Search Results (412)

Peripheral neurons have an intrinsic capacity for repair, albeit still challenging. How the nervous system responds to the cellular stress imposed by nerve injury and adjunct therapies impacts axon regeneration and functional outcomes. Here, we summarize some of the key primarily axonal and neuronal adaptive stress responses and mechanisms that underlie the ability of peripheral neurons to regenerate an axon. This includes activation of the unfolded protein response and endoplasmic reticulum membrane-associated molecules, namely Luman/CREB3, a transmembrane basic leucine zipper transcription factor that regulates the encoding of beneficial adaptive stress responses that drive the ability of an injured sensory neuron to regenerate their axon. We also highlight an emerging novel non-invasive strategy, therapeutic acute intermittent hypoxia, that imposes a level of beneficial adaptive stress that can alter gene programs induced by the injury to enhance regeneration in a manner akin to the more invasive yet highly effective electrical nerve stimulation. The ability to manipulate and significantly elevate the intrinsic adaptive stress/repair responses of injured peripheral neurons holds therapeutic promise, with accumulating evidence supporting its clinical use. Full article

Astragalus membranaceus is an important medicinal plant with considerable pharmacological and economic value; however, its growth and productivity are frequently threatened by drought stress. Basic leucine zipper (bZIP) transcription factors play crucial roles in plant growth, development, and abiotic stress responses, yet a comprehensive investigation of the bZIP gene family in A. membranaceus remains unavailable. In this study, 74 bZIP genes (AmbZIPs) were identified in the A. membranaceus genome and classified into 12 subfamilies based on phylogenetic relationships with Arabidopsis thaliana. Analyses of gene structure, conserved motifs, chromosomal distribution, and duplication events revealed high conservation within subfamilies and indicated that segmental duplication was the major driver of AmbZIP family expansion. Codon usage analysis showed that AmbZIP genes exhibited relatively weak codon usage bias, with codon preference predominantly shaped by natural selection rather than mutation pressure. A total of 23 optimal codons were identified, of which 91.3% were A/T-ending codons. Codon adaptability analysis further demonstrated that tobacco possessed the highest codon compatibility among five tested hosts, whereas Escherichia coli exhibited the lowest adaptability, suggesting that plant expression systems may be more suitable for functional studies of AmbZIP genes. Promoter analysis identified numerous cis-acting elements associated with phytohormone signaling and abiotic stress responses, particularly those related to abscisic acid, methyl jasmonate, salicylic acid, and drought responsiveness. Transcriptome analysis and quantitative real-time polymerase chain reaction (qRT-PCR) validation revealed that several AmbZIP genes were significantly induced under drought stress. Among them, AmbZIP46 displayed strong drought-responsive expression, transcriptional activation activity, and exclusive nuclear localization. These findings provide the first comprehensive characterization of the bZIP gene family in A. membranaceus and establish a valuable foundation for elucidating drought-tolerance mechanisms and facilitating molecular breeding in this medicinal plant. Full article

Basic leucine zipper (bZIP) transcription factors are widely involved in plant development and stress responses. Cymbidium goeringii (Rchb.f.) Rchb.f. is a globally important ornamental orchid whose growth is frequently constrained by extreme heat, yet genome-wide information on its bZIP genes and their responses to heat treatment remains limited. In this study, 67 CgbZIP genes were identified from the C. goeringii genome and assigned to 10 subfamilies based on phylogenetic relationships. RT-qPCR analysis showed that selected CgbZIP genes displayed different transcript-level responses under heat treatment. CgbZIP4 showed increased transcript abundance under heat treatment, whereas CgbZIP49, CgbZIP50, CgbZIP53, and CgbZIP2 showed reduced transcript abundance. CgbZIP25 displayed a fluctuating expression pattern during the 24 h treatment. Yeast two-hybrid assays supported a possible physical interaction between CgbZIP4 and CgbZIP25 in yeast. These results provide candidate CgbZIP genes for further functional studies of heat-stress responses in C. goeringii. Full article

