Biology subjects

Wang, T.

Publications and source records attributed to Wang, T..

At least 73 records · Page 4Linked to original sources

bioRxiv2026

Differences in microbial community structure and soil nutrients between healthy and diseased soils of Zingiber officinale

To investigate the differences in soil nutrients and microbial community structure in the rhizosphere between healthy and diseased Zingiber officinale plants, soil samples were collected from healthy root-zone soil (ZSH), healthy rhizosphere soil (RSH), diseased root-zone soil (ZSD), and diseased rhizosphere soil (RSD). Diseased soils had significantly higher pH values, whereas RSH showed the strongest acidity. Moreover, pH, AN, and AK contents in diseased soils were significantly higher than those in healthy soils, while SOM and AP were significantly lower. The -diversity of microbial communities in diseased soils was significantly reduced, and the community structure was distinctly differentiated from that of healthy soils. In diseased soils, the abundance of potential pathogenic taxa such as Ralstonia solanacearum increased significantly, while beneficial genera such as Bradyrhizobium decreased. Redundancy analysis and correlation analysis indicated that soil pH, AN, SOM, and AP were the major environmental factors driving changes in microbial community structure. The occurrence of soil-borne diseases in Zingiber officinale is closely associated with soil nutrient imbalance and disruption of microbial community structure. The study identified candidate microbial taxa (e.g., beneficial Sphingomonas, Streptomyces) and key soil properties (pH, available nitrogen) that differentiate healthy from diseased ginger soils. Together, these findings provide a theoretical basis for improving diseased soils through microecological regulation strategies, and also serve as a foundation for generating testable hypotheses in future hypothesis-driven research on ginger soil-borne disease suppression.

microbiology↗

bioRxiv2026

Repurposing of the assembly chaperone PAC1-PAC2 defines a specialized proteasome landscape in mature mammalian sperm

Mature mammalian sperm rely on active proteasomes containing the testis-specific subunit 4s for capacitation, acrosomal exocytosis and fertilization, but how these proteasomes are structurally specialized remains unclear. We determine the endogenous proteasome landscape of mature bovine spermatozoa and testis using cryo-electron microscopy. We resolve five sperm proteasome assemblies: PA200-20S, free 20S, a previously unrecognized PA200-20S-PAC1/2 hybrid, and PAC1/2-20S complexes capped at one or both ends. Unexpectedly, the PAC1/2-bound complexes are mature and POMP-free, selectively incorporated for 4s, lack 2, and adopt a PAC1/2 orientation and gate configuration distinct from known assembly intermediates. Together with elevated proteolytic activity, these features indicate that PAC1/2 is repurposed from a transient assembly chaperone into a stable post-assembly regulator in mature sperm. 4s-containing proteasomes assemble through the canonical PAC1-PAC4/POMP pathway yet may follow {beta}2-{beta}3-{beta}1 incorporation ordering; functionally, 4s incorporation remodels the sCP surface and enhances peptidase activities, definining the spermatoproteasomes as a hyperactive 20S variant. PAC1/2-bound proteasomes are absent from testis, where PA200-20S and 26S proteasomes are present, while 26S proteasomes are nearly lost in mature sperm. Our findings define a sperm-specific, ATP-independent proteasome landscape, expand the functional repertoires of 4s and PAC1/2, and provide a structural framework for proteasome specialization in male fertility.

cell biology↗

bioRxiv2026

Molecular grammar of RNA m6A modification in ribonucleoprotein granules

Diverse RNA chemical modifications collectively regulate nearly all aspects of RNA metabolism. Among these, N6-methyladenosine (m6A) is the most prevalent internal modification in eukaryotic messenger RNAs. Recent studies have implicated m6A in the formation and regulation of ribonucleoprotein (RNP) granules--biomolecular condensates that organize RNA metabolism in space and time. However, the underlying biophysical mechanisms remain to be elucidated. Here, building on SMART, a single-molecule platform for quantitatively measuring RNP granule assembly across nanometer-to-mesoscale regimes, we develop SMART-epi to enable precise control of the m6A modification ratio. Using this approach, we show that physiological m6A levels inhibit YTHDF2 RNP granule assembly while directing specific RNA-RNA interaction architectures. Moreover, YTHDF1/2/3 exhibit distinct assembly kinetics, suggesting functional divergence. Together, these findings reveal a molecular grammar by which m6A modulates condensate dynamics and suggest that RNA modifications can encode regulatory information to tune RNP granule behavior, with potential implications for therapeutic intervention.

