Biology subjects

Du, Z.

Publications and source records attributed to Du, Z..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

Cross-Species Transcriptomic Integration Reveals a Conserved, MIRO1-Mediated Macrophage-to-T Cell Signaling Axis Driving Immunosuppression in Glioma

Mitochondrial regulators are increasingly recognized for their influence on immune signaling within the tumor microenvironment (TME). In glioma, where immunosuppression limits therapeutic efficacy, we investigate how targeting the mitochondrial protein MIRO1 alters the TME. We combine single-nucleus RNA sequencing of murine gliomas treated in vivo with a MIRO1-binding compound and bulk RNA sequencing of human glioma resections treated with the same compound ex vivo. Cross-species transcriptomic integration reveals a MIRO1-responsive program in the TME. Among shared targets, we identify PARP11/Parp11 as a consistently upregulated gene in glioma that is downregulated following MIRO1-binding compound treatment in both human and mouse gliomas. Cell-cell communication analysis shows that a specific cluster of macrophages (MAC1), which exhibits robust Parp11 and Pdl1 (encoding PD-L1) expression, sends immunosuppressive signals to CD8+ cytotoxic T cells, and may receive prostaglandin E{square} signals from another cluster of macrophages (MAC4). Targeting MIRO1 eliminates this cell circuitry and reduces the tumor cell population. Our study provides a transcriptomic framework for understanding mitochondria-immune crosstalk and nominates MIRO1-PARP11 as a potential effector axis of brain immune dysfunction. Summary BlurbTranscriptomic integration of single-nucleus RNA sequencing of murine gliomas and bulk RNA sequencing of human gliomas reveals an immunosuppressive signaling axis in the glioma TME, mediated by MIRO1.

cancer biology↗

bioRxiv2025

PTH-Induced Behavioral and Metabolic Alterations in Mouse Models of Hyperparathyroidism

Parathyroid hormone (PTH) is a critical endocrine regulator of calcium homeostasis and bone remodeling and is widely employed in clinical settings through synthetic analogs for the treatment of osteoporosis. Although traditionally considered a peripheral regulator, emerging evidence indicates that PTH also exerts effects through the central nervous system (CNS). This study investigated the neuropsychiatric impact of elevated PTH and explored potential CNS involvement using multiple murine models of hyperparathyroidism (HPT). Distinct behavioral phenotypes were observed across models, indicating that psychiatric symptoms vary depending on disease etiology and progression. The effects of hPTH(1-34), a clinically approved PTH analog, were further assessed in male and female mice. Under pharmacological concentrations, hPTH(1-34) enhanced locomotor activity in males but induced mild anxiety-like behavior in females. These behavioral changes in females were independent of the estrus cycle and were amplified by ovariectomy. Metabolic analysis indicates PTH affects the basic metabolism by inhibiting the respiratory exchange ratio, promotes the energy expenditure and locomotion without affecting the food consumption in a 48hr range. To further investigate the molecular effect of PTH in the brain, a PTH1R-Cre mouse line was generated to map PTH receptor-1 (PTH1R) expression. Widespread expression of PTH1R was detected across the brain, including in both neuronal and non-neuronal cell populations. These findings suggest that PTH may influence behavior through interactions with PTH1R-expressing cells in brain vasculature and circumventricular regions. However, further studies are warranted to define the specific brain nuclei and cell types involved in PTH-driven modulation of neurobehavioral function.

neuroscience↗

bioRxiv2025

Programmable Aptamer-Embedded Circular RNAs for Targeted Antigen-Presenting Cells Immunotherapy

The targeted delivery of mRNA to specific cell types in vivo remains a major unmet need in mRNA-based therapeutics. Conventional strategies rely on nanocarriers engineered with various modifications. However, these exogenous materials could cause adverse reactions, and their complex manufacturing processes often hinder clinical application. By leveraging the innate programmability of RNA sequences, we herein report a carrier-free, scalable, and programmable aptamer-embedded circular RNAs (Apt-circRNAs) design that confers targeting capability through the strategic incorporation of different aptamers at varying densities, while retaining circular RNA stability and protein production capability. Experimental results show that antigen-loaded Apt-circRNAs enable targeted delivery to antigen-presenting cells (APCs), drive endogenous antigen expression, activate antigen-specific T cells, and elicit potent immune responses that mediate clearance of both early-and late-stage tumors in mouse models. In humanized models of colorectal cancer, the combination of Apt-circRNA and PD-1 blockade produced synergistic antitumor effects and significantly reshaped the tumor microenvironment. In a first-in-human (FIH) clinical trial, Apt-circRNA vaccine encoding KRAS G12D/G12V neoantigens exhibited a favorable safety profile and induced robust immune activation, T cell mobilization, and neoantigen-specific immune responses. With this study, we have established a new paradigm in carrier-free, APC-targeted RNA vaccine design, offering a safe and effective platform for next-generation cancer immunotherapy.

