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Biomedical subjects

Feng Liu

Publications and source records attributed to Feng Liu.

14 recordsLinked to original sources

Ancient DNA unveils distinctive ancestries in the Bronze and Iron Ages of East Tianshan.

The East Tianshan Mountains occupy a key corridor between Central and East Asia, but their population history remains poorly understood. Here we report genome-wide data from 135 ancient individuals from 11 archaeological sites. We identify a previously unrecognized Bronze Age admixture between populations related to Yellow River millet farmers and steppe pastoralists associated with the Chemurchek culture. In contrast, we find little genetic contribution from contemporaneous middle-to-late Bronze Age steppe pastoralists, despite their eastward expansion across the Eurasian Steppe. By the Iron Age, regional populations had become more heterogeneous, incorporating additional eastern and steppe-related sources while retaining variable contributions from Early Bronze Age groups. These results reveal sustained demographic interactions in eastern Central Asia nearly 1800 years preceding the establishment of the historic Silk Road.

DNA, Ancient

Shared genetic architecture between major depression and intrinsic brain functional connectome organization.

BACKGROUND: Major depression (MD) is increasingly understood as a disorder characterized by widespread abnormalities in intrinsic brain functional network organization. Although both MD and brain functional connectome architecture are highly heritable, the genetic architecture underlying their relationship remains poorly characterized. METHODS: We integrated genome-wide association studies of MD with 191 ICA-based resting-state functional connectome traits to investigate their shared genetic architecture. These traits captured intrinsic connectome organization across amplitude, functional connectivity, and global connectivity domains. Cross-trait genetic analyses were used to assess pleiotropic overlap between traits. Locus-level and gene-based analyses integrating multi-omics evidence were performed to characterize the biological relevance of shared genetic signals. RESULTS: We identified significant genetic overlap between MD and 148 of 191 brain functional connectome traits. Cross-trait analyses revealed widespread shared genetic signals organized into 627 genomic loci across amplitude, functional connectivity, and global connectivity measures. Among these, 193 loci showed evidence consistent with shared causal variants based on colocalization analyses. Gene-level integration mapped these loci to 1459 protein-coding genes (390 unique genes). Multi-layer prioritization identified 17 high-confidence genes supported by convergent genomic, transcriptomic, and proteomic evidence, with enrichment in neurodevelopmental and lipid-related metabolism pathways. CONCLUSIONS: This study provides a multi-scale characterization of the shared genetic architecture between MD and intrinsic brain functional connectome organization, revealing that shared genetic signals between MD and brain functional systems are distributed across multiple functional levels and converge at the molecular level.

Connectome

Genomics and social practices at Mogou and other Gansu sites during prehistoric trans-Eurasian exchange.

Beginning approximately 4,000 years ago, southwest-Asian-originating domesticated crops and livestock began appearing in Gansu, a key crossroads in northwestern China, yet the population dynamics and social practices underlying these historically transformative events in the region have not been fully explored. Despite the adoption of western domesticates, genome sequences of 149 individuals from the large Mogou cemetery and ten other sites in Gansu, dating between 4,700 and 3,000 years ago, revealed migrations within East Asian regions but no detectable evidence of genetic influence from western or central Eurasia, suggesting that early agricultural dispersals may have followed a model distinct from that documented in Europe and Central Asia. The Mogou cemetery represents a continuous community that interacted with surrounding regions but does not exhibit clear matrilocal or patrilocal residential patterns. We found no strong evidence that co-buried individuals represented biological relatives. Non-local ancestry appears to be linked to lower-status burial practices.

Humans

Unraveling causal links between chronic rhinosinusitis and peripheral artery diseases: insights from genetic correlations through genome-wide association studies.

