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Hui Liu

Publications and source records attributed to Hui Liu.

13 recordsLinked to original sources
PubMed2026

Maize terpene synthase 8 (ZmTPS8) produces a blend of sesquiterpenes and contributes to defense against pests and pathogens.

Maize (Zea mays) produces terpenoid-based chemical defenses through a large family of terpene synthases, but the contributions of individual enzymes to specific compounds and stress resistance remain difficult to predict. Maize terpene synthase 8 (ZmTPS8) produces multiple sesquiterpenes in heterologous systems, but its in planta function remains unknown. We integrated a metabolite genome-wide association study (mGWAS), CRISPR/Cas9 generated tps8 loss-of-function mutants, metabolite profiling, and biotic stress assays to define ZmTPS8's role in terpene synthesis and biotic stress responses. The mGWAS identified ZmTPS8 as the primary locus associated with herbivore-induced emission of the sesquiterpene volatile germacrene D. Consistently, ZmTPS8 expression was induced by foliar and root herbivory, and tps8 mutants exhibited reduced emission of germacrene D, α-copaene, and δ-cadinene during Spodoptera frugiperda feeding. Loss of ZmTPS8 increased S. frugiperda larval growth but did not affect the belowground herbivore Diabrotica virgifera virgifera. ZmTPS8 also contributed to resistance against sugarcane mosaic virus, and the fungal pathogen Fusarium verticillioides, affecting terpenoid profiles, global metabolism, and fungal toxin production, but had no impact on Cochliobolus heterostrophus or Pythium spp. susceptibility. Together, these results demonstrate that ZmTPS8 contributes to maize defense in a threat-dependent manner, shaping volatile emissions and defense outcomes.

Zea mays↗
PubMed2026

Integrative Proteomics and Ubiquitomics Reveal on-Targets and off-Targets of PROTAC dBET1.

Proteolysis-targeting chimeras (PROTACs) are heterobifunctional molecules that induce selective degradation of target proteins by hijacking the ubiquitin-proteasome system (UPS). Despite their transformative potential in eliminating disease-associated proteins, comprehensively identifying off-target degradation events remains technically challenging. Here, we employed an integrated proteomic and ubiquitinomic strategy to systematically profile the degradation landscape of the PROTAC molecule dBET1 in Jurkat T cells. By capturing the upstream ubiquitination events─which serve as earlier and more sensitive indicators than total protein abundance─our approach enabled the identification of previously overlooked off-target candidates. While dBET1 efficiently degraded its canonical BET family targets, our data also revealed the mitochondrial outer membrane protein VDAC1 as a putative off-target, evidenced by its depletion and increased multisite ubiquitination. Notably, our analysis framework enabled site-specific resolution of degradation events within BRD3, revealing preferential ubiquitination at functionally essential bromodomains, suggesting that degron-enriched regions may underlie domain-selective degradation. Additionally, dBET1 treatment was associated with mitochondrial depolarization and calcium homeostasis disruption, defects that we hypothesize may be functionally linked to the observed VDAC1 depletion. Together, this study demonstrates that integrating ubiquitomics provides a superior sensitivity layer for PROTAC safety assessment, capable of uncovering mechanism-based liabilities that escape conventional global proteomic screening.

Humans↗
PubMed2026

Genomic surveillance reveals escalating antimicrobial resistance and plasmid diversity in clinical Salmonella 1,4,[5],12:i:- ST34 isolates from Guizhou Province, China.

