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A novel avian infectious bronchitis virus (IBV) variant, designated as GX-NN160421, was isolated from vaccinated chicken in Guangxi, China, in 2016. Based on analysis of the S1 gene sequence, GX-NN160421 belonged to the New-type 1 (GVI-1) strain. More importantly, three consecutive nucleotides (AAC) deletions were found in the highly conserved structure gene N. The serotype of GX-NN160421 was different from those of the commonly used vaccine strains. The mortality of the GX-NN160421 strain was 3.33%, which contrasted with 50% mortality in the clinical case, but high levels of virus shedding lasted at least 21 days. In conclusion, the first novel IBV variant with three-nucleotide-deletion in the N gene was identified, and this unique variant is low virulent but with a long time of virus shedding, indicating the continuing evolution of IBV and emphasizing the importance of limiting exposure to novel IBV strains as well as extensive monitoring of new IBVs.

Background Bupleurum chinense DC. is a widely used traditional Chinese medicinal plant. Saikosaponins are the major bioactive constituents of B. chinense, but relatively little is known about saikosaponin biosynthesis. In the present study, we performed an integrated analysis of metabolic composition and the expressed genes involved in saikosaponin biosynthetic pathways among four organs (the root, flower, stem, and leaf) of B. chinense to discover the genes related to the saikosaponin biosynthetic pathway. Results Transcript and metabolite profiles were generated through high-throughput RNA-sequencing (RNA-seq) data analysis and liquid chromatography tandem mass spectrometry, respectively. Evaluation of saikosaponin contents and transcriptional changes showed 152 strong correlations (P Conclusions Our results investigated the diversity of the saikosaponin triterpene biosynthetic pathway in the roots, stems, leaves and flowers of B. chinese by integrated transcriptomic and metabolomic analysis, implying that manipulation of P450s genes such as Bc95697 and Bc35434 might improve saikosaponin biosynthesis. This is a good candidate for the genetic improvement of this important medicinal plant.

BACKGROUND: Recent breakthroughs in therapies with immune checkpoint inhibitors (ICIs) have revolutionized the treatment of lung cancer. However, only 15–25% of patients respond to the ICIs therapy, and methods to identify those responsive patients are currently a hot research topic. PD-L1 expression measured on tumor tissues using immunohistochemistry (IHC) was approved as one of the companion diagnostic methods, but it is invasive and cannot be used to monitor dynamic changes in PD-L1 expression during treatments. METHODS: In this study, we developed an Epcam-PD-L1 extracellular vesicle (EV) detection prototype using the Simoa platform. This assay detected PD-L1 expression levels on tumor-derived exosomes from the lung cancer cell lines A549 and SK-MES1. In addition, 35 plasma samples from patients with lung cancer were tested with this assay and the results were compared to the tissue PD-L1 expression levels represented by the tumor proportion score (TPS). RESULTS: PD-L1 TPS-positive patients (≥1% IHC TPS) had significantly higher Simoa Epcam-PD-L1 signals than TPS-negative patients (

Marek's disease (MD) continues to threaten the sustainability of the world poultry industry. In this study, the sequences of the meq gene of 220 MDV strains isolated during the years 1964-2020 were analysed, including 50 from our group plus 170 isolates from the GenBank. Analyses, using phylogenetic trees, amino acid (aa)-mutation screening, evolutionary studies and transmission dynamics were all performed. All strains were divided into two clusters (Clusters 1 and 2), and Cluster 1 includes the mild strains, the vaccine strains and the foreign virulent strains, while Cluster 2 was dominated by the Chinese field strains. Our study identified that the Chinese field strains in Cluster 2 during the years 1995-2020 likely originated in the 1980s from abroad, and the estimated genetic diversity of these strains experienced two growth phases in the years 2005-2007.5 and 2015-2017. Viral phylogeography identified 3 major geographic provincial regions for the Chinese field strains of Cluster 2: the Northeastern Region (Jilin, Liaoning and Heilongjiang), the East-central Region (Henan, Shandong and Jiangsu) and the Southern Region (Guangxi, Guangdong and Yunnan). The spread of Northeastern strains to East-central chicken flocks and the further spread from Guangxi to Guangdong are strongly indicated. The emergence of the mutations A88T and Q93R together in the Southern strains during the years 2017-2020 with molecular characteristics of vv+ MDV were also found later than those in the Northern strains. Overall, the Chinese field strains in Cluster 2 in southern China in recent years have been rapidly evolving. Guangxi Province has become an epicentre for these viruses and the chicken flocks in the Southern region have been facing the adverse effects of the emerging vv+ MDV.

