Biology subjects

Liu, Y.

Publications and source records attributed to Liu, Y..

At least 1,423 records · Page 79Linked to original sources

bioRxiv2023

A human pluripotent stem cell-based somitogenesis model using microfluidics

Emerging human pluripotent stem cell (hPSC)-based embryo models are useful for studying human embryogenesis. Particularly, there are hPSC-based somitogenesis models using free-floating culture that recapitulate somite formation. Somitogenesis in vivo involves intricately orchestrated bio-chemical and -mechanical events. However, none of the current somitogenesis models controls biochemical gradients or biomechanical signals in the culture, limiting their applicability to untangle complex biochemical-biomechanical interactions that drive somitogenesis. Here we report a new human somitogenesis model by confining hPSC-derived presomitic mesoderm (PSM) tissues in microfabricated trenches. Exogenous microfluidic morphogen gradients imposed on PSM cause axial patterning and trigger spontaneous rostral-to-caudal somite formation. A mechanical theory is developed to explain the size dependency between somites and PSM. The microfluidic somitogenesis model is further exploited to reveal regulatory roles of cellular and tissue biomechanics in somite formation. This study presents a useful microengineered, hPSC-based model for understanding the bio-chemical and -mechanical events that guide somite formation.

bioengineering↗

bioRxiv2023

MechPPI: Binding Mechanism-based Machine-Learning tool for Predicting Protein-Protein Binding Affinity Changes Upon Mutations

Protein-protein interactions are essential for various biological processes, including signal transduction, metabolism, vesicle transport, and mitogenic processes. Its crucial to consider them within the context of their interactions with other proteins to understand protein function. Mutations in proteins can affect their binding affinity to partner proteins by introducing various effects, such as changes in hydrophobic regions, electrostatic interactions, or hydrogen bonds. Assessing the impact of mutations on protein interactions can have implications for disease susceptibility and drug efficacy. Understanding the impact of mutations on protein-protein interactions and predicting binding affinity changes computationally can benefit both basic biology and drug development. Different computational methods offer varying levels of accuracy and efficiency, and the choice of method depends on the specific research goals and available resources. We developed MechPPI, a tool that can use potential mechanism features underlying mutation to predict the binding affinity change upon mutation. We showed MechPPI can accurately predict binding affinity change upon a single mutation, and results demonstrate the potential of MechPPI as a powerful and useful computational tool in protein design and engineering.

bioinformatics↗

bioRxiv2023

Neoadjuvant Therapy Differentially Remodels Carcinoma and Tumor Microenvironment in Pancreatic Ductal Adenocarcinoma: Insights from Spatially Resolved Transcriptomics

PurposeNeoadjuvant therapy (NAT) is increasingly being used for pancreatic ductal adenocarcinoma (PDAC) treatment. However, its distinct effects on carcinoma cells and the tumor microenvironment (TME) are not fully understood. This study employs spatial transcriptomics and single-cell RNA sequencing to investigate how NAT differentially remodels PDACs carcinoma cells and TME. Experimental DesignWe used spatial transcriptomics to compare gene expression profiles in carcinoma cells and the TME between NAT-treated and NAT-naive PDAC patients and correlated with their clinicopathologic features. Complementary single-nucleus RNA sequencing (snRNA-seq) analysis was conducted to validate our findings and identify cell types driving NAT-induced gene expression alterations. ResultsWe found NAT not only induces apoptosis and inhibits proliferation in carcinoma cells but also significantly remodels the TME. Notably, NAT induces a coordinated upregulation of multiple key complement genes (C3, C1S, C1R, C4B and C7) in the TME, making the complement pathway one of the most significantly affected pathways by NAT. Patients with higher TME complement expression following NAT exhibit improved overall survival; more immunomodulatory and neurotrophic cancer-associated fibroblasts (CAFs); more CD4+ T cells, monocytes and mast cells; and lower immune exhaustion gene expression. snRNA-seq analysis demonstrates C3 complement upregulation specifically in CAFs but not in other stroma cell types. ConclusionsOur findings indicate that NAT may reduce immunosuppression in PDAC by enhancing complement production and signaling within the TME. These findings suggest that local complement dynamics could serve as a novel biomarker for prognosis, evaluating treatment response and resistance, and guiding therapeutic strategies in NAT-treated PDAC patients. Translational RelevanceAs neoadjuvant therapy (NAT) increasingly becomes the preferred approach in treating resectable and borderline resectable pancreatic ductal adenocarcinoma (PDAC), there is a growing demand for novel biomarkers specifically tailored for post-NAT PDAC patients. Our study focused on how NAT differentially remodels the tumor cells and the tumor microenvironment (TME). We demonstrate that NAT can enhance local complement production and signaling in PDACs TME, which is associated with reduced immune exhaustion and improved overall survival. Our results highlight the importance of local complement dynamics in influencing treatment response, resistance, and overall clinical outcomes in PDAC. This new mechanism provides new opportunities in biomarker development which could facilitate more accurate prognostication and precise treatment stratification, particularly for patients undergoing NAT in PDAC.