INTRODUCTION: Salmonella 1,4,[5],12:i:- ST34 has emerged as a significant public health issue due to its association with various antimicrobial resistance genes (ARGs) and transferable plasmids. However, its genomic characteristics and potential influence on public health in Guizhou have not been comprehensively assessed. METHODS: From 2019 to 2023, a 5-year surveillance was conducted in nine cities (prefectures) of Guizhou Province. We integrated phenotypic and genomic analyses of 281 clinical Salmonella 1,4,[5],12:i:- ST34 isolates to investigate the prevalence of ARGs and plasmids and to analyze the molecular epidemiology and evolution. RESULTS: The isolates exhibited resistance to first-line antibiotics, with 22.4% for ciprofloxacin, 11.4% for azithromycin, 18.5% for ceftazidime, and 39.1% for cefotaxime. ARGs showed substantial agreement with phenotypes for tetracycline, macrolides, third-generation cephalosporins (3GCs), carbapenems, and colistin (80.8-100.0% consistency; Kappa: 0.50-1.00). Plasmid analysis identified IncQ1 (84.3%) and IncHI2/IncHI2A (26.3%) as the main replicons, with the variety of plasmid replicons increasing from 7 to 21 over the 5 years. ARGs associated with resistance to critically important antibiotics (CIAs) were frequently predicted to be located on plasmid-associated contigs, with significant associations observed between IncHI2/IncHI2A plasmids and ARGs conferring resistance to fluoroquinolones, macrolides, and cephalosporins (P < 0.05). Molecular typing divided 281 isolates into 37 cgSTs, with cgST52428 being the most common. Molecular epidemiological analysis revealed that Guizhou isolates primarily clustered together, sharing close genetic ties with those from Sichuan and Guangdong, and exhibited the highest genetic similarity to pork-derived isolates. Phylogenetic analysis revealed clustering of CIA-resistant ARGs and plasmids in Clades 4 and 5, with a significant association between IncHI2/IncHI2A plasmids and CIA-resistant ARGs (&#x3c7;2 = 112.12, P < 0.001). Additionally, class 1 integron was associated with higher ARG burdens, while virulence-associated genes were conserved and predominantly chromosome-associated. Gene-content analysis revealed that isolates in Clades 4 and 5 harbored the largest mean gene complements, and cgST52428 isolates also harbored the largest among dominant cgSTs. DISCUSSION: This study presents a comprehensive genomic profile of Salmonella 1,4,[5],12:i:- ST34 in Guizhou, providing essential data for exploring the resistance characteristics and investigating the molecular epidemiology of Salmonella 1,4,[5],12:i:-.

ST34↗
PubMed2026

Synergistic transcriptional modules in Trichoderma asperellum enhance glutathione detoxification to counteract fungal pathogen toxins.

Trichoderma fungi are potent biocontrol agents. However, their defence mechanisms against pathogen-derived toxins remain poorly understood. We identified two synergistic transcription factor modules in T. asperellum that orchestrate the detoxification of cytotoxic secondary metabolites from the poplar blight pathogen Alternaria alternata. Overexpression of the central regulator TasMYB46 reduced disease lesion area by approximately 22% and was associated with decreased pathogen-induced reactive oxygen species (ROS) accumulation. Mechanistically, TasMYB46 directly activates the glutathione S-transferases TasGST61.1 and TasGST56.1 through distinct promoter binding sites (G-box/as-1/MBS), forming dedicated detoxification modules. Crucially, we identified urolithin C as the most abundant phytotoxin in A. alternata metabolites, which is efficiently detoxified through the TasMYB46-TasGST61.1 module. The transcription enhancer TasbHLH53.8 amplifies this system by binding to TasMYB46, boosting TasGST expression and enhancing glutathione-dependent detoxification capacity. This coordinated response elevates glutathione pools and antioxidant enzyme activities (GST/GPx), conferring increased oxidative stress resistance. This study reveals a novel defence mechanism in Trichoderma in which MYB-bHLH-GST modules enable biocontrol agents to neutralise pathogen-derived toxins. Given that Alternaria toxins threaten crops globally (tomatoes, potatoes, citrus), the discovered regulatory synergy represents a strategic advance in developing next-generation biocontrol solutions against toxin-producing plant pathogens.

Alternaria↗
PubMed2026

Tracing and characterization of a family outbreak of subtype B2 botulism linked to homemade pickled eggs in Jinan, China.

