SAW: an efficient and accurate data analysis workflow for Stereo-seq spatial transcriptomics.

The basic analysis steps of spatial transcriptomics require obtaining gene expression information from both space and cells. The existing tools for these analyses incur performance issues when dealing with large datasets. These issues involve computationally intensive spatial localization, RNA genome alignment, and excessive memory usage in large chip scenarios. These problems affect the applicability and efficiency of the analysis. Here, a high-performance and accurate spatial transcriptomics data analysis workflow, called Stereo-seq Analysis Workflow (SAW), was developed for the Stereo-seq technology developed at BGI. SAW includes mRNA spatial position reconstruction, genome alignment, gene expression matrix generation, and clustering. The workflow outputs files in a universal format for subsequent personalized analysis. The execution time for the entire analysis is ∼148 min with 1 GB reads 1 × 1 cm chip test data, 1.8 times faster than with an unoptimized workflow.

BatchEval Pipeline: batch effect evaluation workflow for multiple datasets joint analysis.

As genomic sequencing technology continues to advance, it becomes increasingly important to perform joint analyses of multiple datasets of transcriptomics. However, batch effect presents challenges for dataset integration, such as sequencing data measured on different platforms, and datasets collected at different times. Here, we report the development of BatchEval Pipeline, a batch effect workflow used to evaluate batch effect on dataset integration. The BatchEval Pipeline generates a comprehensive report, which consists of a series of HTML pages for assessment findings, including a main page, a raw dataset evaluation page, and several built-in methods evaluation pages. The main page exhibits basic information of the integrated datasets, a comprehensive score of batch effect, and the most recommended method for removing batch effect from the current datasets. The remaining pages exhibit evaluation details for the raw dataset, and evaluation results from the built-in batch effect removal methods after removing batch effect. This comprehensive report enables researchers to accurately identify and remove batch effects, resulting in more reliable and meaningful biological insights from integrated datasets. In summary, the BatchEval Pipeline represents a significant advancement in batch effect evaluation, and is a valuable tool to improve the accuracy and reliability of the experimental results. Availability & Implementation: The source code of the BatchEval Pipeline is available at https://github.com/STOmics/BatchEval.

Elucidation of the anti-colon cancer mechanism of Phellinus baumii polyphenol by an integrative approach of network pharmacology and experimental verification.

Colon cancer, a prevalent malignant tumor affecting the digestive system, presents a substantial risk to human health due to its high occurrence and mortality rates. Phellinus baumii polyphenol (PBP), a natural product derived from traditional Chinese medicine, has gained widespread popularity due to its low toxicity and minimal side effects, compared to radiation and chemotherapy. This study used an integrated approach of network pharmacology and experimental verification to elucidate the anti-colon cancer effects of PBP and its potential mechanisms. In network pharmacology, the identification of relevant targets involved a comprehensive search across multiple databases using keywords such as "active components of PBP" and "colon cancer". Venn diagram analysis was subsequently performed to ascertain the shared targets. To identify the key active components and core targets, we constructed a network of "Disease-Drug-Pathways-Targets" and a protein-protein interaction (PPI) network among the targets using Cytoscape 3.9.1. Furthermore, molecular docking was carried out to predict the binding affinity and conformation between the main active compounds (davallialactone and citrinin) of PBP and the core targets (TP53, STAT3, CASP3, CTNNB1, PARP1, MYC). To validate our findings, in vitro experiments were conducted. We verified that PBP exerted an anti-colon cancer effect on human colon cancer HCT116 cells by significantly inhibiting cell proliferation, promoting apoptosis and arresting the cell cycle in S phase by using Cell Counting Kit-8 (CCK-8) and flow cytometry. Finally, we determined the key regulatory proteins related to apoptosis and the cell cycle by western blot analysis, and proposed the potential mechanism by which PBP exerts an anti-colon cancer effect by inducing the caspase-dependent mitochondrial-mediated intrinsic apoptotic pathway and arresting the cell cycle in S phase in HCT116 cells. These results suggest that PBP possesses substantial potential for the treatment of colon cancer and may serve as a viable alternative therapeutic strategy in colon cancer treatment.

Phellinus baumii Polyphenol: A Potential Therapeutic Candidate against Lung Cancer Cells.