genomics↗

bioRxiv2023

Protein Language Model Supervised Precise and Efficient Protein Backbone Design Method

Proteins perform essential roles in numerous biological processes, largely driven by the three-dimensional structure of several key motif residues. Recently, a variety of energy-based and machine learning backbone generation methods have been developed to solve the motif-scaffolding task. However, it is still challenging to generate diverse and accurate scaffold structures around motifs for models either fine-tuned pre-trained multiple sequence alignment-based (MSA-based) structure prediction models or trained from scratch. Here, we introduced Generative Protein Design by Language model (GPDL) for effectively replacing traditional MSA-based pretraining. Using our scalable design strategy, GPDL successfully solved 22 out of 24 benchmark problems and outperformed other methods by generating 33.5% more unique designable clusters than RFdiffusion. This demonstrates that our approach can generate accurate and physically plausible structures across diverse protein design scenarios. GPDL also showed strong robustness in orphan proteins that have low sequence similarity with the training set. Our approach underscores the promise of protein language models in protein design and has the potential to accelerate the discovery of novel functional proteins for a wide range of biological and therapeutic applications.

bioinformatics↗

bioRxiv2023

Structure-Based Discovery of a NPFF1R Antagonist with Analgesic Activity

While opioid drugs remain among the most effective analgesics for pain management, adverse effects limit their use. Molecules that synergize with opioids, increasing analgesia without increasing side effects, could prove beneficial. A potential way to do so is via the RF-amide receptor system, as NPFFR1 agonists reduce {micro}- opioid receptor ({micro}OR)-based analgesia while antagonists increase it. These inferences are, however, clouded by the lack of selectivity of most NPFF1R ligands. Seeking selective antagonists of the NPFF1R, we screened a large virtual library against a homology model of NPFF1R. From 26 high-ranking molecules that were synthesized and tested, one antagonized NPFF1R with a Ki of 319 nM. Structure-based optimization led to a 22 nM antagonist of NPFF1R, compound 56, with selectivity against a large panel of GPCRs. When administered alone, 56 has no activity in mouse tail-flick nociception assays. However, coadministration of compound 56 and morphine produced significantly greater antinociception than did morphine alone, consistent with the notion that NPFF1R nociceptive activity occurs via modulation of {micro}OR signaling. Surprisingly, in the hot-plate assays 56 was analgesic by itself, suggesting that NPFF1R alone can also confer analgesia. At equi-analgesic doses, combinations of 56 with morphine reduced the common constipation side effect of morphine versus using morphine alone. The high selectivity of 56 and its activity in cooperation with morphine supports further analgesic development against NPFF1R and against the RF-amide family of receptors more generally.

pharmacology and toxicology↗

bioRxiv2023

Enhancing Hi-C contact matrices for loop detection with Capricorn, a multi-view diffusion model

High-resolution Hi-C contact matrices reveal the detailed three-dimensional architecture of the genome, but high-coverage experimental Hi-C data are expensive to generate. On the other hand, chromatin structure analyses struggle with extremely sparse contact matrices. To address this problem, computational methods to enhance low-coverage contact matrices have been developed, but existing methods are largely based on resolution enhancement methods for natural images and hence often employ models that do not distinguish between biologically meaningful contacts, such as loops, and other stochastic contacts. We present Capricorn, a machine learning model for Hi-C resolution enhancement that incorporates small-scale chromatin features as additional views of the input Hi-C contact matrix and leverages a diffusion probability model backbone to generate a high-coverage matrix. We show that Capricorn outperforms the state of the art in a cross-cell-line setting, improving on existing methods by 17.8% in mean squared error and 22.9% in F1 score for chromatin loop identification from the generated high-coverage data. We also demonstrate that Capricorn performs well in the cross-chromosome setting and cross-chromosome, cross-cell-line setting, improving the downstream loop F1 score by 15.7% relative to existing methods. We further show that our multi-view idea can also be used to improve several existing methods, Hi-CARN and HiCNN, indicating the wide applicability of this approach. Finally, we use DNA sequence to validate discovered loops and find that the fraction of CTCF-supported loops from Capricorn is similar to those identified from the high-coverage data. Capricorn is a powerful Hi-C resolution enhancement method that enables scientists to find chromatin features that cannot be identified in the low-coverage contact matrix. Implementation of Capricorn and source code for reproducing all figures in this paper are available at https://github.com/CHNFTQ/Capricorn.

