Biology subjects

Jiang, C.

Publications and source records attributed to Jiang, C..

At least 37 records · Page 2Linked to original sources

bioRxiv2026

An atlas of transcriptional dynamics in maternal blood over the course of healthy pregnancy

Pregnancy results in profound physiological changes driven by dynamic and precisely programmed molecular processes. Maternal peripheral blood is generally the specimen of choice for studying these processes, as it is easily accessible and essential for many aspects of maintaining a healthy pregnancy. Here, we present a high-resolution atlas of the dynamic temporal changes in the transcriptome of maternal peripheral blood in healthy human pregnancy. We generated comprehensive RNA sequencing data in 802 weekly samples from 31 healthy pregnant women from the first trimester until after delivery. Using a strict discovery and replication setup, our longitudinal analysis of gene expression identified 720 genes with robust pregnancy-specific expression patterns. Using weighted graph correlation network analysis, we identified nine pregnancy-associated transcriptional modules that reveal a strong, coordinated enrichment of innate/neutrophil and antiviral immune programs, alongside changes in adaptive immunity (T cell differentiation and signaling), erythropoiesis and hemoglobin metabolism. Cell-type deconvolution revealed that these transcriptomic shifts were accompanied by increased relative neutrophil proportions and reduced naive CD4 and CD8 T cells in pregnancy. We provide a comprehensive characterization of dynamic changes across pregnancy, highlighting maternal blood as a key systemic regulator in healthy gestation. Together, our findings establish a reference atlas of healthy pregnancy, which can be used to identify dysregulated processes and mechanisms in women with pregnancy complications. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=168 SRC="FIGDIR/small/715300v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@e6dd97org.highwire.dtl.DTLVardef@de217dorg.highwire.dtl.DTLVardef@168ad94org.highwire.dtl.DTLVardef@15c0dd1_HPS_FORMAT_FIGEXP M_FIG C_FIG O_LI720 genes showed robust pregnancy specific expression patterns. C_LIO_LICo-expression analysis clustered the genes into nine modules with distinct dynamics. C_LIO_LIEnrichment in pathways involved in innate and neutrophil-mediated immunity, antiviral responses, T cell differentiation and signaling, erythropoiesis and hemoglobin metabolism. C_LIO_LICell-type deconvolution showed increases in neutrophils and decreases in naive CD4 and CD8 T cells. C_LIO_LIThe atlas of detailed longitudinal transcriptional changes provides a baseline reference for healthy pregnancy. C_LIO_LIResults for all genes and protein-protein interaction networks are made available for interactive exploration. C_LI

genomics↗

bioRxiv2026

Transporter-Mediated Uptake of Microcystin-LR in Human Trophoblasts: Regulation By Oxygen Concentration and Cell Fusion

BackgroundRising global temperatures and eutrophication are increasing the intensity and frequency of cyanobacterial harmful algal blooms that release toxins including microcystin-LR (MC-LR). MC-LR inhibits protein phosphatases in the human liver and brain, but its accumulation in the placenta is unclear. Placental transporter expression varies across pregnancy and is influenced by physiological cues, such as low oxygen concentrations which activate HIF1A, and trophoblast cell fusion forming syncytiotrophoblasts that engage CREB-driven transcription. This study examined whether MC-LR accumulates in placental cells, which transporters mediate uptake, and how these transporters are regulated by HIF1A and CREB. MethodsIntracellular accumulation of MC-LR (0.1-10 {micro}M, 3 hour) was measured in human cytotrophoblasts (JAR, BeWo) and extravillous trophoblasts (HTR-8/SVneo) by western blotting for MC-LR-adducted proteins. Organic anion transporting polypeptide (OATP) involvement was tested using cyclosporin A (10 {micro}M), an OATP inhibitor, before exposure to the OATP substrate or MC-LR. Cells were also cultured under 3%, 8%, or 20% O2 to induce hypoxic responses or treated with forskolin (a potent intracellular cAMP inducer) to stimulate cell fusion before MC-LR exposure. ResultsMC-LR accumulated in all three placenta cell lines in a concentration-dependent manner. Cyclosporin A reduced MC-LR uptake by 57% in JAR cells, confirming OATP-mediated transport. Low O2 increased OATP4A1 expression and function but reduced protein phosphatase expression, decreasing MC-LR-bound proteins by 52-72%. Forskolin increased OATP4A1 expression and enhanced MC-LR uptake >2.5-fold. ConclusionMC-LR enters placental trophoblasts via active OATP transport, likely OATP4A1, and uptake increases under hypoxia and trophoblast fusion.