bioengineering↗

bioRxiv2025

Structural and dynamic insights into phosphate uptake by PHT1 transporter in rice

Phosphorus is an essential macronutrient for plants, primarily absorbed from the soil as inorganic phosphate (Pi) through root-located Pi transporters. Despite decades of research into these transporters as targets for developing Pi-efficient crops, their mechanisms for Pi import remain poorly understood. Here, we present the cryo-EM structures of the rice Pi importer OsPHT1;11 in both Pi-bound and unbound forms, characterize its conformational dynamics, and reveal how these dynamics contribute to its transport function. Pi is recognized through conserved residues found in plants, with its translocation facilitated by a typical alternating-access mechanism. SmFRET analyses reveal that this transporter undergoes dynamic conformational changes, which are differentially linked to its Pi transport capability, with a predominance of extracellular open conformations favoring Pi transport, while more populated intracellular open conformations hinder it. These findings provide insights into Pi uptake in plants and offer a foundation for designing genetically modified crops with improved phosphate efficiency.

biochemistry↗

bioRxiv2025

Quality assessment of RNA 3D structure models using deep learning and intermediate 2D maps

Accurate quality assessment is critical for computational prediction and design of RNA three- dimensional (3D) structures. In this work, we introduce RNArank, a novel deep learning-based approach to both local and global quality assessment of predicted RNA 3D structure models. For a given structure model, RNArank extracts a comprehensive set of multi-modal features and processes them with a Y-shaped residual neural network. This network is trained to predict two intermediate 2D maps, including the inter-nucleotide contact map and the distance deviation map. These maps are then used to estimate the local and global accuracy (i.e., lDDT). Extensive benchmark tests indicate that RNArank consistently outperforms traditional methods and other deep learning-based methods. Moreover, RNArank demonstrates promising performance in identifying high-quality structure models for targets from the recent CASP15 and CASP16 experiments. We anticipate that RNArank will serve as a valuable tool for the RNA biology community, improving the reliability of RNA structure modeling and thereby contributing to a deeper understanding of RNA function.

bioinformatics↗

bioRxiv2025

Linear scaling reveals low-dimensional structure in observable microbial dynamics

Microbial communities often exhibit apparently complex dynamics driven by myriad interactions among community members and with their environments. Yet, practical modeling and control are often based on limited number of observables, raising a fundamental question: to what extent are these observed dynamics predictable given unobserved background complexity? Here, we report an emergent simplicity that the temporal dynamics of observable microbial populations can be captured by low- dimensional representations. Using variational autoencoders (VAEs), we define a critical latent dimension (Ec) that quantifies the minimal number of variables required to represent observable microbial dynamics. We find that Ec scales linearly with the number of observables, despite the complexity of unobserved background dynamics. This principle holds across simulations of ecological, spatial, and gene-transfer models, experiments with engineered and environment-derived communities, and human microbiomes. Our findings establish a scaling law for microbial community dynamics and demonstrate observable dynamics alone contain sufficient information for prediction and control, even without full knowledge of the community.

systems biology↗

bioRxiv2025

Single oocyte full-length isoform sequencing unveils the impact of transposable elements on RNA diversity and stability during oocyte maturation

The oocyte-specific isoforms play crucial roles in oocyte maturation, while current understanding of the oocyte transcriptome is mainly focused on gene level. Here, we utilized single cell full-length isoform sequencing based on third generation sequencing to detect entire transcripts in human and mouse oocytes. Isoform diversity during oocyte maturation was systematically profiled, including 6,736 and 4,902 putative novel human and mouse transcripts, respectively. More than half of novel isoforms were categorized as the novel-not-in-catalog (NNC) and may serve specific functions in oocytes, including novel isoforms of ARHGAP18, colocalized with microtubules and targeted knockdown disrupting oocyte maturation. Moreover, over 25% of NNC isoforms were derived from transposable elements (TEs), and their incorporation within transcripts could enhance isoform stability during oocyte maturation. Altogether, our findings represent a valuable resource showcasing the complexity and diversity of RNA isoforms in oocytes, as well as TE co-option for novel isoform generation and isoform stability enhancement.