Cyp26a1 had important roles in mouse embryo implantation and was highly expressed in some of NK cells at the human maternal‐foetal interface in early pregnancy. However, the regulatory effect of Cyp26a1 on NK cells remains poorly understood. Through qPCR and flow cytometric assays, we found that Cyp26a1 was expressed by mouse uterine NK cells but not spleen NK cells during the peri‐implantation period and there was a group of NK cells that highly expressed Cyp26a1, that is Cyp26a1+NK cell subset. single cell‐population transcriptome sequencing on Cyp26a1+NK and Cyp26a1−NK cell subsets was performed. We found that there were 3957 differentially expressed genes in the Cyp26a1+NK cell subset with a cut‐off of fold change ≥2 and FDR

Both reticuloendotheliosis (RE) and Marek’s disease (MD) are neoplastic diseases of chickens caused by reticuloendotheliosis virus (REV) and Marek's disease virus (MDV) respectively. The infection of REV and/or MDV may lead to clinical tumors and also result in immunosuppression and easily allow secondary infection by other pathogens. Here, we investigated a breeder flock of Three-Yellow chickens in southern China that had been vaccinated with CVI988/Rispens at hatching and had experienced depression, weakness, reduction in weight gain and an increased death rate after 120 days old. The morbidity and mortality were 20% and 10% respectively at 140 days old when this infection was diagnosed. The necropsy of the birds revealed significant tumor-like lesions in the heart, liver, spleen and ceca. Peripheral blood lymphocytes and tumor-like tissues were sampled for polymerase chain reaction (PCR) detection and for histopathological observation, for virus isolation and the subsequent immunofluorescent assay (IFA) on the cell cultures and for gene sequencing of the isolated viruses. A REV isolate GX18NNR1 and a MDV isolate GX18NNM5 were both recovered from the sampled bird. Further phylogenetic analysis based on the env gene of REV and the meq gene of MDV demonstrated that GX18NNR1 was closely related to the reference REV strain MD-2, which was isolated from a contaminated commercial turkey herpesvirus (HVT) vaccine. Also, the GX18NNM5 was found to belong to the Chinese very virulent (vv) MDV strains’ cluster. The co-infection of REV and MDV may contribute to tumor outbreaks with high morbidity and mortality in Three-Yellow chicken flocks.