OBJECTIVES: Chronic Rhinosinusitis (CRS) shares epidemiological links with Cardiovascular Diseases (CVDs), however, their shared genetic basis remains unclear. We hypothesized that pleiotropic genetic variants underlie CRS-CVDs links via distinct biological pathways. METHODS: Using large-scale GWAS data from European-ancestry individuals, we assessed global and local genetic correlations. We applied Genomic Structural Equation Modeling (Genomic SEM) to dissect shared genetic architecture, performed bidirectional Mendelian Randomization (MR) to infer causality, and conducted cis-eQTL colocalization to identify shared genetic signals. Finally, in vitro endothelial models (HUVECs) validated the functional dynamics of candidate genes under CRS-mimicking inflammatory stress. RESULTS: CRS showed significant genetic correlations with multiple CVDs. Genomic SEM revealed a latent factor structuring shared genetic risk through three pathways: artery diseases, myocardial diseases, and heart failure. Local genetic correlations identified significant local genetic correlations specifically between CRS and Peripheral Atherosclerosis (PAS)/Peripheral Artery Disease (PAD) specifically within the chr6: 31.57&#x2012;33.24 Mb locus. MR demonstrated causal effects of CRS on PAD (OR&#x2009;=&#x2009;1.23, p&#x2009;=&#x2009;0.022) and PAS (OR&#x2009;=&#x2009;1.21, p&#x2009;=&#x2009;0.011), but not vice versa. Genetically predicted HLA-DRB1, APOM, and COL11A2 expression conferred protection, while HLA-DQA2 increased risk. Crucially, in vitro validation corroborated these pathogenic trajectories, inflammatory stress significantly downregulated the protective APOM and upregulated the risk-associated HLA-DQA2 alongside pro-atherogenic VCAM-1, while HLA-DRB1 exhibited a compensatory upregulation (p&#x2009;<&#x2009;0.05). CONCLUSION: CRS shares global genetic liability with CVDs, structured through three primary etiological pathways. Causal effects of CRS on peripheral artery diseases are mediated by immune and lipid-related genes within the chr6 locus, revealing divergent pleiotropic mechanisms. Our integrated genetic and in vitro evidence provides a mechanistic framework wherein chronic mucosal inflammation contributes to systemic endothelial vulnerability, thereby highlighting candidate targets for mechanism-directed therapy.

Humans

Impact of oliceridine versus sufentanil on postoperative nausea and vomiting in patients undergoing thyroid surgery: a prospective, double-blind, randomized controlled trial.

PURPOSE: Postoperative nausea and vomiting (PONV) is a common complication following thyroid surgery, often exacerbated by opioid use. Oliceridine, a novel G protein-biased &#x3bc;-opioid receptor agonist, may reduce opioid-related adverse events. This study aimed to compare the impact of oliceridine versus sufentanil on the incidence and severity of PONV in patients undergoing thyroid surgery. PATIENTS AND METHODS: In this prospective, double-blind, randomised controlled trial conducted between May 2025 and February 2026, 232 patients scheduled for thyroid surgery were randomly assigned to receive either oliceridine or sufentanil for intraoperative analgesia. The primary outcome was the incidence of PONV during the first 48&#x2009;h postoperatively. Secondary outcomes included PONV severity, need for rescue anti-emetics, postoperative pain scores, recovery quality, and other adverse events. RESULTS: The incidence of PONV within 48&#x2009;h postoperatively was significantly lower in the oliceridine group [13/107 (12%)] compared with the sufentanil group [31/110 (28%)] (OR = 0.35, 95% CI: 0.17-0.72, p&#x2009;=&#x2009;0.006). Postoperative pain scores, rescue analgesia requirements, and Quality of Recovery-15 scores were comparable between the two groups (p&#x2009;>&#x2009;0.05). Besides, exploratory unadjusted analyses revealed fewer rescue anti-emetics: O group 8/107 (8%) vs S group 25/110 (23%) (OR = 0.27, 95% CI: 0.12-0.64, p&#x2009;=&#x2009;0.002); and less abdominal distension: O group 4/107 (4%) vs S group 19/110 (17%) (OR = 0.19, 95% CI: 0.06-0.57, p&#x2009;=&#x2009;0.001). CONCLUSION: For young ASA I-II patients undergoing thyroid surgery, oliceridine yields adequate postoperative analgesia and lower PONV rates versus sufentanil. Additional trials involving high-intensity surgical procedures are needed to confirm consistent equivalence.

