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Stuttering, a complex and multifactorial speech disorder, has long presented an enigma regarding its etiology. While earlier approaches often emphasized psychosocial influences, historical clinical and speech-language strategies have considered multiple contributing factors. By integrating genomic, transcriptomic and phenomic evidence, the ongoing research illustrates how functional genomics can unravel the biological architecture of complex speech disorders. In particular, advances in omic technologies have unequivocally positioned genetics and underlying biological pathways at the forefront of stuttering research. I have experienced stuttering and lived with it since my early childhood. This perspective article presents findings from omic studies, highlighting relevant aspects such as gene discoveries, implicated cellular mechanisms, and the intricate genetic architecture of developmental stuttering. As a person who stutters, I offer an intimate perspective on how these scientific insights are not merely academic but profoundly impactful for the affected community. A multi-omic integration strategy, combining large-scale genetic discovery with deep phenotyping and functional validation, is advocated to accelerate understanding in this field. Additionally, a bibliometric analysis using an international database was conducted to map trends and identify directions in stuttering research within the omic context. Ultimately, these scientific endeavors hold the potential to inform not only personalized interventions but also critical policy and regulatory changes, enhancing accessibility, support, and the recognized rights of people who stutter. Full article

Drought stress significantly impairs plant growth and productivity, which triggers complex adaptive responses mediated by diverse gene families. Among these, the TOPLESS (TPL)/TPL-related (TPR) family of transcriptional corepressors plays a crucial role by recruiting epigenetic modifiers through interactions with EAR motif-containing proteins. However, genome-wide studies of this corepressor family and its associated regulatory networks with EAR motif-containing repressors remain limited. This study aimed to characterize the TPL/TPR transcriptional corepressor family in Populus ussuriensis Kom., elucidate their regulatory networks with EAR motif-containing repressors, and validate their functional roles in drought stress adaptation. To this end, we identified 21 TPL/TPR genes in P. ussuriensis (PuTPLs), classified them into five subfamilies, and found they are evolutionarily conserved with Arabidopsis thaliana and Populus trichocarpa, harboring characteristic CTLH and WD40 domains. Given that TPL/TPR proteins are recruited by transcription factors containing repression motifs, we constructed a putative TPL/TPR-EAR motif interaction network representing a core paradigm of negative regulation. Expression profiling under drought stress showed significant upregulation of most PuTPLs in a tissue-specific and temporal manner. Functional validation using transgenic P. ussuriensis lines overexpressing five PuTPLs demonstrated enhanced drought tolerance, evidenced by reduced electrolyte leakage and malondialdehyde content and increased proline accumulation. Our study provides the first comprehensive genome-wide analysis of the TPL/TPR family in P. ussuriensis, establishes a core EAR-mediated negative regulatory network, and validates the critical role of these genes in drought stress adaptation, providing valuable resources for future mechanistic research and breeding of stress-resistant trees. Full article

Populus koreana emits a wide array of volatile organic compounds (VOCs) with potential ecological functions; however, the tissue-specific distribution and underlying regulatory mechanisms of these compounds remain poorly understood. This study employed an integrated approach combining gas chromatography-mass spectrometry (GC-MS)-based metabolomics and RNA-seq to systematically profile VOC composition and gene expression in terminal buds, stems and leaves of P. koreana. A total of 207 VOCs were identified, predominantly terpenes and aromatic compounds, exhibiting distinct tissue-specific accumulation patterns. Terminal buds were enriched in limonene and caryophyllene, while leaves showed higher concentrations of alcohols and phenolic aldehydes. Transcriptomic analysis revealed 12,733 differentially expressed genes (DEGs) among the three organs, with substantial enrichment in terpenoid and phenylpropanoid biosynthetic pathways. Notably, key upregulated genes in buds, including TPS21 and PAL1, correlated with observed VOC profiles. Weighted gene co-expression network analysis (WGCNA) further identified 6365 genes strongly associated with bud-specific VOC biosynthesis. Integrated omics analyses indicated coordinated regulation of phenylalanine metabolism and transcription factors in VOC production. These findings illuminate the molecular mechanisms underlying tissue-specific VOC accumulation in P. koreana, enhancing our understanding of metabolic specialization and ecological adaptation in woody plants. Full article

