Biology subjects

Cui, P.

Publications and source records attributed to Cui, P..

At least 19 recordsLinked to original sources

bioRxiv2026

Sympathoadrenal Lineage Plasticity Drives Intratumoral Heterogeneity in Paraganglioma, Neuroblastoma and Composite Tumors Following KIF1Bb-NF1 Loss

Neuroblastoma (NB) and paraganglioma (PPGL) arise from the sympathoadrenal lineage, yet their developmental relationship and heterogeneity remain unclear. Single-cell and spatial transcriptomics revealed shared, spatially organized developmental states, including populations characteristic of the other tumor type, chromaffin-like cells in NB and neuroblast-like cells in PPGL and hybrids co-expressing adjacent states. Deconvolution of an independent PPGL cohort associated metastatic disease most strongly with chromaffin hybrid states, alongside connecting progenitor-like, cycling neuroblast, and early chromaffin identities, whereas non-metastatic tumors were enriched for differentiated late chromaffin identities. In mice, combined loss of the candidate 1p36 tumor suppressor KIF1B{beta} and NF1 recapitulates these developmental architectures by prolonging developmental plasticity, reactivating embryonic neurogenic programs, and driving chromaffin-to-neuroblast transitions generating pheochromocytoma, neuroblastoma and composite tumors. Mouse tumors contained discrete spatial domains of developmental and neoplastic states that mirrored those in human PPGL. Together, our findings establish chromaffin-neuroblast plasticity as a mechanism of sympathoadrenal tumor heterogeneity and identify hybrid developmental states as a potential indicator of plasticity associated with metastatic PPGL.

cancer 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↗

bioRxiv2025

Beach sand beneath our feet: an overlooked reservoir of antibiotic resistance genes and pathogens, revealed by metagenomic evidence from Qingdao's recreational beaches

Coastal beach environments, especially those with heavy tourist activity, represent a dynamic interface between terrestrial and marine microbiomes. However, beach sand is rarely considered in surveillance of antibiotic resistance. In this study, we combined 16S rRNA gene sequencing and shotgun metagenomics to characterize microbial communities and antibiotic resistance genes (ARGs) at four popular recreational beaches in Qingdao, China. We show that beach sands harbor highly diverse bacterial communities with significantly greater richness than adjacent seawater. Beach sand near sewage discharge points had microbial profiles intermediate between raw sewage and open-ocean water, reflecting contributions from both sources. Metagenomic analysis identified a broad "resistome" of over 300 distinct ARGs in these beach and water samples, spanning 33 antibiotic classes and 6 resistance mechanism categories. Notably, the rifampicin resistance gene rpoB2 was the most abundant ARG, and genes conferring resistance to peptide antibiotics were prevalent. Sewage outfalls were found to be major contributors of ARGs, with waste-influenced sand containing a larger and more diverse ARG pool than sand farther from pollution sources. We also detected a high diversity of bacterial virulence factor genes, particularly in sand. Our findings highlight that tourist beaches can serve as reservoirs and mixing zones for antibiotic-resistant and potentially pathogenic bacteria from land-based pollution. This underscores the need to include beach sand in environmental monitoring for antibiotic resistance and to improve wastewater management at recreational coastlines to mitigate public health risks. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=198 SRC="FIGDIR/small/661489v1_ufig1.gif" ALT="Figure 1"> View larger version (84K): org.highwire.dtl.DTLVardef@18705f3org.highwire.dtl.DTLVardef@1979f8forg.highwire.dtl.DTLVardef@16c9029org.highwire.dtl.DTLVardef@6c778d_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2025

Application of machine learning in the discovery of antimicrobial peptides: Exploring their potential for ulcerative colitis therapy

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with rising global prevalence, yet existing treatments are not universally effective. Antimicrobial peptides (AMPs), produced by the immune system, have diverse antimicrobial and immune-regulatory functions, making them promising candidates for UC therapy. Using machine learning, we developed a machine learning-based prediction model to identify novel AMPs. The predicted peptides demonstrated significant biological activity in vitro and in vivo. In a dextran sulfate sodium-induced UC mouse model, engineered AMPs notably improved UC-related parameters, such as body weight, disease activity index (DAI), and colon length. These effects were likely mediated by modulation of Akkermansia muciniphila. This study highlights the potential of machine learning-identified AMPs as future therapeutic candidates for UC. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=154 SRC="FIGDIR/small/660148v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@187dc6borg.highwire.dtl.DTLVardef@9800deorg.highwire.dtl.DTLVardef@1611c42org.highwire.dtl.DTLVardef@866406_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗

bioRxiv2025

Cytoprotective roles of "E3 ubiquitin ligases-NF-κB-autophagy" axis in Pacific oysters Crassostrea gigas exposed to phenanthrene

