Biology subjects

Huang, P.

Publications and source records attributed to Huang, P..

At least 73 records · Page 4Linked to original sources

bioRxiv2024

Dynamic BMP signaling regulates sclerotome induction and lineage diversification in zebrafish

The sclerotome is an embryonic structure that gives rise to various supportive tissues, including the axial skeleton and connective tissues. Despite its significance, the mechanisms underlying sclerotome induction and diversification during embryonic development remain poorly understood. Sclerotome progenitors exhibit transient bmp4 expression and an active response to BMP signaling. Using BMP gain- and loss-of-function tools, we demonstrate that BMP signaling is both necessary and sufficient for sclerotome induction. Furthermore, through mosaic expression of a dominant-negative tool, we show that BMP signaling induces sclerotome fate in a cell-autonomous manner. Interestingly, different populations of sclerotome-derived cells have distinct BMP signaling requirements. Sclerotome-derived notochord-associated cells in the trunk lack BMP response, and sustained BMP signaling inhibits their differentiation into tenocytes. By contrast, sclerotome-derived fin mesenchymal cells in the fin fold require high levels of BMP signaling for proper morphogenesis. Our findings suggest that dynamic regulation of BMP signaling is crucial for the induction of the sclerotome and the subsequent diversification of sclerotome-derived lineages in zebrafish.

developmental biology↗

bioRxiv2024

Pangenome-Informed Language Models for Privacy-Preserving Synthetic Genome Sequence Generation

Language Models (LM) have been extensively utilized for learning DNA sequence patterns and generating synthetic sequences. In this paper, we present a novel approach for the generation of synthetic DNA data using pangenomes in combination with LM. We introduce three innovative pangenome-based tokenization schemes that enhance DNA sequence generation. Our experimental results demonstrate the superiority of pangenome-based tokenization over classical methods in generating high-utility synthetic DNA sequences, highlighting significant improvements in training efficiency and sequence quality.

bioinformatics↗

bioRxiv2024

A widespread hydrogenase drives fermentative growth of gut bacteria in healthy people

Molecular hydrogen (H2) is among the most central, but least understood, metabolites in the human gastrointestinal tract (gut). H2 gas is produced in large quantities during bacterial fermentation and consumed as an energy source by bacteria and archaea. Disruption of H2 cycling is linked to gastrointestinal disorders, infections, and cancers, with H2 used as an indicator of gut dysfunction through breath tests. Despite this, the microorganisms, pathways, and enzymes mediating H2 production remain unresolved. Here we show that a previously uncharacterised enzyme, the group B [FeFe]-hydrogenase, drives most fermentative H2 production in the human gut. Analysis of stool, biopsy, and isolate (meta)genomes and (meta)transcriptomes show this hydrogenase is encoded by most gut bacteria and is highly expressed. Through analysis of 19 taxonomically diverse gut isolates, the group B [FeFe]-hydrogenase produces large amounts of H2 gas and supports fermentative growth of both Bacteroidetes and Firmicutes. Bacteroides particularly dominate H2 production. Biochemical and spectroscopic characterisation shows purified group B [FeFe]-hydrogenases are catalytically active and bind a di-iron active site. These hydrogenases are highly enriched in the guts of healthy individuals, but significantly depleted in favour of other fermentative hydrogenases in Crohns disease. Furthermore, we show that metabolically flexible respiratory bacteria are the most abundant H2 oxidizers in the gut, not sulfate reducers, methanogens, and acetogens as previously thought. This combination of enzymatic, cellular, and ecosystem-level analysis provides the first detailed understanding of H2 cycling in the human gut and reveals new links between microbiota function and gastrointestinal health.

microbiology↗

bioRxiv2024

PGSFusion streamlines polygenic score construction and epidemiological applications in biobank-scale cohorts