HD-Zip III transcription factors are known to play roles in regulating shoot apical meristem (SAM) and axillary meristem (AM) development, exerting direct effects on plant architecture and branching. However, the HD-Zip III (BjuHDZ) gene family has not been systematically characterized in Brassica juncea L. (B. juncea). Therefore, in this study, we performed a comprehensive bioinformatics analysis of the BjuHDZ gene family and identified a total of 20 members. These genes were randomly and unevenly distributed across the 16 chromosomes of B. juncea, and their encoded proteins exhibited divergent physicochemical properties. Through phylogenetic analysis, the 20 BjuHDZ proteins were divided into five subgroups (REV, HB8, HB9, HB14, and HB15). Conserved exon–intron organization and motif profiles were observed within each BjuHDZ gene subgroup. Furthermore, their promoter sequences harbored a wide array of cis-elements implicated in light responsiveness, hormonal regulation, stress tolerance, and growth/development. The qRT-PCR analysis showed that the expression levels of BjuHDZ7, BjuHDZ13, and BjuHDZ15 were significantly upregulated in the middle and upper axillary buds of two pairs of multi-branching (Bj02 and, Bj08) accessions. Meanwhile, BjuHDZ17 was highly expressed in the upper, middle, and lower axillary buds as well as in the SAM of both multi-branching materials. Taken together, these findings lay a foundation for further investigation into the biological functions of BjuHDZ genes in B. juncea. Full article

Neurospora crassa is a widely distributed ascomycete with high genetic diversity, yet reliance on limited reference genomes has hindered a comprehensive understanding of its genetic landscape. To address this limitation, we integrated the functional annotation of the FGSC2225 genome with a comprehensive comparative genomic analysis of N. crassa strains. FGSC2225 gene and transposable element (TE) proportions mirrored those of FGSC2489, though TE levels were significantly higher than those in sister species Sordaria macrospora. Phylogenetic analysis resolved the N. crassa population into two primary lineages: Clade A (including FGSC2489 and FGSC2225) and Clade B (including FGSC4830), with the former exhibiting larger genome sizes. Leveraging de novo assemblies of 72 high-quality draft genomes, we constructed a comprehensive pangenome to investigate the molecular evolution of various gene families. For example, systematic phylogenetic analysis of the HET-domain-containing gene family and three stress-related families—heat shock transcription factor, basic leucine zipper, and Cytochrome P450—demonstrated varying degrees of conservation and presence/absence variation across the lineages. Addressing the limitations of current genomic resources, this work provides a pangenomic framework to detect rapid adaptive evolution in filamentous fungi. This methodology serves as a robust template for identifying transcription factors, effectors, and structural variations critical to stress response and virulence in diverse fungi. Full article

Background/Objectives: Myelodysplastic syndromes (MDS) carry a highly variable prognosis, stratified by the Revised International Prognostic Scoring System (IPSS-R) and the Molecular IPSS (IPSS-M). CEBPA mutations define a favorable-risk subgroup in acute myeloid leukemia (AML), yet their prognostic significance in MDS has not been characterized. Methods: We analyzed 2442 patients from the International Working Group (IWG) 2022 multi-center MDS registry after pre-specified exclusions. Overall survival (OS) and leukemia-free survival (LFS) were compared between CEBPA-mutated (n = 66; 2.7%) and wild-type patients using Kaplan–Meier estimation and Cox proportional hazards regression, adjusting for age, sex, and IPSS-R score; pre-specified subgroup, sensitivity, competing-risk, and mutation subtype analyses were performed. Results:CEBPA-mutated patients had markedly inferior OS (median 17.2 versus 42.2 months; HR 2.05, 95% CI 1.50–2.79; p < 0.001). After IPSS-R adjustment, the hazard ratio remained adverse (HR 1.39, 95% CI 1.00–1.94; p = 0.053), with uniform directionality across all 13 evaluable subgroups and no significant interaction. Co-mutation adjustment for ASXL1 and STAG2 further attenuated the hazard ratio to HR 1.11 (95% CI 0.79–1.57; p = 0.54), suggesting part of the observed signal reflects co-mutation burden rather than an independent CEBPA effect. Competing-risk analysis suggested that the excess mortality is mediated through AML transformation (CEBPA-mutated versus wild-type subdistribution hazard ratio of 1.89, 95% CI 1.20–2.99; p = 0.006) rather than non-transformative MDS mortality (cause-specific HR 0.97; p = 0.890). Truncating mutations drove the adverse signal (HR 2.21; p = 0.023), while basic leucine zipper (bZIP) domain mutations showed no significant effect (HR 1.25; p = 0.470). Conclusions:CEBPA mutations identify a rare MDS subgroup with markedly inferior survival, driven by truncating loss-of-function mutations and associated with leukemic transformation; the AML-derived bZIP-favorable paradigm does not translate to MDS, and CEBPA mutation status merits a prospective study to assess clinical utility for risk stratification. Full article

