Underexplored Biosynthetic Potential by Initiation Unit Engineering of Nonribosomal Peptide Synthetases in Proteobacteria.

Nonribosomal peptide synthetases (NRPSs) represent a valuable yet underexplored resource for producing bioactive natural products. However, most NRPSs remain silenced potentially due to factors such as dysfunction of the initiation unit. The starter condensation (Cs) domain of the initiation unit catalyzes the lipoinitiation of nonribosomal peptides via the incorporation of an N-terminal fatty acyl chain. The concept of initiation unit engineering introduced herein encompasses the replacement of the native initiation unit of NRPSs with a foreign and well-characterized Cs domain-containing initiation unit to activate the NRPS and optimize its expression. This strategy was employed herein to successfully access three of the six previously silent NRPS pathways in Mycetohabitans rhizoxinica HKI 454, a bacterium of the class β-proteobacteria, resulting in the identification of three classes of lipopeptides. This strategy was then extended to access two NRPS pathways in Pseudomonas syringae (γ-proteobacteria) and obtain novel lipopeptides, thereby establishing a feasible complement to existing genome mining strategies for natural product discovery. Furthermore, change of the initiation regions of biosynthetic pathways of nonlipidated chitinimide (β-proteobacteria) and pseudotetraivprolide (γ-proteobacteria) with heterologous Cs-containing initiation units enabled the successful incorporation of fatty acyl chains into the N-terminus of both peptide backbones, launching a workable approach to create artificial lipopeptides. Overall, this study provides a practical strategy for the rational recovery of silent BGCs and introduction of fatty acyl chains into nonribosomal peptides, at least in Proteobacteria, thereby enriching genome mining and combinatorial biosynthesis approaches for accessing the underexplored biosynthetic potential of NRPSs from various bacteria.

Proteobacteria↗

PubMed2026

Publisher Correction: Targeting cancer-specific mutations with RNA-triggered chromatin shredding.

Explore the source record for details and available documents.

Published Erratum↗

PubMed2026

The Anti-Osteoporosis Effects of Panax japonicus via Downregulation of Inflammatory Factors: A Network Pharmacology and Ovariectomized Rat Model Study.

OBJECTIVE: Osteoporosis is a major and growing public health problem characterized by decreased bone mineral density and destroyed bone microarchitecture. Panax japonicus has been clinically used in the treatment of bone diseases, especially osteoporosis. However, there is a lack of study on the mechanism of osteoporosis treatment with Panax japonicus. MATERIALS AND METHODS: A network pharmacology approach was employed to identify the targets of osteoporosis and Panax japonicus. Cytoscape 3.7.2 and DAVID were used to visualize the pharmacological mechanism of Panax japonicus in treating osteoporosis by building up compound-target and protein-protein interaction (PPI) networks and conducting Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. An ovariectomized SD rat osteoporosis model was used to assess the potential therapeutic effect of Panax japonicus in vivo. The biomechanical properties, pathological changes, inflammatory cytokines, bone density, and bone microstructural parameters in rat bone tissue were carefully measured. The biochemical markers of bone metabolism in serum were detected by Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS AND DISCUSSION: Fifty-two active components and sixty-five target genes of Panax japonicus involved in the treatment of osteoporosis were identified. The PPI network revealed IL-6, TNF, NR3C1, IL-1β, CASP3, ESR1, PGR, and AR to be involved in the treatment of osteoporosis with Panax japonicus. Chikusetsusaponin IVa and Radix ginsenoside-Ro were the main saponins found in Panax japonicus. Panax japonicus was found to exert potent preventive effects on osteoporosis by maintaining biomechanical properties, increasing bone mineral density, and protecting the trabecular microstructure in an ovariectomized rat osteoporosis model. Panax japonicus hindered the initiation of osteoporosis induced by ovariectomy by regulating bone metabolism and downregulating the expression of IL-6 and TNF-α. CONCLUSION: Panax japonicus was found to contain 52 compounds and 65 targets in the treatment of osteoporosis. The administration of Panax japonicus could mitigate osteoporosis in rats induced by ovariectomy, and one of the mechanisms was associated with downregulating the expression of inflammatory factors.

Animals↗

PubMed2025

A Prospective Validation of the Decipher Genomic Classifier in Men With Early Localized Prostate Cancer: The VANDAAM Study.