BackgroundThe polygenic score (PGS) is an estimate of an individuals genetic susceptibility to a specific complex trait and has been instrumental to the development of precision medicine. Clinically, the simplest form of PGS, which is calculated as a weighted sum of variant counts, has been widely applied to conduct disease risk classification. Unfortunately, despite the critical importance of PGS, there are few online resources available to biologists and epidemiologists to calculate PGS in a user-friendly manner. ResultsTo address this need, we have developed a web server, PGSFusion, that streamlines the construction of PGS using a large variety of methods targeting different epidemiological requirements. PGSFusion included 16 PGS methods in four categories, which are single-trait, annotation-based, multiple-trait, and cross-ancestry. In addition, PGSFusion also utilizes UK Biobank data to provide two kinds of in-depth analyses: i) prediction performance evaluation to display the consistency between PGS and specific traits and the effect size of PGS in different genetic risk groups; ii) joint effect analysis to investigate the interaction between PGS and covariates, as well as the genetic effect size in different subgroups of covariates. PGSFusion automatically identifies the required information in uploaded summary statistics files, provides a selection of suitable methods, and outputs calculated PGSs and their corresponding epidemiological results, all without requiring prior programming knowledge. To demonstrate the function of PGSFusion, we showcase three case studies in different application scenario, highlighting its versatility and values to researchers. ConclusionsOverall, PGSFusion presents an easy-to-use, effective, and extensible platform for PGS construction, promoting the accessibility and utility of PGS for researchers in the field of precision medicine.

bioinformatics↗

bioRxiv2024

CHRONIC LUNG INFLAMMATION LEADS TO MYELOID SKEWING OF HEMATOPOIETIC STEM CELLS IN A CYSTIC FIBROSIS MOUSE MODEL

Persistent lung inflammation is a hallmark of Cystic fibrosis (CF) lung disease. Inflammation can lead to functional decline in hematopoietic stem cell (HSCs), tipping the balance towards myelopoiesis and contributing to chronic inflammation. However, its unknown whether the HSCs are dysfunctional in CF. We tested whether chronic lung inflammation impacts hematopoietic stem and progenitor cells (HSPCs) in a CF mouse model. Wild-type (WT) and Cftr-/- mice were nebulized with lipopolysaccharide (LPS) from Pseudomonas aeruginosa for 5 weeks. The mice were euthanized before the exposure (T0), 24 hours after the last LPS nebulization (T1), or 6 weeks (T2) after the last LPS nebulization. The bone marrow (BM) and lung tissue were collected for flow cytometry analysis of the HSPC population and immune cells in the lungs, respectively. Peripheral blood was collected for complete blood count analysis. At baseline, Cftr-/- mice show a larger HSPC population with a myeloid bias, indicated by higher frequencies of LSK, LT-HSC, CD41+ LT-HSC, GMPs, and MkPs. Following chronic LPS nebulization, Cftr-/- mice exhibit greater HSPC expansion and myeloid differentiation, alongside increased peripheral myeloid cell counts. Post-recovery, while most HSPC populations return to baseline, Cftr-/- mice retain elevated myeloid-biased LT-HSCs, suggesting a persistent myeloid bias. These findings underscore a prominent shift toward myeloid hematopoiesis in CF, which is accentuated by chronic inflammation and remains even after recovery. Further experiments are underway to assess maladaptive epigenetic changes in HSC as well as if chronic lung inflammation impacts HSC functionality.

immunology↗

bioRxiv2024

BLEND: Probabilistic Cellular Deconvolution with Automated Reference Selection

Cellular deconvolution aims to estimate cell type fractions from bulk transcriptomic and other omics data. Most existing deconvolution methods fail to account for the heterogeneity in cell type-specific (CTS) expression across bulk samples, ignore discrepancies between CTS expression in bulk and cell type reference data, and provide no guidance on cell type reference selection or integration. To address these issues, we introduce BLEND, a hierarchical Bayesian method that leverages multiple reference datasets. BLEND learns the most suitable references for each bulk sample by exploring the convex hulls of references and employs a "bag-of-words" representation for bulk count data for deconvolution. To speed up the computation, we provide an efficient EM algorithm for parameter estimation. Notably, BLEND requires no data transformation, normalization, cell type marker gene selection, or reference quality evaluation. Benchmarking studies on both simulated and real human brain data highlight BLENDs superior performance in various scenarios. The analysis of Alzheimers disease data illustrates BLENDs application in real data and reference resource integration.

bioinformatics↗

bioRxiv2024

Optimization of gene knockout approaches and practical solutions to sgRNA selection challenges in hPSCs with inducible Cas9 system