Phenanthrene (PHE), as one of the most frequently found polycyclic aromatic hydrocarbons can induce immunotoxicity, oxidative stress, and endocrine disruption in marine organisms. However, whether autophagy can be induced by PHE and the regulatory mechanism and cytoprotective roles of autophagy under PHE stress condition have not been unveiled. Our data first unveil a "E3 ubiquitin ligases-NF-{kappa}B-autophagy" axis, which play cytoprotective roles in Pacific oysters Crassostrea gigas exposed to PHE. The results of confocal laser scanning microscope, flow cytometry and transmission electron microscope confirmed that PHE could induce autophagy in the haemocytes of Pacific oysters, and the presence of autophagosomes was also confirmed. The proteomics results showed that the expression of the E3 ubiquitin ligase HUWE1, TRIM36, and autophagy-related protein 7 (ATG7) were significantly upregulated. The expression of genes of the "axis" were significantly upregulated, and the expression of genes of autophagy was downregulated after the inhibition of the NF-{kappa}B, indicating that the expression of the "axis"-related genes can be stimulated by PHE, and thus autophagy is activated. The upregulation of the expression of "axis"-related genes in mouse macrophages, further demonstrating the existence of the "axis" proposed by this study and the "axis" can be activated by PHE. Incorporating with changes of cell number, apoptosis rate, phagocytic capacity, and ROS levels of lymphocytes, we demonstrated that autophagy plays a cytoprotective role in cellular defence against PHE. This study proposed a novel pathway and supplied a comprehensive understanding of the protective role of autophagy in Pacific oysters to cope with pollutants.

cell biology↗

bioRxiv2025

Metagenomic Analysis Reveals Northwest Pacific Ocean as a Reservoir and Evolutionary Hub of Antibiotic Resistance Genes

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/659680v1_ufig1.gif" ALT="Figure 1"> View larger version (81K): org.highwire.dtl.DTLVardef@139e191org.highwire.dtl.DTLVardef@10834c4org.highwire.dtl.DTLVardef@1c0544aorg.highwire.dtl.DTLVardef@1ddfd8a_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstractC_FLOATNO C_FIG Antibiotic resistance genes (ARGs) were identified as a novel type of environmental contaminants. Ocean is thought to be one of the ultimate environments where ARGs gathered. Marine ecosystems represent vast reservoirs of ARGs, yet their dynamics in open-ocean environments remain poorly characterized. Through large-scale metagenomic profiling of the Kuroshio Extension, a hydrographically dynamic region in the Northwest Pacific, we identified a striking enrichment of ARGs (1.81 x 10-3 ppm) at a frontal zone site (S30). The ARG abundance at this site exceeded coastal levels by 90-fold. Notably, multidrug resistance genes dominated this hotspot, with efflux pumps contributing 62% of the resistance mechanisms, a pattern distinct from the target-alteration strategies prevalent in other regions. The site exhibited unique microbial consortia, including pathogenic Acinetobacter (30.2% abundance) carrying clinically critical determinants (blaOXA-23, adeJ). Co-occurrence networks revealed horizontal transfer risks, linking pelagic Sphingobium to terrestrial-derived {beta}-lactamase variants. Crucially, we discovered three novel plasmid-borne resistance genes circulating in >15% of microbial populations, demonstrating open-ocean ARG diversification independent of direct anthropogenic inputs. These findings redefine oceanic frontiers as crucibles of resistance evolution, demanding urgent integration into global antimicrobial stewardship strategies.

microbiology↗

bioRxiv2025

Synthesizing human-specific spike-in standards for RNA-seq experiments and assessing their technical performance