The SOCS1/JAK2/STAT3 axis is strongly associated with tumor growth and progression, and participates in cytokine secretion in many diseases. However, the effects of the SOCS1/JAK2/STAT3 axis in experimental subarachnoid hemorrhage remain to be studied. A subarachnoid hemorrhage model was established in rats by infusing autologous blood into the optic chiasm pool. Some rats were first treated with JAK2/STAT3 small interfering RNA (Si-JAK2/Si-STAT3) or overexpression plasmids of JAK2/STAT3. In the brains of subarachnoid hemorrhage model rats, the expression levels of both JAK2 and STAT3 were upregulated and the expression of SOCS1 was downregulated, reaching a peak at 48 hours after injury. Simultaneously, the interactions between JAK2 and SOCS1 were reduced. In contrast, the interactions between JAK2 and STAT3 were markedly enhanced. Si-JAK2 and Si-STAT3 treatment alleviated cortical neuronal cell apoptosis and necrosis, destruction of the blood–brain barrier, brain edema, and cognitive functional impairment after subarachnoid hemorrhage. This was accompanied by decreased phosphorylation of JAK2 and STAT3 protein, decreased total levels of JAK2 and STAT3 protein, and increased SOCS1 protein expression. However, overexpression of JAK2 and STAT3 exerted opposite effects, aggravating subarachnoid hemorrhage-induced early brain injury. Si-JAK2 and Si-STAT3 inhibited M1-type microglial conversion and the release of pro-inflammatory factors (inducible nitric oxide synthase, interleukin-1β, and tumor necrosis factor-α) and increased the release of anti-inflammatory factors (arginase-1, interleukin-10, and interleukin-4). Furthermore, primary neurons stimulated with oxyhemoglobin were used to simulate subarachnoid hemorrhage in vitro, and the JAK2 inhibitor AG490 was used as an intervention. The in vitro results also suggested that neuronal protection is mediated by the inhibition of JAK2 and STAT3 expression. Together, our findings indicate that the SOCS1/JAK2/STAT3 axis contributes to early brain injury after subarachnoid hemorrhage both in vitro and in vivo by inducing inflammatory responses. This study was approved by the Animal Ethics Committee of Anhui Medical University and the First Affiliated Hospital of University of Science and Technology of China (approval No. LLSC-20180202) on March 1, 2018.

A new monotypic coelomycetous genus, Loculosulcatispora (type species L. thailandica) is introduced in Pleosporales from woody litter in Thailand. Phylogenetic analysis of combined non-translated loci (SSU, LSU, ITS) and protein-coding regions (tef1-α, rpb2) shows the genus is a distinct lineage in Sulcatisporaceae. Loculosulcatispora is distinguished from other genera in the family, by having 1-celled, oblong, hyaline, smooth-walled conidia with guttules. Comprehensive morphological descriptions and illustrations are provided for the new genus and species.

Background Mounting evidence has demonstrated the vital importance of tumor-associated macrophages (TAMs) and exosomes in the formation of the premetastatic niche. However, the molecular mechanisms by which tumor-derived exosomal miRNAs interact with TAMs underlying premetastatic niche formation and colorectal cancer liver metastasis (CRLM) remain largely unknown. Methods Transmission electron microscopy and differential ultracentrifugation were used to verify the existence of exosomes. In vivo and in vitro assays were used to identify roles of exosomal miR-934. RNA pull-down assay, dual-luciferase reporter assay, etc. were applied to clarify the mechanism of exosomal miR-934 regulated the crosstalk between CRC cells and M2 macrophages. Results In the present study, we first demonstrated the aberrant overexpression of miR-934 in colorectal cancer (CRC), especially in CRLM, and its correlation with the poor prognosis of CRC patients. Then, we verified that CRC cell-derived exosomal miR-934 induced M2 macrophage polarization by downregulating PTEN expression and activating the PI3K/AKT signaling pathway. Moreover, we revealed that hnRNPA2B1 mediated miR-934 packaging into exosomes of CRC cells and then transferred exosomal miR-934 into macrophages. Interestingly, polarized M2 macrophages could induce premetastatic niche formation and promote CRLM by secreting CXCL13, which activated a CXCL13/CXCR5/NFκB/p65/miR-934 positive feedback loop in CRC cells. Conclusions These findings indicate that tumor-derived exosomal miR-934 can promote CRLM by regulating the crosstalk between CRC cells and TAMs. These findings reveal a tumor and TAM interaction in the metastatic microenvironment mediated by tumor-derived exosomes that affects CRLM. The present study also provides a theoretical basis for secondary liver cancer.

In this paper, we described and illustrated a new species of lignicolous fungi, Distoseptispora hydei, found on decaying bamboo in Phitsanulok Province, Thailand. According to the phylogenetic results from combined sequence data (LSU, ITS and RPB2), the new species is distinct from other Distoseptispora species. Distoseptispora hydei is characterized by obpyriform to fusiform conidia with 7–9 distosepta and a hyaline, gelatinous sheath around the tip. Phylogenetic analyses and morphological comparisons with other species of Distoseptispora are provided in this study.