Foodborne botulism (FB) results from the ingestion of food contaminated with botulinum neurotoxin. Here, we report a family outbreak of foodborne botulism caused by Clostridium botulinum subtype B2 linked to homemade pickled eggs. On August 13, 2024, the Jinan Center for Disease Control and Prevention and the Shanghe County Center for Disease Control and Prevention collaborated to investigate an outbreak of botulism poisoning related to a family gathering in Shanghe County, Jinan City. A total of 4 people attended the family gathering, three of whom developed clinical symptoms of botulism after consuming pickled eggs. The diagnosis of botulism was suspected through collaborative efforts by the Qilu Medical Prevention and Control Innovation Integration Mechanism and multidisciplinary consultations across multiple hospitals. We detected the bont gene using real-time quantitative PCR (qPCR) in Jinan CDC, determined the toxin serotype by mouse bioassay (MBA) in China CDC and performed whole-genome sequencing of bacterial strains isolated from patient feces, the homemade pickled eggs and soil in both laboratories. It was shown that the toxin type and bont gene were subtype B2, belonging to the ha gene cluster. The Clostridium botulinum strains isolated from two patients were closely related to the strains from the homemade pickled eggs through whole-genome single nucleotide polymorphism analysis. We also found that Clostridium botulinum strains from soil clustered into one branch with those from patients and food, suggesting that the source of Clostridium botulinum contamination may be from soil, although the contamination pathway was not clear. Importantly, our findings provided a basis for clinical antitoxin treatment, in which one patient successfully gave birth after recovery. These results underscore the importance of strengthening public education about the health risks associated with consuming homemade fermented or preserved foods and enhancing the laboratory detection capabilities.

Botulism↗
PubMed2026

The genome of Thesium ramosoides (Santalales) reveals evolutionary dynamics associated with parasitism and alpine adaptation.

Plant species adapting to complex environments experience contrasting selection pressures that drive the expansion and contraction of different gene families. However, few studies have investigated simultaneous genomic responses to such diverse selective forces. Here, we generate a high-quality genome assembly for the hemiparasitic plant Thesium ramosoides, the first for the largest genus in the Santalales, and explore the genomic basis underlying the evolution of parasitism and alpine adaptation. Unlike many other parasitic plants, the Thesium genome has not undergone additional rounds of whole-genome duplication, making it particularly tractable for studying gene family evolution. Our analyses reveal substantial loss of photosynthesis-related genes and contraction of biotic defense gene families, likely reflecting adaptation to a hemiparasitic lifestyle and reduced pathogen pressure at high altitudes. The absence of key root hair development genes correlates with the degenerate root hair phenotype observed in this species. Furthermore, hallmarks of high-altitude adaptation include the expansion of gene families involved in responses to hypoxia. Notably, expansion of gene families associated with meristem development is consistent with the presence of below-ground crown buds that enable rapid regeneration after mountain fires. Unexpectedly, we detected tandem duplication and diversification of the strigolactone receptor gene D14, which regulates secondary shoot formation, but not of its ancestral paralog KAI2, which mediates seed germination in response to the smoke-derived compound karrikin. This finding suggests divergent signaling mechanisms underlying fire adaptation across different parasitic plant lineages. By integrating time-series transcriptomic data, we propose a post-fire "defense first, repair later, recovery last" model, in which resources are reallocated from immediate defense to rapid repair and ultimately to long-term recovery, to explain the adaptation of T. ramosoides to fire-prone habitats. Our study provides critical insights into the complex and contrasting genomic dynamics that drive adaptation to multiple co-occurring selection pressures.

Genome, Plant↗
PubMed2025

A clinically applicable method for early interstitial lung disease detection in incident rheumatoid arthritis cases: integration of protein biomarkers and clinical factors.