Using spike-in standards for RNA-seq experiments is critical to evaluate technical bias introduced during sample preparation, sequencing and analysis. Although some external RNA spike-in standards have been developed, species-specific spike-in standard was not reported yet. Here we developed the human-specific spike-in standards with 65 controls. We first extracted human endogenous RNAs with various lengths and GC contents, introduced random mutations approximately every 75 bp in each RNA, and then synthesized these RNAs as spike-in RNAs. After that, four mixtures of these spike-in RNAs covering a 220 dynamic range were obtained. To ensure the accuracy of RNA concentration, two rounds of ddPCR were conducted for each spike-in RNA and the intraclass correlation coefficient between two ddPCRs ranged from 0.9954 to 0.9971 after removing the two spike-in RNAs with the largest concentration difference. Furthermore, we showed that the sequencing error profiles were distinct between platforms and the library preparation procedures were related with the discrepancies in spike-in RNA read percent, transcript abundance, sequence coverage distribution, and differential gene expression. In addition, two regression models of sequence coverage were built based on RNA second structure and GC content, and 86.62%-91.78% of the variation can be explained. Our study demonstrates the technical performance of the human-specific spike-in standards for RNA-seq experiments and illustrates the biases across different libraries, platforms, and laboratories.

bioinformatics↗

bioRxiv2024

Lineage-associated Human Divergently-Paired Genes (DPGs) Exhibit Regulatory Characteristics and Evolutionary Trends

Divergently-paired genes (DPGs) represent one of the minimal co-transcriptional units (the rest include tandemly- and convergently-paired genes) of clustered genes; the former and the latter constitute greater than 10% and 75% of the total human genes, respectively. Our previous studies have shown that vertebrate DPGs are more conserved, both organizationally and functionally than invertebrates. Three critical questions remain to be addressed: (1) what are the conserved DPGs over vertebrate lineages, especially among mammals and primates? (2) being bidirectionally transcribed, to what extent do DPGs share their promoter sequences and how mechanistically and stringently are their co-expression regulated within the shared inter-TSS (transcription start site) sequence space? and (3) based on the recently released high-quality human genome assemblies, how do human-associated DPGs distribute over selected primate lineages and what are their possible functional consequences biologically? Our study begins by identifying 1399 human DPGs (12% of all human protein-coding genes), and presents findings from this analysis. First, 1136, 1118, 925, and 830 human DPGs are shared genetically with primates, mammals, avians, and fish, respectively. DPGs are not only functionally enriched toward direct protein-DNA interactions and cell cycle synchronization but also exhibit obvious lineage association, narrow in principle toward synchronization of certain core molecular mechanisms and cellular processes. Second, their inter-TSS distances and expression variables affect both co-expression strength and disparity between the two genes. Finally, our results based on a comparison among the primate DPGs reveal that the human-associated DPGs exhibit intensive diversification in co-expression, duplication, and definite involvement in neural development. Within humans, 55 and 357 DPGs are associated to the Chinese (YAO) and the European (CHM13) assemblies, respectively. Our results offer novel insights into comprehending the structure-function selection of gene clusters over evolutionary time scales, as well as a deeper understanding of the regulatory characteristics of co-expressed neighboring genes.

genomics↗

bioRxiv2024

Deep Learning Driven Cell-Type-Specific Embedding for Inference of Single-Cell Co-expression Networks

The inference of gene co-expression module in specific cell types is important for understanding of cell-type-specific biological processes. We have developed DeepCSCN, an unsupervised deep-learning framework, to infer gene co-expression modules from single-cell RNA sequencing (scRNA-seq) data. Utilizing a global-to-local network construction approach, DeepCSCN can infer co-expression at the whole sample level and construct cell-type-specific co-expression networks. Systematic evaluations on eight public scRNA-seq datasets show that DeepCSCN significantly outperforms eight existing methods in co-expression network construction. Furthermore, DeepCSCN effectively identifies cell-type-specific co-expression networks that are more enriched for cell-specific functional pathways compared to current methods. Finally, application of DeepCSCN on public scRNA-seq data revealed 280 cell-specific gene modules across 27 cell types, including epithelial cells, immune cells, and myonuclei, demonstrating its versatility and accuracy in elucidating cell-type-specific gene co-expression regulation. DeepCSCN offers a powerful tool for researchers to dissect the intricate gene co-expression networks within distinct cell types.

bioinformatics↗

bioRxiv2023

Pan-cancer Analysis Reveals m6A Variation and Cell-specific Regulatory Network in Different Cancer Types

