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LI, Y.

Publications and source records attributed to LI, Y..

At least 19 recordsLinked to original sources

Salt Stress Shifts Isatis indigotica to Prioritize Defense over Goitrin Biosynthesis

Soil salinization threatens the cultivation quality of Isatis indigotica, a medicinal plant whose root bioactivity depends on the glucosinolate-derived compound (R,S)-goitrin. Although moderate abiotic stress is widely assumed to stimulate secondary metabolite accumulation, the temporal dynamics of goitrin biosynthesis under salt stress remain poorly understood. This study quantified goitrin content across four NaCl concentrations (100 - 400 mmol/L) and four time points (2, 6, 12, and 24 h). Time-series transcriptome sequencing was performed under 100 mmol/L NaCl. Contrary to prevailing assumptions, goitrin content declined progressively from 2 to 12 h before partially recovering at 24 h, indicating that salt stress transiently suppresses goitrin accumulation rather than promoting it. Transcriptomic analysis identified 7 glucosinolate biosynthesis genes whose expression positively correlated with goitrin content (p < 0.05), and 6 salt stress-responsive genes negatively correlated with goitrin content (p < 0.05). These opposing patterns suggest that stress defense is transiently prioritized over biosynthesis, with partial metabolic recovery as plants adapt. These findings reveal a defense-biosynthesis trade-off mechanism in I. indigotica roots and provide a transcriptomic framework for understanding how abiotic stress reshapes secondary metabolism in medicinal plants.

plant biology↗

Multiomics Characterization Identifies S1P-secreting USSHigh Skeletal Muscle Stem Cells as Essential Drivers of Niche Remodeling and Muscle Regeneration

Acutely induced cellular senescence is increasingly recognized as vital for tissue repair but the precise roles of senescent cells in skeletal muscle regeneration remain paradoxical. Here, using single-cell RNA sequencing and a Unified Senescence Score (USS) methodology, we identify a distinct USSHigh (USSHi) muscle stem cell (MuSC) subpopulation emerging in early phase of acute injury induced muscle regeneration. Isolation via the surface marker MHCII enables characterization of these cells as exhibiting canonical senescent-like features. Further characterization through integrated transcriptomics, proteomics, and secretomics reveals their highly pro-inflammatory secretory capacity. Moreover, lipidomic profiling uncovers that the USSHi MuSCs undergo profound sphingolipid metabolic remodeling to generate upregulated bioactive lipid Sphingosine-1-phosphate (S1P). In vivo specific ablation of this subpopulation using a Pax7-CreERT; Ccl2-LSL-DTA genetic strategy significantly impaired muscle regeneration. Furthermore, spatial transcriptomics and cell-cell communication analyses revealed that USSHi MuSCs act as critical niche modulators, directing crosstalk with multiple cell types. Specifically, S1P is essential for mediating direct USSHi interaction with endothelial cells and USSLo cells to promote endothelial angiogenesis and MuSC expansion in the regenerating muscle. Crucially, exogenous S1P rescues the regenerative deficits caused by USSHi MuSC ablation. Altogether our findings define a senescent-like MuSC population emerging in acute injury induced muscle regeneration and provide definitive evidence to demonstrate the positive role of these cells in enhancing muscle repair via their robust secretory phenotypes and inter-cellular communicative capacity.

cell biology↗

Total Biosynthesis of Pseudomonas aeruginosa-Derived Azabicyclocarbamates Identifies Distinct Dehydrating Condensation Family Proteins