pharmacology and toxicology↗

bioRxiv2026

A New Information Theoretic Approach Shows that Mixture Models Outperform Partitioned Models for Phylogenetic Analyses of Amino Acid Data

Partitioned and mixture models are widely employed in Maximum Likelihood phylogenetic analyses of large genomic datasets. Comparing the fit of the two types of models has been challenging, because standard information-theoretic approaches cannot be applied. Mixture models are increasingly popular for the analysis of amino acid datasets and can lead to different conclusions compared to partitioned models. This raises an important question - which type of model tends to perform better? Susko et al. (2026) recently introduced the marginal Akaike information criterion (mAIC), which allows mixture models and partitioned models to be directly compared for the first time. Here, we use the mAIC and a range of other approaches to compare the fit of mixture and partitioned models across a diverse set of empirical datasets. We show that mixture models are universally favoured on amino acid datasets. This has important implications for interpreting empirical analyses and suggests that continued development of mixture models is an important avenue for future research.

evolutionary biology↗

bioRxiv2026

Microhomology-Mediated Tandem Duplication Drives Tandem Repeat Formation Across Life

Tandem repeats (TR) are common genomic elements that are highly variable and with major functional consequences. Yet, the evolutionary trajectory for their formation remains poorly understood. One proposed mechanism is microhomology-mediated tandem duplication (MTD), in which single-copy DNA segments flanked by microhomology undergo tandem duplication (TD) and can further expand into TRs. Although MTD was first identified in the fission yeast Schizosaccharomyces pombe, its universal occurrence and postulated role in TR evolution have not been established. Using whole-genome deep sequencing and new analytical tools, we show that MTDs occur de novo universally across bacteria, archaea, fungi, and viruses. Further analysis of 2,245 reference genomes and millions of isolate genomes from 103 prokaryotic and eukaryotic microbial species, combined with human population TD data, somatic-germline mutations, and disease-associated variants, reveals that MTDs are consistently the dominant TD-forming mechanism across domains of life. Evidence suggests that MTDs have initiated the formation of the majority of existing TRs in genomes. Importantly, MTDs also prevail in human pathogenic TR mutations, including those linked to cancers. Mechanistically, deletion of the conserved mutator gene Rad27 specifically increased de novo MTD frequency in the budding yeast Saccharomyces cerevisiae, implicating Rad27-mediated Okazaki fragment maturation in MTD formation. These findings establish MTD as a universal and functionally significant mechanism for TR genesis. Graphic abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=121 SRC="FIGDIR/small/708716v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@db9ff1org.highwire.dtl.DTLVardef@e1a14corg.highwire.dtl.DTLVardef@124be79org.highwire.dtl.DTLVardef@15531ea_HPS_FORMAT_FIGEXP M_FIG C_FIG Significance StatementMicrohomology-mediated tandem duplications (MTDs) represent a universal mechanism driving tandem repeat formation across all domains of life--from viruses to humans. These duplications initiate genome evolution by expanding into functional tandem repeats and are the predominant form of pathogenic tandem duplications in human cancers and heritable disorders. Critically, disruption of the conserved Okazaki fragment processing pathway promotes MTD formation, establishing a fundamental link between DNA replication fidelity and genomic plasticity.