Phellinus baumii, a fungus that grows on mulberry trees and is used in traditional Chinese medicine, exerts therapeutic effects against various diseases, including cancer. Polyphenols, generally considered to be antioxidants, have antitumor and proapoptotic effects. In this study, we identified the composition of Phellinus baumii polyphenol (PBP) and characterized its 17 chemical components by UPLC-ESI-QTOF-MS. Furthermore, to clarify the potential mechanism of PBP against Lung Cancer Cells, network pharmacology and experimental verification were combined. Molecular docking elucidated the binding conformation and mechanism of the primary active components (Osmundacetone and hispidin) to the core targets CASP3, PARP1 and TP53. In addition, potential molecular mechanisms of PBP predicted by network pharmacology analysis were validated in vitro. PBP significantly inhibited the human lung cancer A549 cells and showed typical apoptotic characteristics, without significant cytotoxicity to normal human embryonic kidney (HEK293) cells. Analysis using flow cytometry and western blot indicated that PBP caused apoptosis, cell cycle arrest, reactive oxygen species (ROS) accumulation, and mitochondrial membrane potential (MMP) depression in A549 cells to exercise its antitumor effects. These results reveal that PBP has great potential for use as an active ingredient for antitumor therapy.

Ginsenoside Rg1 exerts anti­apoptotic effects on non­alcoholic fatty liver cells by downregulating the expression of SGPL1.

Non­alcoholic fatty liver disease (NAFLD) has a high incidence, and can lead to liver cirrhosis and even hepatocellular carcinoma in severe cases. To the best of our knowledge, there is currently no safe and effective treatment for the management of this disease. Ginsenoside Rg1 (Rg1) is an active monomer derived from ginseng and notoginseng. In the present study, HHL­5 hepatocytes were used to establish an in vitro cell model of NAFLD by medium­ and long­chain fat emulsion treatment, and the effects of Rg1 on adipose accumulation, apoptosis and the expression levels of apoptosis­related proteins in HHL­5 hepatocytes were examined. The results demonstrated that Rg1 inhibited the accumulation of fat in HHL­5 cells, while inhibiting apoptosis, and Rg1 downregulated the expression levels of the pro­apoptotic protein Bax and upregulated the expression levels of the anti­apoptotic protein Bcl­2, indicating that Rg1 could promote the stability or integrity of mitochondria and exert an anti­apoptotic effect by regulating Bcl­2 family proteins. In addition, Rg1 markedly downregulated the expression levels of sphingosine­1­phosphate lyase 1 (SGPL1), a key enzyme in the sphingosine signaling pathway, in HHL­5 cells with steatosis, and increased the expression levels of the downstream pro­survival signals phosphorylated (p­)Akt and p­Erk1/2. Furthermore, overexpression of SGPL1 abolished the anti­apoptotic effect of Rg1 on SGPL1­overexpressing HHL­5 cells with steatosis, and downregulated the expression levels of pro­survival proteins, such as Bcl­2, p­Akt and p­Erk1/2, whereas the expression levels of pro­apoptotic Bax were markedly increased. In conclusion, although there are some reports regarding the protective effect of Rg1 on fatty liver cells, to the best of our knowledge, the present study is the first to report that Rg1 may exert an anti­apoptotic effect on fatty liver cells by regulating SGPL1 in the sphingosine signaling pathway. Rg1 is the main component of the prescription drug Xuesaitong in China; therefore, the findings of the present study may provide a theoretical molecular basis for the use of Rg1 or Xuesaitong in the treatment of patients with NAFLD.

Identification and characterization of a novel 5-hydroxytryptamine receptor in the sea cucumber Apostichopus japonicus (Selenka).

Serotonin (5-hydroxytryptamine [5-HT]) receptors (5-HTRs) mediate neuroendocrine signaling via interactions with the ligand serotonin (5-HT). The 5-HT signaling system has been well studied in vertebrates, but rarely known in invertebrate animals, especially in the marine invertebrates. In this study, we identified and characterized a novel 5-HTR from the sea cucumber Apostichopus japonicus (Aj5-HT4/6 ). The cloned Aj5-HT4/6 open reading frame comprised 1290 bp and encoded 429 amino acids. Bioinformatic analysis of the receptor indicated that it was a member of the class A of the G protein-coupled receptor family. Further experiments using Aj5-HT4/6 -transfected HEK293 cells demonstrated that treatment with 5-HT could induce rapid internalization of Aj5-HT4/6 fused with enhanced green fluorescent protein from the cell surface into the cytoplasm and triggered a significant increase in levels of the second messenger cAMP as well as mitogen-activated protein kinase phosphorylation in a 5-HT dose-dependent manner. Quantitative real time-polymerase chain reaction demonstrated that Aj5-HT4/6 was predominantly expressed in the muscle and respiratory tree, and its expression was significantly decreased during estivation. Taken together, these results imply that Aj5-HT4/6 is potentially involved in the movement and metabolism of the sea cucumber.