RationaleCRISPR/Cas9 has been extensively used to knock out genes, allowing the study of genetic loss-of-function in human pluripotent stem cells (hPSCs). However, the current use of the Cas9-sgRNA plasmid or iCas9 system for gene editing in hPSCs has resulted in limited and inconsistent editing efficiency, as well as labor-intensive work. Additionally, identifying single-guide RNAs (sgRNAs) with high cleavage efficiency and distinguishing them from ineffective ones, which efficiently induce frameshift INDELs (Indels and Deletions) but fail to eliminate target proteins expression, are major challenges in gene knockout experiments. MethodsThis study addresses above issues using an optimized doxycycline-induced spCas9-expressing hPSCs (hPSCs-iCas9) system. We initially developed this system by optimizing a number of parameters to maximize INDELs introducing efficiency in hPSCs-iCas9 cells. The INDELs determined by this system were then compared to predicted scores from three cleavage efficiency scoring algorithms to validate the algorithms accuracy and consistency. Furthermore, we conducted gene knockout using a set of sgRNAs targeting different exons of the ACE2 gene to achieve approximately 80% INDELs for each targeting locus. Western blotting was then performed to detect ACE2 protein expression levels, enabling the identification of potentially ineffective sgRNAs. ResultsSeveral critical factors, including cell tolerance to nucleofection stress, sgRNA stability, nucleofection frequency, and the cell-to-sgRNA ratio, were found to have significant impact on editing efficiency in hPSCs-iCas9. Fine-tuning these parameters markedly improved this efficiency, resulting in up to 93% INDELs for single gene knockout. The three scoring algorithms exhibited significant differences or even conflicts in scoring cleavage efficiency. Through comparing experimental observations to predicted scores, we discovered that the Benchling algorithm outperformed the other two in terms of accuracy and consistency. Furthermore, a sgRNA targeting exon 2 of ACE2 gene was quickly identified as ineffective, as evidenced by the edited cells pool containing 80% INDELs while ACE2 protein expression retained unchanged detected by Western blot. ConclusionThe findings of this study offer valuable insights into the optimal design of gene knockout experiments in hPSCs and provide practical solutions to sgRNA selection challenges for gene editing.

cell biology↗

bioRxiv2024

Spatial organization of PI3K-PI(3,4,5)P3-AKT signaling by focal adhesions

The class I PI3K-AKT signaling pathway is the master regulator of cell survival, growth, and proliferation, and among the most frequently mutated pathways in cancer. However, where and how the PI3K-AKT signaling is spatially activated and organized in mammalian cells remain poorly understood. Here, we identified focal adhesions (FAs) as the subcellular signaling hubs organizing the activation of PI3K-PI(3,4,5)P3-AKT signaling in mammalian cells. We found that class IA PI3Ks are preferentially and dynamically recruited to FAs for activation, resulting in localized production of the critical signaling lipid PI(3,4,5)P3 around FAs. As the effector protein of PI(3,4,5)P3, AKT molecules are dynamically recruited around FAs for activation. Mechanistically, the spatial recruitment/activation of PI3K-PI(3,4,5)P3-AKT cascade are regulated by the activated FAK. Furthermore, combined inhibition of class I PI3K and FAK results in a more potent inhibitory effect on cancer cells. Thus, our results unveil a growth-factor independent, compartmentalized organization mechanism for PI3K-PI(3,4,5)P3-AKT signaling.

cell biology↗

bioRxiv2024

Characterizing neuroinvasion and neuropathology of SARS-CoV-2 by using AC70 human ACE2 transgenic mice

COVID-19 presents with a plethora of neurological signs and symptoms despite being characterized as a respiratory disease, including seizures, anxiety, depression, amnesia, attention deficits, and alterations in consciousness. The olfactory nerve is widely accepted as the neuroinvasive route by which the etiological agent SARS-CoV-2 enters the brain, but the trigeminal nerve is an often-overlooked additional route. Based on this consensus, we initially conducted a pilot experiment investigating the olfactory nerve route of SARS-CoV-2 neuroinvasion via intranasal inoculation in AC70 human ACE2 transgenic mice. Notably, we found that the trigeminal ganglion is an early and highly efficient site of viral replication, which then rapidly spread widely throughout the brain where neurons were primarily targeted. Despite the extensive viral infection across the brain, obvious evidence of tissue pathology including inflammatory infiltration, glial activation, and apoptotic cell deaths were not consistently observed, albeit inflammatory cytokines were significantly induced. However, the expression levels of different genes related to neuronal function, including the neurotransmitter dopamine pathway as well as synaptic function, and markers of neuronal damage were altered as compared to mock-infected mice. Our findings suggest that the trigeminal nerve can be a neuroinvasive route complementary to the olfactory nerve and that the ensuing neuroinvasion presented a unique neuropathological profile. This study provides insights into potential neuropathogenic mechanisms utilized by coronaviruses. IMPORTANCECOVID-19 presents with extrapulmonary signs and symptoms, the most notable of which involve the central nervous system, such as seizures and alterations in consciousness, and can eventually lead to death if severe enough. Some neurological signs and symptoms may continue to persist in some patients even after the resolution of active viral infection in the form of post-acute sequelae. Since the trigeminal nerve is a commonly under-studied route of entry into the brain in studies of coronaviruses and the neuropathogenic mechanisms of COVID-19 are not entirely elucidated, there is a need to thoroughly investigate this route of neuroinvasion. The significance of our research is in providing insights into the possible routes of SARS-CoV-2 neuroinvasion as well as the discovery of potential neuropathogenic mechanisms which may help guide the development of novel medical countermeasures.

