Biology subjects

Yang, H.

Publications and source records attributed to Yang, H..

At least 91 records · Page 5Linked to original sources

bioRxiv2026

Circulating miR-10b-5p drives Kawasaki vasculitis through endothelial reprogramming and nominates CXCL8 as an early diagnostic biomarker

BackgroundKawasaki disease (KD) is an acute systemic vasculitis of unknown etiology and the leading cause of acquired heart disease in children. Coronary artery aneurysm formation represents its most serious complication, yet no specific biomarker exists for early diagnosis at emergency department (ED) presentation. We sought to define the molecular mechanisms driving KD vasculitis and to identify a clinically actionable early diagnostic marker. MethodsWhole microRNA sequencing was performed on buffy coat specimens from KD patients and febrile controls presenting to the ED. Disease-associated miRNA candidates were validated in two independent murine KD-like vasculitis models: Lactobacillus casei cell wall extract (LCWE; n=12-20) and Candida albicans water-soluble fraction (CAWS; n=12). The functional role of miR-10b-5p was assessed by antagomir-mediated inhibition in the LCWE model. Transcriptomic and chromatin-level reprogramming were characterized by single-cell RNA sequencing (scRNA-seq), bulk RNA-seq, and assay for transposase-accessible chromatin with sequencing (ATAC-seq) in human coronary artery endothelial cells (HCAECs). Transcription factor binding was validated by in vitro binding assays and chromatin immunoprecipitation. Serum chemokine (C-X-C motif) ligand 8 (CXCL8) was quantified by enzyme-linked immunosorbent assay. ResultsForty miRNAs were upregulated in KD patients and fourteen miRNAs were prioritized for further analysis. miR-10b-5p was consistently elevated across both vasculitis models, and its antagomir-mediated inhibition attenuated aortic root inflammation in vivo. In HCAECs, miR-10b-5p suppressed its direct targets marker of proliferation Ki-67 (MKI67)/Chromobox5 (CBX5), driving a cell-state transition from proliferative/metabolic programs toward a pro-inflammatory phenotype. Consistently, analyses of bulk RNA-seq supported cell-cycle arrest and altered chromatin remodeling. ATAC-seq revealed increased chromatin accessibility at the CXCL8 and Matrix metalloproteinases 10 (MMP10) promoters, and motif analysis identified CCAAT/enhancer-binding protein alpha (CEBPA) as the key transcriptional activator; CEBPA knockdown abrogated miR-10b-5p-induced CXCL8 and MMP10 upregulation. Serum CXCL8 was markedly elevated in KD patients relative to febrile controls at first ED presentation, prior to definitive diagnosis, and declined significantly at 8-week follow-up. ConclusionsWe define a miR-10b-5p-MKI67/CBX5-CEBPA-CXCL8 axis as a mechanistic driver of endothelial reprogramming and neutrophil-recruiting inflammation in KD. Serum CXCL8 emerges as a candidate early diagnostic biomarker that may facilitate timely KD recognition at ED presentation.

molecular biology↗

bioRxiv2026

Lempel-Ziv complexity of simultaneous surface electromyography and magnetomyography during muscle fatigue