microbiology↗

bioRxiv2026

Nanopore sequencing reaches amplicon sequence variant (ASV) resolution

Sequencing of ribosomal marker genes remains a cornerstone for profiling complex microbial communities. In recent years, there has been a shift from Illumina to long-read technologies, including PacBio and Oxford Nanopore Technologies (ONT). ONT is attractive due to its low startup cost and portability; however, historically high error rates have prevented direct amplicon sequencing variant (ASV) generation from raw nanopore reads. This has forced most workflows to rely on mapping raw reads against reference databases constraining analyses to taxa covered by these. With recent improvements in ONT sequencing accuracy, we sought to challenge this view by sequencing samples of increasing complexity using primer sets targeting amplicons of different lengths, and by sequencing the exact same PCR libraries on both PacBio and ONT. We demonstrate that error-free ASVs can now be generated directly from raw nanopore reads using standard denoising algorithms originally developed for Illumina data. Current ONT read quality enables reliable reconstruction of amplicons spanning [~]250 bp to [~]4,200 bp and allows resolution of intragenomic rRNA gene variants. These results extend beyond simple mock communities to complex fecal, anaerobic digester, activated sludge, and soil samples. When sequencing depth is sufficient, ONT accurately recovers all or nearly all intra-genomic 16S rRNA gene copy variants, showing perfect sequence identity to curated reference sequences in mock communities and to ASVs inferred from PacBio data in complex communities. Across the primer sets, ONT required higher sequencing depth than PacBio to fully resolve the communities, with this requirement increasing with amplicon length. For complex samples, ONT required approximately 2-3x more reads for V4 ([~]250 bp) and V1-V3 ([~]500 bp), 4.1-5.6x more reads for V1-V8 ([~]1400 bp), and 25-42x more reads for rRNA operon (OPR) amplicons ([~]4200 bp). Consequently, sequencing complex communities with OPR primers on ONT is currently not feasible due to the unrealistically high read depth required. This study provides evidence that ONT amplicon sequencing has matured to the point where true ASV-resolved profiling is practically and economically feasible, moving ONT amplicon analysis beyond reliance on OTU clustering or reference alignment to enable application in environments lacking comprehensive reference databases. Key FindingsO_LIIt is now straightforward to generate ASVs on ONT platforms (250-4200 bp) C_LIO_LIONT can resolve intragenomic 16S rRNA gene variants C_LIO_LIASV recovery is successful in both simple and complex communities C_LI

bioinformatics↗

bioRxiv2026

Geometric-aware and interpretable deep learning for single-cell batch correction via explicit disentanglement and optimal transport

Single-cell RNA sequencing enables high-resolution characterization of cellular heterogeneity, yet integrating datasets from diverse sources remains challenging due to batch effects. Current methods rely on implicit feature disentanglement and and lack geometric constraints, often result in under-correction, over-correction, or compromised biological fidelity. Here, we present iDLC, an interpretable deep learning framework that performs dual-level correction through explicit feature disentanglement and optimal transport-regularized adversarial alignment. iDLC separates biological and technical components within a structured latent space, then leverages high-confidence mutual nearest neighbor pairs to guide geometrically constrained distribution alignment. Systematic evaluation across pancreatic cancer datasets with varying batch effect intensities, multi-source human immune cells, and large-scale cross-species atlases demonstrates that iDLC robustly eliminates complex batch effects while preserving fine-grained cell subtypes, continuous developmental trajectories, and rare populations. The framework scales efficiently to datasets exceeding one million cells and consistently outperforms existing methods in both batch correction and biological conservation metrics. iDLC provides a principled and reliable tool for constructing unified single-cell reference atlases across diverse experimental conditions and biological systems.

bioinformatics↗

bioRxiv2026

Neurons in the Human Substantia Nigra Respond to Cognitive Boundaries and Predict Memory

Segmenting mnemonic episodes from continuous experience is a key aspect of human episodic memory. The brain constantly forms predictions about what will happen next based on previous experience and knowledge, and prediction errors are thought to signal when a new event begins (cognitive boundaries). Dopamine has been closely linked to prediction error signals, yet it remains unknown how human midbrain neurons are modulated by cognitive boundaries and how their responses influence memory. To address these questions, we recorded activity of individual neurons in the human substantia nigra, a critical brain structure for dopamine production and regulation, while participants undergoing deep brain stimulation surgery watched a series of clips embedded with cognitive boundaries and performed a recognition memory task. We found that neural activity in the substantia nigra was robustly modulated by cognitive boundaries during clip viewing. Moreover, a subset of these boundary-responsive neurons also differentiated novel from familiar images during recognition, and their firing rates were indicative of participants memory success. These findings reveal that neurons in the human substantia nigra carry boundary- and novelty-related signals consistent with prediction error mechanisms that influence the encoding and retrieval of episodic memories.

