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Results for “Stability”

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At least 19 recordsLinked to original sources

PubMed2026

Effects of an actuated ankle exoskeleton on walking stability in healthy adults: a controlled laboratory study.

BACKGROUND: Ankle exoskeletons are widely used to reduce the metabolic cost of walking, yet their effects on walking stability during unperturbed gait remain insufficiently understood. Walking stability can be characterized using complementary measures that capture stride-to-stride variability, global temporal organization, and local dynamic stability. Understanding how walking with an actuated ankle exoskeleton system influences these different aspects of gait stability is essential for the safe design and control of wearable robotic devices. METHODS: Eighteen healthy adults walked on a treadmill at a constant speed (1.1 m/s) with and without an actuated bilateral ankle exoskeleton in a randomized crossover design. Spatiotemporal variability was quantified using coefficients of variation (CoV) of stride length, step width, and stance ratio. Global gait stability was assessed using detrended fluctuation analysis of stride time. Local dynamic stability was evaluated using maximum Lyapunov exponent calculated for the trunk, hip, upper leg, lower leg, and foot. Paired-samples two-sided t-tests were used to compare conditions. RESULTS: Walking with the ankle exoskeleton resulted in increased stride-to-stride spatiotemporal variability, reflected by higher CoV values for stride length (p < 0.001) and stance ratio (p = 0.005), while mean stride length and step width remained unchanged. Mean stance ratio was reduced in the exoskeleton condition (p < 0.001). Global gait stability did not differ between conditions, indicating preserved long-range temporal gait organization. Local dynamic stability increased at the lower leg (p < 0.001) and foot (p = 0.019) when walking with the exoskeleton. CONCLUSIONS: Walking with the actuated ankle exoskeleton alters gait control across multiple levels during steady walking. While stride-to-stride variability in stride length and stance ratio increased, global gait stability remained unchanged. Local dynamic stability was increased at the lower leg and foot, suggesting segment-specific effects of ankle-level assistance close to the assisted joint. However, these findings should be interpreted as the combined effect of wearing the exoskeleton and receiving active assistance, rather than the isolated effect of plantarflexion assistance. These results provide insight for the design and control of ankle exoskeletons with respect to stability-related effects during walking.

Humans↗

PubMed2026

[State Changes and Stability Grading of Driver Genes in Non-small Cell Lung Cancer Based on Repeated NGS Testing].

BACKGROUND: Next-generation sequencing (NGS)-based driver gene testing has become a routine component of molecular subtyping and precision therapy for non-small cell lung cancer (NSCLC). Dynamic genomic monitoring facilitates early detection of resistance-related molecular alterations and informs timely therapeutic adjustments. However, standardized criteria for evaluating the stability of serial NGS testing are currently lacking, and the applicability of NGS using formalin-fixed paraffin-embedded (FFPE) specimens for dynamic monitoring remains poorly defined. This study aims to establish a stability grading system for driver gene status alterations based on repeated NGS testing, and to provide evidence-based support for clinical repeat biopsy strategies. METHODS: Data from 1232 patients with NSCLC who underwent two or more NGS tests on FFPE tissue specimens at Beijing Chest Hospital between June 2019 and April 2026 were collected retrospectively. Patients with an interval of ≥4 months between the initial and last tests were included to ensure the representativeness of temporal analysis, resulting in a main analysis cohort of 942 patients. The Kappa consistency test was used to evaluate the state stability of nine core driver genes [epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene homolog (KRAS), anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1, receptor tyrosine kinase (ROS1), mesenchymal‑epithelial transition factor (MET), rearranged during transfection (RET), v-raf murine sarcoma viral oncogene homolog B1 (BRAF), erb‑b2 receptor tyrosine kinase 2 (ERBB2), and phosphatidylinositol‑4,5‑bisphosphate 3‑kinase catalytic subunit alpha (PIK3CA)] and to construct a five‑level grading system. Paired variant allele frequency (VAF) differences were compared using the Wilcoxon signed‑rank test. Independent influencing factors for mutation accumulation were identified by binary Logistic regression. RESULTS: The state stability of the nine genes was classified into five levels: EGFR showed high stability (Kappa=0.838), ROS1/ALK/KRAS good stability, BRAF/PIK3CA/RET moderate stability, and ERBB2 low stability, and MET showed high instability. MET exhibited the highest rate of state change (9.3%) with a raw observed agreement of 90.7%. Its Kappa value (0.172) was influenced by the low prevalence (3.7%) compression effect and should therefore be interpreted alongside the observed agreement (90.7%) and the prevalence-adjusted and bias-adjusted Kappa (PABAK). The VAF of PIK3CA increased significantly (P=0.005). T790M positivity increased from 5.8% to 10.8%, and 30 new C797S mutations were detected at the last test (13 with T790M, 17 without). The overall rate of new driver gene variants in the main cohort was 18.0%. Binary Logistic regression showed that a lower number of initial mutated genes was the only independent predictor of new variants [odds ratio (OR)=0.399, P<0.001], while sex and detection interval showed no independent association. CONCLUSIONS: A five level stability grading system for state changes of driver genes in NSCLC based on repeated NGS testing has been established. MET showed the most frequent state changes, which should be interpreted in conjunction with the prevalence effect. The VAF increase of PIK3CA is an observational finding, and its clinical significance requires further prospective validation. A lower initial mutation burden may reflect tumor clonal complexity and was associated with a higher likelihood of subsequent acquisition of new variants. FFPE based NGS is applicable for repeated testing at clinical treatment decision nodes.