ObjectiveComplexity-based metrics have been applied to surface electromyography (sEMG) to characterize fatigue-related changes in the temporal structure of myoelectric signals beyond amplitude and spectral features. Optically pumped magnetometers (OPM) are sensors that enable non-invasive recordings of magnetomyographic (MMG) signals from skeletal muscle and are increasingly used to complement surface electromyography; however, it remains unclear whether complexity measures derived from magnetic recordings are comparable to those obtained from sEMG. Here, we directly compared fatigue-related dynamics of conventional and complexity-based signal features of sEMG and OPM-MMG measured from the biceps brachii during sustained elbow flexion. ApproachHealthy participants performed isometric contractions at 20% maximal voluntary contraction (MVC; 20 min) or 60% MVC (3 min). sEMG and OPM-based MMG were recorded simultaneously, and signal median frequency, root mean square (RMS), and Lempel-Ziv (LZ) complexity were calculated over time. Main resultsAcross contraction intensities, sEMG and MMG showed consistent fatigue-related changes, characterized by increasing RMS, decreasing median frequency, and a progressive decline in LZ over time. In addition, multiple regression analyses indicated that the decrease in LZ was not fully accounted for by concurrent amplitude or spectral changes, suggesting that complexity captures aspects of signal organization that are not fully explained by established features. Finally, while sEMG showed higher LZ complexity and median frequency at 60% compared to 20% MVC, corresponding intensity-dependent effects were not observed in OPM-based MMG. SignificanceThese findings suggest that complexity-based metrics capture fatigue-related changes in neuromuscular signal organization beyond conventional measures, and that sEMG and OPM-based MMG provide similar, though modality-specific, information. Together, the results support the use of complexity metrics in multimodal electrophysiological and biomagnetic assessments of neuromuscular fatigue.

neuroscience↗

bioRxiv2026

The Receptor Kinase MEE39/ATHE Mediates Cell Wall Integrity Surveillance During Root Vascular Pathogen Infection

Plant cell wall (CW) integrity signaling enables early detection of microbial invasion, yet the receptors involved and their spatial and temporal dynamics during infection remain largely unknown. We identify ATHENA (ATHE)/MEE39, a previously uncharacterized malectin-like leucin-rich repeat receptor kinase (Mal-LRR-RK) that contributes to defense against the root vascular pathogen Fusarium oxysporum (Fo), particularly in outer root layers where colonization begins. ATHE abundance, localization, and endocytic trafficking are rapidly remodeled during infection, and loss of ATHE compromises basal immunity and early pathogen-induced transcriptional reprogramming. ATHE responds to altered cellulose synthesis, cellulose-derived oligosaccharides, mechanically induced CW perturbations, and the fungal secreted peptide Fo-RALF. In most of these contexts, ATHE acts together with the LRR-RK MIK2, forming a pathogen-strengthened RK complex that fine-tunes root responses to Fo. This represents the first example of a receptor complex visualized subcellularly in vivo during a plant-microbe interaction. Although Brassicaceae-specific, heterologous expression of ATHE enhanced tomato resistance to Fo, highlighting its functional relevance across plant lineages and its potential use for crop engineering. Our work reveals a previously unrecognized strategy by which plants decode microbial threats through dynamic CW-integrity surveillance.

plant biology↗

bioRxiv2026

Helicobacter pylori allelic variation in cell surface genes influences human exoproteome binding and stomach tissue adherence

Helicobacter pylori, the primary etiological agent of gastric cancer, requires chronic infection to promote severe disease. Throughout colonization, the bacteria accumulate genetic variation, which can reshape the interaction between host and pathogen. In this study, we probed adherence as one important characteristic of this relationship. We leveraged a panel of H. pylori strains, representing both inter- and intra-host diversity, and BASEHIT, a comprehensive barcoded yeast display library of the human exoproteome, to evaluate the human exoprotein binding characteristics of H. pylori. We identified a set of lineage-correlated binding phenotypes and a set of polymorphic cell surface-associated loci that we predict to govern heterogeneous binding. We also identified a general increase in gastric tissue adherence during mouse passage and structural modifications in the O-antigen component lipopolysaccharide. Subsequent sequence analyses identified C-terminal repeat length reduction in either futB or glycosyltransferase family 25 galactose transferases as sufficient to alter lipopolysaccharide. Shorter repeat variants were favored during both acute and chronic colonization and conferred a colonization advantage in coinfection. Our data indicate that shorter enzymes, and the resulting shorter O-antigen repeats, are favored during infection. We hypothesize that repeat length polymorphisms modulate enzyme efficiency and disrupt the balance of competing reactions required for O-antigen synthesis. ImportanceIn this study, we used a high throughput assay to evaluate the adherence of genetically diverse Helicobacter pylori isolates to human proteins they may encounter in the stomach. We showed that more closely related H. pylori strains bind human proteins similarly. We linked changes in bacterial binding to genetic differences affecting cell surface components. In particular, H. pylori strains passaged through mice exhibited increased adherence to stomach tissue, which we associated with structural variation in the enzymes responsible for synthesizing the O-antigen portion of lipopolysaccharide. We also showed that shorter enzyme variants produce distinct O-antigen structures that enhance colonization of the mouse stomach.