pathology↗

bioRxiv2024

MegaKG: Toward an explainable knowledge graph for early drug development

In biomedical research, the utilization of Knowledge Graph (KG) has proven valuable in gaining deep understanding of various processes. In this study, we constructed a comprehensive biomedical KG, named as MegaKG, by integrating a total of 23 primary data sources, which finally consisted of 188, 844 nodes/entities and 9, 165, 855 edges/relations after stringent data processing. Such a massive KG can not only provide a holistic view of the entities of interest, but also generate insightful hypotheses on unknown relations by applying AI computations. We focused on the interplay of the key elements in drug development, such as genes, diseases and drugs, and aimed to facilitate practical applications that could benefit early drug development in industries. More importantly, we placed much emphasis on the exploitability of the predictions generated by MegaKG. This may greatly help researchers to assess the feasibility or design appropriate downstream validation experiments, making AI techniques more than just black-box models. In this regard, NBFNet was adopted, which combines the advantages of both traditional path-based methods and more recently developed GNN-based ones. Performance evaluation experiments indicated superior results by MegaKG. We also conducted real case studies to validate its practical utility in various scenarios, including target prediction, indication extension and drug repurposing. All these experiments highlighted the potential of MegaKG as a valuable tool in driving innovation and accelerating drug development in pharmaceutical industry.

bioinformatics↗

bioRxiv2024

Charting the Spatial Transcriptome of the Human Cerebral Cortex at Single-Cell Resolution

In our pursuit of creating a comprehensive human cortical atlas to understand human intelligence, we examined the single-nuclei transcriptomes of 307,738 cells alongside spatial transcriptomics data from 46,948 VISIUM spots and 1,355,582 Stereo cells. Atlases reveal distinct expression patterns and spatial arrangements of cortical neural cell types. Glutamatergic neurons exhibit precise laminar patterns, often mirroring expression patterns in adjacent cortical regions. Overlaying our atlas with functional networks delineated substantial correlations between neural cell types and cortical region function. Notably, regions involved in processing sensory information (pain) display a pronounced accumulation of extratelencephalic neurons. Additionally, our atlas enabled precise localization of the thicker layer 4 of the visual cortex and an in-depth study of the stabilize the subplate structure, known as layer 6b, revealed specific marker genes and cellular compositions. Collectively, our research sheds light on the cellular foundations of the intricate and intelligent regions within the human cortex.

neuroscience↗

bioRxiv2024

A general platform for targeting MHC-II antigens via a single loop

Class-II major histocompatibility complexes (MHC-IIs) are central to the communications between CD4+ T cells and antigen presenting cells (APCs), but intrinsic structural features associated with MHC-II make it difficult to develop a general targeting system with high affinity and antigen specificity. Here, we introduce a protein platform, Targeted Recognition of Antigen-MHC Complex Reporter for MHC-II (TRACeR-II), to enable the rapid development of peptide-specific MHC-II binders. TRACeR-II has a small helical bundle scaffold and uses an unconventional mechanism to recognize antigens via a single loop. This unique antigen-recognition mechanism renders this platform highly versatile and amenable to direct structural modeling of the interactions with the antigen. We demonstrate that TRACeR-II binders can be rapidly evolved across multiple alleles, while computational protein design can produce specific binding sequences for a SARS-CoV-2 peptide of unknown complex structure. TRACeR-II sheds light on a simple and straightforward approach to address the MHC peptide targeting challenge, without relying on combinatorial selection on complementarity determining region (CDR) loops. It presents a promising basis for further exploration in immune response modulation as well as a broad range of theragnostic applications.