Basic-region leucine zipper (bZIP) transcription factors are crucial for plant stress responses, but their characterization in the wild species Juglans mandshurica remains limited. Here, we identified 80 bZIP genes in the J. mandshurica genome and classified them into 13 subgroups, with notable enrichment in subgroups S, A, D, and I. All subgroup D members contain both bZIP and DELAY OF GERMINATION 1 (DOG1) domains, forming characteristic dual-module fusion proteins. Evolutionary analysis detected three orthologous gene pairs under positive selection since divergence from Juglans regia. Promoter cis-elements, especially MYB and MYC motifs, are abundant in JmbZIP genes. Protein–protein interaction networks suggest potential functional specialization and coordination among JmbZIP members. Expression profiling revealed distinct patterns across subgroups, with S, A, and D showing high activity across various physiological processes and light stress responses. qRT-PCR validated the dynamic expression of six ABA pathway marker genes, the ABRE-rich JmbZIP41 and JmbZIP42 genes, together with the highly expressed JmbZIP12 gene under salt and drought stress. Our genome-wide analysis enabled the functional screening of bZIP members across subgroups. The key genes identified in this study provide valuable genetic resources for stress-resistance breeding in forest trees, with JmABI5 (JmbZIP40) and JmbZIP42 serving as prime candidates for enhancing tree stress tolerance. Full article

D-box binding protein (DBP) is a high-amplitude proline- and acidic amino acid-rich basic leucine zipper (PAR bZIP) transcription factor that functions as a key circadian output regulator downstream of the core molecular clock. Although DBP is widely recognized as a clock-controlled gene, its broader role in converting circadian timing into tissue-specific physiological programs remains incompletely integrated. In this review, we synthesize current evidence supporting DBP as a context-dependent D-box-centered regulatory node. We first summarize the upstream mechanisms that establish rhythmic Dbp expression, including CLOCK–BMAL1-dependent transcription, promoter-level amplification, signaling-dependent modulation, and post-translational control of DBP stability. We then discuss how DBP, together with related PAR bZIP activators and the opposing repressor E4 promoter-binding protein 4/nuclear factor interleukin 3 regulated (E4BP4/NFIL3), regulates D-box-mediated transcriptional output. Finally, we examine tissue-selective DBP functions in hepatic metabolism, pancreatic β-cell secretory competence, neural and behavioral regulation, reproductive neuroendocrine timing, and T helper 9 (Th9)-associated antitumor immunity. Across these systems, DBP does not act as a universal circadian effector; rather, its function depends on chromatin accessibility, cofactor availability, competing transcription factors, and local signaling context. We also highlight the current limits of human translational evidence and propose that DBP-centered signatures may be useful for interpreting circadian output failure in disease. Overall, DBP provides a mechanistically informative framework for understanding how circadian time is transformed into organ-specific physiological function and pathological vulnerability. Full article

Gene duplication is a primary evolutionary driver of gene family expansion and functional diversification in plants, yet how different duplication processes reshape the evolutionary architecture of transcription factor repertoires remains poorly resolved in lineage-specific genomic contexts. Here, we performed a comprehensive evolutionary and transcriptomic analysis of the basic leucine zipper (bZIP) family across 17 representative species, with a focus on Pooideae. We identified 1878 bZIP genes and found that, although copy numbers were relatively conserved in most diploid grasses, polyploid Triticeae showed substantial expansion. Genome-wide and Ks analyses indicated that bZIP genes were preferentially retained after whole-genome/segmental duplication, with many copies tracing back to the ancient grass-specific ρ-WGD event, the most recent shared polyploidization event in Poaceae. Phylogenetic analyses and orthology inference further resolved four evolutionary models linking ancient duplication with lineage-specific retention and expansion. Transcriptome analyses revealed structured expression divergence across developmental and stress-related contexts, and wheat homoeologous triads exhibited widespread subgenome expression bias that was dynamically reconfigured under stress and hormone treatments. Differences in transposable element landscapes among duplication models and subgenomes further suggest a role for local genomic context in regulatory divergence. Together, these findings establish a unified framework linking ancient duplication, selective retention, and transcriptional diversification of the bZIP family in Pooideae. Full article

Retinitis pigmentosa (RP) is a genetically heterogeneous group of inherited retinal degenerations with primary degeneration of rod photoreceptors followed by secondary cone loss. We investigated whether downregulating Nrl (neural retina leucine zipper), a key transcription factor specifying rod fate, can reprogram rods into a more resilient state. In a transgenic Nrl^N/N mouse in which Nrl was markedly downregulated, the rod phenotype became more like a rod precursor, particularly in the inferior retina. Crossing Nrl^N/N mice with two rod degeneration models, rd1 (Pde6b^rd1/rd1) and rhodopsin P23H knock-in (Rho^P23H/P23H) mice, showed significantly improved photoreceptor survival in double-mutant mice. In addition, AAV-mediated delivery of shRNA targeting Nrl mRNA substantially enhanced photoreceptor survival in rd10 (Pde6b^rd10/rd10) mice. These findings demonstrate that downregulation of Nrl reprograms rods and confers broad resistance to degeneration across multiple RP models. AAV-mediated Nrl knockdown represents a promising mutation-independent therapeutic strategy for autosomal recessive and dominant forms of RP. Full article