biophysics↗

bioRxiv2026

Pansoma, a machine learning tool for identifying somatic variants using pangenome graphs

Somatic variant calling, the identification of mutations in non-germline cells acquired over an individuals lifetime, is critical for studying diseases, including cancer, and for developing precision oncology strategies. Traditional somatic variant calling methods rely on linear reference genomes, which do not adequately capture human genetic diversity and result in reference bias, compromising the accuracy of somatic variant detection. Recently developed graph-based human pangenome reference represents diverse genetic variants across human populations and has promised to drive advances in many genetics and genomics studies. In this study, we introduced Pansoma, a novel pangenome-native and machine learning-based tool specifically designed for somatic variant calling using a pangenome graph reference. Pansoma performs somatic variant detection from both short- and long-read sequencing data by learning tensor representations of alignment on graph nodes rather than on a linear reference. Pansoma outputs variant representations anchored to the pangenome graph paths and conventional somatic variant calls remapped to the linear reference. Additionally, we provide accompanying bioinformatics tools tailored for graph-based genomic data management and variant calling results analysis. Benchmarking shows that Pansoma not only improves tumor-only somatic variant detection but also preserves graph-specific variant representations that are not directly recoverable from linear- reference outputs.

genomics↗

bioRxiv2026

An SE(3)-equivariant Crystal Structure Prediction Framework for Prospective Identification and Development of Bioactive Nucleoside Self-Assembling Materials

Flexible organic small molecules can assemble into supramolecular biomaterials whose properties are intrinsically governed by their crystal structures, yet experimental structure determination remains difficult to scale during molecular modification and materials optimization. Crystal structure prediction (CSP) provides a potential solution, but its prospective power is limited for flexible molecules owing to incomplete conformational sampling and the difficulty of identifying experimentally realized structures from large candidate sets. Here, an SE(3)-equivariant deep-learning workflow, SE3CSP, is developed for organic crystal structure prediction. By learning molecular conformations, unit-cell parameters and packing patterns from experimentally resolved crystal structures and integrating these predictions with MACE-based structure optimization, SE3CSP establishes an end-to-end pipeline from two-dimensional molecular representations to three-dimensional crystal structures. Using nucleosides as representative flexible self-assembling building blocks, SE3CSP achieves an overall prediction accuracy of [~]57%, substantially outperforming the benchmark MACE-based Genarris 3.0 workflow ([~]14%). Furthermore, a prospective prediction strategy is developed in which an SE3CSP-predicted density window ({+/-} 0.15 g/cm3) is applied prior to energy ranking and structural deduplication, enabling all experimentally realized structure to be consistently ranked within the top 1-2% of all generated candidates. Beyond structure prediction, SE3CSP-derived energy landscapes provide insight into potential single-crystal-to-single-crystal transformations and enable the identification of a nucleoside supramolecular material with dynamic breathing porosity, which is further developed as an adsorptive platform for inflammatory mediator removal with excellent anti-inflammatory performance and biocompatibility. These results establish SE3CSP as a practical framework for prospective CSP and highlight its utility in guiding the discovery and design of bioactive self-assembled materials.

bioengineering↗

bioRxiv2026

Transgenic human dipeptidyl peptidase-4 Syrian hamsters support MERS coronavirus infection and contact transmission