developmental biology↗

bioRxiv2025

Development, validation, and evidence of frequent exchange of mating type HD alleles of Puccinia striiformis f. sp. tritici provide an insight into highly genetic diversity

Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is a worldwide destructive wheat disease. It possesses the potential to generate novel virulence races through sexual reproduction, which is the primary cause of its extensive epidemics. Mating type (MAT) of Pst lacks direct experimental evidence to account for the role of sexual recombination on high genetic diversity in evolution. Herein, we developed 11 pairs of HD alleles of Pst MAT genes, and 2 pairs HD alleles of P. striiformis f. sp. hordei (Psh, the causal agent of barley stripe rust) MAT genes. HD alleles in Pst are different from those in Psh. We tested that mating system of Pst is tetrapolar responsible for sexual genetic recombination via HD genes by experiments of selfing and sexual hybridization on alternate (secondary) hosts. Multiple HD gene types and HD gene recombination types were detected in Chinese natural Pst populations of 200 Pst isolates and 13 Psh isolates from 92 sampling sites in 11 provinces, supporting that sexual reproduction accounts for frequent emergence of new races and high genetic diversity of Pst population in northwestern oversummering variable region (hotspot) than other stripe rust-occurring regions in China. Overall, these results provide an insight into diverse types and frequent exchange of Ps MAT alleles, revealing the important role of sexual recombination via MAT alleles in virulence variation, high genetic diversity and epidemics of Pst, and also provide a basis for wheat stripe rust control in those regions where sexual reproduction occurs. Author summaryHeteroecism of the wheat stripe rust pathogen Puccinia striiformis f. sp. tritici (Pst) was discovered a decade ago. The significance of sexual reproduction in maintaining genetic diversity has emerged as a pressing concern in contemporary scientific discourse. In this study, we elucidated the presence of multiple HD gene types (HD1 linked to HD2) in Puccinia striiformis f. sp. tritici (Pst), distinguishing it from P. striiformis f. sp. hordei. Through biological experiments on sexual reproduction, we demonstrated that the mating system of Pst is tetrapolar. Furthermore, we observed that sexual reproduction, particularly selfing (individual race) and crossing (between two races), facilitates sexual recombination via HD genes, leading to pathogenic variation and a high level of genetic diversity. We established a model illustrating sexual reproduction of Pst by selfing and crossing, respectively. In China, we have observed that the Pst population exhibits a diverse range of HD gene types and HD gene recombination types. Notably, northwestern oversummering variable regions (hotspot) have a higher number of HD genes compared to other epidemic region. Population structure and cluster analyses based on HD genes indicate that Pst populations in Tibet and Xinjiang are distinct from those in other inland regions. These findings provide valuable insights into comprehending the intricate interplay between sexual reproduction and genetic diversity of Pst, thereby elucidating the reasons behind the high genetic diversity of the Chinese Pst population.

microbiology↗

bioRxiv2025

Discovery of D2469079A, A novel selective Toll-Like Receptor 7/8 Antagonist with Brain Penetrance

Aberrant activation of endosomal Toll-like receptors (TLRs) 7 and 8, which recognize single-stranded RNA, is strongly implicated in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). And the frequent neuropsychiatric involvement in SLE highlights the need for brain-penetrant therapies. Here, we report the identification and characterization of D2469079A, a novel, potent dual TLR7/TLR8 antagonist (low nM IC50 in humanized HEK-Blue assays) selective against hTLR9. D2469079A demonstrates favorable in vitro properties, including adequate solubility and high microsomal stability. It exhibited desirable pharmacokinetic profiles across multiple preclinical species (mice, rats, dogs) and achieved significant cerebrospinal fluid (CSF) exposure, confirming its high permeability and brain penetration. Consistent in vivo efficacy was observed in both acute and chronic stimulation models. Importantly, D2469079A displayed a favorable safety profile, lacking significant liabilities related to CYP450 inhibition/induction, hERG interaction, or toxicity in a 14-day rat study. These findings position D2469079A as a promising drug candidate with excellent drug-like characteristics for the treatment of TLR7/8-driven autoimmune diseases, potentially including neuropsychiatric manifestations. We are actively seeking partners for collaborative clinical development.