microbiology↗

bioRxiv2026

Hierarchical membrane-chromatin tethering buffers nuclear envelope assembly against alterations in lipid flux

In open mitosis, a single nuclear envelope (NE) forms around segregated chromosomes despite an excess of membrane-chromatin tethers. Here, we identify a hierarchical relationship between the BAF binding membrane tethers LEM-2 and Emerin, in which LEM-2 preferentially accumulates at BAF binding sites during postmitotic NE assembly and limits Emerin accumulation in C. elegans embryos. When LEM-2 is absent, Emerin occupies these sites and compensates for LEM-2 loss; however, NE formation becomes sensitized to ER membrane abundance - excessive phospholipid production through loss of CTDNEP1/CNEP-1 causes membrane invasions in interchromosomal regions and, across multiple systems, formation of lobulated, unstable nuclei with abnormal Emerin accumulations. We find that human CTDNEP1 regulates the NE-associated enzyme CCT to maintain phosphatidylcholine (PC) homeostasis through preventing delayed PC breakdown. Restoring PC levels rescues Emerin assembly and nuclear morphology defects resulting from the combined loss of CTDNEP1 and LEMD2. Together, these findings link membrane-chromatin tethering to ER lipid content and reveal preferential tethering as a determinant of NE assembly fidelity, with broad relevance to disease-related nuclear defects.

cell biology↗

bioRxiv2026

Combined Antibiotic and Herbicide Pollution Accelerates the Horizontal Transfer of Antibiotic Resistance Genes in Coastal Microbial Communities

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/708170v1_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@4c2513org.highwire.dtl.DTLVardef@116256corg.highwire.dtl.DTLVardef@f30846org.highwire.dtl.DTLVardef@1a44e00_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstractC_FLOATNO C_FIG The extensive use of herbicides and antibiotics in aquaculture has led to compounded pollution of coastal waters, marked by the co-occurrence of herbicides, antibiotic residues, and antibiotic resistance genes (ARGs). Plasmid-mediated conjugative transfer is a major driver of the dissemination and evolution of ARGs, yet the influence of herbicides alone or in combination with antibiotics on this process in aquatic bacterial communities remains unclear. In this study, we demonstrated that triazine herbicides, alone and in combination with a fluoroquinolone antibiotic, significantly promote the conjugative transfer of the broad-host-range RP4 plasmid. Using Escherichia coli DH5 as a donor, we observed increased plasmid transfer to multiple recipients, including E. coli HB101, Pseudomonas putida KT2440, and a natural coastal seawater microbial community. The enhanced transfer under co-exposure was associated with several interacting mechanisms, including elevated intracellular reactive oxygen species (ROS) and adenosine triphosphate (ATP) levels, increased cell membrane permeability, altered extracellular polymeric substance (EPS) composition, and upregulated expression of conjugation-related genes. Overall, this work underscores the potential role of combined herbicide and antibiotic contamination in shaping the microbial resistome of coastal ecosystems and provides insights to inform strategies for mitigating the spread of antibiotic resistance.

microbiology↗

bioRxiv2026

Mitotic bookmarking by Prox1 preserves mammalian neuronal lineage identity memory via promoting timely H3K27me3 restoration