Middle East respiratory syndrome coronavirus (MERS-CoV) is a global health concern due to a high fatality rate associated with human infections and no approved vaccines or therapeutics. While Syrian hamsters are a value animal model for coronavirus research, including SARS-CoV-2, MERS-CoV does not infect wild-type hamsters. Here, we generated transgenic Syrian hamsters expressing human dipeptidyl peptidase-4 (hDPP4), the cellular receptor for MERS-CoV., MERS-CoV replicated efficiently in the respiratory tract tissues of hDPP4 hamsters, causing lethal disease. Treatment with the 3CLpro inhibitor nirmatrelvir significantly reduced viral titers in the lower respiratory tract of infected hDPP4 hamsters. While airborne transmission was not observed, direct contact transmission was observed in all contact hDPP4 hamsters cohoused with infected cage mates. Immunization with purified MERS receptor-binding domain protein reduced virus replication and disease severity but did not prevent direct contact transmission. Collectively, our findings demonstrate that hDPP4 transgenic Syrian hamsters are useful for studying MERS-CoV pathogenesis, transmission, and countermeasure efficacy.

microbiology↗

bioRxiv2026

An N-terminal amphipathic helix governs activity and conformational dynamics of Nramp metal transporters

Nramps are a family of proton-coupled divalent metal ion transporters that play critical roles in maintaining homeostasis of essential metals. In humans, Nramp2 (DMT1) mediates iron uptake to support both cellular and systemic iron homeostasis, whereas Nramp1 exports metals from phagosomes, contributing to antimicrobial defense. A survey of experimentally solved Nramp structures reveals that an N-terminal helix (A) immediately preceding TM1 is folded only in the outward-facing or outward-facing occluded states, raising the question of its role in Nramp transport. Here, we combined mutagenesis, transport assays, and molecular dynamics simulations to investigate A. Our results show that deletion or substitution of conserved residues in A markedly reduces Fe2+ transport. Simulations indicate that A behaves as an amphipathic helix in the outward-facing state and preferentially stabilizes this conformation over the inward-facing state, thus acting as a key player in controlling conformational equilibrium. This study provides new insights into structural dynamics of Nramps and potentially sheds light on other LeuT-fold transporters.

biochemistry↗

bioRxiv2026

AAV-NRF2 protects retinal and choroidal vasculature in a GDF15-dependent manner in an oxidative damage model of AMD

Oxidative stress is proposed to be a driver of age-related diseases. Age-related macular degeneration is one such disease, where the retinal pigment epithelium (RPE) is affected early in the disease. Vasculature damage also occurs, sometimes preceding RPE damage. To model some aspects of dry AMD, we used the NaIO3 mouse model of oxidative damage. Disruption of the deep retinal vascular plexus, disorganization and death of capillaries within the choriocapillaris, and marked electroretinographic decline were observed. AAV overexpressing the transcription factor, NRF2, which induces anti-oxidation enzymes and represses inflammation, was tested for protection of damage. The BEST1 promoter limited expression to the RPE. The RPE, photoreceptors, and vascular architecture in both retinal and choroidal compartments were protected. Conditioned medium from RPE-choroid explants, infected by AAV8/BEST1-NRF2, was sufficient to transfer partial protection in vivo, indicating that NRF2 induces a protective secreted factor(s). Analysis of RNA-seq data identified growth differentiation factor 15 (GDF15) as a candidate downstream mediator. Injection of recombinant GDF15 reproduced key protective phenotypes in vivo, whereas Gdf15-deficiency attenuated NRF2-mediated rescue. Pharmacologic inhibition of TGF-{beta} receptor signaling diminished NRF2 associated protection, supporting involvement of this signaling pathway. In a laser-induced choroidal neovascularization model, intravitreal GDF15 injection reduced fluorescein leakage and lesion size. These findings support a model in which NRF2 activation in the RPE induces expression of GDF15, which is capable of protecting the RPE, photoreceptors, and the retinal and choroidal vasculature. NRF2 and GDF15 have therapeutic potential for ocular diseases, as well as for other diseases with vascular pathology.