BACKGROUND: The emergence of genomic precision oncology has advanced personalized care for some patients with prostate cancer (PCa), while threatening to widen existing disparities due to the historically low recruitment of African American men (AAM), who have the highest disease burden. Here, we report the first prospective validation of a genomic classifier (GC) to predict rapid-onset biochemical recurrence (BCR) in AAM. METHODS: Between 2016 and 2021, this multicenter prospective validation study recruited 243 patients with low- or intermediate-risk PCa who received treatment for their disease. Patients were recruited on a 1:1 basis (AAM:White) and matched by CAPRA score. Patients who elected active surveillance were ineligible for participation. Decipher GC testing was ordered for all patients using their biopsy and/or radical prostatectomy (RP) tumor tissue. The primary outcome was to determine whether the GC could predict 2-year BCR rates-used as a surrogate for disease aggressiveness-following standard treatment. The secondary outcome evaluated the concordance between biopsy- and RP-derived GC risk scores for treatment recommendations. RESULTS: The final analytical cohort included 226 matched patients with genomic information, and 207 evaluable cases (104 AAM, 103 White) with both genomic and complete clinical outcome data. Overall, a high genomic-risk GC score was associated with a 5.25-fold increase in the odds of rapid-onset 2-year BCR compared with the low-risk group (odds ratio, 5.25 [95% CI, 1.27-21.66]; P=.021). In a subset of the surgical cohort (n=74), biopsy- and RP-derived GC scores exhibited a 77% concordance rate, defined as no reclassification in GC risk-based categories. CONCLUSIONS: This study represents the first prospective validation of GC performance in predicting early 2-year BCR in both AAM and White men. The findings provide strong evidence supporting the integration of the GC into clinical practice guidelines to improve risk stratification and management of AAM with early-stage PCa. CLINICALTRIALS: gov identifier: NCT02723734.

Aged↗

PubMed2025

Efficient site-specific integration of kilobase-length DNA fragments in plant cells via Kp03 recombinase.

Targeted insertion of large DNA sequences into plant genomes remains a major challenge in synthetic biology. Here, we evaluate the large serine recombinase Kp03 for site-specific integration of DNA fragments in rice and Arabidopsis. In transient protoplast assays, Kp03 mediates efficient insertion of donor DNA up to 27.3 kilobases (kb), with plasmid integration efficiencies reaching 99.1% for fragments up to 3.4 kb. Truncation experiments reveal that a minimal 15-bp attB sequence is necessary for integration. As a proof of concept, Kp03 successfully incorporates a 3.4-kb donor DNA into the rice genome at a locus containing this minimal attB sequence. Moreover, in rice callus, combining Kp03 with the NM-PE genome editing system to install a 26-bp attB site enables targeted integration of a 3.4-kb donor at the desired genomic locus. These findings establish Kp03 as a versatile tool for plant genome engineering, with broad applications for synthetic biology.

Oryza↗

PubMed2025

Fluorinated Ionizable Lipids for Efficient Spleen-Targeted mRNA Delivery in Cancer Immunotherapy.

Efficient and selective mRNA delivery to immune-related organs, particularly the spleen, remains a major barrier to the broader clinical translation of mRNA therapeutics. Here, leveraging the clinically approved SM-102/ALC-0315 ionizable lipid scaffold, we rationally designed a combinatorial library of fluorinated ionizable lipids (FILs) by systematically modulating hydrophobic tails and fluorine stoichiometry. Through synthesis and evaluation of 74 candidate FILs, we identify SSC6F5 lipid nanoparticles (LNPs) as a lead formulation with exceptional spleen-targeting specificity (>90%) across intravenous, intramuscular, and subcutaneous administrations. Compared to clinically approved SM102 LNPs and spleen-tropic SM102/18PA (SORT) LNPs, intravenously administered SSC6F5 LNPs achieve 10.6-fold and 63.1-fold higher splenic mRNA transfection, respectively. Proteomic analysis of protein corona on SSC6F5 LNPs reveals significant enrichment of apolipoprotein D (Apod) and reduction in apolipoprotein H (Apoh), implicating a novel endogenous recognition pathway driving enhanced spleen targeting. Functionally, SSC6F5 LNPs enable efficient genome editing in splenic macrophages, dendritic cells, T cells, and B cells in Ai9 mice, and elicit potent CD8+ T cell and humoral responses in a B16-OVA murine melanoma model, resulting in significant tumor growth inhibition. These findings establish fluorinated lipids as a mechanistically distinct and translationally versatile platform for precision spleen-targeted mRNA delivery in gene editing and cancer immunotherapy.