Mitosis poses a daunting challenge to transgenerational inheritance of cell identity memory. How neuronal lineage identity is faithfully transmitted across mitosis remains largely unexplored. Here we report that, in mouse hippocampus, the transcription factor Prox1 acts as a mitotic bookmark for safeguarding neuronal lineage identity across cell divisions. Prox1 exhibits mitotic retention in dentate gyrus (DG) neural stem cells and defines DG lineage identity by suppressing the alternative cornu ammonis (CA) identity. Mitotic bookmarking by Prox1 at key bivalent CA identity genes promotes timely and precise restoration of Polycomb repressive complex 2 (PRC2)-mediated H3K27me3 deposition to avoid ectopic expression of CA identity genes and lineage identity crisis. Remarkably, specific mitotic retention-deficient Prox1 conditional knock-in mice produce severe DG developmental defects. Thus, mitotic bookmarking imprints neuronal lineage identity in mouse hippocampus, which is likely to represent a fundamental principle underlying the preservation of lineage identity memory in mammalian brain development.

developmental biology↗

bioRxiv2026

Unified Transcriptome and Mechanics Map of the Intact Mammalian Preimplantation Embryo In Situ

The development and maintenance of multicellular tissues requires that cell states be closely coupled to their local environment, including geometric and mechanical cues. However, studying this coupling in intact tissues has been challenging, because existing measurement technologies cannot simultaneously assess mechanical properties and molecularly defined cell states. To address this gap, we introduce the Unified Transcriptome and Mechanics Map (UTMM), a method for concurrent measurement of the transcriptome and cytoplasmic stiffness (high-frequency elastic modulus) within intact 3D multicellular structures. UTMM relies on two innovations: (1) a targeted in situ RNA sequencing approach for intact 3D embryos (3DISS), and (2) a strategy that leverages high-frequency intracellular organelle fluctuations to infer cell-level stiffness in vivo. We applied UTMM to mouse embryos from the zygote through the morula stage to characterize how RNA expression and cytoplasmic stiffness become coupled during early lineage specification. Our data reveal that, in the early morula, transcriptional and morphological distinctions emerge between trophectoderm and inner cell mass (ICM) lineages, coinciding with a gradual decrease in cytoplasmic stiffness (softening) across all cells from the 2-cell through morula stages. Furthermore, we observe that early lineage biases align with differential mechanical properties, reflecting distinct emerging developmental programs. When we delayed this softening process via mechanical perturbation, embryonic progression was impeded, highlighting the functional importance of coordinated mechanical and transcriptional changes. Together, these results demonstrate UTMMs ability to bridge molecular and mechanical dynamics in multicellular systems, providing a powerful framework for investigating how biomechanical cues shape cell fate decisions in intact tissues. One Sentence SummaryJoint 3D in situ quantification of spatial transcriptome and cytoplasm mechanics in preimplantation mammalian embryos

developmental biology↗

bioRxiv2026

Cell Type Architecture and Positional Gene Gradients in an Adult Animal at Subcellular Resolution

The spatial organization of cell types and gene expression underlies tissue architecture and organismal physiology. However, resolving complete cellular and molecular landscapes within a three-dimensional context remains challenging, particularly in organisms with high cellular heterogeneity and complex geometry. Here, we developed a semi-supervised workflow to reconstruct high-resolution three-dimensional spatial transcriptomic models of the planarian Schmidtea mediterranea at single-cell resolution. Planarians are basal bilaterians capable of regenerating body structures after injury. Our reconstruction maps the distribution of cell types and spatially patterned gene expression across the intact organism and identifies 119 candidate positional control genes (PCGs). These genes are expressed across muscle, neural, and epidermal populations. Functional perturbation of selected candidates, including pitx3, ptpn11, pi4ka, upf3b, and cul1, revealed roles in regeneration following injury. In addition, we identify intestinal cells as prominent components of the microenvironment surrounding adult tgs1 pluripotent stem cells (neoblasts). Together, these results demonstrate the utility of three-dimensional spatial transcriptomic reconstruction for mapping cellular architecture and positional gene regulation in complex adult organisms.