immunology↗

bioRxiv2025

PepBERT: Lightweight language models for peptide representation

Protein language models (pLMs) have been widely adopted for various protein and peptide-related downstream tasks and demonstrated promising performance. However, short peptides are significantly underrepresented in commonly used pLM training datasets. For example, only 2.8% of sequences in the UniProt Reference Cluster (UniRef) contain fewer than 50 residues, which potentially limits the effectiveness of pLMs for peptide-specific applications. Here, we present PepBERT, a lightweight and efficient peptide language model specifically designed for encoding peptide sequences. Two versions of the model--PepBERT-large (4.9 million parameters) and PepBERT-small (1.86 million parameters)--were pretrained from scratch using four custom peptide datasets and evaluated on nine peptide-related downstream prediction tasks. Both PepBERT models achieved performance superior to or comparable to the benchmark model, ESM-2 with 7.5 million parameters, on 8 out of 9 datasets. Overall, PepBERT provides a compact yet effective solution for generating high-quality peptide representations for downstream applications. By enabling more accurate representation and prediction of bioactive peptides, PepBERT can accelerate the discovery of food-derived bioactive peptides with health-promoting properties, supporting the development of sustainable functional foods and value-added utilization of food processing by-products. The datasets, source codes, pretrained models, and tutorials for the usage of PepBERT are available at https://github.com/dzjxzyd/PepBERT.

bioinformatics↗

bioRxiv2025

Genomic insights into polysaccharide substrate utilization and novel genera resource mining in macroalgal epiphytic bacteria

Marine macroalgae, among the fastest photosynthesizing organisms, play a crucial role in the ocean carbon cycle by converting fixed carbon dioxide into polysaccharides. Macroalgal epiphytic bacteria possessing specific polysaccharide utilization loci (PULs) have a generalized polysaccharide degradation potential that facilitates their growth and colonization. In this study, we conducted extensive research on their polysaccharide degradation potential. Through sampled and purified epiphytic bacteria and metagenomic analysis revealed a high prevalence of novel genera and species. Two novel genera, 1117T and 3-347T, were taxonomically characterized and conducted detailed functional analyses. The results demonstrated that these genera possess abundant PULs and strong capabilities for synthesizing secondary metabolites. Furthermore, their high relative abundance on macroalgal surfaces aligns with global ecological distribution patterns. These traits facilitate their colonization, growth, and environmental adaptation on macroalgal surfaces. We further performed in-depth annotation of a large number of PULs and CAZyme genes of macroalgal epiphytic bacteria. Potential polysaccharide substrates for their degradation can be predicted and focused on. Additionally, we conducted growth curve analyses by starch, xylan, {beta}-1,3-glucan, and carboxymethyl cellulose substrates to validate the genomic predictions. In summary, our findings demonstrate that macroalgal epiphytic bacteria possess significant potential for degrading algal polysaccharides. This capability may enhance their competitiveness and survival probability on macroalgal surfaces. These bacteria, originating from different sources and genera, possess similar PULs, which may result from horizontal gene transfer or evolutionary relationships. ImportanceMacroalgae are major primary producers in coastal areas and their carbon sequestration capacity per unit area far exceeds that of terrestrial forests. In this work, we extensively studied macroalgal epiphytic bacteria with polysaccharide degradation potential. We found that epiphytic bacteria from different macroalgal sources and genera share similar PULs to degrade the same polysaccharide, which may be the result of horizontal gene transfer or evolutionary relationships. Core taxa on the macroalgal surface have gradually evolved polysaccharide-degrading abilities of different marine macroalgae in order to expand their colonization and survival chances. We also identified a large number of uncultivated algal biosphere species and unreported new genera and species for expansion of macroalgal epiphytic bacteria studies. These studies have thus highlighted the important ecological and research value of macroalgal epiphytic bacteria, especially in influencing polysaccharide carbon storage and marine carbon cycling.

microbiology↗

bioRxiv2025

Genomic Characterization and New Species Identification of Winogradskyella with Comparative Analysis of Polysaccharide Utilization Loci