Bacterial azabicyclocarbamates and related pyrrolizidine alkaloids play important roles in microbial interactions, and are scaffolds of therapeutic potential. Their biosynthesis involves a bimodular non-ribosomal peptide synthetase (NRPS), as well as a Baeyer-Villiger monooxygenase and tailoring enzymes, the latter contributing to the structural diversification of these compounds. Azetidomonamide A, a core metabolite produced by the major human opportunistic pathogen Pseudomonas aeruginosa, is a rare 4,7-bicyclocarbamate involved in modulating bacterial virulence that belongs to a unique family of natural products targeting ClpP proteases. In this study, we elucidated the full set of reactions leading to the 7-membered cyclocarbamate warhead, and reconstituted in vitro the biosynthesis of azetidomonamide A. Notably, this approach allowed for detailed characterization of a condensation (C) domain-catalyzed online dehydration via chemical capture of NRPS-tethered intermediates. Furthermore, we identified the dehydratase AzeD as the founding member of a distinct group of standalone proteins of the C domain family. Via combined structural, docking and biochemical analyses, we provided evidence that AzeDs catalytic mechanism is distinct from that of dehydrating C domains, further expanding the known chemistry of these key biosynthetic enzymes.

biochemistry↗

Multiscale Mechanisms of Human Memory Modulation by Deep Brain Stimulation

The highly variable effects of deep brain stimulation (DBS) on cognition highlight a fundamental gap in our understanding of how external perturbations interface with the brains ongoing, task-engaged state. The current study addressed this challenge by combining intracranial EEG recordings with hippocampal DBS stimulation in human participants during spatial sequence memory task. We found 50 Hz stimulation targeting hippocampal white matter enhanced memory performance, whereas 5 Hz stimulation targeting hippocampal gray matter impaired memory. These opposing behavioral outcomes were both governed by two dissociated mechanisms: a region-specific modulation of theta rhythms in an engagement-dependent fashion, and a global modulation of the fidelity of memory representations across the cortex. Our results suggest targeted stimulation can concurrently fine-tune specialized circuits and govern the brains global state, which not only offers a novel roadmap for understanding how external inputs shape human cognition, but also helps to design precise, state-dependent neuromodulation therapies.

neuroscience↗

Partial Differential Equation (PDE) Based Spatial Pharmacometrics in NONMEM: Method of Lines (MOL) Implementation With AI-Assisted Model Development

Spatial heterogeneity in drug distribution, particularly within solid tumors, can compromise target engagement and drive therapeutic failure in oncology, yet it is rarely represented in population pharmacokinetic (PopPK) analyses. Standard empirical compartmental or semi-mechanistic models assume "well-stirred" tissues, and physiologically based pharmacokinetic (PBPK) models focus on organ-level distribution; neither framework directly captures intra-tumoral drug concentration gradients. Reaction-diffusion PDEs provide a mechanistic representation of penetration, spatial gradients, and washout, but routine implementation in NONMEM has been limited by operational complexity in the pharmacometrics field: native numerical templates (e.g., DOPDE/DOEXPAND-style expansions offered by NONMEM) remain cumbersome, and manual MOL coding quickly becomes labor-intensive and error-prone as geometry, initial and boundary conditions, and grid resolution change. With the emergence of advanced AI technologies, this operational barrier can be substantially reduced. This work presents a streamlined workflow for implementing spatial PDEs in NONMEM via AI tools. Using AI-assisted explicit code generation, we show how continuous spatial models can be systematically translated into coupled ordinary differential equation (ODE) systems that are directly executable in NONMEM, while keeping the resulting $DES block implementation transparent and reviewable. We illustrate the approach with one-dimensional, spherical, and two-dimensional rectangular reaction-diffusion models and provide practical guidance for iterative refinement across discretization and boundary-condition settings using appropriate prompt engineering with AI. Although AI does not reduce stiffness, remove numerical constraints, or resolve identifiability limitations, it reduces the engineering and maintenance burden of large MOL systems. When coupled with disciplined verification and appropriate scientific restraint, AI-assisted code generation can make PDE-based spatial pharmacometrics in NONMEM practical, transparent, and maintainable--supporting wider adoption of spatial modeling to interrogate target-site exposure and penetration-driven efficacy.