bioengineering↗

bioRxiv2024

The Gut Microbiome Controls Liver Tumors via the Vagus Nerve

Liver cancer ranks amongst the deadliest cancers. Nerves have emerged as an understudied regulator of tumor progression. The parasympathetic vagus nerve influences systemic immunity via acetylcholine (ACh). Whether cholinergic neuroimmune interactions influence hepatocellular carcinoma (HCC) remains uncertain. Liver denervation via hepatic vagotomy (HV) significantly reduced liver tumor burden, while pharmacological enhancement of parasympathetic tone promoted tumor growth. Cholinergic disruption in Rag1KO mice revealed that cholinergic regulation requires adaptive immunity. Further scRNA-seq and in vitro studies indicated that vagal ACh dampens CD8+ T cell activity via muscarinic ACh receptor (AChR) CHRM3. Depletion of CD8+ T cells abrogated HV outcomes and selective deletion of Chrm3 on CD8+ T cells inhibited liver tumor growth. Beyond tumor-specific outcomes, vagotomy improved cancer-associated fatigue and anxiety-like behavior. As microbiota transplantation from HCC donors was sufficient to impair behavior, we investigated putative microbiota-neuroimmune crosstalk. Tumor, rather than vagotomy, robustly altered fecal bacterial composition, increasing Desulfovibrionales and Clostridial taxa. Strikingly, in tumor-free mice, vagotomy permitted HCC-associated microbiota to activate hepatic CD8+ T cells. These findings reveal that gut bacteria influence behavior and liver anti-tumor immunity via a dynamic and pharmaceutically targetable, vagus-liver axis.

cancer biology↗

bioRxiv2023

Lymphatic muscle cells are unique cells that undergo aging induced changes

Lymphatic muscle cells (LMCs) within the wall of collecting lymphatic vessels exhibit tonic and autonomous phasic contractions, which drive active lymph transport to maintain tissue-fluid homeostasis and support immune surveillance. Damage to LMCs disrupts lymphatic function and is related to various diseases. Despite their importance, knowledge of the transcriptional signatures in LMCs and how they relate to lymphatic function in normal and disease contexts is largely missing. We have generated a comprehensive transcriptional single-cell atlas--including LMCs--of collecting lymphatic vessels in mouse dermis at various ages. We identified genes that distinguish LMCs from other types of muscle cells, characterized the phenotypical and transcriptomic changes in LMCs in aged vessels, and uncovered a pro-inflammatory microenvironment that suppresses the contractile apparatus in advanced-aged LMCs. Our findings provide a valuable resource to accelerate future research for the identification of potential drug targets on LMCs to preserve lymphatic vessel function as well as supporting studies to identify genetic causes of primary lymphedema currently with unknown molecular explanation.

cell biology↗

bioRxiv2023

The MYC axis in advanced prostate cancer is impacted through concurrent targeting of ERβ and AR using a novel ERβ-selective ligand alongside Enzalutamide

We have dissected the role of Estrogen receptor beta (ER{beta}) in prostate cancer (PCa) with a novel ER{beta} ligand, OSU-ERb-12. Drug screens revealed additive interactions between OSU-ERB-12 and either epigenetic inhibitors or the androgen receptor antagonist, Enzalutamide (Enza). Clonogenic and cell biolody studies supported the potent additive effects of OSU-ERB-12 (100nM) and Enza (1{micro}M). The cooperative behavior was in PCa cell lines treated with either OSU- ERB-12 plus Enza or combinations involving 17{beta}-estradiol (E2). OSU-ERb-12 plus Enza uniquely impacted the transcriptiome, accessible chromatin, and the AR, MYC and H3K27ac cistromes. This included skewed transcriptional responses including suppression of the androgen and MYC transcriptomes, and repressed MYC protein. OSU-ERb-12 plus Enza uniquely impacted chromatin accessibility at approximately 3000 nucleosome-free sites, enriched at enhancers, enriched for basic Helix-Loop-Helix motifs. CUT&RUN experiments revealed combination treatment targeting of MYC, AR, and H3K27ac again shaping enhancer accessibility. Specifically, it repressed MYC interactions at enhancer regions enriched for bHLH motifs, and overlapped with publicly-available bHLH cistromes. Finally, cistrome-transcriptome analyses identified [~]200 genes that distinguished advanced PCa tumors in the SU2C cohort with high androgen and low neuroendocrine scores. Statement of ImplicationTargeting ER{beta} has potentially to augment AR antagonism to restrain MYC signaling and limit growth of advanced prostate cancer.

cancer biology↗

bioRxiv2023

Combined blockade of CXCR4 and PD-1 enhances intratumoral dendritic cell activation and immune responses against HCC