neuroscience↗

bioRxiv2026

A national baseline for methane sink habitats and methanotroph diversity

Methane emissions account for nearly a third of the Earths effective radiative forcing, with methanotrophs playing a critical role in mitigating emissions by oxidising methane in diverse environments1. Despite their ecological importance, methanotrophic diversity and environmental distribution remain incompletely characterised due to cultivation challenges, incomplete or low-quality metagenome-assembled genomes, and limited taxonomic resolution in marker gene surveys. Here, we present a national study of the biogeography of novel and known methanotrophs across Denmarks major natural, urban and agricultural habitats, using genome-resolved classification of 10,683 metagenomes2 and 102 new methanotrophic species3. By linking metabolic potential to habitat-specific distributions, we reveal uncharacterised methanotrophs as dominant in natural ecosystems. These findings provide a comprehensive baseline of methanotroph diversity, reveal clear contrasts between natural and disturbed habitats, and highlight candidate species and habitats for future methane-mitigation strategies.

microbiology↗

bioRxiv2026

Shared Maturation Pathways of HIV-1 Envelope-reactive V3-glycan bnAb Lineages in Human and Rhesus Macaque

ABSTRACTUnderstanding broadly neutralizing antibody (bnAb) lineage development in rhesus macaques (RMs) infected with Simian-HIV (SHIV) may inform HIV-1 vaccine designs. We analyzed HIV-1 envelope-antibody coevolution in 18 RMs infected by SHIV.BG505 (subtype A) and found highly conserved patterns of antibody recognition and Env escape, including in three animals that developed V3-glycan bnAbs. From one RM with V3-glycan targeted plasma breadth, we isolated 203 members of a single clonal Ab lineage designated DH1030. DH1030 Abs demonstrated striking genetic, functional and structural similarities with the human V3-glycan bnAb lineage DH270, which was isolated from an individual with subtype C HIV-1 CH848 infection. Notably, human-DH270 and macaque-DH1030 bnAbs shared early improbable mutations in HCDR2 that were critical for bnAb development. Thus, key improbable mutations and convergent patterns of antibody evolution and epitope recognition were shared across primate species and distinct HIV-1 subtypes, findings that may be leveraged in new HIV-1 vaccine designs. ONE SENTENCE SUMMARYBroadly neutralizing antibodies targeting HIV-1 envelope surface protein develop via a common maturation pathway across primate phylogeny.

immunology↗

bioRxiv2026

Exploring Multi-Scale Local and Global Features in Whole Slide Images Using State Space Models

Whole slide image (WSI) classification is crucial in computational pathology, yet the gigapixel scale of WSIs makes it challenging to extract discriminative and compact WSI-level features for disease diagnosis. In this paper, we propose MambaWSI, a novel method that leverages the state space model (SSM) for WSI classification by exploring multi-scale local and global features. Unlike existing approaches that sequentially traverse WSI tiles and rely on vanilla SSMs for long-range dependency modeling, we exploit a traversal strategy in a higher-dimensional discrete space that preserves spatial proximity, enabling a first-local-then-global feature extraction process. Furthermore, to align with the clinical workflow of pathologists when examining WSIs at multiple scales, we propose a two-stage hierarchical fusion strategy: inter-scale feature alignment and aggregation, followed by attention-based fusion across magnifications, integrating complementary information from multiple magnifications. Experiments on two datasets demonstrate that MambaWSI outperforms state-of-the-art methods in classification performance.1

pathology↗

bioRxiv2026

PRSS56 acts as an intrinsic retinal signal driving postnatal ocular axial growth and myopia susceptibility