pharmacology and toxicology↗

Spatial proximity sequencing maps developmental dynamics in the germinal center

Spatial profiling of proteins and protein interactions is essential for immunology, signaling, development, and cancer. We present Spatial Proximity-Sequencing (Sprox-seq), a multi-omic technique that simultaneously measures proteins, protein complexes and mRNAs, where location of each molecule is also recorded. Sprox-seq profiled 32 proteins, 528 pairwise protein interactions and thousands of mRNAs across human tonsil tissues and germinal centers. Mapping protein interactions recapitulated RNA-defined tissue architecture in germinal centers, but also revealed much higher interaction complexity in the Light zone. Developmental trajectories inferred from protein interactions uncovered a B cell maturation pathway distinct from that inferred by RNA. Integrated protein-complex and mRNA analysis related spatially-enriched complexes with immune regulation and mitotic gene-expression pathways. Furthermore, Sprox-seq captured B cell-Follicular Dendritic Cell interactions mediated by the protein complex VLA-4-VCAM1 in the Light zone. Sprox-seq provides a multi-modal view of cell states and a powerful tool for studying protein and cellular interactions across tissues.

immunology↗

Decoding cancer metabolism: A pan-cancer proteomics perspective

Metabolic reprogramming fuels cancer progression, but whether common metabolic patterns exist across tumor types remains elusive. To address this, we developed parseMetab, an R package that integrates large-scale proteomic, transcriptomic, and spatial transcriptomic datasets from 24 human cancers and 3,226 samples to map pan-cancer metabolic dysregulation. Strikingly, glycan biosynthesis pathways - especially those driving fucosylation and sialylation - were consistently upregulated, while early sugar nucleotide precursors were suppressed. Nucleotide metabolism was broadly enhanced, uncovering conserved metabolic programs that enable tumor growth, adaptation, and immune evasion. Our results highlight universal metabolic vulnerabilities that may be therapeutically exploited across diverse cancer contexts. Significance statementWhile metabolic reprogramming is a known hallmark of cancer, identifying universal patterns across diverse tumor types remains a major challenge. We developed parseMetab, a computational framework to integrate large-scale proteomic and transcriptomic data from over 3,200 samples across 24 human cancers. Our analysis reveals a striking, conserved "glyco-switch": tumors consistently prioritize the production of complex, immune-evading surface sugars (fucosylation and sialylation) while depleting their own internal sugar precursor pools. Furthermore, we demonstrate that nucleotide metabolism is broadly hyperactivated across nearly all studied malignancies. By defining these ubiquitous metabolic signatures, this study uncovers conserved vulnerabilities that transcend specific cancer types, providing a map for developing broad-spectrum metabolic therapies to combat tumor growth and immune evasion.

cancer biology↗

OmicsNavigator: an LLM-driven multi-agent system for autonomous zero-shot biological analysis in spatial omics

Translating high-dimensional, spatially resolved molecular datasets into testable biological findings remains a major research bottleneck. Here, we present Omic-sNavigator, an autonomous large language model-powered system for end-to-end data exploration and hypothesis validation on spatial omics data. OmicsNaviga-tor reasons directly over the multi-modal inputs of spatial omics data, including visual and molecular signatures, to perform knowledge-guided annotation of spatial structures. We show that by transforming high-dimensional data into textual interpretations, OmicsNavigator enables zero-shot semantic retrieval of tissue biomarkers and the reconstruction of patient-level disease profiles from raw omics observations. Furthermore, OmicsNavigator features an objective hypothesis validation engine governed by pre-registered, human-audited blueprints. By validating the system across datasets spanning diverse pathological conditions including diabetic kidney disease, kidney transplant rejection, and COVID-19 pulmonary pathology, we demonstrate that OmicsNavigator generates evidence-based, human-readable insights from spatial omics data, with potential to accelerate spatial biology discoveries.

bioinformatics↗

ODFormer: a Virtual Organoid for Predicting Personalized Therapeutic Responses in Pancreatic Cancer