Endometriosis is one of the most common gynecological diseases that adversely effects the lives of women. Our previous studies showed that LINC01541 plays a key role in 17β-estradiol (17β-E2)-stimulated endometrial stromal cells (ESCs); however, the mechanism by which LINC01541 exerts if effects requires further elaboration. Here, we report that LINC01541 serves to reduce the bioavailability of miR-506-5p by acting as a molecular sponge. Samples of control endometrial tissue and ectopic endometrial tissue were obtained from 10 healthy volunteers and 18 patients with endometriosis, respectively, and the levels of LINC01541 and miR-506-5p expressions in those tissues were measured. The relationship between LINC01541 and miR-506-5p was verified in 17β-E2-stimulated ESCs. Overexpression or silencing of miR-506-5p in ESCs was performed explore its role in endometriosis, and we also investigated whether WNT inhibitory factor 1 (WIF1) might be a target gene of miR-506-5p. Our results showed that LINC01541 was expressed at low levels and miR-506-5p was expressed at high levels in ectopic tissues. LINC01541 expression was negatively correlated with miR-506-5p expression. We also found that miR-506-5p activated the Wnt/β-catenin pathway by inhibiting WIF1 expression, and thereby induced the proliferation, migration, and invasion of ESCs. Furthermore, silencing of miR-506-5p promoted apoptosis and suppressed the proliferation of 17β-E2-treated ESCs. Overexpression of miR-506-5p could reverse the inhibitory effect of LINC01541 in endometriosis. In summary, this study found that in endometriosis, LINC01541 functions as a ceRNA that modulates the Wnt/β-catenin pathway by decoying miR-506-5p.

Standardized mechanical planting of single-bud seedcane sett can improve planting efficiency and reduce costs in sugarcane production and is a research focus at present. Small RNA (miRNA) is an important regulator of life activities, which regulates many plant physiological processes such as gene expression, growth, development and metabolism. In this study, miRNAs in six germinating bud samples (S, bud of single-bud sett; D1, upper bud of double-bud sett; D2, lower bud of double-bud sett; T1, upper bud of three-bud sett; T2, median bud of three-bud sett; T3, lower bud of three-bud sett) derived from sugarcane variety GT42 were analyzed. As a result, 8,055,449, 19,172,991, 8,163,579, 11,748,126, 13,547,550 and 12,861,743 clean tags were obtained respectively, and their length was ranged from 16 to 35 nt. For different bud samples, S, D1, D2, T1, T2 and T3, 174, 600, 318, 425, 466, and 317 novel miRNAs were identified respectively, and a total of 1797 miRNAs, 28,042 target genes and 53,141 target sites were obtained from them. As compared with D1, D2, T1, T2 and T3, it was found the sample S showed 219, 157, 108, 44 and 41 up-regulated miRNAs, respectively. Plant hormone signal transduction pathway was the unique pathway enriched by KEGG analysis, and the enriched gene number was 67, 48, 54, 44 and 40 in S_VS_D1, S_VS_D2, S_VS_T1, S_VS_T2 and S_VS_T3, respectively. Furthermore, a total of 19 allelic genes were co-enriched. Among them, the most abundant allelic gene was found to be IAA gene, with a total of 32 gene sequences. All the up-regulated genes were involved in eight aspects metabolic regulation in plant hormone information transduction. The results showed that plant hormone information transduction played a dominant role in the single-bud sett germinating process, which might be the main reason for promoting the early germination and growth. These results can be referred for popularization and application of standardized mechanical planting of single-bud sett in sugarcane.