Myopia is a leading cause of visual impairment worldwide, and high myopia markedly increases the risk of irreversible vision loss. Although visual experience guides postnatal ocular elongation, the role of intrinsic retinal growth signals remains poorly defined. Here we identify the serine protease PRSS56 as a retinal factor that promotes ocular axial growth beyond early development. Using genetic mouse models, we show that conditional inactivation of Prss56 in Muller glia reduces axial length and causes hyperopia even under dark-rearing conditions, demonstrating that PRSS56 drives axial elongation independently of light-evoked visual input during emmetropization. Conversely, Muller glia-specific overexpression of Prss56 induces axial elongation in a proteolysis-dependent manner, supporting its role as an autonomous retinal growth signal. In concordance, human genetic analyses reveal that the common PRSS56 variant rs2853447 is associated with increased axial length in individuals with myopia and high myopia, but not in non-myopes, suggesting that this variant confers a selective growth advantage in individuals predisposed to ocular elongation. Functional genomic analyses further identify a myopia-associated variant, rs2741297, within a retinal enhancer in intron 4 of PRSS56 marked by open chromatin and transcription factor occupancy. Together, these findings establish PRSS56 as an intrinsic retinal growth factor that functions beyond early eye development and support a model in which genetic and environmental factors converge on retinal pathways to modulate myopia susceptibility.

genetics↗

bioRxiv2026

Diet-Driven Gut Microbiome Differences Between Cohabiting Han and Yi Ethnic Groups in Liangshan, China

BackgroundWhile ethnic variations in gut microbiota are well-documented, their persistence in genetically distinct populations sharing the same geographic environment remains poorly understood. This study investigates the Han and Yi ethnic groups cohabiting rural Southwest China, where contrasting dietary traditions persist under identical environmental conditions. MethodsWe analyzed fecal samples from 100 healthy adults (50 Yi/50 Han) using 16S rRNA gene sequencing (V3-V4 region). Dietary intake was quantified via three 24-hour recalls validated with plasma biomarkers. Multivariate analyses (DESeq2, PERMANOVA) controlled for age, sex, and BMI covariates. ResultsYi individuals exhibited significantly higher Prevotellaceae (log2FC=1.82, padj=0.028) and Succinivibrionaceae (log2FC=2.15, padj=0.013) abundances, corresponding to their buckwheat-rich diet (58.5 {+/-} 12.3% vs Han 3.3{+/-}1.8%, p<0.001) Han microbiota showed enriched Bacteroidaceae (log2FC=1.24, padj=0.041), associated with higher animal fat intake (23.6% vs Yi 1.8%, p<0.001) Dietary factors (buckwheat/animal fat intake) explained greater microbiota variation than ethnic genetic ancestry (PERMANOVA R{superscript 2}=0.10 vs 0.07, p < 0.05) ConclusionCohabiting Han and Yi populations maintain distinct gut microbiota compositions primarily driven by dietary differences. These findings highlight diet as a stronger determinant than genetic ancestry in shaping microbial communities under shared environments. Future studies should validate these observations with metagenomic sequencing.

microbiology↗

bioRxiv2026

Glucose is a ligand-like trigger for secretion of postprandial GLP-1

Glucagon-like peptide 1 (GLP-1) is secreted from the intestinal L cells in a glucose-dependent manner. However, the mechanism underlying how glucose stimulates the secretion remains unclear. Here, we found that glucose at postprandial concentrations near the Km of GK for glucose ([~]10 mM), as well as nonmetabolizable glucose analogs, triggers GLP-1 secretion by intestinal L cells through directly binding to glucokinase (GK), without increasing intracellular ATP levels. We also show that in postprandially high glucose, glucose-bound GK interacts and inhibits KATP, as assessed by immunoprecipitation and FRET-FLIM analyses, as well as patch clamping. In addition, we have utilized GK mutants identified in diabetics, demonstrating that those mutants defective in binding to glucose impair GLP-1 secretion in however high glucose, whereas mutants constitutively bound to glucose with defects in catalysis, promote GLP-1 secretion even in low glucose. Furthermore, the KATP mutant unable to bind to GK blocks GLP-1 secretion in high glucose. We have also provided evidence showing that sodium-glucose cotransporter 1 (SGLT1) plays an important role in the basal secretion of GLP-1, but not in high glucose. We have thus revealed that glucose the molecule itself and GK act as a ligand and the receptor, respectively, to induce GLP-1 secretion in response to high glucose, providing new therapeutic avenues targeting metabolic diseases.