Humans↗

PubMed2026

Generational variation and stabilization in resynthesized allotetraploid Brassica juncea derived from diploid progenitors B. rapa and B. nigra.

BACKGROUND: Polyploidy is a major driver of plant evolution and crop improvement, generating novel variation in morphology, physiology, and agronomic traits. Brassica juncea (AABB, 2n = 36), a natural allotetraploid derived from B. rapa (AA) and B. nigra (BB), is an important oilseed and vegetable crop; however, its narrow genetic base limits further breeding gains. Resynthesized B. juncea (RBJ), developed from known progenitors, provides a tractable system to investigate polyploid stabilization, trait diversification, and generational variation. This study evaluated RBJ across nine generations (F1-S8) to elucidate generational variation in morphological, molecular, cytological, and oil content traits during progressive stabilization. RESULTS: Substantial variation was observed for key yield-related traits, including siliqua length, seeds per siliqua, and thousand-seed weight. High estimates of heritability, genotypic variance, and genetic advance indicated their potential utility in selection based improvement. Comparative analyses revealed a clear generational progression, characterized by relatively enhanced performance in early generations, increased recombination-driven variability in intermediate generations, and the partial stabilization of several traits in later generations. Generation mean analysis suggested the involvement of additive, dominance, and epistatic gene effects in trait inheritance. Molecular analysis using SSR markers confirmed the amphidiploid origin and genomic integrity of RBJ generations. Cytological assessments, pollen viability assays, and flow cytometric analysis collectively demonstrated stable chromosome numbers, improved fertility, and maintenance of ploidy stability across successive generations. CONCLUSIONS: The study provides valuable insights into the generational variation and stabilization of morphological, molecular, and oil content traits in resynthesized B. juncea. The findings suggest that variability arising from polyploidization and interspecific hybridization undergoes gradual reorganization across successive generations, leading to increased trait stabilization and more consistent expression of selected agronomic characteristics. Collectively, these results contribute to the understanding of early stabilization processes in RBJ, highlighting resynthesized polyploids as useful systems for studying variation and stabilization in allopolyploid crops.

Mustard Plant↗

PubMed2026

Finlay-Wilkinson random regression for yield and yield stability prediction in cereals.