Marine macroalgae convert a substantial fraction of fixed carbon dioxide into various polysaccharides. Winogradskyella is a genus within the phylum Bacteroidota with a clear marine origin especially from marine macroalgae. Most members of this genus have been found associated with macroalgae or microalgae. Using a combination of genomic, phylogenetic, and biochemical approaches, we characterized five novel Winogradskyella species capable of degrading marine macroalgal polysaccharides. Bioinformatic PUL annotations suggest usage of a large array of polysaccharides, including laminarin, -glucans, and alginate as well as mannose- and fucose-, highlighting the genus involvement in the marine carbon cycle. Many of the PULs exhibit new genetic architectures and suggest substrates rarely described for marine environments. Using the SusC/D trees, we analyzed evolutionary relationships of SusC/D homologs and found indications for profound changes in microbial utilization of laminarin, alginate, -glucans, {beta}-mannan, and sulfated xylan. Through the genomic study and annotation of PULs, we explored the complex relationship between genome size and polysaccharide degradation potential of Winogradskyella. These findings underscore the ecological significance of Winogradskyella in marine ecosystems and their role in polysaccharide degradation, providing a basis for biogeochemical cycling and future biotechnological applications.

microbiology↗

bioRxiv2025

Physical Activity and Depressive Mood Shared the Structural Connectivity between Motor and Reward Network: a population-based study from the UK Biobank

BackgroundExercise has been revealed to leave a positive effect on alleviating depressive symptoms by various existing studies. However, the neural basis behind this phenomenon remains unknown, as well as its underlying biological mechanism.AimsUsing a large neuroimaging cohort from UK Biobank, this study aimed to identify structural connectivity (SC) patterns simultaneously linked with physical activity and depression, as well as its biological interpretation.Method492 participants with major depression disorder (MDD) and 535 healthy controls (HC) were extracted from the UK Biobank dataset. Partial least squares regression was first utilized to explore a replicable SC pattern simultaneously associated with physical activity and depressive mood. The neuromaps toolbox was applied to interpret the biological ontologies of the identified SC pattern. Neuroimaging-transcriptome association and enrichment analyses were conducted to explore its underlying genetic basis, pathways and cell types. The reproducibility and generalizability were tested on another independent MDD dataset (N=3,496) and bipolar disorder (BD) dataset (N=81).ResultsA SC pattern linked with exercise was identified to be both significantly correlated with depressive mood and group discriminative between MDDs and HCs, which primarily located between the motor-related regions and reward-related regions. This pattern was associated with multiple neurotransmitter receptors, such as serotonin and GABA receptors, and enriched in pathways like synaptic signaling and astrocytes cell type. The SC pattern and genetic results were also replicated in another independent MDD dataset and present commonalities with BD.ConclusionsThis study not only initially identified a reproducible shared SC pattern between physical activity and depressive mood, but also elucidated the underlying biological mechanisms, which enhanced our understanding of how exercise helps alleviate depression and may inform the development of novel neuromodulation targets.

neuroscience↗

bioRxiv2025

High-throughput 3D super-resolution imaging in deep tissue

Fluorescence images obtained with optical microscopes intrinsically suffer from blur and noise, which can be partially reversed by the deconvolution process. However, the deconvolution process is ill-conditioned, leading to a trade-off between detail preservation and noise suppression. Here, we develop 3D-FUDIP to fully decouple the deconvolution process into two parts: deblurring and denoising, achieving an 8-fold improvement in spatial resolution. By adopting the Poisson model, which obeys the quantum nature of photons, our 3D-FUDIP can be successfully applied to various noise conditions, especially low-light conditions where the photon number is generally extremely small. The results show that our 3D-FUDIP improves the SNR by up to 6-fold with only a one-fifth photon budget. Besides, 3D-FUDIP boosts the spatial bandwidth product (SBP) by one order of magnitude, allowing more spine details to be resolved within a larger imaging volume. By synergizing deep learning with these advances, we propose 3D-FUDIPn to further improve the imaging resolution. We demonstrate 3D-FUDIPs performance in various imaging systems, including confocal, two-photon, and light-sheet microscopes, showing compatibility and potential applications in biological science.

neuroscience↗

bioRxiv2025

Nucleoporins shape germ granule architecture and balance small RNA silencing pathways

Animals have evolved distinct small RNA pathways, including piRNA and siRNA, to silence invasive and selfish nucleic acids. piRNA pathway factors are concentrated in perinuclear germ granules that frequently associate with nuclear pore complexes (NPCs). However, the factors mediating germ granule-NPC association and the functional relevance of such association remain unknown. Here we show that the conserved nucleoporins NPP-14 (NUP-214) and NPP-24 (NUP-88), components of the cytoplasmic filaments of NPC, play critical roles in anchoring germ granule to NPC and in attenuating piRNA silencing In C. elegans. Proximity labeling experiments further identified EPS-1 (enhanced piRNA silencing) as a key germ granule factor contributing to germ granule-NPC interaction. In npp-14, npp-24, or eps-1 mutant animals, we observed fewer but enlarged, unorganized germ granules, accompanied by the over-amplification of secondary small RNAs at piRNA targeting sites. Nonetheless, we found this enhancement of piRNA silencing comes at the cost of dampened RNAi efficiency and RNAi inheritance. Together, our studies uncovered factors contributing to germ granule-NPC association and underscored the importance of spatial organization of germ granules in balancing small RNA silencing pathways.