BACKGROUND: This study aimed to develop an early diagnostic method integrating proteomic biomarkers and clinical parameters for screening interstitial lung disease (ILD) in patients with newly diagnosed rheumatoid arthritis (RA) through a multi-phase research strategy. METHODS: A three-phase study was conducted: (1) Discovery: Tandem mass tag (TMT)-labeled quantitative proteomics with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyzed serum protein profiles in 5 RA-ILD and 5 RA-non-ILD patients, identifying candidates via bioinformatics. (2) Verification: Enzyme-linked immunosorbent assay (ELISA) validated candidates in an independent cohort (13 RA-ILD vs 14 RA-non-ILD). (3) Application: Biomarkers combined with clinical indicators (Krebs von den Lungen-6 [KL-6], age, sex) were evaluated in 110 patients (51 RA-ILD vs 59 RA-non-ILD) to build a predictive model. RESULTS: Proteomic analysis identified matrix metalloproteinase-3 (MMP3), von Willebrand factor (VWF), and other significantly differentially expressed proteins. ELISA validation confirmed that serum MMP3 and VWF levels were significantly higher in the RA-ILD group than in the RA-non-ILD group (p&#x2009;=&#x2009;0.025 and 0.027, respectively). Expanded validation demonstrated superior diagnostic performance when combining MMP3 and VWF with KL-6 (area under the curve [AUC]&#x2009;=&#x2009;0.90). The nomogram prediction model based on univariate analysis exhibited excellent discrimination (AUC = 0.89) and calibration. CONCLUSION: This systematic study from discovery to validation identified MMP3 and VWF as potential biomarkers for RA-ILD. The integrated predictive model combining these biomarkers with clinical parameters (KL-6, age, sex) provides a potential tool for early ILD screening in RA patients, offering novel strategies for early diagnosis and intervention of RA-ILD.

Humans↗
PubMed2025

C6ORF120 regulates hepatic lipid metabolism through PPAR signaling pathway in metabolic dysfunction-associated steatotic liver disease.

Background Emerging evidence indicates that C6ORF120 is highly expressed in the liver and may modulate immune responses in various hepatic disorders. However, its role in hepatic lipid metabolism and metabolic dysfunction-associated steatotic liver disease (MASLD) is unexplored. This study aimed to elucidate the effects and potential mechanisms of C6ORF120 on hepatic lipogenesis. Methods C6ORF120 expression in MASLD was assessed using patient serum and the Gene Expression Omnibus (GEO) database. A high-fat diet-induced MASLD model was established in C6orf120-KO rats. Fatty acid-induced lipid accumulation models were generated in primary hepatocytes, HepG2 and Huh7 cells. These models were employed to investigate the effects of C6ORF120 on hepatic lipogenesis and MASLD progression. Results C6ORF120 expression was significantly upregulated in MASLD patients and obese rat models. Genetic deletion of C6ORF120 markedly alleviated high-fat diet-induced steatosis in the liver of rats. In vitro, C6orf120 gene deficiency attenuated lipid accumulation and suppressed key lipogenic genes (such as fatty acid synthase (Fasn), phospho-acetyl coenzyme carboxylase (p-ACC), sterol regulatory element binding protein-1c (Srebp1c)) in primary hepatocytes and HepG2 cells. Conversely, C6ORF120 overexpression increased lipid accumulation in HepG2 cells. RNA sequencing analysis showed that lipid metabolism pathway and peroxisome proliferators activated receptor (PPAR) signaling pathway were significantly altered in the liver of C6orf120-KO rats. We demonstrated that C6ORF120 may regulate lipid metabolism through the hepatic PPAR&#x3b1;, which is involved in fatty acid production and lipid oxidation. Further, we found that serum C6ORF120 expression was correlated with clinical indicators in patients with MASLD. Conclusion This study preliminarily revealed a novel function for C6ORF120 in hepatic lipid metabolism via affecting the PPAR pathway. The result identifies C6ORF120 as a novel regulator of hepatic lipid metabolism through PPAR&#x3b1;-dependent mechanisms, offering potential therapeutic targets for MASLD.