Year-to-year climate variability poses a challenge for agriculture by increasing crop yield variability; therefore, there is a need to identify genotypes that can withstand these fluctuations. With the right selection criteria, genotypes with yield stability across variable environmental conditions can be selected. Methods such as Finlay-Wilkinson random regression (FWRR) may allow us to use sparse datasets-common in plant breeding pipelines-and incorporate genomic data to leverage phenotypic information from related genotypes to predict yield stability. Our objective was to examine how the number of environments and the variance among those environments affect stability predictions. We also integrate FWRR as a genomic prediction tool for characterizing yield stability, comparing it to the traditional genomic prediction models as a reference. We used three datasets: one highly unbalanced dataset for oats (Avena sativa L.) and two completely balanced datasets with different numbers of environments for barley (Hordeum vulgare L.) and wheat (Triticum aestivum L.). We fit standard Finlay-Wilkinson (FW) and FWRR models to estimate grain yield and stability under various scenarios. We found that the estimated stability values obtained were similar using balanced datasets for FW or FWRR. FWRR also achieved moderate predictive ability for stability using unbalanced datasets under 10-fold cross-validation (CV1) with new genotypes. In terms of environmental representation, selecting the right set of environments for inclusion in the model was more important than adding more environments. Our results suggest the possibility of using FWRR to select stable genotypes earlier in line development, as well as to design resource-efficient stability-testing schemes.

Hordeum↗

PubMed2025

G4STAB: a multi-input deep learning model to predict G-quadruplex thermodynamic stability based on sequence and salt concentration.

MOTIVATION: G-quadruplexes (G4s) are non-canonical nucleic acid structures formed in guanine-rich regions that modulate gene regulation and genomic stability. The thermodynamic stability of G4s directly influences their biological functions and potential as therapeutic targets. However, current quantitative frameworks for predicting G4 stability rely on predetermined structural features, limiting their effectiveness for diverse G4 topologies, and fail to account for environmental factors such as ion concentration and pH that significantly modulate G4 stability in cellular contexts. RESULTS: We present G4STAB, a multi-input deep learning neural network that accurately predicts DNA G4 melting temperatures based on sequence features, salt concentration, and pH. Trained on 2382 diverse DNA G4 sequences, our model achieves high accuracy (R 2=0.8) without relying on predetermined G4 structural features. G4STAB successfully captures established G4 stability determinants and proposes previously unobserved sequence-stability relationships. Analysis of 391 502 experimentally validated G4s reveals that cancer-like ionic environments alter G4 stability profiles, with a 13.5-fold increase in the number of structures exhibiting physiological melting temperatures (36-42°C). These findings suggest systematic genomic patterns in G4 stability responses across chromosomes and gene types. AVAILABILITY AND IMPLEMENTATION: G4STAB is available at https://github.com/donn-liew/G4STAB; G4STAB web database interface is available at https://donn-liew.github.io/g4stab-web-database/.

G-Quadruplexes↗

PubMed2026

Associations of Trajectories of Loneliness and Neighborhood Stability with Depression, Alcohol and Substance Use, and Quality of Life among Women Living with HIV.

Social relationships are an important social determinant of health. Loneliness, the perceived gap between one's actual and desired relationships, has emerged as an important mechanism through which social relationships impact health. Like other intrapersonal-level factors associated with health, loneliness is influenced by broader social and structural factors, including characteristics of one's neighborhood social environment. Although neighborhood-level protective and risk factors for loneliness and for mental health have been identified, prior studies have often focused solely on self-reported perceptions of the neighborhood environment. Further, few have considered aspects of the neighborhood social environments, such as neighborhood stability (i.e., stability of the community with long or short-term residents), independent of neighborhood socioeconomic conditions. In the current analysis, we explored longitudinal patterns of loneliness in conjunction with neighborhood stability among women with HIV (WWH) enrolled into the MACS/WIHS Combined Cohort Study (MWCCS) from 2014-2019 (N 2019=1,394) to examine whether trajectories of loneliness and neighborhood stability were associated with depressive symptoms, non-prescription substance use, past-year cannabis use, number of alcoholic drinks per week, and several domains of quality of life. Loneliness at baseline (Betas = 0.24 - 0.54) and changes in loneliness over time (Betas = 0.11 - 0.26) were associated with each outcome, except for the association between changes in loneliness over time and drinks per week (Beta=0.13, p = 4.14x10-2), which did not persist after correcting for multiple comparisons. Neighborhood stability at baseline was associated with past year cannabis use (Beta=0.26, p = 1.00x10-2), depressive symptoms (Beta=-0.12, p = 1.54x10-3), and overall self-reported health (Beta=-0.08, p = 2.05x10-2). Changes in neighborhood stability across time were not associated with any outcome. Neighborhood stability moderated the association between changes in loneliness and general health perceptions. Our results demonstrate both overall loneliness and changes in loneliness over time have implications for current mental health in WWH, while changes in neighborhood stability did not.

