Biology subjects

Zhang, Z.-H.

Publications and source records attributed to Zhang, Z.-H..

5 recordsLinked to original sources

bioRxiv2026

Elevated procoagulant platelets driven by necroptosis and pyroptosis aggravate pulmonary thrombosis via suppressing monocyte efferocytosis in severe pneumonia

BACKGROUND: Severe influenza pneumonia with secondary bacterial infection is complicated by progressive pulmonary thrombus exacerbation, a key contributor to respiratory failure, yet anticoagulant therapies show limited efficacy and bleeding risks. Although platelet-monocyte crosstalk initiates thrombosis, whether and how it drives thrombus exacerbation via procoagulant platelets and monocyte efferocytosis remains unclear. METHODS: Clinical samples, mouse models, and isolated platelets challenged with influenza A virus followed by methicillin-resistant Staphylococcus aureus (MRSA) were analyzed. Procoagulant platelet, platelet programmed cell death and monocyte efferocytosis were assessed, and pharmacological inhibition, platelet depletion and systemic/platelet-specific Gsdmd knockout were used. Platelet proteomics and exogenous C1qa supplementation identified C1qa as a key mediator. RESULTS: We showed that elevated procoagulant platelet-driven thrombus exacerbation, rather than initial thrombus formation, was a critical driver of disease progression in influenza pneumonia with secondary bacterial infection, whereas influenza alone caused milder illness. Procoagulant platelet formation was induced via MLKL-mediated necroptosis and GSDMD-mediated pyroptosis. These platelets exacerbated pulmonary thrombosis and lung injury by inhibiting monocyte efferocytosis via complement C1qa. Platelet depletion reduced monocyte efferocytosis and worsened pneumonia, while pharmacological inhibition or platelet-specific Gsdmd knockout decreased procoagulant platelet levels, restored monocyte efferocytosis, and alleviated thrombotic and pulmonary injury. Mechanistically, C1qa impaired efferocytosis both by directly suppressing monocyte function and by reducing the proportion of reparative (M2-like) monocytes. Clinical relevance was confirmed by detection of MLKL/GSDMD-dependent procoagulant platelets and reduced efferocytosis receptor levels on monocytes in bronchoalveolar lavage fluid from severe pneumonia patients. CONCLUSIONS: Necroptosis/pyroptosis-driven procoagulant platelets exacerbate pulmonary thrombosis by suppressing monocyte efferocytosis in a C1qa-dependent manner. These findings extend platelet-monocyte crosstalk from thrombus initiation to thrombus exacerbation, identifying modulation of the interaction between procoagulant platelets and monocyte efferocytosis as a potential therapeutic strategy for thrombus-exacerbating diseases, especially in subpopulations of patients with severe pneumonia and progressive pulmonary thrombosis.

cell biology↗

bioRxiv2026

Deciphering the epitranscriptomic code of RNA degradation with nanopore direct RNA sequencing

The precise regulation of RNA degradation is crucial for gene expression homeostasis, yet how multiple molecular features coordinate on a single transcript remains poorly understood. Here, we use nanopore direct RNA sequencing (DRS) to simultaneously track alternative isoforms, m6A modifications, and poly(A) tail dynamics at single-molecule resolution during a time course of RNA decay. We show that m6A regulates RNA degradation in a stoichiometry-dependent manner, where modification levels quantitatively modulate decay kinetics. Mechanistically, m6A is functionally coupled to deadenylation, promoting accelerated poly(A) tail shortening and coordinated RNA turnover. At the isoform level, we identify regional m6A clusters (RMCs) as structural elements that associate with isoform-selective degradation and remodel protein-coding potential. Furthermore, transcript splicing architecture is associated with distinct m6A deposition patterns, suggesting that gene structure encodes RNA decay kinetics through m6A-mediated regulation. A machine learning model integrating these multi-modal features highlights the central contribution of m6A and deadenylation in shaping RNA decay, while revealing substantial regulatory heterogeneity across transcripts. Collectively, our study deciphers the multi-layered, cooperative principles of RNA degradation and provides an epitranscriptomic perspective for understanding how RNA fate is encoded at the single-molecule resolution.

bioinformatics↗

bioRxiv2025

Bacterial, fungal and protist communities affect differentially in succession stage of karst soil