As the most abundant mRNA modification in mRNA, N6-methyladenosine (m6A) plays a crucial role in RNA fate, impacting cellular and physiological processes in various tumor types. However, our understanding of the function and role of the m6A methylome in tumor heterogeneity remains limited. Herein, we collected and analyzed m6A methylomes across nine human tissues from 97 m6A-seq and RNA-seq samples. Our findings demonstrate that m6A exhibits different heterogeneity in most tumor tissues compared to normal tissues, which contributes to the diverse clinical outcomes in different cancer types. We also found that the cancer type-specific m6A level regulated the expression of different cancer-related genes in distinct cancer types. Utilizing a novel and reliable method called "m6A-express", we predicted m6A- regulated genes and revealed that cancer type-specific m6A-regulated genes contributed to the prognosis, tumor origin and infiltration level of immune cells in diverse patient populations. Furthermore, we identified cell-specific m6A regulators that regulate cancer-specific m6A and constructed a regulatory network. Experimental validation was performed, confirming that the cell-specific m6A regulator CAPRIN1 controls the m6A level of TP53. Overall, our work reveals the clinical relevance of m6A in various tumor tissues and explains how such heterogeneity is established. These results further suggest the potential of m6A for cancer precision medicine for patients with different cancer types.

bioinformatics↗

bioRxiv2023

CLAIR: An integrated lipid database across multiple crop species

Oilseed crops, which are rich in plant lipids, provide essential fatty acids for human consumption and serve as major sources of biofuels and essential raw materials for the chemical industry. As a result of population growth and ecological changes, the demand for vegetable oil is increasingly outpacing supply. A comprehensive understanding of the genes involved in lipid metabolism in oilseed crops and the regulatory relationships among these genes is essential for improving oil content. However, current studies on lipid metabolism genes rely heavily on a decade-old database of genes involved in lipid metabolism in Arabidopsis thaliana. To address this issue, we mined the literature, integrated data from various databases and studies, and aligned homologs of lipid metabolism genes from nine oilseed crops to construct a comprehensive set of lipid metabolism genes in plants. Using this approach, we identified 221 additional lipid metabolism genes. In addition, we created a user-friendly lipid database called CLAIR (Crop Lipid-Associated Information Resource) by integrating and mining multi-omics data from nine major oil crops. The database is available at http://www.clipair.cn/. These resources should facilitate further research and exploration of lipid metabolism in oil crops, ultimately contributing to improved oil production.

plant biology↗

bioRxiv2023

Local recurrent circuits modulate visual center and surround interactions in the mouse superior colliculus

Center-surround interactions are fundamental to visual saliency computation, but debate continues over whether and how subcortical visual circuits actively contribute. To address this, we developed an optogenetic approach to delineate the visual center and surround zones of individual neurons in the superficial layer of the superior colliculus (SCs) using only retinal ganglion cell input. Using whole-cell recordings, we demonstrate that surround network activation suppresses center excitability, indicating that SCs circuitry is self-sufficient in driving center-surround dynamics. Through cell-type-specific trans-synaptic tracing and large-scale modeling, we identified an SCs-based circuit with two key motifs driving surround modulation: recurrent excitation and feedback inhibition. We propose that subcortical visual circuits in the SCs have evolved to perform surround suppression alongside retinal and cortical suppression, facilitating the distribution of parallel saliency computations across different levels. Significance statementThis study questions the notion that the superior colliculus (SC) merely acts as a passive recipient of saliency information from upstream circuits. We demonstrate that the SC can independently generate center-surround interactions that could contribute to visual saliency through local circuits without top-down input. This ability represents a computation that has been conserved since the dawn of vertebrate evolution. By mapping these interactions, we reveal that the mouse SC actively induces visual surround suppression. These findings suggest that phylogenetically older circuits in the SC may play a more independent role in active vision than previously acknowledged, prompting a reevaluation of visual saliency processing across subcortical brain regions.

neuroscience↗

bioRxiv2022

ESCRT pathway-dependent MVBs contribute to the morphogenesis of the fungus Arthrobotrys oligospora