Journal Article↗

PubMed2026

Dual recognition drives site-directed G-quadruplex stabilization: Oligonucleotide design in G4 ligand-oligonucleotide conjugates.

G-quadruplex (G4) DNA structures are increasingly recognized for their roles in transcriptional regulation and genome stability, making them attractive therapeutic targets. Selective recognition of individual G4s remains challenging due to the high structural similarity among G4 motifs. G4 Ligand-Oligonucleotides conjugates (GL-Os) address this challenge by combining small-molecule G4 ligands with the sequence specificity of oligonucleotides, targeting sequences flanking the intended G4 target. Here, we systematically investigate how oligonucleotide length, backbone composition, and sequence complementarity govern GL-O binding, selectivity, and G4 stabilization. We show that effective G4 recognition depends on the interdependence between oligonucleotide hybridization and G4 ligand binding, such that both elements cooperatively reinforce complex stability and site specificity. Longer oligonucleotides promote more stable complexes and stronger G4 stabilization, whereas central mismatches disrupt this dual-recognition mechanism. Replacement of DNA with peptide nucleic acids (PNAs) enhances binding strength, thermal stability, and metabolic stability. Importantly, ligand conjugation redirects PNA oligonucleotides from nonspecific polymerase stalling toward selective G4 stabilization. Finally, we demonstrate receptor-mediated cellular uptake of modified GL-Os, supporting the feasibility of cellular delivery while highlighting remaining delivery barriers. Together, these findings show the molecular design principles governing GL-O behavior and provide a foundation for the future development and evaluation of selective G4-targeting therapeutics.

G-quadruplex DNA↗

PubMed2026

Multivalent cations stabilize DNA duplexes beyond charge neutralization.

Multivalent cations are abundant in cells and play essential roles in DNA duplex stability, genome packaging, and DNA-protein interactions. They can also condense DNA, making it challenging to determine their influence on DNA duplex stability. To overcome this challenge, we studied DNA unpeeling at equilibrium under high tension using magnetic tweezers, thereby preventing condensation. Experiments show that DNA duplex stability first increases and then decreases as cation concentration increases and the maximum DNA duplex stability increases with cation valence. The maximum free energy change of DNA was 3.33 k B T/bp for Na+ and increased to 3.98 k B T/bp for protamine, which is a small arginine-rich protein with a highly positive charge (≈21 for salmon sperm), corresponding to a relative increase of 19.5%. Consistently, all-atom molecular dynamics simulations show that higher-valent cations preferentially embed in the minor groove of DNA and clamp the minor groove, in contrast to the major-groove clamping reported for RNA, thereby stabilizing the helix more efficiently. These findings establish a single-molecule framework for quantifying DNA thermodynamics in complex ionic environments, which contributes to understanding ionic control of genome stability and to designing ion-tunable DNA-based nanostructures and delivery systems.

Journal Article↗

PubMed2026

Grain protein and yield stability study in rainfed durum wheat RILs.