cell biology↗

bioRxiv2026

Near-Infrared-II Chemo-Optogenetics for Deep-Brain Stimulation

Precise activation of ion channels enables fine-tuned control of neuronal excitability, providing a powerful strategy for dissecting and modulating neural circuits. Although optogenetics offers high spatiotemporal neuronal manipulation with cell-type specificity, its reliance on visible light (400-650 nm) limits tissue penetration to millimeter depths, restricting applications in deep-brain stimulation. Here we report a near-infrared-II (NIR-II)-sensitive calcium channel, HaloNeu, created by genetically fusing a circularly permuted HaloTag (cpHaloTag) to the thermo-sensitive transient receptor potential vanilloid 1 (TRPV1) and covalently conjugating NIR-II photothermal nanotransducers (HPN). The HaloNeu enables non-invasive neuromodulation at depths up to 1.0 cm at ultralow laser power ([~]60 mW/cm2) and up to 5.0 cm under the safe exposure limit ([~]1 W/cm2) with 1064 nm laser illumination. Remarkably, HaloNeu maintains stable, on-demand neuron-specific modulation for over two months in vivo, providing sustained activation of ventral tegmental area (VTA) circuits and effective alleviation of Parkinsonian symptoms in mouse models. These results establish HaloNeu as a robust and versatile platform for cell-type-specific, deep-tissue, and chronic neuromodulation, with broad implications for neuroscience and neurotherapeutics.

neuroscience↗

bioRxiv2026

Symmetry Analysis and Ancestral Sequence Reconstruction Reveal a Symmetrical Translocation Pathway and Activity Determinants of ZIP Metal Transporter

Membrane transporters frequently exhibit internal structural symmetry, reflecting evolutionary origins through gene duplication and fusion events, and this feature has been widely used to infer transport mechanisms. Yet its application to the ZIP (Zrt-/Irt-like protein) family of divalent metal transporters, which are crucial for trace metal homeostasis, has not been fully explored. Here, we apply combined symmetry analysis and ancestral sequence reconstruction to study the ZIP family. We show that internal symmetry is broadly present across prokaryotic ZIPs and is more prominent in reconstructed ancestral sequences, supporting an evolutionary pathway in which the modern 8-transmembrane (TM) ZIP fold arose from duplication, domain rearrangement, and fusion of an ancestral 4-TM protein. Leveraging this symmetry framework, we identify a continuous and symmetric metal translocation pathway composed of symmetric entrance, transport, and exit sites in the ZIP fold, and define gates that ensure alternating access. Application of this structural model to human ZIP4 enables identification of the gate-forming residues, and functional studies reveal that two residues (T529 and V533) in the external gate play a crucial role in controlling metal transport. In addition, comparison with ancestral sequences uncovers a set of LIV-1 subfamily-specific metal chelating residues (D504, E541, and D544) that break the symmetry in the ancestral sequences. Functional studies showed that these residues play distinct roles in transport. Together, our study demonstrates that combining internal symmetry analysis and ancestral sequence reconstruction for the ZIP family facilitates elucidation of metal translocation mechanism and identification of the subfamily-specific features that confer functional specialization.

biochemistry↗

bioRxiv2026

Functional screening of ZIP8 naturally occurring variants identifies pathogenic mutations and trafficking defects