developmental biology↗

bioRxiv2026

Super-resolution single-cell spatial atlas of plant de novo regeneration

Plant de novo regeneration, a capacity absent in animals, relies on stem-cell-niche formation rather than pre-existing reservoirs. Growth hormones such as auxin and cytokinin, together with numerous genetic regulators, participate in regeneration, but the architectural principles coordinating extensive cellular reprogramming at the individual-cell scale remain elusive. Using super-resolution multimodal spatial transcriptomics to 1.16 million cells, we tracked tomato regeneration across temporal intervals from wounding to organogenesis. Datasets are available at http://www.single-cell-spatial.com.

cell biology↗

bioRxiv2026

4D Single-Cell Spatial Transcriptomics Reveals Dynamic Morphogenetic Gradients and Regenerative Domains in Planarians

Regeneration relies on precise spatiotemporal gene expression and cellular responses to establish tissue identity and body patterning. Using high-resolution Stereo-seq (715 nm) on 353 sections from 16 whole animals at 8 regeneration timepoints, we constructed a 4D spatiotemporal transcriptomic map of planarian regeneration. Our analysis captured 36 refined cell types from 3,508,004 segmented cells, enabling genome-wide transcriptional imputation of gene expression dynamics across body axes at cellular, tissue, and organismal scales. We identified dynamic positional gradients and distinct spatially distributed cell types during regeneration, including an injury-induced Anterior Regenerative Zone (ARZ). The ARZ exhibited enriched positional signals in epidermal, muscle, and neural cells and was regulated by Mediator 8, which is crucial for polarity remodeling and blastema formation. This study provides a comprehensive spatial molecular and cellular map of regenerative processes, highlighting injury-induced spatial domains and key regulatory factors in planarian regeneration. We also provide an interactive web portal, offering a valuable resource for exploring and analyzing regeneration mechanisms in a spatiotemporal context.

developmental biology↗

bioRxiv2026

Mechanism of substrate recognition and catalysis in a mammalian phosphatidylserine synthase 2

Mammalian phosphatidylserine synthase-1 and -2 synthesize phosphatidylserine (PS) by replacing the headgroup of either phosphatidylcholine (PC, PTDSS1) or phosphatidylethanolamine (PE, PTDSS2) with a serine. We determined structures of PTDSS2 from Equus caballus in complex with either PE or serine substrates to resolutions of 2.8-3.2 [A]. The structures define substrate binding sites and reveal that the phosphate group of PE is coordinated by two Ca2+. In addition, we found that PTDSS2 has significant phospholipase D (PLD) activity in the absence of serine, which was not reported previously, and that Ca2+ is required for the PLD activity. These discoveries enrich our knowledge in the mechanism of mammalian PTDSS.

biochemistry↗

bioRxiv2026

The genetic repertoire of the deep sea: from sequence to structure and function

The deep sea as the largest and maybe most hostile environment on Earth is still underexplored especially regarding its genetic repertoire. Yet, previous work has revealed significant habitat-specific deep-sea biodiversity. Here, we present an integrated deep-sea genetic dataset comprising 502 million nonredundant genes from 2,138 samples and 2.4 million predicted structures, and used it to link specific protein structures with genetic variants associated with life in the deep sea and to assess their biotechnology potential. Combining global sequence analysis with biophysical and biochemical measurements revealed unprecedented sequence diversity, yet substantial structural conservation of proteins. Especially proteins involved in replication, recombination, and repair were identified to be under rapid evolution and with specialized properties. Among these, a structurally divergent helicase exhibited advantages in controlling nanopore sequencing speed. Thus, our work positions the deep sea as a unique evolutionary engine that generates and hosts genetic diversity and bridges genetic knowledge with biotechnology.

bioinformatics↗

bioRxiv2026

Batrachotoxin Sensitive Sodium Channels in Toxic Birds Challenge "Target Mutation" Strategy of Toxin Autoresistance