Humans

Shared genetic architecture between ADHD and intelligence varies across ADHD subtypes.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous neurodevelopmental condition frequently accompanied by cognitive difficulties. Although previous genetic studies have demonstrated substantial overlap between ADHD and intelligence, most have treated ADHD as a single phenotype. However, whether this shared genetic architecture differs across ADHD subtypes remains unclear. METHODS: We conducted a genome-wide cross-trait analysis integrating large-scale genome-wide association study (GWAS) datasets of overall ADHD, its subtypes-childhood ADHD, persistent ADHD, and late-diagnosed ADHD-and intelligence (total N&#x2009;>&#x2009;300,000). Genome-wide genetic correlations, polygenic overlap, local genetic correlations, and variant-level associations between ADHD phenotypes and intelligence were evaluated to characterize their shared genetic architecture. Shared variants were identified through cross-trait enrichment analyses and subsequently mapped to genes for functional annotation and gene-set enrichment. Bidirectional associations were evaluated using two-sample Mendelian randomization with sensitivity analyses. Additional GWAS datasets were used to validate the robustness of shared loci by assessing the consistency of effect directions. RESULTS: All ADHD phenotypes showed significant negative genetic correlations with intelligence (rg ranging from -0.3442 to -0.4205). Despite these modest genome-wide correlations, cross-trait analyses revealed substantial genetic overlap, including polygenic overlap, local genetic correlations, and variant-level associations. We identified 184 loci jointly associated with ADHD traits and intelligence, including 64 novel loci, whereas no shared loci were detected for persistent ADHD under the current analysis. Functional annotation revealed biologically distinct enrichment patterns across subtypes: childhood ADHD loci were linked to early neurodevelopmental processes, while late-diagnosed ADHD loci were enriched in synapse-related and neuronal signaling pathways. Mendelian randomization analyses suggested bidirectional associations, with stronger evidence supporting a directional association from intelligence to ADHD risk. Furthermore, these shared loci showed largely consistent effect directions across additional GWAS datasets, providing support for the robustness of the findings. CONCLUSIONS: The shared genetic architecture between ADHD and intelligence varies across ADHD subtypes, highlighting distinct biological pathways underlying cognitive heterogeneity in ADHD. These findings suggest that the relationship between ADHD liability and general cognitive ability is not uniform across ADHD subtypes and may inform future research on risk stratification and early identification in child and adolescent psychiatry.

Humans

Shared genetic architecture between DTI-ALPS traits and neurodegenerative diseases.

INTRODUCTION: Diffusion tensor image analysis along the perivascular space (DTI-ALPS) index is associated with neurodegenerative diseases (NDDs), but its shared genetic basis with NDDs remains unclear. METHODS: By integrating genome-wide association datasets for three DTI-ALPS traits and seven NDDs, we quantified polygenic overlap using MiXeR, identified shared loci using conditional and conjunctional false discovery rate analyses, and performed gene mapping, enrichment, temporal expression, and transcriptome-wide association analyses. RESULTS: DTI-ALPS traits showed widespread but heterogeneous polygenic overlap with NDDs. We identified 22 shared loci, including novel associations implicating GAK and SIAH3, with the strongest convergence at 17q21.31. Shared loci mapped to 183 protein-coding genes enriched in the endolysosomal system and microtubule cytoskeleton. These genes showed similar temporal expression patterns, and 45 were associated with both DTI-ALPS traits and NDDs. DISCUSSION: These findings reveal a shared genetic architecture between DTI-ALPS traits and NDDs, highlighting mechanisms that may contribute to their overlap.

Neurodegenerative Diseases

CaMYB121-CaABF2 negative feedback loop modulates CaNHX2 expression to confer salt tolerance in pepper.

Salt stress is a major abiotic factor that severely restricts pepper (Capsicum annuum) production. Although abscisic acid (ABA) is vital for salt tolerance, the transcriptional regulatory networks governing ABA-mediated salt defense remain largely unknown. Here, we uncovered a negative feedback loop between CaMYB121 and CaABF2.1/2 that modulates the expression of CaNHX2.1/2/3, thereby enhancing salt tolerance in pepper plants. RNA-seq analysis revealed that CaMYB121 displayed an expression pattern consistent with that of CaNHX2 after salt treatment. Silencing CaMYB121 markedly reduced salt tolerance and inhibited root growth. Mechanistically, CaMYB121 directly binds to the CaNHX2 promoter to activate transcription, thereby promoting salt resilience. Salt stress also robustly triggered ABA signaling genes, with CaABF2.1/2 displaying expression patterns closely mirroring those of CaMYB121. Transient silencing of CaABF2.1/2 results in phenotypes similar to those observed with CaMYB121 suppression. Notably, CaMYB121 activates CaABF2.1/2 transcription by binding to its promoters, whereas CaABF2.1/2 represses CaMYB121 expression by directly targeting its promoter, forming a self-regulating feedback loop that prevents excessive defense activation. Collectively, our findings reveal a CaMYB121-CaABF2 feedback circuit that dynamically balances growth and defense to optimize salt tolerance in pepper plants.

Salt Tolerance

Molecular mechanisms and breeding strategies for heat tolerance in vegetable crops under global warming.