Peanut (Arachis hypogaea L.) is an important oil and cash crop, but its growth and productivity are severely constrained by low-temperature stress. Growth-regulating factors (GRFs) are plant-specific transcription factors involved in development and stress responses, yet their roles in peanut remain poorly understood. In this study, we identified AhGRF3b as a direct target of ahy-miR396 using degradome sequencing, which demonstrated precise miRNA-mediated cleavage sites within the AhGRF3b transcript. Expression profiling confirmed that ahy-miR396 suppresses AhGRF3b via post-transcriptional cleavage rather than translational repression. Functional analyses showed that overexpression of AhGRF3b in Arabidopsis thaliana promoted leaf expansion by enhancing cell proliferation. Specifically, leaf length, width, and petiole length increased by 104%, 22%, and 28%, respectively (p < 0.05). Under cold stress (0 °C for 7 days), transgenic lines (OE-2 and OE-6) exhibited significantly better growth than Col-0, with fresh weight increased by 158% and 146%, respectively (p < 0.05). Effect size analysis further confirmed these differences (Cohen’s d = 11.6 for OE-2 vs. Col-0; d = 6.3 for OE-6 vs. Col-0). Protein–protein interaction assays, performed using the yeast two-hybrid (Y2H) system and 3D protein–protein docking models, further supported that AhGRF3b interacts with Catalase 1 (AhCAT1), vacuolar cation/proton exchanger 3 (AhCAX3), probable polyamine oxidase 4 (AhPAO4), and ACT domain-containing protein 11 (AhACR11), which are involved in reactive oxygen species (ROS) scavenging and ion homeostasis. These interactions were associated with enhanced CAT and PAO enzymatic activities, reduced ROS accumulation, and upregulation of stress-related genes under cold stress. These findings suggest that the ahy-miR396/AhGRF3b module plays a potential regulatory role in leaf morphogenesis and cold tolerance, providing valuable genetic resources for breeding cold-tolerant peanut varieties. Full article

Randomized controlled trials (RCTs) have been regarded as the gold standard for evaluating the efficacy of treatments for chronic pain and are the foundation for regulatory approval and guideline development. However, their restrictive design and dependence on idealized populations can limit their applicability to the diverse patients seen in routine chronic pain management. Real-world data (RWD), collected from electronic medical records, registries, claims databases, and digital health platforms, can offer a more comprehensive view of treatment adherence and safety that RCTs often overlook. A key issue in pain medicine is the efficacy–effectiveness gap, where discrepancies exist between the outcomes of therapies and interventions in RCTs versus in real-world practice due to variations in patient populations and adherence. Bridging this gap ensures that observed improvements align with patients’ preferred outcomes and functional goals. Integrating the strengths of RCTs and RWD provides a more comprehensive evidence base to guide clinical decision-making, influence reimbursement policies, and develop equitable guidelines. The primary aim of this paper is to identify factors used in FDA-regulated RCTs and RWD that could be implemented or enhanced in everyday practice to deliver more holistic and patient-centered care in the management of chronic pain. Full article

Genetic transformation serves as a critical tool for gene function research and crop improvement. However, its efficiency is often low and highly dependent on species, genotypes, and explant types, significantly restricting its broader application. Many developmental factors have been proven pivotal not only for plant growth and development but also for the regulation of callus formation and shoot regeneration, which are key steps in the process of genetic transformation. Thus, this review focuses on the application of developmental factors in enhancing transformation efficiency across species. Developmental factors are classified into four regulatory pathways: morphogenesis, wound signaling, epigenetic modification, and hormone signaling. Among them, morphogenic factors have been extensively studied for enhancing transformation efficiency, while the potential of the other three pathways remains less explored in species beyond Arabidopsis. We summarize these established mechanisms and regulatory networks, providing a valuable reference for elucidating these mechanisms in other plant species. Furthermore, we also propose strategies for identifying species-specific efficient developmental factors and improving molecular mechanisms. Ultimately, this review provides a comprehensive summary of the mechanism and application of developmental factors and offers theoretical support to overcome the bottlenecks in genetic transformation. Full article