Pancreatic cancer (PC) patient-derived organoids (PDOs) faithfully recapitulate therapeutic responses but face clinical translation barriers, including high costs and technical complexity. To address these problems and the lack of frameworks for PDO-based drug-response assays, we developed ODFormer, a computational framework that simulates PC PDOs to predict clinically actionable, patient-specific drug responses by integrating transcriptomic and mutational profiles. ODFormer first employed two encoders, pretrained on 30,000 pan-cancer bulk transcriptomics and 1 million PC single-cell profiles respectively, to distil tissue-and organoid-specific representations. Then, trained on our curated 14,000 PDO drug-response assay (across 183 PDOs and 98 drugs) using a transformer-augmented hybrid contrastive network, ODFormer significantly outperformed state-of-the-art methods, notably achieving a PCC >0.9 in predicting standardized drug response. Multi-cohort retrospective analyses further demonstrated that ODFormer-guided personalized therapy significantly improves clinical outcomes, without requiring physical organoid assays. Furthermore, ODFormer identified novel clinico-biological PC subtypes and revealed therapy resistance biomarkers by stratifying predicted responders and non-responders. These were validated using independent datasets including TCGA-PDAC. Notably, ODFormer-guided treatment efficacy showed high concordance with prospective clinical responses by CA19-9.

bioinformatics↗

Emergence of a New ST617 Hypervirulent Klebsiella pneumoniaewith ESBL+ and Strong Biofilm Forming Ability in China

The increasing infections caused by hypervirulent Klebsiella pneumoniae (hvKP) resistant to carbapenem, broad-spectrum {beta}-lactam and colistin has posed great challenges to global public health. However, the typing and detailed molecular features of the multi-drug resistant hvKP remain to be improved. Here, we characterized a broad-spectrum {beta}-lactam-resistant K. pneumoniae ST617 isolate that has not been previously reported to cause severe disease in China. We obtained the whole-genome sequence of one K. pneumoniae ST617 isolate--HZ7--from a patient with bile duct infection. Phylogenetic reconstruction was performed to investigate the possible host evolutionary origin of HZ7, and the virulence property was studied in comparison with the nearest ST617 neighbours--YZ strains isolated from patient blood infections. Our studies indicated that the HZ7 is an ESBL+ Kp that is likely evolved from environmental or animal-derived sources. Importantly, the virulence assay showed that HZ7 was highly virulent and compared with the well known hvKP strain--NTUH-K2044 and the highly virulent clinical strain ST11-K64--HZ54--isolated from a patient with severe pneumonia. In addition, HZ7 showed strong biofilm formation ability. Whole-genome sequencing analysis identified seven potential virulence genes in HZ7: kp7_000748, kp7_002156, kp7_002157, kp7_002158, kp7_002159, kp7_003103, kp7_003104, which are absent in K. pneumoniae patient isolates from Yangzhou and the environmental samples. Finally, transcriptomic analysis of HZ7 identified six genes--wcaJ, fimA, mrkH, pgaA, ugd, and gndA that are associated with biofilm formation. Given its high virulence likely associated with the seven unique genes acquired via horizontal transfer and strong biofilm forming ability, this strain should be closely monitored to prevent wider spread in the clinic.

microbiology↗

Gut meta-virome reveals potential zoonotic pathogens and environmental RNA viruses carried by non-human primates