Chinese Propolis Inhibits the Proliferation of Human Gastric Cancer Cells by Inducing Apoptosis and Cell Cycle Arrest.

Special Chinese propolis sourced from the Changbai Mountains (CBMP) in Northeast China is rich in specific flavonoids and phenolic acids and its bioactivity has not been reported. This study aimed to investigate the antiproliferative effect of CBMP on cancer cells and its molecular mechanisms. Different cancer cell lines were treated with the ethanol extracts of CBMP for 24 hours before the cell viability and mechanism measurements. The results showed CBMP had weak activities against human pancreatic cancer cell PANC1, human lung cancer cell A549, human colon cancer cell HCT116, human liver cancer cell HepG2, human bladder cancer cell T24, and human breast cancer cell MDA-MB-231, but it significantly inhibited the growth of human gastric cancer SGC-7901 cells, caused cell apoptosis and cell cycle arrest in S phase, with increased production of reactive oxygen species (ROS) and reduced mitochondrial membrane potential (MMP). The results indicate that Chinese propolis sourced from the Changbai Mountains selectively inhibits the proliferation of human gastric cancer SGC-7901 cells by inducing both death receptor-induced apoptosis and mitochondria-mediated apoptosis, and cell cycle arrest in S phase. These activities and mechanisms help understand the anticancer action of propolis and its active compounds.

N6-(2-hydroxyethyl)-Adenosine Induces Apoptosis via ER Stress and Autophagy of Gastric Carcinoma Cells In Vitro and In Vivo.

Gastric cancer is the most common malignant tumor of the digestive tract and is great challenge in clinical treatment. N6-(2-Hydroxyethyl)-adenosine (HEA), widely present in various fungi, is a natural adenosine derivative with many biological and pharmacological activities. Here, we assessed the antineoplastic effect of HEA on gastric carcinoma. HEA exerted cytotoxic effects against gastric carcinoma cells (SGC-7901 and AGS) in a dose and time-dependent manner. Additionally, we found that HEA induced reactive oxygen species production and mitochondrial membrane potential depolarization. Moreover, it could trigger caspase-dependent apoptosis, promoting intracellular Ca2+-related endoplasmic reticulum (ER) stress and autophagy. On the other hand, HEA could significantly inhibit the growth of transplanted tumors in nude mice and induce apoptosis of tumor tissues cells in vivo. In conclusion, HEA induced apoptosis of gastric carcinoma cells in vitro and in vivo, demonstrating that HEA is a potential chemotherapeutic agent for gastric carcinoma.

The genomes of two parasitic wasps that parasitize the diamondback moth.

BACKGROUND: Parasitic insects are well-known biological control agents for arthropod pests worldwide. They are capable of regulating their host's physiology, development and behaviour. However, many of the molecular mechanisms involved in host-parasitoid interaction remain unknown. RESULTS: We sequenced the genomes of two parasitic wasps (Cotesia vestalis, and Diadromus collaris) that parasitize the diamondback moth Plutella xylostella using Illumina and Pacbio sequencing platforms. Genome assembly using SOAPdenovo produced a 178 Mb draft genome for C. vestalis and a 399 Mb draft genome for D. collaris. A total set that contained 11,278 and 15,328 protein-coding genes for C. vestalis and D. collaris, respectively, were predicted using evidence (homology-based and transcriptome-based) and de novo prediction methodology. Phylogenetic analysis showed that the braconid C. vestalis and the ichneumonid D. collaris diverged approximately 124 million years ago. These two wasps exhibit gene gains and losses that in some cases reflect their shared life history as parasitic wasps and in other cases are unique to particular species. Gene families with functions in development, nutrient acquisition from hosts, and metabolism have expanded in each wasp species, while genes required for biosynthesis of some amino acids and steroids have been lost, since these nutrients can be directly obtained from the host. Both wasp species encode a relative higher number of neprilysins (NEPs) thus far reported in arthropod genomes while several genes encoding immune-related proteins and detoxification enzymes were lost in both wasp genomes. CONCLUSIONS: We present the annotated genome sequence of two parasitic wasps C. vestalis and D. collaris, which parasitize a common host, the diamondback moth, P. xylostella. These data will provide a fundamental source for studying the mechanism of host control and will be used in parasitoid comparative genomics to study the origin and diversification of the parasitic lifestyle.