The rapid expansion of human genomic data has revealed a large number of naturally occurring variants, creating a major challenge for functional annotation. The human metal transporter SLC39A8 (ZIP8) is a clinically important, promiscuous divalent metal transporter, yet most of its documented variants remain uncharacterized. Here, we developed a workflow to functionally evaluate ZIP8 variants by integrating laser ablation inductively coupled plasma time-of-flight mass spectrometry (LA-ICP-TOF-MS) with scaled-up cell-based transport assays. Using this method, we systematically analyzed 33 naturally occurring missense variants located in the extracellular domain (ECD) of ZIP8. The assay enables direct quantification of intracellular metal accumulation with substantially improved throughput ([~]150 samples per hour). Functional screening identified 14 potential pathogenic variants with significantly reduced transport activity. Comparison with computational predictions revealed a moderate correlation between activity and AlphaMissense pathogenicity scores (R2 = 0.423), while an error rate of [~]20% underscores the need for experimental validation. Flow cytometry analysis showed that most loss-of-function variants exhibit impaired trafficking of the protein to the cell surface possibly due to mutation-caused protein misfolding or instability. Structural mapping of activity-compromised variants, together with functional assessment of the ZIP8-ECD, highlights the importance of this domain in ZIP8 expression and intracellular trafficking. Together, this work establishes a scalable approach for functional screening of metal transporter variants and provides new insights into the structure-function relationships of ZIP8.

biochemistry↗

bioRxiv2026

HTRA1 deficiency in COL4A1 mutant hiPSC-derived astrocytes, a convergent mechanism of cerebral small vessel disease

Cerebral small vessel disease (cSVD) is a major contributor to stroke and cognitive decline, ultimately leading to vascular dementia (VaD). Genetic factors play a key role in disease susceptibility and progression, and variants in COL4A1 cause one of the most common forms of genetic cSVD. COL4A1 encodes the 1 chain of collagen type IV which is the major structural component of the basement membrane, a specialised extracellular matrix (ECM) structure, in the vasculature. In addition to this vascular basement membrane (vBM), in the central nervous system (CNS), the neurovascular unit (NVU) also has a unique parenchymal basement membrane (pBM) that is largely produced by astrocytes and forms a critical interface anchoring astrocyte end-feet to vascular cells. Together, these BMs play essential roles in regulating blood-brain barrier (BBB) function. However, the role of the pBM in cSVD has been relatively less investigated compared to the vBM. The lack of relevant human disease models that faithfully recapitulate the pBM, makes it difficult to dissect pBM-related cell-cell and cell-matrix interactions specific to cSVD, hindering the identification of effective therapeutic targets. In this study, we hypothesised that astrocyte-mediated ECM remodelling contributes to BBB dysfunction in COL4A1-associated cSVD. To investigate this, human induced pluripotent stem cells (iPSCs) derived from a patient carrying the COL4A1G755Rvariant and its isogenic control line were differentiated into astrocytes and brain microvascular endothelial cells (BMECs). Comparing to isogenic controls, the COL4A1G755Rastrocytes significantly reduced the expression of ECM-related genes and increased glutamate uptake. ECM preparations from COL4A1G755R astrocytes significantly damaged the tight junction (TJ) structure formed by control iPSC-BMECs and failed to rescue the TJ integrity in COL4A1G755R BMECs. The secretome from COL4A1G755Rastrocytes exacerbated the ECM defects in COL4A1G755R BMECs. Most importantly, COL4A1G755R astrocytes exhibited reduced expression of HTRA1, a serine protease that regulates both ECM turnover and homeostasis, and increased TGF-{beta} signalling. Functional rescue by recombinant human HTRA1 protein rescues TJ defects in COL4A1G755R BMECs, and normalized TGF-{beta} signalling and glutamate uptake in COL4A1G755R astrocytes. Together, these findings define a previously unrecognised astrocyte-driven pBM mechanism in COL4A1-associated cSVD and highlight HTRA1 in ECM remodelling as a therapeutic target for cSVD.

neuroscience↗

bioRxiv2026

Somatic-to-germline transmission of horizontally acquired extrachromosomal circular DNA in Brassica graft chimeras