The majority of human infectious diseases originate from mammals and are inherently zoonotic. Non-human primates (NHPs) are not only carriers of many zoonotic pathogens, but also the best intermediary for virus shift from harmless to harmful due to their similar phylogenetic relationship with humans. Knowledge of NHP viral composition and its underlying information can therefore provide an assessment of the risk of cross-species transmission and spillover of zoonotic diseases. However, studies that have successfully eliminated the effects of different natural habitat environments on viral carriage have been limited, making it difficult to identify which zoonotic viruses and potentially species-barrier-crossing viruses are carried by widely distributed NHP hosts. Here, we analyze viruses excreted in feces from NHP hosts and reveal the presence of possible zoonotic pathogens. Most of the viruses found come from plants that are eaten by them. Analysis of the evolutionary relationships of potential pathogens suggests that other clinical isolates are genetically correlated to HIV, PBV, and EV we identified. This study provides foundational data for surveillance of NHP enteroviruses that could help to be challenging to track potential human viruses carried by NHP in the absence of clinical surveillance. ImportanceAs a result of internationalization and other factors, many viruses have broken through the limits of geographical units and spread into human society, causing many emerging and re-emerging infectious disease hazards. However, the virus spreads and is by no means infectious to humans overnight. There is a phenomenon of host shift, in which the virus does not necessarily cause disease in an intermediate host, but causes significant damage when transmitted to humans. We focus on captive non-human primates, close relatives of humans in cities, because the phenomenon of host shifts is related to both biological similarity and geographical proximity of the host. Primates may carry zoonotic viruses and viruses that are currently incapable of infecting humans but have evolved with pathogenic potential. In summary, comprehensive viral surveillance and screening of captive nonhuman primates is necessary.

ecology↗

Chemically Induced Nuclear Pore Complex Protein Degradation via E3 Ligase TRIM21

Despite the exciting progress of the bifunctional degrader molecules, also known as proteolysis-targeting chimeras (PROTACs), the rapidly expanding field is still significantly hampered by the lacking of available E3 ligase ligands. Our research bridges this gap by uncovering a series of small-molecule ligands to the E3 ligase TRIM21 through DNA-Encoded Library (DEL) technology. We confirmed their interaction with TRIM21 using crystallography and demonstrated their anti-proliferative effects across various cancer cell types. Furthermore, proteomic studies identified that the mRNA Export Factor GLE1, and the Nuclear Pore Complex Protein NUP155, were significantly down-regulated upon TRIM21 ligand treatment. This degradation required TRIM21 and was ubiquitin-proteasome-dependent. More specifically, NUP155 was the primary target for the TRIM21 ligands, while GLE1 was considered a passenger target upon the initial degradation of NUP155. Using immunofluorescence techniques, we further demonstrated that the degradation of GLE1 and NUP155 proteins impaired the integrity of the nuclear envelope, leading to cell death. Highlighted by this research, a novel mode of action has been discovered for the TRIM21 E3 ligase ligand, acting as a monovalent degrader that triggers de novo interaction with functional complex proteins and induces their degradation.

cell biology↗

Tobacco smoke exposure is a driver of altered oxidative stress response and immunity in head and neck cancer

PurposeExposomes are critical drivers of carcinogenesis. However, how they modulate tumor behavior remains unclear. Extensive clinical data link cigarette smoke as a key exposome that promotes aggressive tumors, higher rates of metastasis, reduced response to chemoradiotherapy, and suppressed anti-tumor immunity. We sought to determine whether smoke itself can modulate aggressive tumor behavior in head and neck squamous cell carcinoma (HNSCC) through reprogramming the cellular reductive state. Experimental designUsing established human and murine HNSCC cell lines and syngeneic mouse models, we utilized conventional western blotting, steady state and flux metabolomics, RNA sequencing, quantitative proteomics and flow cytometry to analyze the impact of smoke exposure on HNSCC tumor biology. ResultsCigarette smoke persistently activated Nrf2 target genes essential for maintenance of the cellular reductive state and survival under conditions of increased oxidative stress in HNSCC regardless of HPV status. In contrast to e-cigarette vapor, conventional cigarette smoke mobilizes cellular metabolism toward oxidative stress adaptation, resulting in development of cross-resistance to cisplatin. In parallel, smoke exposure modulates both expression of PDL1 and the secretory phenotype of HNSCC cells through activation of NF-{kappa}B resulting in an altered tumor immune microenvironment (TIME) in syngeneic mouse models and altered PBMC differentiation that includes downregulated expression of antigen presentation and costimulatory genes in myeloid cells. ConclusionCigarette smoke exposome is a potent activator of the Nrf2 pathway and is a likely primary trigger for the tripartite phenotype of aggressive HNSCC consisting of: 1) reduced chemotherapy sensitivity, 2) enhanced metastatic potential and 3) suppressed anti-tumor immunity. Statement of significanceThe smoke exposome drives aggressive tumor behavior, treatment resistance and suppressed immunity through coordinated metabolic reprogramming. Successfully targeting this adaptation is critical to improving survival in smokers with head and neck cancer.