Author Correction: Liriodendron genome sheds light on angiosperm phylogeny and species-pair differentiation.

In the Supplementary Information file originally published with this Letter, the authors mistakenly omitted Supplementary Table 14; this has now been amended.

Ethanolic extract of Cordyceps cicadae exerts antitumor effect on human gastric cancer SGC-7901 cells by inducing apoptosis, cell cycle arrest and endoplasmic reticulum stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Cordyceps cicadae (Miq.) Massee is a traditional Chinese medicine that has been used for approximately 1600 years in China. C. cicadae, a member of the Cordyceps genus, exerts a therapeutic effect on many diseases, such as cancer. OBJECTIVE: This study aimed to evaluate the antineoplasmic activity of C. cicadae and to identify its molecular mechanism of cell death. MATERIALS AND METHODS: The toxicity of the ethanolic extract of C. cicadae (EEC) against different cancer cell lines was determined through MTT assay. Human gastric cancer SGC-7901 cells were treated with EEC for 48 h. Cell morphology was examined by using an Olympus phase-contrast microscope. The cell apoptosis was quantified through Annexin V-FITC/PI staining. Cells were stained with PI and then subjected to flow cytometry for the investigation of cell cycle status. Cells were subjected to mitochondrial membrane potential (MMP) assay after incubation with JC-1 probes and to intracellular Ca2+ measurement through flow cytometry after incubation with Fluo-3 AM fluorescent probes. Western blot analysis was conducted to quantify the expression of proteins related to apoptosis, cell cycle and endoplasmic reticulum stress. High-performance liquid chromatography (HPLC) analysis was performed to analyse the biological activity components of EEC. RESULTS: EEC suppressed the proliferation of SGC-7901 cells and induced the development of abnormal morphological features in a dose-dependent manner. Flow cytometry results indicated that EEC treatment caused cell apoptosis and arrested the cell cycle in the S phase. In addition, EEC treatment triggered MMP depolarization and Ca2+ overloading in the cytosol of SGC-7901 cells. Western blot analysis demonstrated that EEC increased Bax, AIF, caspase-8, caspase-6 and caspase-3 activities and decreased Bcl-2 activity. The release of cytochrome c from mitochondria was associated with mitochondrial dysfunction, which was caused by the activation of the cell surface receptor Fas and the cleavage of PARP. EEC-induced S phase arrest was associated with the up-regulation of E2F1, cyclin A2, cyclin E and p53 expression levels and the down-regulation of CDK2 expression. In addition, EEC increased the expression of endoplasmic reticulum stress-related proteins, such as calpain-1, caspase-12 and caspase-9. HPLC assay results suggested that EEC contained adenine, uridine, adenosine and N6-(2-Hydroxyethyl)-adenosine. CONCLUSION: EEC inhibited the proliferation of SGC-7901 cells by inducing caspase-dependent apoptosis, arresting the cell cycle in the S phase and increasing endoplasmic reticulum stress. This study revealed that C. cicadae is a potential natural source of anticancer drugs.

Liriodendron genome sheds light on angiosperm phylogeny and species-pair differentiation.

The genus Liriodendron belongs to the family Magnoliaceae, which resides within the magnoliids, an early diverging lineage of the Mesangiospermae. However, the phylogenetic relationship of magnoliids with eudicots and monocots has not been conclusively resolved and thus remains to be determined1-6. Liriodendron is a relict lineage from the Tertiary with two distinct species-one East Asian (L. chinense (Hemsley) Sargent) and one eastern North American (L. tulipifera Linn)-identified as a vicariad species pair. However, the genetic divergence and evolutionary trajectories of these species remain to be elucidated at the whole-genome level7. Here, we report the first de novo genome assembly of a plant in the Magnoliaceae, L. chinense. Phylogenetic analyses suggest that magnoliids are sister to the clade consisting of eudicots and monocots, with rapid diversification occurring in the common ancestor of these three lineages. Analyses of population genetic structure indicate that L. chinense has diverged into two lineages-the eastern and western groups-in China. While L. tulipifera in North America is genetically positioned between the two L. chinense groups, it is closer to the eastern group. This result is consistent with phenotypic observations that suggest that the eastern and western groups of China may have diverged long ago, possibly before the intercontinental differentiation between L. chinense and L. tulipifera. Genetic diversity analyses show that L. chinense has tenfold higher genetic diversity than L. tulipifera, suggesting that the complicated regions comprising east-west-orientated mountains and the Yangtze river basin (especially near 30° N latitude) in East Asia offered more successful refugia than the south-north-orientated mountain valleys in eastern North America during the Quaternary glacial period.