Developing durum wheat cultivars with stable grain yield across diverse environments remains a key breeding objective. This study evaluated 118 recombinant inbred lines (RILs) derived from a cross between the drought-adapted cultivar 'Zardak' (Triticum durum) and the landrace 'Iran-249' (T. turanicum) with desirable seed characteristics, across four heterogeneous rainfed environments in Italy and Iran. The assessment focused on grain yield (GY) and grain protein content (GPC) stability. Combined analysis of variance revealed significant (p < 0.01) effects for genotype, environment, and their interaction for both traits. Line ZD-050 showed the highest GY (3.91 t ha⁻¹), while ZD-032 had the highest GPC (14.27%). Stability analysis using parametric and non-parametric methods, along with AMMI and GGE biplot modeling, identified ZD-050 as among the most promising genotypes according to yield-integrating and dynamic-stability approaches. This line showed high grain yield in methods such as the Superiority Index and Kang's rank-sum, although stability rankings differed across the used methods. This line maintained superior yield, demonstrated broad adaptability across environments, and had moderate protein levels, identifying it as an optimal candidate for breeding programs targeting yield stability and wide adaptation under rainfed conditions.

Triticum↗

PubMed2019

RETRACTED: Investigation of the effect of UV-B light on Arabidopsis MYB4 (AtMYB4) transcription factor stability and detection of a putative MYB4-binding motif in the promoter proximal region of AtMYB4.

Here, we have investigated the possible effect of UV-B light on the folding/unfolding properties and stability of Arabidopsis thaliana MYB4 (AtMYB4) transcription factor in vitro by using biophysical approaches. Urea-induced equilibrium unfolding analyses have shown relatively higher stability of the wild-type recombinant AtMYB4 protein than the N-terminal deletion forms after UV-B exposure. However, as compared to wild-type form, AtMYB4Δ2 protein, lacking both the two N-terminal MYB domains, showed appreciable alteration in the secondary structure following UV-B exposure. UV-B irradiated AtMYB4Δ2 also displayed higher propensity of aggregation in light scattering experiments, indicating importance of the N-terminal modules in regulating the stability of AtMYB4 under UV-B stress. DNA binding assays have indicated specific binding activity of AtMYB4 to a putative MYB4 binding motif located about 212 bp upstream relative to transcription start site of AtMYB4 gene promoter, while relatively weak DNA binding activity was detected for another putative MYB4 motif located at -908 bp in AtMYB4 promoter. Gel shift and fluorescence anisotropy studies have shown increased binding affinity of UV-B exposed AtMYB4 to the promoter proximal MYB4 motif. ChIP assay has revealed binding of AtMYB4 to the promoter proximal (-212 position) MYB4 motif (ACCAAAC) in vivo. Docking experiments further revealed mechanistic detail of AtMYB4 interaction with the putative binding motifs. Overall, our results have indicated that the N-terminal 62-116 amino acid residues constituting the second MYB domain plays an important role in maintaining the stability of the C-terminal region and the overall stability of the protein, while a promoter proximal MYB-motif in AtMYB4 promoter may involve in the regulation of its own expression under UV-B light.

Arabidopsis↗

PubMed2026

Systematic differences in protein stability underlie species-specific developmental tempo.

Human embryonic development proceeds more slowly than in mice. The segmentation clock offers a tractable model for studying species-specific developmental tempo, as its oscillation period in human induced presomitic mesoderm (iPSM) cells is approximately twice that of mouse. While the core clock gene HES7 exhibits slower protein degradation in human cells, it remains unclear whether such cross-species differences in protein stability reflect a general principle. Here, we perform a dynamic stable isotope labeling of amino acids in cell culture (SILAC)-based proteomic analysis of ∼5,000 proteins in human and mouse iPSM, and we uncover a broad trend of slower protein degradation in human cells, regardless of subcellular localization or degradation pathways. Moreover, inhibition of glycolysis in mouse iPSM partially phenocopies the human protein stability profile, and modulation of protein stability alters the tempo of both the segmentation clock and cellular differentiation. Our findings establish protein stability, with systematic differences across species, as a key mediator linking metabolism to developmental tempo.

Animals↗

PubMed2026

From stress signaling to yield stability: physiological and molecular mechanisms of wheat resilience to heat and drought stress.