cancer biology↗

Elucidating the Diversity and Potential Function of Ribosomally Synthesized and Post-translationally Modified Peptides in the Human Microbiome

The human microbiome holds tremendous potential for generating specialized peptides, specifically ribosomally synthesized and post-translationally modified peptides (RiPPs), significantly affecting human health by mediating interactions with other microbes and the human host. However, the capacity of our microbiome to produce these peptides and their links with human health are poorly understood. This study systematically analyzes 306,481 human microbiota-associated genomes, uncovering a broad array of yet-to-be-discovered RiPPs. These RiPPs are distributed across various body sites but show a specific enrichment in the gut and oral microbiome. Big data omics analysis reveals that numerous RiPP families are inversely related to various diseases, suggesting their potential protective effects on health. For a proof of principle study, guided by biosynthetic prediction, nine autoinducing peptides (AIPs) were chemically synthesized for in vitro and ex vivo assay. Our findings revealed that five AIPs effectively inhibited the biofilm formation of disease-associated pathogens, with one demonstrating significant anti-inflammatory capabilities. Furthermore, when ex vivo testing gut bacteria from mice with inflammatory bowel disease, we observed that two AIPs could regulate the microbial community and reduce harmful species. These findings highlight the vast potential of human microbial RiPPs in regulating microbial communities and maintaining human health, emphasizing their potential for therapeutic development.

microbiology↗

Dynamic and topological properties of large-scale brain networks in rapid eye movement behavior disorder

IntroductionThere is a lack of research in the existing literature when it comes to analyzing the dynamics of resting-state functional magnetic resonance imaging to understand the underlying mechanisms of isolated rapid eye movement sleep behavior disorder (iRBD). This study aims to contribute to our understanding of abnormalities in brain network dynamics in iRBD and their association with alpha-synucleinopathy. Additionally, I employed graph theoretical metrics to obtain a topological insight into the brain network of iRBD. MethodsResting-state fMRI data from 55 iRBD patients and 97 healthy controls (HCs) were utilized. A sliding window approach, functional connectivity analysis, and graph theory analysis were applied to the data. I calculated the mean, standard deviation, skewness, and kurtosis of the time series for both dynamic functional connectivity (dFC) and four graph metrics (clustering coefficient, global efficiency, assortativity coefficients, and eigenvector centrality). Subsequently, I compared the those metrices between iRBDs and HCs. Relationships between clinical scales and abnormal dFC were assessed using a general linear model. ResultsiRBD patients exhibited abnormal mean dFC, particularly in the default mode network, sensorimotor network, basal ganglia network, and cerebellum. Kurtosis of dFC revealed abnormalities between the middle temporal gyrus and cerebellum. Group differences were also observed in the mean eigenvector centrality of the precentral gyrus and thalamus. ConclusionThe mean of dFC identified impairments putatively in movement functions and various compensatory mechanisms. Moreover, mean eigenvector centrality revealed topological changes in motor-related network in iRBDs. The use of kurtosis as a potential index for extracting dynamic information may provide additional insights into pathophysiology in iRBDs.

neuroscience↗

The exotic thymidine modification 5-hydroxymethyluridine in dinoflagellate Amphidinium carterae