genetics↗

bioRxiv2025

1,3- and 1,4-linked Polysaccharides Uptake in Intestinal Cells Relies on Clathrin/Dynamin 1/Rab5-dependent Endocytosis

Natural polysaccharides are considered to be a promising feedstock for manufacturing sustainable materials. However, polysaccharides are believed by most biologists that they could not be absorbed by intestinal mucosa to enter circulation system owing to their high hydrophilicity and large molecule size. Herein, {beta}-1,3-linked glucan (GFPBW1) and -1,4-linked glucan (WGE) is used as the model polysaccharide and the transport experiments show that different linked and charged polysaccharides can permeate Caco-2 cell monolayers. The in vivo experiments demonstrate that GFPBW1 and WGE are detectable in rodent plasma and liver after oral administration the isotope (99mTc, 3H) and fluorescein labeled polysaccharides. Further study show that polysaccharide uptake requires clathrin heavy chain (CLTC) and its associated factors Rab5 and dynamin1 in intestinal cells using gene-knockdown strategies and inhibitors. Strikingly, polysaccharide absorption is attenuated in both CLTC intestine deficient mice and Rab5, dynamin1 conventional-knockout mice. Importantly, membrane receptors bone morphogenetic protein receptor type IA (BMPRIA), Dectin-1 and epidermal growth factor receptor (EGFR) are also critical for specific structural polysaccharide internalization. These findings provide novel insight to understand polysaccharide absorption mechanism and lay foundation for oral polysaccharide- based new drugs development.

pharmacology and toxicology↗

bioRxiv2024

D-glucuronyl C5-epimerase binds to EGFR to suppress kidney fibrosis

Renal tubular cells may actively participate in fibrosis processes leading to end-stage renal failure. However, which molecule play pivotal role in the fibrogenesis is still vague. Glucuronyl C5-epimerase (Hsepi, gene name, Glce) is a key enzyme that catalyzes biosynthesis of Heparan sulfate (HS) chains attached to HS proteoglycan which are ubiquitously located on cell membrane. Homozygous Glce-/- mice may cause embryonic lethality and multi-organ defects. However, whether Glce plays a key role in kidney fibrosis is unknown. Here, we show that Glce expression is significant attenuated in kidneys of patients with renal fibrosis and the animal models. Further study shows that renal tubular-specific Glce deletion in mice exacerbate kidney fibrosis while AAV-mediated overexpressing of Glce in UUO-treated mice may ameliorate kidney fibrosis associated with epithelial-mesenchymal transition (EMT) progress via the TGF-{beta}/Smad2/3 signaling pathway. Mechanism study demonstrates that Glce protein may bind to EGFR to inactivate EGFR/ERK signaling and further impede TGF-{beta}/Smad-driven EMT and renal fibrosis in Glce-/- and the wild type mice. Interestingly, the anti-fibrosis function is independent of Glce enzymatic activation. These data uncover a novel function for Glce which plays a key role in kidney tissues against fibrosis.

pathology↗

bioRxiv2024

Enalapril mitigates aging by targeting antioxidative genes via phosphorylated Smad1/5/9

Aging increases the risk of a myriad of chronic diseases, which are expensive and difficult to treat owing to their various risk factors. Repurposing existing medications has accelerated the development of therapies aimed at slowing aging. In this study, we revealed that enalapril, a drug widely prescribed for hypertension, can improve both cellular senescence and individual health. Mechanistically, phosphorylated Smad1/5/9 act as pivotal mediators of the anti-senescence properties of enalapril. It stimulates downstream genes involved in cell cycle regulation and antioxidative defense, facilitating cell proliferation and diminishing the production of reactive oxygen species (ROS), thus increasing the antioxidative ability of enalapril. At the organismal level, enalapril has been shown to bolster the physiological performance of various organs; it notably enhances memory capacity and renal function and relieves lipid accumulation. Our work highlights the potential of enalapril to augment antioxidant defenses and combat the effects of aging, thereby indicating its promise as a treatment strategy for aging-associated diseases and its use for healthy aging.

cell biology↗