(1) Background: The BMP/GDF (Bone Morphogenetic Protein/Growth Differentiation Factor) subfamily (Decapentaplegic-Vg1-related, DVR) within the transforming growth factor beta (TGF-β) superfamily plays critical roles in governing biological developmental processes and physiological functions. (2) Methods: In this study, we systematically investigated the DVR gene family in hexaploid Qihe gibel carp (Carassius gibelio var. Qihe) through comprehensive genomic identification, phylogenetic analysis, chromosome mapping, and cis-regulatory element prediction. The experimental design for gene expression analysis involved collecting samples from multiple tissues (brain, muscle, liver, kidney, etc.) and different developmental stages (20, 45, and 60 days post hatching, dph) to examine the expression patterns of four GDF8 genes using quantitative real-time PCR (qRT-PCR). (3) Results: We identified 50 DVR members in Qihe gibel carp. Phylogenetic analysis classified the 50 DVR family members into 20 distinct protein types, with 29 BMPs (Bone Morphogenetic Proteins) and 21 GDFs (Growth Differentiation Factors) identified. All 50 DVR proteins of Qihe gibel carp have similar TGF-β domains except for four BMP1 proteins. Chromosomal localization revealed widespread distribution of DVR members across 36 chromosomes, a pattern potentially linked to the hexaploid genome of Qihe gibel carp. Genes within the same subgroup exhibited conserved intron–exon architectures and similar intron numbers; syntenic conservation within subgroups may reflect functional constraints after polyploidization, implying evolutionary pressure to maintain functional domains. Through spatiotemporal expression profiling, we uncovered functional divergence among four GDF8 (myostatin) paralogs: GDF8-1 and GDF8-2 were predominantly expressed in brain and muscle tissues (dorsal and caudal), while GDF8-3 and GDF8-4 showed hepatic, cerebral, and renal specificity. Intriguingly, all paralogs exhibited a gradual upregulation during late development (20–60 days post hatching, dph), with peak expression staggered between 45 dph (GDF8-1/2) and 60 dph (GDF8-3/4). (4) Conclusions: These findings suggest that GDF8 plays a critical regulatory role in the growth and development of Qihe gibel carp. Collectively, these results provide a foundation for further investigations into the functional roles of the DVR gene family during the ontogenetic development of this species. Full article

Background: G-quadruplexes (G4s) are non-canonical higher-order nucleic acid structures that form at guanine-rich motifs, with features spanning both secondary and tertiary structural levels. These dynamic structures play pivotal roles in diverse cellular processes. Endogenous G4s (eG4s) function through their dynamically formed structures, prompting the hypothesis that their thermostability, as a key structural property, may critically influence their functionality. This study investigates the relationship between G4 stability and other functional genomic signals within eG4 regions and examines its broader impact on chromatin organization and transcriptional regulation. Methods: We developed a mapping strategy to associate in vitro-derived thermostability metrics and multi-omics functional signals with eG4 regions. A stability-centric analytical framework combining correlation analysis and causal inference using the Bayesian networks was applied to decipher causal relationships between G4 stability and the other related signals. We further analyzed the association between the stability of transcription start site (TSS)-proximal eG4s and the biological functions of their downstream genes. Results: Our analyses demonstrate that G4 thermostability exerts causal effects on epigenetic states and transcription factor binding, thereby influencing chromatin and transcription regulation. We further show distinct network architectures for G4-binding versus non-binding transcription factors. Additionally, we find that TSS-proximal eG4s are enriched in genes involved in core proliferation and stress-response pathways, suggesting that eG4s may serve as regulatory elements facilitating rapid stress responses through genome-wide coordination. Conclusions: These findings establish thermostability—though measured in vitro—as an intrinsic property that shapes eG4 functionality. Our study not only provides novel insights into the functional relevance of G4 thermostability but also introduces a generalizable framework for high-throughput G4 data interpretation, significantly advancing the functional decoding of eG4s across biological contexts. Full article

With the continuous expansion of the digital economy, its share in China’s overall economy has been steadily increasing. Against the backdrop of the national “dual-carbon” goals, an important question arises: how does the digital economy contribute to carbon reduction? This study selects panel data from nine cities in the Pearl River Delta (PRD) urban agglomeration between 2011 and 2023. The development level of the digital economy is measured using the entropy weight method and an index system. A two-way fixed effects model and a mediation effect model are then employed to empirically examine the relationship and mechanisms between the digital economy and urban carbon emissions. The main findings are as follows: (1) the development of the digital economy exerts a significant negative regulatory effect on carbon emissions, which remains robust after a series of tests; (2) heterogeneity analysis reveals that the inhibitory effect of the digital economy on carbon emissions is more evident in economically advanced cities, and the development level of metropolitan areas significantly influences this relationship; (3) mechanism analysis indicates that stronger environmental regulation significantly enhances the carbon reduction effect of the digital economy; and (4) the scale of e-commerce in the PRD plays a “suppression effect”, offsetting the original carbon-increasing effect of the digital economy and emerging as the key factor underlying its net carbon-reducing impact. Based on these results, the paper provides policy recommendations to better leverage the digital economy in supporting regional carbon reduction. Full article