Dinoflagellate chromosomes are extraordinary, as their organization is independent of architectural nucleosomes unlike typical eukaryotes and shows a cholesteric liquid crystal state. 5-hydroxymethyluridine (5hmU) is present at unusually high levels and its function remains an enigma in dinoflagellates chromosomal DNA. Here, we demonstrate that 5hmU exhibits content variations in different dinoflagellates and is generated at the poly-nucleotide level through hydroxylation of thymidine. Importantly, we identified the enzyme, which is a putative dinoflagellate TET/JBP homologue, catalyzing 5hmU production using either in vivo or in vitro biochemical assay. Based on the near-chromosomal level genome assembly of dinoflagellate Amphidinium carterae, we depicted a comprehensive 5hmU landscape and found that most 5hmU peaks share a conserved TG-rich motif, and are significantly enriched in repeat elements, which mark partially overlapping regions with 5-methylcytosine (5mC) sites. Moreover, inhibition of 5hmU via dioxygenase inhibitor leads to transcriptional activation of 5hmU-marked transposable elements (TEs), implying that 5hmU appears to serve as epigenetic marks for silencing retrotransposon. Together, our results revealed the biogenesis, genome-wide landscape and molecular function of dinoflagellate 5hmU, providing mechanic insight into the function of this enigmatic DNA mark.

molecular biology↗

The highly abundant mRNA m1A modification: a new layer of gene regulation in dinoflagellates

The N1-methyladenosine (m1A) is a positively charged RNA modification known to disrupt base pairing and influence RNA stability. Despite its limited presence in the mRNA of various organism models, including yeast, mouse, and human, the exact processes of m1A biosynthesis, distribution, regulation, and function remain controversial. Dinoflagellates are a major group of single-celled eukaryotic phytoplankton having peculiar crystalline chromosomes. Their genes are arranged in unidirectional gene clusters along the chromosomes and only have minimal transcriptional regulation, implying the involvement of other critical regulatory mechanisms in gene expression. Here, we found that m1A rather than m6A is the most prevalent mRNA modification in dinoflagellates and asymmetrically distributed along mature transcripts. Utilizing the dinoflagellate species Amphidinium carterae as a study model, we identified 13481 m1A peaks characterized by a non-tRNA T-loop-like sequence motif within the transcripts of 10794 genes, many of which are involved in carbon and nitrogen metabolism. With enrichment around stop codon region and 3 UTR, dinoflagellate mRNA m1A exhibits negative correlation with translation efficiency. Notably, nitrogen depletion (N-depletion) treatment led to significant global decrease of mRNA m1A amount, causing dramatic variation in translation rates with minimal changes in transcription. Additionally, our analysis uncovered distinctive methylation patterns of m1A modification that appears to post-transcriptionally modulate gene expression through regulating translation efficiency. Thus, our findings provide the first comprehensive m1A map of dinoflagellate mRNA, shedding light on its crucial role as a post-transcriptional regulatory layer to compensate the degeneration of transcriptional regulation in dinoflagellate. This study also sets the stage for further investigation into the biogenesis and functional significance of mRNA m1A in eukaryotes.

molecular biology↗

Actomyosin-II Proactively Shields Axons of the Central Nervous System from Mild Mechanical Stress

SummaryPan et al found that actomyosin-II-driven radial contractility underpins the resilience of central axons to mild mechanical stress by suppressing the propagation and firing of injurious Ca2+ waves. Boosting actomyosin-II activity alleviates axon degeneration in mice with traumatic brain injury. Traumatic brain injury (TBI) remains a significant and unmet health challenge. However, our understanding of how neurons, particularly their fragile axons, withstand the abrupt mechanical impacts within the central nervous system remains largely unknown. Using a microfluidic device applying discrete levels of transverse forces to axons, we identified the stress levels that most axons could resist and explored their instant responses at nanoscale resolution. Mild stress induces rapid and reversible axon beading, driven by actomyosin-II-dependent radial contraction, which restricts the spreading and bursting of stress-induced Ca2+ waves. More severe stress causes irreversible focal swelling and Ca2+ overload, ultimately leading to focal axonal swelling and degeneration. Up-regulating actomyosin-II activity prevented the progression of initial injury in vivo, protecting commissural axons from degeneration in a mice TBI model. Our study established a scalable axon injury model and uncovered the critical roles of actomyosin-II in shielding neurons against detrimental mechanical stress.

neuroscience↗