bioinformatics↗

bioRxiv2023

Transport and inhibition mechanism for VMAT2-mediated synaptic loading of monoamines

Monoamine neurotransmitters such as serotonin and dopamine are loaded by vesicular monoamine transporter 2 (VMAT2) into synaptic vesicles for storage and subsequent release in neurons. Impaired VMAT2 function underlies various neuropsychiatric diseases. VMAT2 inhibitors reserpine and tetrabenazine are used to treat hypertension, movement disorders associated with Huntingtons Disease and Tardive Dyskinesia. Despite its physiological and pharmacological significance, the structural basis underlying substrate recognition, and inhibition by varying mechanisms remains unknown. Here we present cryo-EM structures of human apo VMAT2 in addition to states bound to serotonin, tetrabenazine, and reserpine. These structures collectively capture three states, namely the lumen-facing, occluded, and cytosol-facing conformations. Notably, tetrabenazine induces a substantial rearrangement of TM2 and TM7, extending beyond the typical rocker-switch movement. These functionally dynamic snapshots, complemented by biochemical analysis, unveil the essential components responsible for ligand recognition, elucidate the proton-driven exchange cycle, and provide a framework to design improved pharmaceutics targeting VMAT2.

biophysics↗

bioRxiv2023

Impact of Memory T Cells on SARS-COV-2 Vaccine Response in Hematopoietic Stem Cell Transplant

During the COVID-19 pandemic, hematopoietic stem cell transplant (HSCT) recipients faced an elevated mortality rate from SARS-CoV-2 infection, ranging between 10-40%. The SARS-CoV-2 mRNA vaccines are important tools in preventing severe disease, yet their efficacy in the post-transplant setting remains unclear, especially in patients subjected to myeloablative chemotherapy and immunosuppression. We evaluated the humoral and adaptive immune responses to the SARS-CoV-2 mRNA vaccination series in 42 HSCT recipients and 5 healthy controls. Peripheral blood mononuclear nuclear cells and serum were prospectively collected before and after each dose of the SARS-CoV-2 vaccine. Post-vaccination responses were assessed by measuring anti-spike IgG and nucleocapsid titers, and antigen specific T cell activity, before and after vaccination. In order to examine mechanisms behind a lack of response, pre-and post-vaccine samples were selected based on humoral and cellular responses for single-cell RNA sequencing with TCR and BCR sequencing. Our observations revealed that while all participants eventually mounted a humoral response, transplant recipients had defects in memory T cell populations that were associated with an absence of T cell response, some of which could be detected pre-vaccination.

immunology↗

bioRxiv2023

NIEND: Neuronal Image Enhancement through Noise Disentanglement

MotivationThe full automation of digital neuronal reconstruction from light microscopic images has long been impeded by noisy neuronal images. Previous endeavors to improve image quality can hardly get a good compromise between robustness and computational efficiency. ResultsWe present the image enhancement pipeline named Neuronal Image Enhancement through Noise Disentanglement (NIEND). Through extensive benchmarking on 863 mouse neuronal images with manually annotated gold standards, NIEND achieves remarkable improvements in image quality such as signal-background contrast (40-fold) and background uniformity (10-fold), compared to raw images. Furthermore, automatic reconstructions on NIEND-enhanced images have shown significant improvements compared to both raw images and images enhanced using other methods. Specifically, the average F1 score of NIEND-enhanced reconstructions is 0.88, surpassing the original 0.78 and the second-ranking method, which achieved 0.84. Up to 52% of reconstructions from NIEND-enhanced images outperform all other 4 methods in F1 scores. In addition, NIEND requires only 1.6 seconds on average for processing 256x256x256-sized images, and images after NIEND attain a substantial average compression rate of 1% by LZMA. NIEND improves image quality and neuron reconstruction, providing potential for significant advancements in automated neuron morphology reconstruction of petascale. Availability and ImplementationThe study is conducted based on Vaa3D and Python 3.10. Vaa3D is available on GitHub (https://github.com/Vaa3D). The proposed NIEND method is implemented in Python, and hosted on GitHub along with the testing code and data (https://github.com/zzhmark/NIEND). The raw neuronal images of mouse brains can be found at the BICCNs Brain Image Library (BIL) (https://www.brainimagelibrary.org).