Anthocyanins, key flavonoid-derived secondary metabolites, not only confer diverse pigmentation but also function in photoprotection, antioxidative defense, and cold acclimation. In woody species, bark anthocyanin turnover is tightly linked to environmental adaptation, stress resilience, and ornamental traits, yet its molecular regulation remains largely unresolved. Here, we investigated Salix alba L. bark by integrating anthocyanin quantification, transcriptome profiling, and weighted gene co-expression network analysis (WGCNA) to dissect the temporal dynamics and regulatory architecture of anthocyanin degradation. Anthocyanin content peaked at D2 (late December 2024), declined through D3 (mid-January 2025) and D4 (mid-February 2025), and partially rebounded at D5 (early March 2025), coinciding with peak expression of structural genes LAC1/2, POD1/2, and BGLU10. These enzymes co-expressed with multiple transcription factors, including MYB, bHLH, and WRKY families, forming putative core modules. Functional enrichment indicated that differentially expressed genes were enriched in redox processes, glycoside hydrolysis, flavonoid metabolism, and hormone signaling, suggesting a degradation mechanism mediated by reactive oxygen species, glycosidic cleavage, and hormone–transcription factor interplay. This study provides the first comprehensive framework of bark anthocyanin degradation in white willow, advancing the understanding of pigment dynamics, gene–environment crosstalk, and breeding strategies for ornamental woody plants. Full article

Pulmonary fibrosis is a progressive interstitial lung disease that involves stimulated growth of fibroblasts, over-deposition of extracellular matrix (ECM), and permanent damage of the lung structure. Among its various forms, idiopathic pulmonary fibrosis (IPF) is the most common and life-threatening type with few treatment options and a poor prognosis. Such obstacles highlight the urgency to find new molecular targets by better understanding the cellular and signaling processes that contribute to the pathogenesis of the disease. Chemerin is an adipokine and chemoattractant protein that has recently come into the limelight as a major controller of immune cell trafficking, inflammation, and tissue remodeling. Its biological activity is mainly mediated by binding to its receptors Chemokine-like receptor 1 (CMKLR1), G protein-coupled receptor 1 (GPR1), and C-C chemokine receptor-like 2 (CCRL2), and has been linked to numerous pathological conditions, such as metabolic diseases, cancer, and inflammatory diseases. Emerging data now indicate that chemerin can also be a key factor in the initiation and progression of pulmonary fibrosis. The aim of the review is to overview the existing evidence regarding regulatory processes of chemerin expression, signaling pathways, and effects of this protein in cells in the fibrotic lung microenvironment. Moreover, we will comment on the findings of in vitro and in vivo experiments supporting the possibility of chemerin as a promising molecular target in basic research on pulmonary fibrosis. Full article

Fragrant rice is regarded as a premium variety due to its distinctive aroma, delicate texture, and rich nutritional value. This aroma primarily originates from 2-acetyl-1-pyrroline (2-AP), but the metabolic basis of 2-AP remains elusive to this day, and the genetic basis for metabolite accumulation is largely unknown. While several researchers have investigated differences in 2-AP synthesis pathways between fragrant and non-fragrant rice, few studies have examined the 2-AP synthesis pathways in fragrant rice varieties exhibiting 2-AP differences. Therefore, after conducting gene similarity analyses on six fragrant rice varieties, we measured the expression levels of substances and related genes involved in multiple metabolic pathways within the 2-AP synthesis pathway, along with the specific enzyme activities associated with these pathways. Results indicate that XG12 (Guizhou Fragrant Rice Variety) exhibits the highest 2-AP content, yet its efficiency in synthesizing 2-AP is not the highest across any individual metabolic pathway. This finding reveals that among fragrant rice varieties, 2-AP content negatively correlates with OsBadh2 expression levels and GABA content, while showing no linear correlation with other related substances or metabolic genes. At this point, variations in the major effect gene OsBadh2 no longer dominate; instead, subtle differences in 2-AP content are jointly determined by numerous minor effect genes and environmental factors. This phenomenon not only resolves apparent contradictions but profoundly illuminates the complex regulatory mechanisms governing 2-AP biosynthesis. 2-AP synthesis represents a dynamic equilibrium process, with different fragrant rice varieties potentially accumulating 2-AP through distinct metabolic pathways. Additionally, this study analyzed the volatile organic compounds (VOCs) of six fragrant rice varieties through metabolomics. Results revealed that DLX, which exhibited the lowest 2-AP content, contained the richest array of aggregated VOCs, indicating no correlation between 2-AP and numerous VOCs. Our findings provide a clear research direction for elucidating the genetic regulatory mechanisms of 2-AP underlying fragrant rice and lay the foundation for technological research aimed at enhancing the aroma of fragrant rice varieties. Full article