Animals↗

PubMed2025

Thyroid disease and breast cancer, benign breast neoplasm: a two-sample Mendelian randomization study.

BACKGROUND: Breast cancer (BC) is a prevalent and significant health issue and a major contributor to global cancer incidence, accounting for 31% of all reported cases in women. Benign breast neoplasm, as a benign tumor with a high incidence in women, may play an important role in the development of BC. Previous studies have shown that thyroid dysfunction and thyroid cancer (TC) can lead to the occurrence of many cancers. Therefore, we conduct Mendelian randomization (MR) analysis to explore the causality of thyroid dysfunctions, TC, and breast neoplasm. METHODS: The data of the analysis from the genome-wide association study (GWAS) dataset. The exposure includes FT4, TSH, hypothyroidism, hyperthyroidism, and TC. Meanwhile, the outcome consists of BC, HER2-enriched BC, HER2-negative BC, and benign breast neoplasm. We used five methods (inverse variance weighted (IVW) random effects model, IVW fixed effects model, MR-Egger method, median weighted method, and the weighted mode method). We used the MR-PRESSO test and MR-Egger intercept test to detect horizontal pleiotropy and Cochran's Q test to detect heterogeneity. RESULTS: The IVW method showed a positive relationship between high FT4 levels and BC (OR = 1.210 p = 0.008) and an inverse association between TSH levels (OR IVW = 0.908 p = 0.007), hypothyroidism (OR IVW = 0.959, p = 0.014) and BC. For HER2-positive BC, an elevated FT4 level was associated with an increased risk (OR IVW = 1.314, p = 0.001). Genetically predicted high TSH levels (OR IVW = 0.899, p = 0.02) and hypothyroidism (OR IVW = 0.944, p = 0.003) were associated with a decreased risk of HER2-positive BC. Meanwhile, individuals with TC (OR = 1.003, p = 0.048), and hyperthyroidism (OR IVW = 1.127, p = 0.006) were associated with an increasing risk of development of benign breast neoplasm. Hyperthyroidism was associated with an elevated risk of benign breast neoplasm. CONCLUSIONS: The present MR study explains the association between thyroid diseases and BC (mainly in HER2-positive BC). Furthermore, it demonstrates that hyperthyroidism, low levels of TSH, and TC may contribute to the development of benign breast neoplasm.

Humans↗

PubMed2025

Distinct evolutionary trajectories of subgenomic centromeres in polyploid wheat.

BACKGROUND: Centromeres are crucial for precise chromosome segregation and maintaining genome stability during cell division. However, their evolutionary dynamics, particularly in polyploid organisms with complex genomic architectures, remain largely enigmatic. Allopolyploid wheat, with its well-defined hierarchical ploidy series and recent polyploidization history, serves as an excellent model to explore centromere evolution. RESULTS: In this study, we perform a systematic comparative analysis of centromeres in common wheat and its corresponding ancestral species, utilizing the latest comprehensive reference genome assembly available. Our findings reveal that wheat centromeres predominantly consist of five types of centromeric-specific retrotransposon elements (CRWs), with CRW1 and CRW2 being the most prevalent. We identify distinct evolutionary trajectories in the functional centromeres of each subgenome, characterized by variations in copy number, insertion age, and CRW composition. By utilizing CENH3-ChIP data across various ploidy levels, we uncover a series of CRW invasion events that have shaped the evolution of AA subgenome centromeres. Conversely, the evolutionary process of the DD subgenome centromeres involves their expansion from diploid to hexaploid wheat, facilitating adaptation to a larger genomic context. Integration of complete einkorn centromere assemblies and Aegilops tauschii pan-genomes further revealed subgenome-specific centromere evolutionary trajectories. By inclusion of synthetic hexaploid from S2-S3 generations, alongside 2x/6 × natural accessions, we demonstrate that DD subgenome centromere expansion represents a gradual evolutionary process rather than an immediate response to polyploidization. CONCLUSIONS: Our study provides a comprehensive landscape of centromere adaptation, evolution, and maturation, along with insights into how retrotransposon invasions drive centromere evolution in polyploid wheat.