Heat stress (HS), increasingly intensified by climate change, severely restricts tomato growth and productivity. Although core heat shock factor-mediated transcriptional networks have been extensively characterized, how lipid metabolic reprogramming is transcriptionally coordinated during thermotolerance remains unclear. Using SlHDZ19 overexpression and mutant lines together with transcriptomic, biochemical, promoter-binding, and gene-silencing analyses, we show that the homeobox-leucine zipper transcription factor SlHDZ19 promotes tomato (Solanum lycopersicum) thermotolerance by activating a PLA2-dependent lipid-metabolic transcriptional program in leaves. SlHDZ19 overexpression generally improved heat-stress performance, while SlHDZ19 mutant lines exhibited heightened sensitivity, including more severe wilting, higher electrolyte leakage, and reduced proline accumulation and CAT activity under heat stress. Transcriptomic analysis revealed that SlHDZ19 is required for the full induction of canonical heat-responsive genes and that the linoleic acid metabolism pathway was repeatedly implicated in SlHDZ19-dependent transcriptional changes. SlHDZ19 binds to and activates the promoters of SlPLA_2α, which encodes a phospholipase A2 involved in releasing linoleic acid from membrane lipids, and three lipoxygenase genes (SlLox7, SlLox8, and SlLoxC), accompanied by elevated overall PLA2 and LOX activities in SlHDZ19-overexpressing plants. Moreover, genetic silencing of SlPLA_2α in both wild-type and SlHDZ19-overexpressing backgrounds supported its functional requirement downstream of SlHDZ19 in thermotolerance. Collectively, our findings support a thermotolerance module in which SlHDZ19 transcriptionally regulates PLA2- and LOX-associated steps of linoleic acid metabolism, potentially linking lipid-associated signaling and membrane remodeling with heat stress adaptation in tomato. Full article

Beyond its function as a carrier of hereditary information, recent research has uncovered novel properties of extracellular DNA, including its role in the adaptation to the environment when released from plants. The secreted DNA has been shown to exert insecticidal effects against insect pests, which play an adaptive role in plant-insect interactions, particularly in regulating populations of economically important sap-feeding insects. The molecular mechanisms underlying this insecticidal effect are underinvestigated and remain largely unknown. Therefore, there is a need for more efforts to uncover these mechanisms to better understand plant–pest interactions, which would provide new insights into natural pest control strategies and inspire biotechnological applications. In the current study, we show that Pittosporum tobira (P. tobira) secretes single-stranded DNA (ssDNA) that exerts an insecticidal effect on Coccus hesperidum (C. hesperidum). We collected extracellular DNA from P. tobira leaves and tested its potential insecticidal effect by applying it to C. hesperidum, which is a well-known pest that causes damage to P. tobira. Our results revealed that the outermost layer of the leaf cuticle of P. tobira predominantly contains ssDNA of approximately 100 nt in length, originating from both chloroplast and nuclear genomes. This DNA exhibited pronounced insecticidal activity against C. hesperidum, with chloroplast-derived sequences significantly enriched compared to the total DNA in intact plant cells. These findings suggest that the microevolution of the P. tobira nucleome and plastome contributed to the formation of extracellular DNA with insecticidal properties (eci-DNA), which is part of its defense strategy against insect pests. Moreover, in this article, for the first time, we show that antisense DNA (illustrated with oligonucleotide insecticide Coccus-11) is capable of activating insect retrotransposons and upregulating their RT-RNase H, a crucial enzyme for the DNA containment mechanism and successful action of oligonucleotide insecticides. Notably, the laboratory-developed ssDNA-based ‘genetic zipper’ technology, designed for sustainable pest management, possesses characteristics similar to eci-DNA found in nature, highlighting a potential natural parallel to this biotechnological approach for sustainable pest management. Full article