biochemistry↗

bioRxiv2026

Natural variation of gibberellin levels in maize tissues across North America

Gibberellins (GA) are endogenous phytohormones that regulate growth and development throughout the plant lifecycle. While GA has been extensively studied under controlled conditions for their fundamental role in plant adaptation and agronomic trait development, field-based data on their natural variation across diverse agricultural genotypes and environments remains limited. To address this knowledge gap, we analyzed bioactive gibberellin A1 (GA1) and gibberellin A4 (GA4) across multiple maize hybrids grown in diverse field environments using high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS). This study provides comprehensive quantitation of GA1 and GA4 levels in maize tissues across diverse commercial hybrids grown under standard agricultural practices, revealing hormonal variation due to genetic background and environmental conditions. Our findings demonstrate that GA1 and GA4 concentrations from conventional maize samples varied across tissue types and field sites. Analysis of variance components indicated that the site variation was statistically significant at the 5% significance level in five out of ten GA and tissue combinations, while the genetic component was significant only for GA4 in grain samples. Notably, significant interaction between hybrid and site was observed for both GA1 and GA4 in stalk tissue. Positive correlations between GA1 and GA4 were observed consistently across tissues except root. These results underscore the common metabolic pathways involved in regulating GA levels in maize and provide the first comprehensive dataset of GA1 and GA4 variation under real-world agricultural conditions. Our findings offer insights into the interplay between genetics, environment, and hormonal regulation in maize and suggest potential targets for breeding programs aimed at improving agronomic traits such as yield.

plant biology↗

bioRxiv2025

Signaling induced biophysical disruption of repressed chromatin domains drives immune cell fate

Cell fate transitions require signal-induced chromatin derepression, yet mechanisms governing transitions from repressed to active chromatin states are poorly understood. We discover, at fate-defining genes across immune cell types, a signal-induced histone code, and describe domains of H3 serine 28 phosphorylation (H3S28ph) spanning architectural features, often coincident with repressive H3 lysine 27 trimethylation (H3K27me3). Employing biophysical, single cell, and functional approaches to study signal-induced cell differentiation in the immune system, we uncover epigenomic transitions and cell fate choices precipitated by histone phosphorylation (H3ph). Mechanistically, H3ph overrides Polycomb Repressive Complex 2 (PRC2) chromatin repression, biophysically disrupts polynucleosome compaction, and promotes loss of H3K27me3, while increasing activating H3K27 acetylation and H3K36 dimethylation to drive domain interactivity and stabilize transcription. We demonstrate the activity of H3ph in several cell fate transitions and illuminate biophysical mechanisms enabling rapid signal-activated chromatin derepression, processes with general relevance for cellular differentiation and activation.

immunology↗

bioRxiv2025

Hepatocyte MLKL Drives Obesity-Driven Hepatocellular Carcinoma Progression via Mitochondrial Dysfunction Independent of Necroptosis in MASLD

Background and AimsMetabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of hepatocellular carcinoma (HCC), particularly in obesity, yet mechanisms linking hepatocyte dysfunction to tumorigenesis remain unclear. Mixed lineage kinase domain-like protein (MLKL), the effector of necroptosis, is elevated in MASLD, but its hepatocyte-intrinsic role in obesity-driven MASLD-HCC is unknown. Approach and ResultsUsing a long-term Western diet (WD)-induced MASLD-HCC model in hepatocyte-specific MLKL knockout (MlklHepKO) mice, we defined MLKLs hepatocyte-intrinsic function. WD increased hepatocyte MLKL protein expression without detectable necroptosis activation, indicating a necroptosis-independent role. MLKL deficiency did not alter WD-induced inflammation, fibrosis, or liver injury but increased hepatic lipid accumulation while reducing lipotoxic lipid species and preserving mitochondrial function. WD-fed MlklHepKO mice developed fewer and smaller tumors with reduced incidence, multiplicity, proliferation, and stemness. Transcriptomic analysis revealed upregulation of mitochondrial oxidative phosphorylation pathways in MlklHepKO livers. WD suppressed the mitochondrial fusion protein and tumor suppressor MFN2, whereas MLKL deficiency restored MFN2 expression post-translationally. In HCC cells, MLKL deletion reduced proliferation, improved mitochondrial respiration, and decreased glycolysis; these effects were reversed by MFN2 deletion. MLKL localized to nuclear and mitochondrial compartments, consistent with organelle-intrinsic functions. The human MLKL inhibitor necrosulfonamide (NSA) suppressed HepG2 xenograft growth, and elevated MLKL expression in human HCC correlated with poorer overall survival. ConclusionsHepatocyte MLKL promotes MASLD-associated HCC through a non-necroptotic mechanism involving MFN2 suppression, impaired mitochondrial function, and increased tumor proliferation and stemness. These findings identify MLKL as a potential therapeutic target in MASLD-associated HCC.