Wheat resilience depends on coordinated signaling, reproductive protection, and source-sink regulation, providing a framework to breed robust trait combinations that stabilize yield under combined heat and drought. Climate change is increasing the frequency and severity of heat and drought events, posing a major threat to wheat productivity, yield stability, and food security. Because these stresses often coincide in the field, their combined effects can impair growth, reproductive development, grain filling, and final yield more severely than either stress alone. Wheat resilience under such conditions depends on coordinated physiological adjustment and molecular regulation that sustain cellular homeostasis, protect reproductive tissues, and preserve yield-related traits. This review synthesizes current knowledge on the physiological and molecular bases of wheat resilience to heat and drought, with emphasis on their combined effects. We discuss major physiological responses, including photosynthetic adjustment, stomatal regulation, canopy cooling, osmotic balance, antioxidant defense, membrane stability, and source-sink coordination. We also examine key regulatory pathways involved in stress perception and adaptation, including calcium and reactive oxygen species signaling, mitogen-activated protein kinase cascades, phytohormonal crosstalk, transcriptional regulation, heat shock proteins, late embryogenesis abundant proteins, and osmoprotective and redox-associated pathways. In addition, we highlight the growing contribution of transcriptomics, proteomics, metabolomics, and phenomics to the identification of candidate genes, biomarkers, and adaptive traits. Finally, we consider how mechanistic insights can be translated into wheat improvement through molecular markers, genomic selection, gene editing, and climate-realistic phenotyping. An integrated understanding of stress signaling and adaptive trait deployment will be essential for developing wheat cultivars with improved resilience and yield stability under future climates.

Triticum↗

PubMed2025

Haplotype stacking to improve stability of stripe rust resistance in wheat.

Genotype-by-environment interaction analysis and haplotype-level characterisation provide novel insights into the stability of stripe rust resistance. Breeding selection strategies are proposed to achieve rapid and stable genetic gains across environments. This study investigated stripe/yellow rust (YR) responses in the Vavilov wheat diversity panel evaluated across 11 field experiments conducted in Australia and Ethiopia during 2014-2021. Genotype-by-environment interaction (GEI) was analysed using a factor analytic (FA) model. Genotype-level selection was performed with overall performance (OP) and root-mean-square deviation (RMSD), which reflected average performance and stability of YR resistance across environments, respectively. Genomic estimated breeding values (GEBV) for these traits were calculated and compared with those from a multi-trait GBLUP model with average performance represented by the mean GEBV across environments and stability by the standard deviation of GEBV across environments. The FA-based and multi-trait GBLUP GEBV had high correlations. Haplotypes with large effects on OP and RMSD were identified using the local GEBV method. Favourable haplotypes were then used for stacking in breeding simulations, using the Vavilov collection as a base. Compared to truncation selection, optimal haplotype selection (OHS) using an artificial intelligence (AI)-based algorithm achieved longer-term genetic gains for both OP and RMSD (after many generations) by initially selecting founder parents that maximised favourable haplotypes. Simulations using YR responses from diverse environments that mimicked fluctuating environmental conditions across seasons were conducted to evaluate strategies for selection of YR resistance that is stable across years. Strategies which gave most weight to OP, but some weight to RMSD were optimal in these conditions, and substantially reduced variation of performance across years. This study provides useful information for breeding cultivars with both high YR resistance and high stability of resistance across environments.

Triticum↗

PubMed2026

Sequence optimization targeting mRNA stability enhances monoclonal antibody titers in CHO cells.

This study presents a DNA sequence optimization approach that integrates mRNA stability as a tunable design parameter to enhance monoclonal antibody expression in Chinese hamster ovary (CHO) cells. A comprehensive combinatorial library of synonymous coding-sequence variants of an IgG1 light chain was integrated as single copies at a defined genomic locus in CHO cells with identical regulatory elements. Steady-state mRNA abundance, quantified by deep sequencing of gDNA and mRNA, served as a proxy for mRNA stability. These data were used to train a machine learning model that predicts mRNA abundance from coding sequence using embeddings from a pre-trained nucleotide transformer. This abundance predictor, together with established translational metrics, was incorporated into a genetic algorithm for multi-objective codon optimization. As proof-of-concept, we optimized sequences encoding Trastuzumab to either maximize or minimize the abundance criterion and obtained benchmark sequences from two commercial providers. Using targeted integration, we generated CHO cell lines and measured protein titer and cell-specific productivity. Sequences optimized for high abundance significantly increased intracellular mRNA levels (+41%), protein titer (+59%), and cell-specific productivity (+85%) relative to low-abundance designs, while viable cell densities remained comparable. Compared to commercial benchmarks, high-abundance sequences achieved significantly higher titer (+70%) and cell-specific productivity (+98%). These findings establish mRNA stability as a practical and complementary design parameter for codon optimization in monoclonal antibody production, with potential applicability to other proteins and expression systems.