Basic leucine zipper (bZIP) transcription factors are widely involved in plant growth, development, environmental adaptation, and secondary metabolism. However, the bZIP gene family in Taxus yunnanensis has not been systematically characterized, and its potential involvement in shading-responsive regulation of paclitaxel biosynthesis remains unclear. In this study, a genome-wide analysis was performed to identify and characterize the bZIP family in T. yunnanensis. Phylogenetic analysis, conserved motif and domain identification, promoter cis-element analysis, chromosomal localization, and expression profiling were conducted to investigate their structural features and regulatory potential. A total of 18 TyubZIP genes were identified and classified into 10 subfamilies. These genes exhibited variation in physicochemical properties but showed conserved structural features and nuclear localization. Promoter analysis revealed abundant light-responsive, hormone-related, and stress-related cis-elements. Expression profiling indicated tissue-specific expression patterns and diverse responses to shading treatment. WGCNA further identified candidate TyubZIP genes potentially associated with paclitaxel biosynthesis. Among them, TyuHY5 was selected for functional analysis. Subcellular localization and transcriptional assays demonstrated that TyuHY5 can bind to the promoter of TyuDBTNBT and positively regulate its activity. These findings provide the first genome-wide characterization of the bZIP family in T. yunnanensis and identify TyuHY5 as a shading-responsive candidate regulator of paclitaxel biosynthesis, providing insights that may inform the genetic improvement and cultivation strategies of Taxus for enhanced paclitaxel production. Full article

Low-temperature stress significantly limits plant growth, development, and productivity, posing a major environmental constraint. The potato (Solanum tuberosum L.) is particularly vulnerable to low temperatures, underscoring the crucial need to enhance cold tolerance in potato breeding efforts for sustainable production. Basic leucine zipper (bZIP) transcription factors serve as central regulators of plant developmental processes and stress responses; however, their functional role in cold tolerance in tetraploid potato remains poorly understood. Here, we report a systematic characterization of the bZIP gene family in tetraploid potato and provide preliminary evidence that StbZIP104 enhances plant cold tolerance. A total of 191 StbZIP genes were identified and classified into 11 subfamilies, exhibiting uneven chromosomal distribution and expansion primarily driven by whole-genome and segmental duplication. Promoter cis-element analysis, together with GO and KEGG enrichment analyses, indicated that StbZIP genes are broadly associated with hormone signaling, stress responses, signal transduction, and environmental adaptation. Expression profiling under low-temperature treatment revealed eight cold-inducible StbZIP genes (log₂FC ≥ 1 and FDR < 0.05), among which StbZIP104 was strongly induced (log₂FC ≥ 2) and showed 5.36-fold higher expression in highly cold-resistant cultivars than in cold-sensitive cultivars. Subcellular localization confirmed that StbZIP104 is a nuclear-localized protein. Functional validation confirmed that overexpressing StbZIP104 notably improved cold tolerance in transgenic Samsun NN tobacco (Nicotiana tabacum cv. Samsun NN). This was supported by heightened superoxide dismutase and peroxidase activities, increased levels of soluble protein and soluble sugars, and decreased malondialdehyde content compared to the wild type under cold stress. This study establishes a basis for the functional characterization of the bZIP gene family in tetraploid potato and serves as a theoretical reference for understanding the mechanisms that govern cold tolerance in this species. Full article

Multi-stage fracturing of shale gas is currently the core technology for achieving the economic development of shale gas. However, during post-fracturing production, issues such as fracture closure, proppant backflow, and fracturing fluid loss can inevitably occur, causing damage to the reservoir. To investigate the backflow performance of shale gas fracturing, this study establishes a high-precision fluid–solid coupled geomechanical model based on actual data from Changning shale gas wells and performs history matching. The history matching results indicate that neglecting factors such as geomechanics and capillary pressure leads to overly smooth curves, poor convergence, and results inconsistent with the actual production trends. A comprehensive model incorporating gas adsorption, geomechanics, capillary pressure, and secondary fractures provides the best fit. After validating the model’s accuracy, the effects of proppant concentration, proppant injection method, fracture parameters, well spacing, and fracturing design on fracturing backflow were analyzed. The study shows that proppant concentration, distribution pattern, fracture geometry, and well spacing are key factors influencing the effectiveness of shale gas fracturing stimulation. An optimal proppant concentration exists, as excessively high concentrations accelerate fracture closure and reduce production gains. Proppants should be primarily distributed near the wellbore to ensure high production and sufficient backflow. Fracture spacing and half-length should be optimized to balance production increase and fracturing fluid retention. Among the vertically non-uniform fracture distributions, staggered patterns offer the highest production potential, while uniform distributions yield the best backflow performance. In the Changning shale gas region, a well spacing of 300 m is recommended, and zipper fracturing can improve backflow efficiency. Full article