Immune checkpoint inhibitors (ICIs) have transformed systemic therapy for unresectable hepatocellular carcinoma (HCC). Nevertheless, their efficacy is limited to a small percentage of patients, leaving an opportunity for enhancement through synergistic combination therapies. We tested here the combined blockade of programmed death receptor 1 (PD-1) and CXCR4, a receptor for CXCL12 and a key mediator of immunosuppression in the tumor microenvironment in orthotopic grafted and autochthonous models of HCC. We evaluated tumor growth and survival outcomes and examined the underlying mechanisms using immunofluorescence, flow cytometry, RNA-sequencing, and transgenic mice experiments. Combined anti-CXCR4/PD-1 therapy had a robust impact on tumor growth and significantly prolonged survival in all murine preclinical models. The combination treatment successfully reprogrammed antigen-presenting cells, revealing the role of conventional type 1 dendritic cells (cDC1s) in the tumor microenvironment. Moreover, DC reprogramming enhanced anti-cancer immunity by facilitating CD8 T-cell accumulation and activation in the HCC tissue. The effectiveness of the anti-CXCR4 antibody/ICI combination treatment was compromised entirely in Batf3-KO mice deficient in cDC1 cells. Thus, combined ICI therapy with an anti-CXCR4 antibody has the potential to augment the anti-cancer effects and improve survival outcomes in HCC via reprogramming intra-tumoral cDC1 cells.

cancer biology↗

bioRxiv2023

Preventing NK cell activation in the damaged liver induced by cabozantinib/PD-1 blockade increases survival in hepatocellular carcinoma models

Combining multikinase inhibitors with immune checkpoint blockade improves tumor control in hepatocellular carcinoma (HCC), but survival benefits remain inconsistent. To define this discordance, we integrated COSMIC-312 with orthotopic and autochthonous murine HCC models with or without liver fibrosis. In patients treated with cabozantinib plus atezolizumab, baseline liver function stratified overall survival but not progression-free survival, indicating uncoupling of tumor control from survival. In contrast, sorafenib outcomes tracked with both endpoints, supporting a treatment-specific effect rather than a purely prognostic effect of liver status. In murine HCC models, cabozantinib plus PD-1 blockade induced comparable tumor regression regardless of liver condition, but improved survival only in mice with preserved liver function, whereas fibrotic hosts developed hepatotoxicity. Immune profiling revealed compartment-specific remodeling, with enhanced cytotoxic T-cell programs in tumors but expansion of NK-lineage innate lymphocytes with ILC1-like features in fibrotic liver. Depletion of NK1.1-positive cells reduced liver injury and restored survival without compromising antitumor efficacy, whereas CD4-positive or CD8-positive T-cell depletion did not protect from hepatotoxicity. Transcriptomic, single-cell, adoptive-transfer, and human in vitro studies supported a model in which the fibrotic liver niche promotes NK-to-ILC1-like reprogramming, hepatocyte stress signaling, and TNF/TRAIL-associated epithelial injury. Consistently, cabozantinib and nivolumab showed liver-predominant remodeling of CD56-positive innate lymphocyte-enriched populations in human HCC samples, and ex vivo TGF-beta induced ILC1-like phenotypic changes in human NK cells. These findings identify liver fibrosis as a host determinant that can limit the survival benefit of multikinase inhibitor immunotherapy by promoting innate immune-mediated hepatotoxicity despite preserved tumor control in HCC. One Sentence SummaryLiver fibrosis limits the survival benefit of multikinase inhibitor immunotherapy in hepatocellular carcinoma by promoting innate immune-mediated hepatotoxicity despite preserved tumor control.

cancer biology↗

bioRxiv2023

Alasemenia, the earliest ovule with three wings and without cupule

The ovules or seeds (fertilized ovules) with wings are widespread and especially important for wind dispersal. However, the earliest ovules in the Famennian of the Late Devonian are rarely known about the dispersal syndrome and usually surrounded by a cupule. From Xinhang, Anhui, China, we report a new taxon of Famennian ovules, Alasemenia tria gen. et sp. nov. Each ovule possesses three integumentary wings evidently extending outwards, folding inwards along abaxial side and enclosing most part of nucellus. The ovule is borne terminally on smooth dichotomous branches and lacks a cupule. Alasemenia suggests that the integuments of the earliest ovules without a cupule evolved functions in wind dispersal and probable photosynthetic nutrition. It indicates that the seed wing originated earlier than other wind dispersal mechanisms such as seed plume and pappus, and that three- or four-winged seeds were followed by seeds with less wings. Mathematical analysis shows that three-winged seeds are more adapted to wind dispersal than seeds with one, two or four wings under the same condition.

paleontology↗