Ammonia opens trap formation in the nematode-trapping (NT) fungus Arthrobotrys oligospora, an intriguing morphological switch in NT fungi, where saprophytic mycelia are converted to pathogenic organs. Endocytosis plays a prominent role in nutrient uptake, signaling cascades, and maintenance of cellular homeostasis in higher eukaryotes. Here, we demonstrate that ammonia efficiently promotes endocytosis via the formation of 3D-adhesive mycelial nets in A. oligospora. Trap production is followed by the presence of massive multivesicular bodies (MVBs) and membrane rupture and repair. Additionally, both the ubiquitin-proteasome system and the endosomal sorting complex for transport (ESCRT) pathway are immediately linked to endocytosis regulation and MVB formation in ammonia-induced trap formation. Moreover, disruption of the ESCRT-1 complex subunit proteins AoHse and AoVps27 led to the complete loss of membrane endocytosis and trap formation. Finally, the deletion of the deubiquitinase AoSst2 caused a significant reduction in the number of trap structures produced in response to exposure to ammonia or nematodes. Overall, our results increase our knowledge of the molecular mechanisms underlying the phenotypic changes in the NT fungal group, demonstrating that the endocytosis-ESCRT-MVB pathway participates in the regulation of trapping organs. Author SummaryThe lifestyle switch of nematode-trapping (NT) fungi is a significant event that increases their pathogenicity to nematode prey, which has resulted in large losses to agricultural crops worldwide. Here, we describe the molecular mechanism underlying how this fungal group forms a NT structure in response to ammonia, a widely preferred nitrogen source in soil niches. Ammonia enhances the endocytosis process, ubiquitin-proteasome system, and endosomal sorting complex for transport (ESCRT) pathway of the model NT fungus A. oligospora, thereby generating enriched multivesicular bodies (MVBs) during trap formation. In this process, the cell membrane morphology is remarkably damaged and then repaired. We further found that disruption of the ESCRT-0 subcomplex or ubiquitinase severely blocked trap production and membrane reorganization. Our study provides a new understanding of endocytosis-ESCRT-MVB flux in the transition of fungal NT organs.

microbiology↗

bioRxiv2021

The First High-Quality Reference Genome of Sika Deer Provides Insights for High-Tannin Adaptation

Sika deer are known to prefer oak leaves, which are rich in tannins and toxic to most mammals; however, the genetic mechanisms underlying their unique ability to adapt to living in the jungle are still unclear. In identifying the mechanism responsible for the tolerance of a highly toxic diet, we have made a major advancement in the elucidation of the genomics of sika deer. We generated the first high-quality, chromosome-level genome assembly of sika deer and measured the correlation between tannin intake and RNA expression in 15 tissues through 180 experiments. Comparative genome analyses showed that the UGT and CYP gene families are functionally involved in the adaptation of sika deer to high-tannin food, especially the expansion of UGT genes in a subfamily. The first chromosome-level assembly and genetic characterization of the tolerance toa highly toxic diet suggest that the sika deer genome will serve as an essential resource for understanding evolutionary events and tannin adaptation. Our study provides a paradigm of comparative expressive genomics that can be applied to the study of unique biological features in non-model animals.

genomics↗

bioRxiv2021

A Chromosome-level Assembly of a Wild Castor Genome Provides New Insights into the Adaptive Evolution in a Tropical Desert

Wild castor grows in the high-altitude tropical desert of the African Plateau, a region known for high ultraviolet radiations, strong lights and extremely dry conditions. To investigate the potential genetic basis of adaptation to both highland and tropical deserts, we generated a chromosome-level genome sequence of the wild castor accession WT05, with genome size of 316 Mb and scaffold and contig N50 sizes of 31.93 Mb and 8.96 Mb, respectively. Compared with cultivated castor and other Euphorbiaceae species, the wild castor exhibits positive selection and gene family expansion for genes involved in DNA repair, photosynthesis and abiotic stress responses. Genetic variations associated with positive selection were identified in several key genes, such as LIG1, DDB2, and RECG1, involved in nucleotide excision repair. Moreover, a study of genomic diversity among wild and cultivated accessions revealed genomic regions containing selection signatures associated with the adaptation to extreme environments. The identification of the genes and alleles with selection signatures provides insights into the genetic mechanisms underlying the adaptation of wild castor to the high-altitude tropical desert and would facilitate direct improvement of modern castor varieties.

genomics↗

bioRxiv2020

Induction of hyperandrogenism and insulin resistance differentially modulates ferroptosis in uterine and placental tissues of pregnant rats