CHO↗

PubMed2026

Engineering Protein Stability with Small Molecules: A Review of the ecDHFR Destabilizing Domain System.

The E. coli dihydrofolate reductase (ecDHFR) destabilizing domain (DD) is a versatile post-translational tool for the conditional control of protein stability via ligand-induced stabilization. In this system, a DD-tagged protein is rapidly degraded by the proteasome unless stabilized by the antibiotic trimethoprim (TMP), allowing for conditional control of protein abundance. The ecDHFR-DD system has been successfully applied across diverse biological systems, including yeast, invertebrate models such as Drosophila, and mammalian cells, to study a broad spectrum of cellular and developmental processes. Compared with DNA- and RNA-based regulatory approaches, post-translational systems offer faster response times and more precise control, making them valuable for processes that require tight, reversible regulation. In this review, we synthesize current knowledge on the mechanisms, performance, and optimization of the ecDHFR-DD system across organisms and evaluate its advantages and limitations relative to most conditional gene expression systems. We also highlight emerging opportunities for applying the system across diverse areas, ranging from functional genomics and synthetic biology to biomedical research. Additionally, we discuss its potential application in applied biological systems, such as pest and vector management, positioning the ecDHFR-DD system as a broadly applicable platform for the precise and tunable control of protein function across diverse disciplines.

Tetrahydrofolate Dehydrogenase↗

PubMed2025

Phase separation of hnRNPA1 and TERRA regulates telomeric stability.

Telomeres are the complexes composed of repetitive DNA sequences and associated proteins located at the end of chromatin. As a result of the DNA replication ending issue, telomeric DNA shortens during each cell cycle. The shelterin protein complex caps telomeric ends and forms a high-order protein-DNA structure to protect telomeric DNA. The stability of telomeres is critical for cellular function and related to the progression of many human diseases. Telomeric repeat-containing RNA (TERRA) is a noncoding RNA transcribed from telomeric DNA regions. TERRA plays an essential role in regulating and maintaining the stability of telomeres. Heterogeneous nuclear ribonucleoproteins (hnRNPs) are RNA-binding proteins associated with complex and diverse biological processes. hnRNPA1 can recognize both TERRA and telomeric DNA. Previous research reported that hnRNPA1, TERRA, and POT1, a component of the shelterin complex, work coordinately and displace replication protein A from telomeric single-stranded DNA after DNA replication, promoting telomere capping to preserve genomic integrity. However, the detailed molecular mechanism has remained unclear for >20 years. Here, our study revealed the molecular structure through which the hnRNPA1 UP1 domain interacts with TERRA and identified critical residues on the interacting surface between UP1 and TERRA. Furthermore, we proved that nucleic acids significantly increase the phase-separating ability of hnRNPA1, while disrupting the UP1-TERRA interaction extraordinarily affects hnRNPA1 droplet formation both in vitro and in vivo. Taken together, these data reveal the molecular mechanism of the phase separation of hnRNPA1 and TERRA and the potential contribution of the droplets to maintaining genomic stability.

Heterogeneous Nuclear Ribonucleoprotein A1↗

PubMed2026

E2F7 promotes lung adenocarcinoma progression by affecting phosphorylation and stabilization of β-catenin.