Expression plasticity and evolutionary changes extensively shape the sugar-mimic alkaloid adaptation of nondigestive glucosidase in lepidopteran mulberry-specialist insects.

During the co-evolutionary arms race between plants and herbivores, insects evolved systematic adaptive plasticity to minimize the chemical defence effects of their host plants. Previous studies mainly focused on the expressional plasticity of enzymes in detoxification and digestion. However, the expressional response and adaptive evolution of other fundamental regulators against host phytochemicals are largely unknown. Glucosidase II (GII), which is composed of a catalytic GIIα subunit and a regulatory GIIß subunit, is an evolutionarily conserved enzyme that regulates glycoprotein folding. In this study, we found that GIIα expression of the mulberry-specialist insect was significantly induced by mulberry leaf extract, 1-deoxynojirimycin (1-DNJ), whereas GIIß transcripts were not significantly changed. Moreover, positive selection was detected in GIIα when the mulberry-specialist insects diverged from the lepidopteran order, whereas GIIß was mainly subjected to purifying selection, thus indicating an asymmetrically selective pressure of GII subunits. In addition, positively selected sites were enriched in the GIIα of mulberry-specialist insects and located around the 1-DNJ-binding sites and in the C-terminal region, which could result in conformational changes that affect catalytic activity and substrate-binding efficiency. These results show that expression plasticity and evolutionary changes extensively shape sugar-mimic alkaloids adaptation of nondigestive glucosidase in lepidopteran mulberry-specialist insects. Our study provides novel insights into a deep understanding of the sequestration and adaptation of phytophagous specialists to host defensive compounds.

Structural characterization and antitumor activity of a polysaccharide from ramulus mori.

This study investigated the chemical characterization and antitumor effects of a polysaccharide from ramulus mori. A water-soluble polysaccharide, RMP1 with the estimated molecular weight of 137 kDa, was isolated and purified from ramulus mori through gel permeation chromatography. RMP1 is mainly composed of arabinose, xylose, glucose, galactose and rhamnose in a ratio of 0.56:0.37:0.17:1.00:0.08. Methylation and NMR analysis revealed that RMP1 had a backbone composed of 1,6-ß-d-Galp, 1,3,6-ß-d-Galp and 1,3-ß-d-Galp residues, two main branches of 1,2-α-l-Araf, 1,3,6-ß-d-Galp and 1,4-ß-d-Xylp; it also had α-l-Araf and ß-d-Glcp as terminals. In the MTT assay, RMP1 showed significant anticancer effects against the SGC-7901 and HeLa cells. In addition, no cytotoxicity was observed on the HEK-293 and RAW 264.7 cells. Flow cytometry showed that RMP1 exerted a stimulatory effect on the SGC-7901 cells apoptosis and induced the cell cycle arrest at the S phases. These findings suggest that RMP1 may serve as a potential novel antitumor agent.

Silkworm Pupa Protein Hydrolysate Induces Mitochondria-Dependent Apoptosis and S Phase Cell Cycle Arrest in Human Gastric Cancer SGC-7901 Cells.