Voltage-gated sodium channels (NaVs) are essential for muscle and nerve activity, and are therefore prime targets of natural toxins. Batrachotoxin (BTX) is uniquely potent among NaV-directed alkaloids. Southern and Central American Phyllobates poison dart frogs and multiple species of New Guinean toxic birds accumulate dietary BTX without self-poisoning. Two broad autoresistance models have been proposed: 1) "target mutation," in which NaV substitutions reduce BTX action, and 2) "toxin sequestration," in which high-affinity binding proteins or compartmentalization limit toxin access to channels. A recent report identified two NaV1.4 substitutions, D1050N and S1568P, under positive selection in toxic birds, including two newly discovered BTX-bearing birds, Pachycephala schlegelii and Aleadryas rufinucha, and suggested a "target mutation" strategy for these passerines. Here, we test that hypothesis using structure-guided mapping and electrophysiology. The substitutions map to solvent-exposed positions tens of angstroms away from inner-cavity BTX sites, inconsistent with direct effects on BTX binding. Heterologously expressed mutant channels exhibit wild-type activation and steady-state inactivation, lacking the biophysical "costs" typical of pore-lining resistance mutations. Importantly, all constructs remain fully BTX-sensitive, showing canonical shifts in activation and persistent currents upon toxin exposure. These data argue that NaV1.4 substitutions do not confer BTX autoresistance in toxic birds. This finding, together with prior work in BTX-carrying frogs and birds, is consistent with a generalized sequestration model. Identifying the responsible BTX-binding factors could enable antidote design and broaden strategies for neutralizing NaV-targeting toxins.

biophysics↗

bioRxiv2026

Macrophage Antigen Presentation Is Unleashed by Pan-RAS Inhibition to Promote Antitumor Immunity

Pan-RAS inhibitors have emerged as potent targeted therapies designed to suppress oncogenic signaling in RAS-mutant tumors. However, whether these inhibitors possess therapeutic utility beyond tumors with intrinsic RAS dependency remains unclear. Here we show that the clinical-stage pan-RAS(ON) inhibitor RMC-6236 (Daraxonrasib) induces robust regression of NRAS-wild-type B16 tumors in immunocompetent mice, a response mediated by a mechanism independent of direct tumor-cell targeting. Instead, RMC-6236 acts by remodeling the tumor microenvironment, specifically enhancing the antigen-presenting capacity of tumor-associated macrophages through upregulated MHC-I expression. This anti-tumor efficacy is abrogated in T cell-deficient hosts, identifying a macrophage-dependent, T cell-mediated mechanism of control. Mechanistically, RMC-6236 does not directly block canonical RAS signaling in macrophages. Rather, it suppresses a Myc-Hdac2 epigenetic program, leading to enhanced histone H4 acetylation at the Nlrc5 locus and subsequent activation of the MHC-I master regulator NLRC5. Together, our findings reveal a macrophage-centered, epigenetically wired immune mechanism for pan-RAS inhibition that broadens the therapeutic scope of targeting the "undruggable" RAS pathway beyond tumor genotype towards systemic immune modulation.

immunology↗

bioRxiv2026

Spatially resolved transcriptome-metabolome integration reveals region-specific glial lipid dysregulation associated with Alzheimer's pathology

Glial cells maintain the brains lipid and energy balance, and their breakdown is increasingly recognized as a causal contributor to Alzheimers disease (AD). While this concept is established, no approach has directly shown how glial homeostatic failure manifests across brain regions and microenvironments or how it links local pathology, such as plaques, to global metabolic imbalance. To address this gap, we developed iMIST, an integrated platform that combines MALDI-based metabolite imaging, histology, and spatial transcriptomics within a single tissue section to align molecular and anatomical information. Using a mouse model of late-onset AD that recapitulates both amyloid deposition and metabolic vulnerability, iMIST revealed that glial lipid dysregulation is widespread but spatially specialized. In gray matter, plaque-associated microglia were associated with upregulated glycerophospholipid-remodeling in cortico-thalamic areas indicating metabolic stress around local pathology. In contrast, white matter tracts rich in lipid-producing oligodendrocytes show plaque-independent deficits in galactosylceramide metabolism reflecting their high myelin demand. Both processes intensify with age, transforming adaptive glial responses into persistent metabolic dysfunction. Together, these findings demonstrate the spatial interplay between global glial metabolic imbalance and local microenvironmental stressors associated with AD pathology. By integrating transcriptomic and metabolomic information in situ, iMIST provides a framework for uncovering how regional glial vulnerability shapes the pathogenesis of neurodegenerative diseases.