Pyrrosia petiolosa, Pyrrosia lingua and Pyrrosia sheareri are recorded as original plants of Pyrrosiae Folium (PF) and commonly used as Chinese herbal medicines. Due to the similar morphological features of PF and its adulterants, common DNA barcodes cannot accurately distinguish PF species. Knowledge of the chloroplast (cp) genome is widely used in species identification, molecular marker and phylogenetic analyses. Herein, we determined the complete cp genomes of three original species of PF via high-throughput sequencing technologies. The three cp genomes exhibited a typical quadripartite structure with sizes ranging from 158 165 to 163 026 bp. The cp genomes of P. petiolosa and P. lingua encoded 130 genes, whilst that of P. sheareri encoded 131 genes. The complete cp genomes were compared, and five highly divergent regions of petA-psbJ, matK-rps16, ndhC-trnM, psbM-petN and psaC-ndhE were screened as potential DNA barcodes for identification of Pyrrosia genus species. The phylogenetic tree we obtained indicated that P. petiolosa and P. lingua are clustered in a single clade and, thus, share a close relationship. This study provides invaluable information for further studies on the species identification, taxonomy and phylogeny of Pyrrosia genus species.

During the process of transmission and spread of avian leukosis virus subgroup J (ALV-J) in chickens worldwide, the viral genome is constantly changing. A comprehensive and systematic study of the evolutionary process of ALV-J in China is needed. In this study, we amplified the full-length viral cDNA sequences of 16 ALV-J isolates of Yellow-chicken origin and analyzed and compared these sequences with another 69 ALV-J strains isolated during the years 1988-2018. These isolates were then sorted into 2 clusters: cluster I included isolates that mainly originated from the layers and White-feather broilers from northern China; cluster II included isolates mainly from the Yellow-chicken, most of them being from southern China. According to the sequence homologies of the whole genome and gag, pol, gp85, and gp37 genes, the ALV-J strains are more likely to randomly change in different directions from the original strain HPRS-103 as time passes. The results of entropy analysis of the sequences of gag, pol, and env revealed that the env gene had the largest variation, and the gag gene nonconserved sites are mainly concentrated in p19, p10, and p12. In addition, 84.71% (72/85) of the isolates had the 205-nucleotide (nt) deletion in the 3'UTR region, and 30.59% (26/85) of the isolates had the 125-nt to 127-nt deletion in the E element. Our study provides evidence for the coexistence of 2 extremely different clusters of ALV-J prevailing in China and in some other countries during the period of 1988-2018 and implies that the clusters are highly dependent on the host genetic background and the geographic location.

In multiple sclerosis (MS), Th17 cells are critical drivers of autoimmune central nervous system (CNS) inflammation and demyelination. Th17 cells exhibit functional heterogeneity fostering both pathogenic and nonpathogenic, tissue-protective functions. Still, the factors that control Th17 pathogenicity remain incompletely defined. Here, using experimental autoimmune encephalomyelitis, an established mouse MS model, we report that therapeutic administration of activin-A ameliorates disease severity and alleviates CNS immunopathology and demyelination, associated with decreased activation of Th17 cells. In fact, activin-A signaling through activin-like kinase-4 receptor represses pathogenic transcriptional programs in Th17-polarized cells, while it enhances antiinflammatory gene modules. Whole-genome profiling and in vivo functional studies revealed that activation of the ATP-depleting CD39 and CD73 ectonucleotidases is essential for activin-A–induced suppression of the pathogenic signature and the encephalitogenic functions of Th17 cells. Mechanistically, the aryl hydrocarbon receptor, along with STAT3 and c-Maf, are recruited to promoter elements on Entpd1 and Nt5e (encoding CD39 and CD73, respectively) and other antiinflammatory genes, and control their expression in Th17 cells in response to activin-A. Notably, we show that activin-A negatively regulates the metabolic sensor, hypoxia-inducible factor-1α, and key inflammatory proteins linked to pathogenic Th17 cell states. Of translational relevance, we demonstrate that activin-A is induced in the CNS of individuals with MS and restrains human Th17 cell responses. These findings uncover activin-A as a critical controller of Th17 cell pathogenicity that can be targeted for the suppression of autoimmune CNS inflammation.