bioinformatics↗

bioRxiv2023

Discovery of CMX990: A Potent SARS-CoV-2 3CL Protease Inhibitor Bearing a Novel Covalent Warhead

There remains a need to develop novel SARS-CoV-2 therapeutic options that improve upon existing therapies by increased robustness of response, fewer safety liabilities, and global-ready accessibility. Functionally critical viral main protease (Mpro, 3CLpro) of SARS-CoV-2 is an attractive target due to its homology within the coronaviral family, and lack thereof towards human proteases. In this disclosure, we outline the advent of a novel SARS-CoV-2 3CLpro inhibitor, CMX990, bearing an unprecedented trifluoromethoxymethyl ketone warhead. Compared with the marketed drug nirmatrelvir (combination with ritonavir = PaxlovidTM), CMX990 has distinctly differentiated potency ([~]5x more potent in primary cells) and human in vitro clearance (>4x better microsomal clearance and >10x better hepatocyte clearance), with good in vitro-in vivo correlation. Based on its compelling preclinical profile and projected once or twice a day dosing supporting unboosted oral therapy in humans, CMX990 advanced to a Phase 1 clinical trial as an oral drug candidate for SARS-CoV-2.

microbiology↗

bioRxiv2023

Cell-type-resolved somatic mosaicism reveals clonal dynamics of the human forebrain

Debate remains around anatomic origins of specific brain cell subtypes and lineage relationships within the human forebrain. Thus, direct observation in the mature human brain is critical for a complete understanding of the structural organization and cellular origins. Here, we utilize brain mosaic variation within specific cell types as distinct indicators for clonal dynamics, denoted as cell-type-specific Mosaic Variant Barcode Analysis. From four hemispheres from two different human neurotypical donors, we identified 287 and 780 mosaic variants (MVs), respectively that were used to deconvolve clonal dynamics. Clonal spread and allelic fractions within the brain reveal that local hippocampal excitatory neurons are more lineage-restricted compared with resident neocortical excitatory neurons or resident basal ganglia GABAergic inhibitory neurons. Furthermore, simultaneous genome-transcriptome analysis at both a cell-type-specific and single-cell level suggests a dorsal neocortical origin for a subgroup of DLX1+ inhibitory neurons that disperse radially from an origin shared with excitatory neurons. Finally, the distribution of MVs across 17 locations within one parietal lobe reveals restrictions of clonal spread in the anterior-posterior axis precedes that of the dorsal-ventral axis for both excitatory and inhibitory neurons. Thus cell-type resolved somatic mosaicism can uncover lineage relationships governing the development of the human forebrain.

neuroscience↗

bioRxiv2023

Mammalian circadian clock proteins form dynamic interacting microbodies distinct from phase separation

Liquid-liquid phase separation (LLPS) underlies diverse biological processes. Because most LLPS studies were performed in vitro or in cells that overexpress protein, the physiological relevance of LLPS is unclear. PERIOD proteins are central mammalian circadian clock components and interact with other clock proteins in the core circadian negative feedback loop. Different core clock proteins were previously shown to form large complexes. Here we show that when transgene was stably expressed, PER2 formed nuclear phosphorylation-dependent LLPS condensates that recruited other clock proteins. Super-resolution microscopy of endogenous PER2, however, revealed formation of circadian-controlled, rapidly diffusing microbodies that were resistant to protein concentration changes, hexanediol treatment, and loss of phosphorylation, indicating that they are distinct from the LLPS condensates caused by overexpression. Surprisingly, only a small fraction of endogenous PER2 microbodies transiently interact with endogenous BMAL1 and CRY1, a conclusion that was confirmed in cells and in mice tissues, suggesting an enzyme-like mechanism in the circadian negative feedback process. Together, these results demonstrate that the dynamic interactions of core clock proteins is a key feature of mammalian circadian clock mechanism and the importance of examining endogenous proteins in LLPS and circadian studies.