Extreme heat driven by climate change poses a catastrophic threat to global vegetable production, undermining nutritional security because of the heightened physiological sensitivity and succulent tissues of these crops. This review synthesizes the multistage impacts of heat stress across critical developmental phases-from germination to reproduction-emphasizing morphological impairments (such as leaf wilting and floral abortion) and physiological disruptions (including photosynthetic inhibition and oxidative damage). We systematically dissect thermotolerance mechanisms in vegetables, highlighting transcriptional reprogramming by HSFs, WRKY, and NAC transcription factors; chaperone-mediated proteostasis via HSPs; epigenetic remodeling; Ca2+-ROS signaling pathways; and the role of phase separation dynamics. Importantly, we propose six strategic pathways to develop heat-resilient vegetables: harnessing natural variation through pan-genome-driven allele mining; employing biotechnological interventions such as CRISPR-mediated editing and synthetic promoters; engineering multistress tolerance by targeting conserved 'core response' pathways; exploiting epigenetic memory to achieve transgenerational resilience; optimizing source-sink dynamics with ''Climate-Responsive Carbon Optimization; and applying plant growth regulators and nanotechnology to enhance thermotolerance. Together, these strategies chart a clear roadmap for climate-smart vegetable breeding and call for interdisciplinary collaboration to translate molecular discoveries into practical breeding approaches for sustainable food systems under escalating thermal extremes.

Journal Article

Analysis of genetic differences underlying chilling stress tolerance using whole genome Re-Sequencing in walnut (Juglans regia L.).

Walnut (Juglans regia L.) is prized worldwide for both its nutritional value and economic importance, yet it remains vulnerable to cold stress, with significant differences in tolerance among varieties. This study combined physiological analyses with whole-genome resequencing (WGS) to evaluate the cold stress responses of two varieties, &#x2018;Qingxiang&#x2019; and &#x2018;Liaoning No.8&#x2019;. Under chilling stress (0&#xa0;&#xb0;C), we measured electrolyte leakage and antioxidant enzyme activity, applying both exogenous methyl jasmonate (MeJA) and the jasmonate inhibitor DIECA. Genomic variations were analyzed using WGS. Results showed that &#x2018;Liaoning No.8&#x2019; exhibited superior cold tolerance. Application of MeJA reduced electrolyte leakage by 37% and MDA accumulation by 52% on average, whereas DIECA exacerbated stress-related damage. WGS achieved 16.24&#x2013;16.26&#xd7; coverage and identified 2.73&#x2013;2.78&#xa0;million SNPs, 378&#x2013;382k InDels, 25&#x2013;26k SVs, and 7.2&#x2013;7.9k CNVs. Twenty genes containing sequence variants showed transcriptional responses under cold stress that were significantly correlated with mutation density (r&#x2009;=&#x2009;0.62, P&#x2009;<&#x2009;0.01). One gene, XM_018985465.2, which lacked SNPs in &#x2018;Liaoning No.8&#x2019;, was expressed 4.2 times more in this variety, suggesting cis-regulatory influence. These findings highlight the role of jasmonic acid signaling in enhancing cold tolerance in walnut and offer genomic insights into its underlying adaptive mechanisms.

Juglans

Survival and safety evaluation of Bifidobacterium longum subsp. longum ZS-8 in healthy adults, determined using PMAxx-qPCR and amplicon sequencing.

UNLABELLED: Species-level quantitative PCR (qPCR) provides in-depth knowledge of oral probiotics in the human gastrointestinal tract (GIT). However, it lacks the capability to differentiate exogenous strains from native microbiota, nor can it distinguish between live and dead bacteria. In this study, we employed improved propidium monoazide (PMAxx)-qPCR to evaluate the survival and colonization of Bifidobacterium longum subsp. longum ZS-8 (designated ZS-8) on the strain level in the GIT and its impact on human gut microbiota. By spiking in live and dead ZS-8, we demonstrated that strain-level PMAxx-qPCR could identify and quantify the viable ZS-8 in fecal samples accurately. Using this method, we found that, in healthy humans, oral administration of ZS-8 can transiently survive in the GIT, and multi-layer seamless capsules (MLSC) significantly improve the gastrointestinal tolerance and survivability of ZS-8 compared to its powder form. Furthermore, through selective cultivation and PMAxx-microbiome sequencing, we investigated the response of gut viable microbiome to ZS-8. Results showed that, while the microbiota diversity and total viable counts of Bifidobacterium and Lactobacillus remained stable, certain indigenous species of Bifidobacterium and Lactobacillus increased in abundance, confirming ZS-8's probiotic potential in healthy individuals. Overall, our study demonstrates the effectiveness of combining strain-specific comparative genomics with PMAxx-qPCR for evaluating probiotic survival and colonization in the human gut and highlights the safety of ZS-8 oral administration in healthy individuals. IMPORTANCE: The survival and colonization of probiotics in the gut are critical for their functional efficacy, yet conventional species-level quantitative PCR (qPCR) fails to distinguish exogenous strains from native microbiota or differentiate live from dead bacteria. By integrating strain-specific comparative genomics with propidium monoazide (PMAxx)-qPCR, we precisely quantified the viability of Bifidobacterium longum ZS-8 at the strain level in the human gut after its oral administration. Our study demonstrated that 1.53-6.90% of cells surviving transit and multi-layer seamless capsules (MLSC) significantly enhanced the gastrointestinal tolerance of ZS-8. While ZS-8 administration did not alter gut microbiota diversity or total viable counts of Bifidobacterium and Lactobacillus, it selectively increased the abundance of specific indigenous beneficial species. This method overcomes the dual limitations of traditional techniques (strain-level specificity and viability discrimination), providing a robust tool for probiotic research. Furthermore, our findings confirm the safety of ZS-8 in healthy individuals and its potential to modulate gut ecology, offering a scientific foundation for personalized probiotic development and clinical translation.