Whether somatically acquired traits can contribute to heritable variation has remained an open question in plant biology for over a century. Here, using graft-induced periclinal chimeras between Brassica juncea and Brassica oleracea, we identified extrachromosomal circular DNA (eccDNA) as mobile genetic elements capable of crossing histological boundaries and entering the germline. We demonstrated that grafting could promote the horizontal transfer of eccDNA between somatic cell layers, enabling its stable maintenance in recipient tissues and permitting transmission through sexual reproduction across multiple generations. We found that transmitted eccDNA is non-randomly distributed across the genome, preferentially originating from gene-dense regions, and enriched for features associated with molecular persistence, such as inverted repeats, hairpin-forming sequences, and autonomously replicating sequence (ARS) consensus motifs. These genetic regions conferred replication competence, as evidenced by autonomous propagation in an ARS-less heterologous yeast system. Sexual progeny carrying graft-acquired eccDNA exhibited reproducible and lineage-dependent alterations in leaf morphology and drought tolerance, accompanied by coordinated transcriptional reprogramming. Notably, a subset of inherited eccDNA remained transcriptionally active in progeny, producing transcripts absent from self-grafted controls. Our findings establish eccDNA as heritable extrachromosomal elements that link graft-mediated somatic genetic transfer with stable germline transmission, thereby expanding the molecular scope of heritable variation in plants and providing a conceptual framework for graft-based trait transmission.

plant biology↗

bioRxiv2026

AI-enabled virtual immunopeptidomics links quantitative neoantigen presentation to immunogenicity

Effective anti-tumor T cell response depends on both neoantigen quality (non-selfness) and quantity (abundance). However, existing methods for neoantigen prioritization largely overlook peptide abundance because it is difficult to measure and model. To bridge this gap, we developed epiVIP, a deep learning framework that predicts the abundance of individual HLA-I peptides using widely available (sc)RNA-seq data. Trained on 1.7 million immune peptides paired with gene expression profiles, epiVIP demonstrated strong generalizability across unseen samples. Analyzing 33,711 neoantigens from clinical datasets revealed a compensatory relationship between abundance and non-selfness in determining antigenicity, providing quantitative support for the TCR avidity theory. Importantly, abundance independently predicted tumor reactivity and patient survival across multiple neoantigen vaccine cohorts and immune checkpoint blockade cohorts. Mechanistic interpretation of epiVIP further identified directional regulation of MAGEA3 epitope presentation by PSME4, which was validated experimentally using T cell functional assays. Together, these findings established AI-enabled virtual immunopeptidomics as a powerful strategy to improve cancer immunotherapy.

bioinformatics↗

bioRxiv2026

Phage-assisted continuous evolution of enzymes for noncanonical tyrosine biosynthesis

Genetic code expansion introduces new-to-nature chemical moieties into ribosomally synthesized proteins. In practice, the scope of functional groups that can be accessed using this method is often limited by noncanonical amino acid (ncAA) availability. Producing ncAAs directly in cells can circumvent poor ncAA uptake or commercial unavailability, but limited enzymes suitable for this application exist. In vitro evolution campaigns have been remarkably successful in yielding synthetically useful "ncAA synthases." However, these enzymes are optimized for preparative-scale synthesis and their activities often do not translate well to cellular biosynthesis. Thus, expanding strategies to engineer enzymes specifically for ncAA production within cells will benefit further implementation of genetic code expansion. Here, we use phage-assisted noncontinuous and continuous evolution to evolve enzymes for improved synthesis of non-canonical tyrosine derivatives in E. coli. Using simple serial passaging, we uncovered mutations that doubled the production of an expensive ncAA, 3-methoxytyrosine, by tyrosine phenol lyase, and furthermore evolved variants that enable 3-iodotyrosine biosynthesis, a transformation the parent enzyme is unable to catalyze. Additionally, we evolved a recently reported tyrosine synthase for improved production of 3-halogenated tyrosines, identifying variants that exhibit high activity even at low substrate concentrations owing to a [~]8-fold reduction in KM. Our results demonstrate that phage assisted evolution can be used to rapidly improve the activity of enzymes for ncAA production in cells.

synthetic biology↗

bioRxiv2026

A massively parallel reporter assay of MECP2 cis-regulatory elements reveals genetic candidates for male-biased autism