Centromere↗

PubMed2025

Identification of an antifungal lipopeptide from Bacillus amyloliquefaciens HAU3 inhibiting the growth of Fusarium graminearum using preparative chromatography and 2D-NMR.

UNLABELLED: The presence of fungal contamination and its mycotoxins in animal feed is pervasive, posing a significant threat to the well-being and performance of animals, as well as the safety of animal-derived food products. In this work, we screened a strain of Bacillus amyloliquefaciens (B. amyloliquefaciens) HAU3 that exhibits efficient antifungal activity against the growth of Fusarium graminearum (F. graminearum). The antifungal activity was detected in the supernatant, with 20% sterile supernatant demonstrating an impressive antifungal rate of 98.46% against F. graminearum. The antifungal activity of the strain was evaluated through spectrum analysis and silage trials, revealing its effective antifungal activity against multiple fungal species. Furthermore, the strain is capable of degrading ZEN and its derivatives. The targeted disruption of fungal mycelial membrane was observed using scanning electron microscopy and transmission electron microscopy. Additionally, staining with the reactive oxygen species (ROS)-sensitive fluorogenic dye DCFH-DA and propidium iodide (PI) revealed that the strain induces accumulation of ROS in fungal mycelia. The active compounds underwent further separation, purification, and detection. The prominent active peak was identified through mass spectrometry and magnetic resonance spectroscopy. The molecular structure of the active compounds was predicted to be lipopeptides composed of 8 amino acids known as fengycin. The whole genome sequencing and informatics analysis unveiled a total of 13 gene clusters responsible for the synthesis of secondary metabolites. The antifungal effects of B. amyloliquefaciens HAU3 are exerted through the synthesis of fengycin, which selectively targets and compromises the integrity of fungal mycelia membranes, thereby making it a potential biocontrol agent for mitigating mycotoxin contamination in feed. IMPORTANCE: Mycotoxin contamination in animal feed, predominantly driven by Fusarium graminearum, represents a persistent threat to livestock health and food chain integrity. Here, we report the isolation of a soil-derived Bacillus amyloliquefaciens HAU3, exhibiting potent and broad-spectrum antifungal activity alongside efficient biodegradation of zearalenone and its derivatives. Mechanistic dissection reveals that fengycin, the principal bioactive metabolite, compromises fungal membrane integrity and elicits intracellular oxidative stress, culminating in hyphal collapse. Genomic profiling uncovers a diverse repertoire of biosynthetic gene clusters underpinning secondary metabolite production. These findings establish strain HAU3 as a promising microbial chassis for the development of next-generation biocontrol strategies aimed at mitigating mycotoxin burden in agroecosystems.

Bacillus amyloliquefaciens↗

PubMed2025

Deep learning guided programmable design of Escherichia coli core promoters from sequence architecture to strength control.

Core promoters are essential regulatory elements that control transcription initiation, but accurately predicting and designing their strength remains challenging due to complex sequence-function relationships and the limited generalizability of existing AI-based approaches. To address this, we developed a modular platform integrating rational library design, predictive modelling, and generative optimization into a closed-loop workflow for end-to-end core promoter engineering. Conserved and spacer region of core promoters exert distinct effects on transcriptional strength, with the former driving large-scale variation and the latter enabling finer gradation. Based on this insight, Mutation-Barcoding-Reverse Sequencing approach was used and constructed a synthetic promoter library comprising 112 955 variants with minimal redundancy and a 16 226-fold expression range. A Transformer-based model trained on this dataset achieved a Pearson correlation of 0.87 with experimentally measured promoter strengths. When combined with a conditional diffusion model, the system enabled de novo generation of promoter sequences with defined strengths, achieving a design-to-measurement correlation of 0.95 and maintaining high accuracy (R = 0.93) across varied sequence contexts. The designed promoters consistently preserved their intended strength gradients, demonstrating robust plug-and-play functionality. This work establishes a scalable and extensible platform (www.yudenglab.com) for deep learning-guided programmable design of Escherichia coli core promoters, enabling precise transcriptional control.

Promoter Regions, Genetic↗