Driven by the rapid evolution of AI technology, compatible management mechanisms have become a systematic project involving the participation of multiple stakeholders. However, constrained by the rigidity and lag of traditional laws, the “one-size-fits-all” regulatory model will exacerbate the vulnerability of the complex system of AI governance, hinder the sustainable evolution of the AI ecosystem that relies on the dynamic balance between innovation and responsibility, and ultimately fall into the dilemma of “chaos when laissez-faire, stagnation when over-regulated”. To address this challenge, this study takes the multi-stakeholder collaborative mechanism co-established by governments, enterprises, and third-party technical audit institutions as its research object and centers on the issue of “strategic fluctuations” caused by key factor disturbances. From the perspective of the full life cycle of technological development, the study integrates the historical compliance performance of stakeholders and develops a nonlinear dynamic reward and punishment mechanism based on Credit Entropy. Through evolutionary game simulation, it further examines this mechanism as a realization path to promote the transformation from passive campaign-style AI supervision to agile governance of AI, which is characterized by rapid response and minimal intervention, thereby laying a foundation for the sustainable development of AI technology that aligns with long-term social well-being, resource efficiency, and inclusive growth. Finally, the study puts forward specific governance suggestions, such as setting access thresholds for third-party institutions and strengthening their independence and professionalism, to ensure that the iterative development of AI makes positive contributions to the sustainability of socio-technical systems. Full article

The color of radish taproot skin is an important commercial quality trait that directly affects the visual judgment of consumers. The green/white coloration of radish taproots is caused by chlorophyll accumulation or fading; however, research on the mechanisms of color regulation in green/white variations remains limited. Therefore, we analyzed transcriptome data from the green radish ‘QZ-16’ and white radish ‘55’ and identified a key color-regulating gene, RsNAC134. The expression of RsNAC134 was significantly reduced in green radish ‘QZ-16’ but markedly increased in white radish ‘55’. Heterologous overexpression of RsNAC134 in transgenic tomatoes resulted in chlorotic phenotypes. Quantitative real-time polymerase chain reaction revealed significant upregulation of chlorophyll degradation pathway genes SlSGR and SlPAO in transgenic tomatoes. Similarly, in white radish, expression of the key chlorophyll degradation genes, RsSGR, RsPAO1, and RsPAO2, was notably increased. Yeast one-hybrid and luciferase assays demonstrated that RsNAC134 directly bound to the promoters of RsSGR, RsPAO1, and RsPAO2. These findings suggest that RsNAC134 regulates chlorophyll degradation by modulating RsSGR, RsPAO1, and RsPAO2 expression, ultimately influencing the radish color transition (loss of green pigmentation) or retention of green coloration. This work unravels novel regulatory factors of chlorophyll degradation and elucidates the molecular network governing chlorophyll degradation, providing crucial insights into the molecular basis of epidermal color variation in radish taproots. Full article

IgA nephropathy (IgAN) is the most prevalent type of primary glomerulonephritis, with heterogeneous clinical outcomes. Conventional prognostic factors, such as proteinuria, eGFR, and Oxford histologic classification, have poor sensitivity and specificity. Recently, transcriptomic profiling has been employed to provide insights into the molecular definition of IgAN and facilitate patient stratification in those at risk of disease progression. In this review, we summarize our current understanding of IgAN derived from bulk RNA sequencing, single-cell transcriptomics, spatial transcriptomics, and gene expression profiling to elucidate the molecular characteristics of IgAN. Bulk transcriptomics of glomerular and tubulointerstitial compartments highlighted consistently upregulated genes (e.g., CCL2, CXCL10, LCN2, HAVCR1, COL1A1) and altered pathways (e.g., NF-κB, TGF-β, JAK/STAT, and complement) that are associated with clinical decline. Single-cell and single-nucleus RNA-sequencing has also identified the value of pathogenic cell types and regulatory networks in mesangial cells, tubular epithelium, and immune infiltrates. Furthermore, noninvasive transcriptomic signatures developed from urine and blood may represent useful real-time surrogates of tissue activity. With the advent of integrated analyses and machine learning approaches, personalized risk models that outperform traditional metrics are now available. While challenges remain, particularly related to standardization, cohort size, and clinical deployment, transcriptomics is likely to revolutionize IgAN by providing early risk predictions and precision therapeutics. Unlike prior reviews, our work provides an integrative synthesis across bulk, single-cell, spatial, and noninvasive transcriptomics, linking molecular signatures directly to clinical translation in risk stratification and precision therapeutics. Full article