Autism affects males four times more often than females, yet the basis of this sex bias remains unclear. One hypothesis is that hypomorphic variants in X-linked genes--genes where loss-of-function alleles cause syndromic neurodevelopmental disorders (NDDs) predominantly in females--produce milder, non-syndromic phenotypes in hemizygous males. We tested this by investigating cis-regulatory elements (CREs) of MECP2, a dosage-sensitive X-linked gene. Using a massively parallel reporter assay in human neurons, we mapped transcription factor binding sites within MECP2 CREs and tested autism-associated variants for functional impact. We identified two noncoding variants that change CRE activity, each with a male-biased phenotype. One of these, a promoter variant, disrupts NFY binding and reduces MECP2 expression by [~]30%, a magnitude that produces autism-like phenotypes in mice. These findings suggest noncoding MECP2 variants can cause non-syndromic, male-biased autism, and provide a framework for uncovering regulatory variants in other X-linked NDD genes that may contribute to autisms missing heritability.

genetics↗

bioRxiv2026

Ovipositor morphology and mechanosensory divergence drive niche breadth expansion in Drosophila

Ecological niche breadth is key factor associated with adaptive radiation and speciation. For most Drosophila species, the firm surface of intact ripe fruit acts as a physical barrier to oviposition, effectively restricting them to the saprophagous resources. How species overcome such mechanical constraints at the behavioral and sensory levels, and whether doing so leads to niche breadth expansion or niche specialization, remain poorly understood. Here, using comparative behavioral assays across ten Drosophila species, we show that substrate physical hardness is a critical barrier preventing most species from exploiting ripe fruit. Among species capable of puncture oviposition, there are two distinct evolutionary strategies among Drosophila species. With its serrated ovipositor and strong preference for fresh fruit, D. suzukii represents a case of ripe-fruit specialization. In contrast, D. immigrans with the needle-like ovipositor, gains access to fresh fruit while retaining the ability to exploit decaying substrates, thereby expanding its resource niche. Thus, D. suzukii considered as the typical evolutionary niche specialization, while D. immigrans represents niche expansion. Furthermore, using the genetic toolkit of D. melanogaster, we further identify the Inactive (IAV) mechanosensory channel as important regulator of stiffness-dependent oviposition inhibition. Loss of iav reduced inhibition on firm substrates, while cross-species rescue experiments showed that IAV orthologs differed in their ability to restore this response in a common genetic background. Puncture oviposition was also associated with successful offspring development on firm fruit and with the use of firm-surfaced hosts under natural conditions. Together, these findings identified a novel niche expansion of D. immigrans among the saprophagous Drosophila.

evolutionary biology↗

bioRxiv2026

Microbiome-derived hydroxyphenyl propanoates enhance antitumour immunity by potentiating gasdermin D activity in tumour-associated myeloid cells

The microbiome plays a critical role in immune health and response to immune-stimulating treatments, including cancer immunotherapy. However, the molecular mechanisms by which commensal microbes influence cancer immunology remain poorly understood. Here, we report a class of microbiome-derived metabolites called hydroxyphenyl propanoates (HPP) that enhance tumour immune surveillance and response to immune checkpoint blockade (ICB) therapy in mice. HPPs function as potentiators of innate immune signalling in tumour-associated myeloid cells by promoting cleavage of the pore-forming protein gasdermin D (GSDMD), a critical effector of inflammasome function. This enhances the secretion of proinflammatory cytokines, such as IL-1 family members, while simultaneously protecting against pyroptosis. Secreted IL-1 family cytokines in turn elicit autocrine and paracrine inflammatory signaling in tumour-infiltrating leukocytes. HPP supplementation increases anticancer T cell function, improves disease control and extends overall survival (OS) in tumour-bearing mice harboring complex microbiomes or those treated with broad-spectrum antibiotics. In humans, GSDMD activation is associated with a favourable response to PD-1 blockade therapy in patients with advanced stage melanoma. Our study uncovers a molecular mechanism of regulation over host antitumour immunity that is modifiable and can be harnessed for improved cancer immunotherapy in a broad spectrum of patients.

cancer biology↗