Karst soil microbial communities are major drivers of cycling of soil nutrients that sustain plant growth and productivity. Yet, a holistic understanding of the impact of different succession stage on the karst soil microbiome is still pooly understood. Here, we used a field experiment to investigate the loog-term consequences of changes in succession stage: rocky desertification(RD), grassland(GL), shrubs(SH), forest plantation(FP) and natural forest(NF) based on plant frequency on bacteria, protist and fungal communites. We showed that the shannon index of bacteria and fungi were higher in NF compared to GL, while protist shannon index was higher in SH that GL. The bacterial simpson_e index in NF and PF were higher than that in GL, SH and RD, howerer fungal and protist simpson_e index were similar across the five succession stages. Significant differences were observed in observed outs and phylogenetic diversity index in NF, SH were higher than GL, RD for fungi and protist, whereas bacterial observed outs and phylogenetic diversity index were relatively similar in five succession stage. The five succession stage differed markedly in the compositions of bacterial, fungi and protist communities. In bacterial, dominant phyla were Actinobacteriota, Proteoprotist, Acidobacteriota. Protist communities were dominated by Phragmoplastophyta, Arthropoda phyla. Regarding protist taxa, the dominant phyla were Ascomycota and Basidiomycota. Our findings provided evidence indicating that the microbial community compositions of RD, GL, SH, PF, and NF have their respective characteristics. These characteristics stem from differences in vegetation coverage, plant debris, root formation and other factors, leading to changes in the diversity and taxonomic group of bacteria, fungi and protists at different successional stages. Overall, this study provides a comprehensive perspective, showing the differences in microbial communities at different successional stages in karst soil.

microbiology↗

bioRxiv2025

Enhanced Functional Potential of Pseudogene-associated lncRNA Genes in Mammals

The functional significance of long non-coding RNAs (lncRNAs) remains a subject of debate, largely due to the complexity and cost associated with their validation experiments. However, emerging evidence suggests that pseudogenes, once viewed as genomic relics, may contribute to the origin of functional lncRNA genes. In this study spanning eight species, we systematically identified pseudogene-associated lncRNA genes using our PacBio long-read sequencing data and published RNA-seq data. Our investigation revealed that pseudogene-associated lncRNA genes exhibit heightened functional attributes compared to their non-pseudogene-associated counterparts. Notably, these pseudogene-associated lncRNAs show protein-binding proficiency, positioning them as potent regulators of gene expression. In particular, pseudogene-associated sense lncRNAs retain protein-binding capabilities inherited from parent genes of pseudogenes, thereby demonstrating greater protein-binding proficiency. Through detailed functional characterization, we elucidated the unique advantages and conserved roles of pseudogene-associated lncRNA genes, particularly in the context of gene expression regulation and DNA repair. Leveraging cross-species expression profiling, we demonstrated the prominent contribution of pseudogene-associated lncRNA genes to aging-related transcriptome changes across nine human tissues and eight mouse tissues. Overall, our findings demonstrate enhanced functional attributes of pseudogene-associated lncRNA genes and shed light on their conserved and close association with aging.

genomics↗

bioRxiv2020

SFPQ intron retention, reduced expression and aggregate formation in central nervous system tissue are pathological features of amyotrophic lateral sclerosis

BackgroundSplicing factor proline and glutamine rich (SFPQ, also known as polypyrimidine tract-binding protein-associated-splicing factor, PSF) is a RNA-DNA binding protein with roles in key cellular pathways such as DNA transcription and repair, RNA processing and paraspeckle formation. Dysregulation of SFPQ is emerging as a common pathological feature of multiple neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). Increased retention of SFPQ intron nine and nuclear loss of the protein have been linked to multiple genetic subtypes of ALS. Consequently, SFPQ dysregulation has been hypothesised to be a common pathological feature of this highly heterogeneous disease. MethodsThis study provides a comprehensive assessment of SFPQ pathology in large ALS patient cohorts. SFPQ gene expression and intron nine retention were examined in multiple neuroanatomical regions and blood from ALS patients and control individuals using RNA sequencing (RNA-Seq) and quantitative PCR (RT-qPCR). SFPQ protein levels were assessed by immunoblotting of patient and control motor cortex and SFPQ expression pattern was examined by immunofluorescent staining of patient and control spinal cord sections. Finally, whole-genome sequencing data from a large cohort of sporadic ALS patients was analysed for genetic variation in SFPQ. ResultsSFPQ intron nine retention was significantly increased in ALS patient motor cortex. Total SFPQ mRNA expression was significantly downregulated in ALS patient motor cortex but not ALS patient blood, indicating tissue specific SFPQ dysregulation. At the protein level, nuclear expression of SFPQ in both control and patient spinal motor neurons was highly variable and nuclear depletion of SFPQ was not a consistent feature in our ALS cohort. However, we did observe SFPQ-positive cytoplasmic ubiquitinated protein aggregates in ALS spinal motor neurons. In addition, our genetic screen of ALS patients identified two novel, and two rare sequence variants in SFPQ not previously reported in ALS. ConclusionsThis study shows that dysregulation of SFPQ is a feature of ALS patient central nervous system tissue. These findings confirm SFPQ pathology as a feature of ALS and indicate that investigations into the functional consequences of this pathology will provide insight into the biology of ALS.

neuroscience↗