Lipid Metabolism↗
PubMed2025

Genetic analysis of three patients from two unrelated Chinese families with autosomal recessive spastic ataxia of Charlevoix-Saguenay.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare early-onset neurodegenerative disorder characterized by progressive cerebellar ataxia, spasticity, and sensorimotor peripheral neuropathy. This disorder is caused by homozygous or compound heterozygous variants in the sacsin (SACS) gene on chromosome 13q12.12. Three patients with ARSACS from two unrelated Chinese families were recruited for this study. Patient #1 was an 18-year-old male who had been walking unstably for 12 years. Patient #2, the younger sister of Patient #1, was a 5-year-old girl who had been walking unstably for 2 years. Patient #3 was a 19-year-old female who had been walking unstably and a tendency to fall for 17 years. For Patient #1, whole-exome sequencing (WES) identified a hemizygous variant c.8310_8313delAGAT (p.Asp2771fs4*) in SACS (NM_014363.6), with the father being heterozygous, the mother wild-type, and Patient #2 hemizygous, as verified by Sanger sequencing. Additional copy number variant analysis of the WES data indicated that Patient #1 had a heterozygous gross deletion of chr13q12.12 (chr13:23,808,732&#x2009;-&#x2009;24,890,322). Low-coverage whole-genome sequencing results revealed that Patient #2 carried a chr13q12.12 deletion (chr13:23,520,000-24,940,000). Together with Sanger sequencing results, this gross deletion was speculated to have been inherited from the mother, further explaining the hemizygous state of c.8310_8313delAGAT (p.Asp2771fs4*) in Patients #1 and #2. Through WES, Patient #3 was identified as having suspected compound heterozygous variants of c.2881&#xa0;C&#x2009;>&#x2009;T (p.Arg961*) and c.6409&#xa0;C&#x2009;>&#x2009;T (p.Gln2137*), inherited from the father and mother, respectively, as confirmed by Sanger sequencing. This study identified three variants in SACS. The c.8310_8313delAGAT (p.Asp2771fs4*) is novel, whereas c.2881&#xa0;C&#x2009;>&#x2009;T (p.Arg961*) and c.6409&#xa0;C&#x2009;>&#x2009;T (p.Gln2137*) have been reported previously. Moreover, this study highlights the growing trend that ARSACS has become increasingly prevalent worldwide rather than being localized to a specific region or race. As an increasing number of patients with ARSACS are diagnosed, the genetic spectrum of ARSACS will gradually broaden, providing an accurate genetic basis for prenatal diagnosis of mothers in the years ahead, if possible.

Adolescent↗
PubMed2025

Pan-Genome Analysis Reveals Local Adaptation to Climate Driven by Introgression in Oak Species.

The genetic base of local adaptation has been extensively studied in natural populations. However, a comprehensive genome-wide perspective on the contribution of structural variants (SVs) and adaptive introgression to local adaptation remains limited. In this study, we performed de novo assembly and annotation of 22 representative accessions of Quercus variabilis, identifying a total of 543,372 SVs. These SVs play crucial roles in shaping genomic structure and influencing gene expression. By analyzing range-wide genomic data, we identified both SNPs and SVs associated with local adaptation in Q. variabilis and Quercus acutissima. Notably, SV-outliers exhibit selection signals that did not overlap with SNP-outliers, indicating that SNP-based analyses may not detect the same candidate genes associated with SV-outliers. Remarkably, 29%-37% of candidate SNPs were located in a 250&#x2005;kb region on chromosome 9, referred to as Chr9-ERF. This region contains 8 duplicated ethylene-responsive factor (ERF) genes, which may have contributed to local adaptation of Q. variabilis and Q. acutissima. We also found that a considerable number of candidate SNPs were shared between Q. variabilis and Q. acutissima in the Chr9-ERF region, suggesting a pattern of repeated selection. We further demonstrated that advantageous variants in this region were introgressed from western populations of Q. acutissima into Q. variabilis, providing compelling evidence that introgression facilitates local adaptation. This study offers a valuable genomic resource for future studies on oak species and highlights the importance of pan-genome analysis in understating mechanism driving adaptation and evolution.