BACKGROUND: E2F transcription factor 7 (E2F7) has been implicated in the tumorigenesis and progression of multiple cancer types; however, the molecular mechanisms through which E2F7 regulates malignant phenotypes in cancer cells remain largely undefined. In this study, we investigated the biological functions and underlying mechanisms of E2F7 in lung adenocarcinoma (LUAD). METHODS: E2F7 expression in LUAD was analyzed using The Cancer Genome Atlas (TCGA) datasets and further validated in clinical specimens via quantitative real-time polymerase chain reaction (PCR) and immunohistochemistry. The effects of E2F7 on cancer cell self‑renewal and epithelial-mesenchymal transition (EMT) were assessed using sphere formation and Transwell assays, respectively. In vivo tumorigenicity and metastasis were evaluated using xenograft models combined with extreme limiting dilution analysis to assess tumor-initiating capacity. Wnt/β‑catenin pathway activity was measured using T-cell factor optimal promoter luciferase reporter plasmid/far-from optimal promoter luciferase reporter plasmid (TOP/FOP) flash reporter assays. β‑Catenin expression, stability, and ubiquitination were examined via western blotting, cycloheximide chase assays, and ubiquitination assays. Protein-protein interactions among E2F7, β‑catenin, and glycogen synthase kinase 3 beta (GSK3β) were verified through co‑immunoprecipitation (Co‑IP), glutathione S‑transferase (GST) pull‑down, and immunofluorescence assays. Truncated mutants were generated to map the functional binding domains of E2F7. In vitro immunoprecipitation and kinase assays were further performed to confirm that E2F7 regulates GSK3β autophosphorylation and β‑catenin phosphorylation. RESULTS: Bioinformatic analyses revealed that E2F7 was significantly upregulated in LUAD tissues, and elevated E2F7 expression correlated with poor patient prognosis. Functional assays demonstrated that E2F7 promoted LUAD cell self‑renewal and EMT. Mechanistically, cytoplasmic E2F7 directly associated with β‑catenin through its DNA‑binding domain (DBD) and PHA03247 domain. E2F7 modulated β‑catenin phosphorylation at Ser675 and Ser33/37/T41, thereby inhibiting ubiquitin‑mediated degradation and enhancing β‑catenin protein stability. Furthermore, E2F7 interacted with GSK3β and suppressed its autophosphorylation at Tyr216, concomitant with reduced β-catenin phosphorylation at Ser33/37/T41 and its accumulation. CONCLUSION: Collectively, these findings indicate that E2F7 drives LUAD malignant progression through regulation of the GSK3β/β‑catenin signaling axis and stabilization of β‑catenin. This study unveils a novel oncogenic mechanism of E2F7 in LUAD and identifies E2F7 as a promising therapeutic target for clinical intervention in LUAD.

E2F7↗

PubMed2026

Minimal Transport Units Govern Oxygen-Defect Stabilization and Transport for Lightweight Solid Electrolytes.

Solid electrolytes are central to electrochemical energy technologies, including fuel cells, sensors, catalysis, membrane separation, and electrolyser. However, most established oxide-ion solid electrolytes are built around heavy B-site cations embedded in rigid and highly connected coordination frameworks, leading to widespread high-weight and sluggish ionic transport that is strongly coupled to large-amplitude lattice relaxations. This intrinsic challenge hinders further performance optimization and constrains the rational design of lightweight electrolytes. Herein, we propose a minimal transport unit-based design paradigm that combines simplified structural motifs with light-element chemistry, enabled by the exceptional flexibility of B-O polyhedra in coordination, rotation, deformation, and connectivity. As a proof of concept, Sc1- xZnxBO3- x /2, constructed from isolated BO3 units, exhibits high oxide ion conductivity (σ(1000°C) ∼ 1.5 × 10-2 S/cm), alongside excellent thermo-mechanical stability. Oxygen vacancies are stabilized through the formation of B2O5 units rather than isolated BO2 species. Long-range oxide-ion migration is mediated by dynamic oxygen exchange between minimal BO3 and B2O5 units via continuous breaking and reforming of B2O5 units, with transient BO2 configurations as intermediates. This study demonstrates minimal transport units as a governing principle for defect stabilization and ionic conduction in lightweight solid electrolytes, offering a general design framework for portable and scalable high-temperature energy technologies.

NMR spectroscopy and variable‐temperature P↗