Silkworm pupae (Bombyx mori) are a high-protein nutrition source consumed in China since more than 2 thousand years ago. Recent studies revealed that silkworm pupae have therapeutic benefits to treat many diseases. However, the ability of the compounds of silkworm pupae to inhibit tumourigenesis remains to be elucidated. Here, we separated the protein of silkworm pupae and performed alcalase hydrolysis. Silkworm pupa protein hydrolysate (SPPH) can specifically inhibit the proliferation and provoke abnormal morphologic features of human gastric cancer cells SGC-7901 in a dose- and time-dependent manner. Moreover, flow cytometry indicated that SPPH can induce apoptosis and arrest the cell-cycle in S phase. Furthermore, SPPH was shown to provoke accumulation of reactive oxygen species (ROS) and depolarization of mitochondrial membrane potential. Western blotting analysis indicated that SPPH inhibited Bcl-2 expression and promoted Bax expression, and subsequently induced apoptosis-inducing factor and cytochrome C release, which led to the activation of initiator caspase-9 and executioner caspase-3, cleavage of poly (ADP-ribose) polymerase (PARP), eventually caused cell apoptosis. Moreover, SPPH-induced S-phase arrest was mediated by up-regulating the expression of E2F1 and down-regulating those of cyclin E, CDK2 and cyclin A2. Transcriptome sequencing and gene set enrichment analysis (GSEA) also revealed that SPPH treatment could affect gene expression and pathway regulation related to tumourigenesis, apoptosis and cell cycle. In summary, our results suggest that SPPH could specifically suppress cell growth of SGC-7901 through an intrinsic apoptotic pathway, ROS accumulation and cell cycle arrest, and silkworm pupae have a potential to become a source of anticancer agents in the future.

Molecular evolutionary mechanisms driving functional diversification of α-glucosidase in Lepidoptera.

The digestive tract of lepidopteran insects is unique given its highly alkaline pH. The adaptive plasticity of digestive enzymes in this environment is crucial to the highly-efficient nutritional absorption in Lepidoptera. However, little is known about the molecular adaptation of digestive enzymes to this environment. Here, we show that lepidopteran α-glucosidase, a pivotal digestive enzyme, diverged into sucrose hydrolase (SUH) and other maltase subfamilies. SUH, which is specific for sucrose, was only detected in Lepidoptera. It suggests that lepidopteran insects have evolved an enhanced ability to hydrolyse sucrose, their major energy source. Gene duplications and exon-shuffling produced multiple copies of α-glucosidase in different microsyntenic regions. Furthermore, SUH showed significant functional divergence (FD) compared with maltase, which was affected by positive selection at specific lineages and codons. Nine sites, which were involved in both FD and positive selection, were located around the ligand-binding groove of SUH. These sites could be responsible for the ligand-binding preference and hydrolytic specificity of SUH for sucrose, and contribute to its conformational stability. Overall, our study demonstrated that positive selection is an important evolutionary force for the adaptive diversification of α-glucosidase, and for the exclusive presence of membrane-associated SUHs in the unique lepidopteran digestive tract.

Genomic Analysis of an Ascomycete Fungus from the Rice Planthopper Reveals How It Adapts to an Endosymbiotic Lifestyle.

A number of sap-sucking insects harbor endosymbionts, which are thought to play an important role in the development of their hosts. One of the most important rice pests, the brown planthopper (BPH), Nilaparvata lugens (Stål), harbors an obligatory yeast-like symbiont (YLS) that cannot be cultured in vitro. Genomic information on this YLS would be useful to better understand its evolution. In this study, we performed genome sequencing of the YLS using both 454 and Illumina approaches, generating a draft genome that shows a slightly smaller genome size and relatively higher GC content than most ascomycete fungi. A phylogenomic analysis of the YLS supported its close relationship with insect pathogens. We analyzed YLS-specific genes and the categories of genes that are likely to have changed in the YLS during its evolution. The loss of mating type locus demonstrated in the YLS sheds light on the evolution of eukaryotic symbionts. This information about the YLS genome provides a helpful guide for further understanding endosymbiotic associations in hemiptera and the symbiotic replacement of ancient bacteria with a multifunctional YLS seems to have been a successful change.

A host plant genome (Zizania latifolia) after a century-long endophyte infection.

Despite the importance of host-microbe interactions in natural ecosystems, agriculture and medicine, the impact of long-term (especially decades or longer) microbial colonization on the dynamics of host genomes is not well understood. The vegetable crop 'Jiaobai' with enlarged edible stems was domesticated from wild Zizania latifolia (Oryzeae) approximately 2000 years ago as a result of persistent infection by a fungal endophyte, Ustilago esculenta. Asexual propagation via infected rhizomes is the only means of Jiaobai production, and the Z. latifolia-endophyte complex has been maintained continuously for two centuries. Here, genomic analysis revealed that cultivated Z. latifolia has a significantly smaller repertoire of immune receptors compared with wild Z. latifolia. There are widespread gene losses/mutations and expression changes in the plant-pathogen interaction pathway in Jiaobai. These results show that continuous long-standing endophyte association can have a major effect on the evolution of the structural and transcriptomic components of the host genome.