cancer biology↗

bioRxiv2025

A programmable mRNA platform for miRNA detection via miRNA-mRNA2 triplex-mediated ribosomal frameshifting

Programmed -1 ribosomal frameshifting (-1 PRF) is a recoding mechanism utilized by viruses to expand their coding capacity and modulate the stoichiometric ratio of -1 frame and 0 frame translation products. The stability of mRNA secondary structure at the ribosomal entry site within the frameshifting stimulating elements (FSEs) determines the frameshifting efficiency. Here, we report the development of a programmable mRNA-based platform that detects specific mature microRNA (miRNA or miR) by converting their presence into a quantifiable protein output through miRNA-triggered -1 PRF. We designed a triplex-forming mRNA (TF-mRNA) platform to selectively trap target miRNAs through the formation of major-groove mRNA-miRNA-mRNA (miR-mRNA2) triplexes. Bio-layer interferometry and fluorescence binding studies confirmed that TF-mRNA forms stable complexes with cognate miRNAs with low nanomolar affinity and prolonged dissociation rate. Critically, the formation of miR-mRNA2 triplex robustly stimulated ribosomal frameshifting in a cell-free dual-luciferase translation system, acting as a miRNA-dependent molecular switch. The generality of this TF-mRNA platform has been verified for several disease-associated purine-rich miRNAs, and it is suitable for targeting a wide range of other purine-enriched miRNAs. This programmable TF-mRNA platform establishes a foundation for developing novel diagnostic tools and synthetic biology circuits that convert the presence of miRNA into a quantifiable protein output. TOC Figure O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=106 SRC="FIGDIR/small/690164v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@1d6d9f7org.highwire.dtl.DTLVardef@8008e6org.highwire.dtl.DTLVardef@1c8344borg.highwire.dtl.DTLVardef@e153ec_HPS_FORMAT_FIGEXP M_FIG C_FIG

synthetic biology↗

bioRxiv2025

Rapid and Complete Inactivation of Enveloped Viruses by Electrochemical Disinfection: Unraveling the Contribution of Reactive Chlorine Species

Waterborne viruses pose significant threats to global water safety. Electrochemical (EC) disinfection is considered a promising next-generation technology to address this challenge. However, its efficacy against enveloped viruses remains inadequately under-stood. In this study, we employed bacteriophage Phi6 as a surrogate to systematically eval-uate the inactivation efficiency and damage mechanisms of enveloped viruses in a flow-through EC reactor. Experimental results indicated that Phi6 was more susceptible to EC disinfection than common bacterial surrogates. Comprehensive damage was observed across all major viral components, including structural proteins, the lipid envelope, and the RNA genome. The electrogenerated reactive chlorine species (RCS) were identified as the primary agent responsible for this inactivation, exhibiting higher reactivity than conven-tional free chlorine. Furthermore, radical chlorine species were also confirmed to be pro-duced during EC disinfection, contributing to rapid and extensive viral inactivation. This study demonstrates the feasibility of EC disinfection for inactivating enveloped viruses and provides deeper mechanistic insights into its highly efficient viral inactivation performance. SYNOPSISOur results elucidate the rapid inactivation and thorough damage of the enveloped virus surrogate Phi6 by electrogenerated reactive chlorine species during electrochemical disinfection. TOC O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=104 SRC="FIGDIR/small/688411v1_ufig1.gif" ALT="Figure 1"> View larger version (46K): org.highwire.dtl.DTLVardef@7e8c29org.highwire.dtl.DTLVardef@23fcedorg.highwire.dtl.DTLVardef@b26312org.highwire.dtl.DTLVardef@1864ab1_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