genetics↗

bioRxiv2023

Multi-locus CRISPRi targeting with a single truncated guide RNA

A critical goal in functional genomics is evaluating which non-coding elements contribute to gene expression, cellular function, and disease. Functional characterization remains a challenge due to the abundance and complexity of candidate elements. Here, we develop a CRISPRi- based approach for multi-locus screening of putative transcription factor binding sites with a single truncated guide. A truncated guide with hundreds of sequence match sites can reliably disrupt enhancer activity, which expands the targeting scope of CRISPRi while maintaining repressive efficacy. We screen over 13,000 possible CTCF binding sites with 24 guides at 10 nucleotides in spacer length. These truncated guides direct CRISPRi-mediated deposition of repressive H3K9me3 marks and disrupt transcription factor binding at most sequence match target sites. This approach is valuable for elucidating functional transcription factor binding motifs or other repeated genomic sequences and is easily implementable with existing tools.

molecular biology↗

bioRxiv2023

GRAMD2+ alveolar type I cell plasticity facilitates cell state transitions in organoid culture

Alveolar epithelial regeneration is critical for normal lung function and becomes dysregulated in disease. While alveolar type 2 (AT2) and club cells are known distal lung epithelial progenitors, determining if alveolar epithelial type 1 (AT1) cells also contribute to alveolar regeneration has been hampered by lack of highly specific mouse models labeling AT1 cells. To address this, the Gramd2CreERT2 transgenic strain was generated and crossed to RosamTmG mice. Extensive cellular characterization, including distal lung immunofluorescence and cytospin staining, confirmed that GRAMD2+ AT1 cells are highly enriched for green fluorescent protein (GFP). Interestingly, Gramd2CreERT2 GFP+ cells were able to form organoids in organoid co-culture with Mlg fibroblasts. Temporal scRNAseq revealed that Gramd2+ AT1 cells transition through numerous intermediate lung epithelial cell states including basal, secretory and AT2 cell in organoids while acquiring proliferative capacity. Our results indicate that Gramd2+ AT1 cells are highly plastic suggesting they may contribute to alveolar regeneration.

cell biology↗

bioRxiv2023

The Interferon-inducible NAMPT acts as a protein phosphoribosylase to restrict viral infection

As obligate intracellular pathogens, viruses often activate host metabolic enzymes to supply intermediates that support progeny production. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of the salvage NAD+ synthesis, is an interferon-inducible protein that inhibits the replication of several RNA and DNA viruses with unknown mechanism. Here we report that NAMPT restricts herpes simplex virus 1 (HSV-1) replication via phosphoribosyl-hydrolase activity toward key viral structural proteins, independent of NAD+ synthesis. Deep mining of enriched phosphopeptides of HSV-1-infected cells identified phosphoribosylated viral structural proteins, particularly glycoproteins and tegument proteins. Indeed, NAMPT de-phosphoribosylates viral proteins in vitro and in cells. Chimeric and recombinant HSV-1 carrying phosphoribosylation-resistant mutations show that phosphoribosylation promotes the incorporation of structural proteins into HSV-1 virions and subsequent virus entry. Moreover, loss of NAMPT renders mice highly susceptible to HSV-1 infection. The work describes a hidden enzyme activity of a metabolic enzyme in viral infection and host defense, offering a system to interrogate roles of phosphoribosylation in metazoans.

molecular biology↗

bioRxiv2023

New insights into tissue-specific responses and interactive characteristics of crop-microbe "One Health" system to soil chromium and ofloxacin pollution

This study firstly investigated the tissue-specific responses and interactive characteristics of the crop-microbe system to co-pollution with ofloxacin (OFL) and chromium (Cr) in soil. The results emphasized the hormesis effect induced by low-dose OFL (1 mg L-1) on ginger plants subjected to soil Cr stress. However, high-dose OFL (100 mg L-1) and Cr co-stressed plants exhibited reduced growth, root activity, antioxidant enzyme activities and photosynthesis-fluorescence performances, while the reactive oxygen species (ROS) reflected by O2{middle dot}- and H2O2 significantly increased up to 43.34% and 78.63%, respectively, compared to other treatments. In addition, high-throughput sequencing indicated that OFL influenced rhizosphere microbial diversity, composition, and evolution, favoring Proteobacteria proliferation under co-pollution. Meanwhile, root exudate patterns shifted, with humic-like exudates, potentially interacting with pollutants and microbes. Notably, enrichments of antibiotic resistance gene (qnrS) in edible rhizome and potential pathogenic bacteria in ginger rhizosphere were observed under OFL and Cr co-pollution, raising environmental and food chain concerns. Through structural equation modeling, we quantitatively established correlations within soil-crop-microbe factors, emphasizing their interconnected nature. Overall, this study sheds light on the complex responses of the crop-microbe system to OFL and Cr co-pollution, highlighting the importance of understanding pollutant interactions for enhancing plant resilience and mitigating environmental risks. HighlightsO_LIRevealed a hormesis from low-dose OFL on Cr-polluted ginger, enhancing resilience. C_LIO_LIRhizosphere microbial composition shift under co-pollution, favoring Proteobacteria. C_LIO_LIqnrS and potential pathogens increased under co-pollution, posing food chain risks. C_LIO_LIStructural equation modeling quantified correlations in soil- crop-microbe factors. C_LIO_LIClarified crop-microbe "One Health" interactions role under Cr & OFL co-pollution. C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=128 SRC="FIGDIR/small/561380v1_ufig1.gif" ALT="Figure 1"> View larger version (61K): org.highwire.dtl.DTLVardef@bd3d20org.highwire.dtl.DTLVardef@1f8024eorg.highwire.dtl.DTLVardef@15f6154org.highwire.dtl.DTLVardef@ef0aeb_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗

bioRxiv2023

Ependymocytes control cerebrospinal fluid flow to the peripheral organs through periaxonal pathway

Mechanisms controlling movement of the CSF through the central canal towards the peripheral nerves are poorly characterized. We found that fluorescent dyes injected into cisterna magna are carried with cerebrospinal fluid (CSF) through the central canal and peripheral nerves to the peripheral organs such as liver, and pancreas. We also found close connection between spinal axons and ependymocytes, suggesting synaptic interactions. Serotonin, acting through the 5-HT2B receptors abundantly expressed in ependymal cells, trigger Ca2+ signal that induces polymerization of cytoskeleton protein F-actin, consequently reducing the volume of ependymocytes. Shrinkage of the latter opens one-way route to facilitate CSF outflow from the central canal into the spinal cord parenchyma and peripheral nerves. In liver, CSF is received by stellate cells. Ependymal control over transfer of the CSF from central canal to peripheral organs by the periaxonal space (PAS) represents a novel mechanism dynamically connecting the CNS with the periphery. In briefEpendymocytes control CSF flow from CNS to peripheral organs by periaxonal pathway, and serotonin evokes the ependymal shrinkage by the aggregation of F-actin. HighlightsEpendymocytes control CSF flow from central canal to peripheral organs; CSF flows through the peripheral periaxonal space to reach the peripheral organs; Serotonin makes ependymocytes shrunk by 5-HT2B receptor-mediated Ca2+ signaling and F-actin polymerization; The hepatic stellate cells are potential collectors of CSF in the liver.

neuroscience↗

bioRxiv2023

Live soil ameliorated the negative effects of biodegradable but not non-biodegradable microplastics on the growth of plant communities

O_LIPlastic pollution has become a global environmental problem. Alternative use of biodegradable plastics has been proposed to mitigate the pollution problem caused by the traditional non-biodegradable plastics but the relative impacts of both types of microplastics on plant community productivity and diversity remain unknown. Microplastics can affect growth of individual plants directly by altering plant physiological processes and indirectly by altering soil biota that in turn influence plant growth. However, it remains unknown whether soil biota can mediate impact of biodegradable and non-biodegradable microplastics on plant community productivity and diversity due to a lack of studies on the topic. C_LIO_LIHere, we performed a greenhouse experiment with six plant communities and five biodegradable and five non-biodegradable microplastics to test whether: 1) biodegradable microplastics have a less negative effect on plant community biomass production and diversity than non-biodegradable microplastics, and 2) soil microorganisms differentially mediate the effects of non-biodegradable and biodegradable microplastics on plant community biomass production and diversity. We employed a fully crossed factorial design to grow the six plant communities in the presence vs. absence of the 10 microplastics individually and in live soil vs. sterilized soil. C_LIO_LIResults show that live soil ameliorated the negative effects of biodegradable microplastics on shoot biomass of the plant communities, but microplastics suppressed plant community diversity more strongly in live soil than in sterilized soil regardless of microplastics types under averaged across all treatments. Furthermore, the specific microplastics polymers were the main drivers of these results. C_LIO_LISynthesis and applications: Overall, our findings indicate that even biodegradable microplastics, e.g. PBS, which are considered environmentally friendly, still pose significant ecological risks to the structure and productivity of plant communities with potential implications for functioning of terrestrial ecosystems. Future studies may identify the specific taxa of soil microorganisms that may have degraded the microplastics that we studied, their rates of biodegradation, and the effects thereof on plant community structure and productivity under more natural field conditions in contrasting climatic conditions. C_LI

ecology↗