Ferroptosis, a form of regulated necrotic cell death, plays roles in diverse physiological processes and diseases. Women with polycystic ovary syndrome (PCOS) have hyperandrogenism and insulin resistance (HAIR) and an increased risk of miscarriage and placental dysfunction during pregnancy. However, whether maternal HAIR alters mechanisms leading to ferroptosis in the gravid uterus and placenta remains unknown. Previous studies in rats showed that maternal exposure to 5-dihydrotestosterone (DHT) and insulin (INS) from gestational day 7.5 to 13.5 induces HAIR and subsequently leads to placental insufficiency and fetal loss. We therefore hypothesized that maternal HAIR triggers ferroptosis in the uterus and placenta in association with fetal loss in pregnant rats. Compared with controls, we found that co-exposure to DHT and INS led to decreased levels of Gpx4 and glutathione (GSH), increased GSH+glutathione disulfide (GSSG) and malondialdehyde (MDA), aberrant expression of ferroptosis-associated genes (Acsl4, Tfrc, Slc7a11, and Gclc), increased iron deposition, and activated ERK/p38/JNK phosphorylation in the gravid uterus. However, in the placenta, DHT and INS exposure only partially altered the expression of ferroptosis-related markers (e.g., region-dependent Gpx4, GSH+GSSG, MDA, Gls2 and Slc7a11 mRNAs, and phosphorylated p38 levels). In the uteri co-exposed to DHT and INS, we also observed shrunken mitochondria with electron-dense cristae, which are key features of ferroptosis-related mitochondrial morphology, as well as increased expression of Dpp4, a mitochondria-encoded gene responsible for ferroptosis induction. In contrast, in placentas co-exposed to DHT and INS we found decreased expression of Dpp4 mRNA and increased expression of Cisd1 mRNA (a mitochondria-encoded iron-export factor). Further, DHT+INS-exposed pregnant rats exhibited decreased apoptosis in the uterus and increased necroptosis in the placenta. Our findings suggest that maternal HAIR causes the activation of ferroptosis in the gravid uterus and placenta, although this is mediated via different mechanisms operating at the molecular and cellular levels. Furthermore, our data suggest other cell death pathways may play a role in coordinating or compensating for HAIR-induced ferroptosis when the gravid uterus and placenta are dysfunctional. Suppl Figures: https://doi.org/10.6084/m9.figshare.11794059.v5

physiology↗

bioRxiv2020

Population sequencing enhances understanding of tea plant evolution

Tea is an economically important plant characterized by a large genome size and high heterozygosity and species diversity. In this study, we assembled a 3.26 Gb high-quality chromosome-scale genome for tea using the Longjing 43 cultivar of Camellia sinensis var. sinensis. Population resequencing of 139 tea accessions from around the world was used to investigate the evolution of tea and to reveal the phylogenetic relationships among tea accessions. With the spread of tea cultivation, hybridization has increased the heterozygosity and wide-ranging gene flow among tea populations. Population genetics and transcriptomics analyses revealed that during domestication, the selection for disease resistance and flavor in C. sinensis var. sinensis populations has been stronger than that in C. sinensis var. assamica populations. The data compiled in this study provide new resources for the marker assisted breeding of tea and are a basis for further research on the genetics and evolution of tea.

genomics↗

bioRxiv2019

Fibroblast Protection of Borrelia burgdorferi from Doxycycline, Cefuroxime and Daptomycin Combination is Eliminated by Oregano or Carvacrol Essential Oil

Borrelia burgdorferi could be occasionally recovered from patients after antibiotic treatment, which indicates it may resist eradication by antibiotic and host defense mechanisms. Skin fibroblast cells have previously been shown to protect the killing of B. burgdorferi by ceftriaxone, a powerful antibiotic commonly used to treat Lyme disease. In this study, we evaluated if fibroblast cells could also protect against the doxycycline+ cefuroxime+ daptomycin drug combination which has previously been shown to completely eradicate highly persistent biofilm-like microcolonies of B. burgdorferi. To do so, we utilized a GFP-labeled B. burgdorferi for infection of murine fibroblast cells and assessed the effect of the drug combination on killing the bacteria in the presence or absence of the fibroblast cells. Surprisingly, we found that fibroblasts could protect B. burgdorferi from being completely killed by the drug combination doxycycline, cefuroxime and daptomycin, which eradicated B. burgdorferi completely in the absence of fibroblast cells. Interestingly, addition of essential oil carvacrol or oregano at 0.1% could enhance the activity of the doxycycline+ cefuroxime+ daptomycin drug combination and led to complete eradication of B. burgdorferi even in the presence of fibroblast cells. Further studies are needed to determine if the essential oil drug combinations could eradicate persistent B. burgdorferi infection in vivo in animal models. Our study provides a useful and convenient ex vivo model for evaluating different drug regimens needed for developing more effective treatment of persistent Lyme disease in the future.

microbiology↗