Quercus↗
PubMed2025

Insights into dill (Anethum graveolens) flavor formation via integrative analysis of chromosomal-scale genome, metabolome and transcriptome.

INTRODUCTION: Dill (Anethum graveolens) is a significant medicinal herb belonging to the Apiaceae family. Owing to its high levels of volatile organic compounds (VOCs), dill is commonly utilized for essential oil extraction and medicine purpose. However, the biosynthesis of the crucial VOC in dill remains obscure. OBJECTIVES: Identify the key VOCs related to the flavor formation in dill and dissect the regulatory mechanism of their synthesis. METHODS: The dill chromosomal-level genome was constructed by PacBio HiFi, Hi-C, and BGISEQ second generation sequencing and assembly. The VOCs in dill leaves were identified through GC-MS. The potential mechanism involved in regulating the VOC accumulation in dill flavor formation was analyzed by multi-omics analysis. RESULTS: A 1.17&#xa0;Gb chromosome-scale genome of dill with a contig N50 of 10.78&#xa0;Mb was constructed. A total of 46,538 genes were annotated across 11 assembled chromosomes. Comparative genomics analysis suggested that transposable element insertions, especially LTR-Gypsy, have contributed to the evolution and expansion of the dill genome. The flavor formation of dill was mainly attributed to terpenoids, especially &#x3b1;-phellandrene, &#x3b2;-ocimene, and o-cymene. The contribution of expansion and replication of terpenoid synthesis pathway genes, especially terpene synthase (TPS), to the abundant terpenoid production of dill was identified. Differential gene expression patterns observed at various developmental stages and tissues provided key candidate genes for the regulation of terpenoid synthesis, as well as transcription factors. The different accumulation of esters and aromatics also affected the flavor formation of dill. The key genes implicated in the synthesis of anethole, namely AIS and AMT were further identified. CONCLUSION: This study constructed the chromosome level genome and identified the main VOCs and related key genes in flavor formation of dill, shedding lights on our understanding of terpenoid biosynthesis but also offered guidance for future genetic research on molecular breeding in Anethum graveolens.

Transcriptome↗
PubMed2024

Super Enhanced Purification of Denatured-Refolded Ubiquitinated Proteins by ThUBD Revealed Ubiquitinome Dysfunction in Liver Fibrosis.

Ubiquitination is crucial for maintaining protein homeostasis and plays a vital role in diverse biological processes. Ubiquitinome profiling and quantification are of great scientific significance. Artificial ubiquitin-binding domains (UBDs) have been widely employed to capture ubiquitinated proteins. The success of this enrichment relies on recognizing native spatial structures of ubiquitin and ubiquitin chains by UBDs under native conditions. However, the use of native lysis conditions presents significant challenges, including insufficient protein extraction, heightened activity of deubiquitinating enzymes and proteasomes in removing the ubiquitin signal, and purification of a substantial number of contaminant proteins, all of which undermine the robustness and reproducibility of ubiquitinomics. In this study, we introduced a novel approach that combines denatured-refolded ubiquitinated sample preparation (DRUSP) with a tandem hybrid UBD for ubiquitinomic analysis. The samples were effectively extracted using strongly denatured buffers and subsequently refolded using filters. DRUSP yielded a significantly stronger ubiquitin signal, nearly three times greater than that of the Control method. Then, eight types of ubiquitin chains were quickly and accurately restored; therefore, they were recognized and enriched by tandem hybrid UBD with high efficiency and no biases. Compared with the Control method, DRUSP showed extremely high efficiency in enriching ubiquitinated proteins, improving overall ubiquitin signal enrichment by approximately 10-fold. Moreover, when combined with ubiquitin chain-specific UBDs, DRUSP had also been proven to be a versatile approach. This new method significantly enhanced the stability and reproducibility of ubiquitinomics research. Finally, DRUSP was successfully applied to deep ubiquitinome profiling of early mouse liver fibrosis with increased accuracy, revealing novel insights for liver fibrosis research.

Animals↗