Humans

The proteome of the late Middle Pleistocene Harbin individual.

Denisovans are a hominin group primarily known through genomes or proteins, but their precise morphological features remain elusive because of the fragmentary nature of the discovered fossils. Here, we report 95 endogenous proteins retrieved from a nearly complete cranium from Harbin, China, dating to at least 146,000 years ago and previously assigned to a new species, Homo longi. This individual has three Denisovan-derived amino acid variants and clusters with Denisova 3, suggesting that the Harbin individual belongs to a Denisovan population. This study fills the gap between morphological and molecular evidence, enhancing our understanding of Denisovans' spatiotemporal dispersal and evolutionary history.

Animals

Ancient Mitogenomes Reveal the Maternal Genetic History of East Asian Gray Wolves (Canis lupus).

The gray wolf (Canis lupus) is the only wild ancestor of dogs (Canis lupus familiaris) and serves a crucial role in understanding the highly controversial issue of dog origins. Recently, ancient DNA studies on gray wolves from different regions of the Eurasian continent have achieved significant breakthroughs, providing important clues about the dog origins. As one of the potential origin areas for dogs, East Asia has seen some research on ancient dogs; however, reports related to gray wolves remain limited. In this study, we sequenced seven new mitogenomes of ancient gray wolves from Northern China, integrating them with 497 ancient and modern canid mitogenomes from published data. Our results reveal the following: (1) East Asian gray wolves have maintained high genetic diversity from ancient times to the present; (2) multiple haplogroup A gray wolves from Northern China support the hypothesis that Northeastern Eurasia is a core region for dog origins; (3) a deep gray wolf lineage in East Asia has been identified in this study; (4) different mitogenomes concentrated at the Jinchankou site indicate that admixture may have frequently occurred in the northeastern edge of the Tibetan Plateau. These findings enhance our understanding of the maternal genetic history of gray wolves in East Asia.

Animals

ZNF593 regulates the cGAS-mediated innate immune response by attenuating cGAS-DNA binding.

The enzyme cyclic GMP-AMP synthase (cGAS) is essential for detecting aberrantly located double-stranded DNA (dsDNA) from genomic, mitochondrial, and microbial origins. Through the synthesis of 2'3'-cGAMP, cGAS triggers the activation of the stimulator of interferon genes pathway, which initiates in vivo innate immune responses. Here, we identify zinc finger proteins ZNF593, which translocate from the nucleus to the cytoplasm after viral infection, as a negative regulator of antiviral type I IFN (IFN-I) production. ZNF593 directly binds to cGAS and suppresses its activation by inhibiting the cGAS-dsDNA interaction. ZNF593 deficiency increases IRF3 nuclear translocation and promotes DNA virus-triggered IFN production. Furthermore, ZNF593 deficiency promotes antiviral innate responses in vivo, improving survival rates in mice against HSV-1 infection. We further find that ZNF593 plays a protective role in systemic lupus erythematosus (SLE) pathology. Notably, replenishing ZNF593 effectively reduced IFN production in peripheral blood mononuclear cells (PBMCs) of SLE patients or in the TMPD-induced murine SLE model. Our findings suggest that ZNF593 negatively regulates IFN-&#x3b2; signaling by targeting cGAS activation, providing new insights into the regulatory mechanisms for antiviral defenses and autoimmune diseases.

Nucleotidyltransferases