neuroscience↗

bioRxiv2026

Cannabidiol Inhibits PIEZO Channels to Mitigate Red Blood Disorders

Hyperactivity of the mechanosensitive ion channel PIEZO1 promotes pathologic Ca{superscript 2} overload in red blood cells (RBCs), driving dehydration, TMEM16F-dependent phosphatidylserine (PS) exposure, microparticle shedding, and increased thrombotic and vaso-occlusive risks in hereditary xerocytosis (HX) and sickle cell disease (SCD). However, clinically deployable PIEZO inhibitors to treat these blood disorders are lacking. Here we report that cannabidiol (CBD), a non-psychoactive cannabinoid commonly used in SCD patients for pain management, inhibits PIEZO1 activity and restores aberrant mechanotransduction in HX and SCD RBCs. Micromolar concentrations of CBD blocks PIEZO1 currents and suppresses PIEZO1-mediate Ca{superscript 2} entry. In HX and SCD RBCs, CBD attenuates PIEZO1-TMEM16F coupling, thereby reducing PS exposure, microparticle release, thrombin generation, RBC-endothelium adhesion, and sickling. Beyond RBCs, CBD also blocks PIEZO2 currents and PIEZO2-dependent mechanical sensation in mice, suggesting broader effects of CBD-mediated PIEZO inhibition on nociceptive functions. Together, our findings identify CBD as a potent PIEZO inhibitor that restores calcium and membrane homeostasis, supporting the repurposing of CBD or the development of CBD-derived, PIEZO-selective analogs as a promising disease-modifying strategy for SCD, HX, and other PIEZO-mediated mechanosensing disorders. HighlightsO_LICBD inhibits PIEZO channels and disrupts the PIEZO1-TMEM16F axis in diseased RBCs C_LIO_LICBD shows a therapeutic window to prevent PS exposure and translational promise for HX and SCD C_LI

pharmacology and toxicology↗

bioRxiv2026

A patient derived xenograft repository capturing clinical and molecular heterogeneity of large B-cell lymphoma

Large B-cell lymphomas (LBCLs) are a clinically and molecularly diverse group of malignancies with a rapidly evolving therapeutic landscape that has introduced new areas of clinical need such as post-CD19 chimeric antigen receptor T (CART19) progression. Patient derived xenograft (PDX) models are an important tool for mechanistic studies and preclinical evaluation of new therapies and can be generated from a variety of clinical contexts that capture tumor-intrinsic resistance mechanisms. We therefore undertook a comprehensive effort to generate PDX models that encompass the molecular landscape of LBCLs and include important clinical scenarios for new drug development. Here we describe the first 48 models within this publicly available repository, capturing the transcriptional and genetic subsets of LBCL. These models also include 23 generated from post-CART progression biopsies which reproduce patterns of progression driven by CD19 mutation or expression loss, as well as tumor cell-intrinsic CART19 resistance that we validate in vivo. STATEMENT OF SIGNIFICANCEYang et al. describe X-LYMPH (Xenografts of Lymphoma), a publicly available and molecularly annotated PDX repository that captures the heterogeneity of large B-cell lymphoma. X-LYMPH includes models of chimeric antigen receptor T cell resistance, providing a shared foundation for mechanistic research and therapeutic development for lymphomas.

cancer biology↗