In present study, we have mined a transaminase (TA) from Rhizobium sp. from the pool of fully sequenced genomes by using an ω-TA sequence from Vibrio fluvialis JS17 as a template in a BLASTP search. The protein sequence of the TA from Rhizobium sp. exhibits 53% sequence identity to that from V. fluvialis. The TA with S-selectivity showed close evolutionary relationship with a pyruvate transaminase from Alcaligenes denitrificans Y2k-2 and an S-selective aminotransferase from Sphaerobacter thermophilus. The gene of the ω-TA was inserted into pET-28a and functionally expressed in E. coli BL21. Results showed that the recombinant ω-TA has a specific activity of 7.46 U/mg at pH 8.0, 30 ℃. The substrate specificity test found the ω-TA presented significant reactivity toward aromatic amino donors and amino acceptors containing aldehydes. More importantly, the ω-TA also exhibited a good affinity towards some cyclic substrates. The homology model of the ω-TA was built by Discovery Studio and docking was performed to describe the relative activity towards some substrates.

Fungal diversity notes is one of the important journal series of fungal taxonomy that provide detailed descriptions and illustrations of new fungal taxa, as well as providing new information of fungal taxa worldwide. This article is the 11th contribution to the fungal diversity notes series, in which 126 taxa distributed in two phyla, six classes, 24 orders and 55 families are described and illustrated. Taxa in this study were mainly collected from Italy by Erio Camporesi and also collected from China, India and Thailand, as well as in some other European, North American and South American countries. Taxa described in the present study include two new families, 12 new genera, 82 new species, five new combinations and 25 new records on new hosts and new geographical distributions as well as sexual-asexual reports. The two new families areEriomycetaceae(Dothideomycetes, familyincertae sedis) andFasciatisporaceae(Xylariales, Sordariomycetes). The twelve new genera compriseBhagirathimyces(Phaeosphaeriaceae),Camporesiomyces(Tubeufiaceae),Eriocamporesia(Cryphonectriaceae),Eriomyces(Eriomycetaceae),Neomonodictys(Pleurotheciaceae),Paraloratospora(Phaeosphaeriaceae),Paramonodictys(Parabambusicolaceae),Pseudoconlarium(Diaporthomycetidae, genusincertae sedis),Pseudomurilentithecium(Lentitheciaceae),Setoapiospora(Muyocopronaceae),Srinivasanomyces(Vibrisseaceae) andXenoanthostomella(Xylariales, generaincertae sedis). The 82 new species compriseAcremonium chiangraiense,Adustochaete nivea,Angustimassarina camporesii,Bhagirathimyces himalayensis,Brunneoclavispora camporesii,Camarosporidiella camporesii,Camporesiomyces mali,Camposporium appendiculatum,Camposporium multiseptatum,Camposporium septatum,Canalisporium aquaticium,Clonostachys eriocamporesiana,Clonostachys eriocamporesii,Colletotrichum hederiicola,Coniochaeta vineae,Conioscypha verrucosa,Cortinarius ainsworthii,Cortinarius aurae,Cortinarius britannicus,Cortinarius heatherae,Cortinarius scoticus,Cortinarius subsaniosus,Cytospora fusispora,Cytospora rosigena,Diaporthe camporesii,Diaporthe nigra,Diatrypella yunnanensis,Dictyosporium muriformis,Didymella camporesii,Diutina bernali,Diutina sipiczkii,Eriocamporesia aurantia,Eriomyces heveae,Ernakulamia tanakae,Falciformispora uttaraditensis,Fasciatispora cocoes,Foliophoma camporesii,Fuscostagonospora camporesii,Helvella subtinta,Kalmusia erioi,Keissleriella camporesiana,Keissleriella camporesii,Lanspora cylindrospora,Loratospora arezzoensis,Mariannaea atlantica,Melanographium phoenicis,Montagnula camporesii,Neodidymelliopsis camporesii,Neokalmusia kunmingensis,Neoleptosporella camporesiana,Neomonodictys muriformis,Neomyrmecridium guizhouense,Neosetophoma camporesii,Paraloratospora camporesii,Paramonodictys solitarius,Periconia palmicola,Plenodomus triseptatus,Pseudocamarosporium camporesii,Pseudocercospora maetaengensis,Pseudochaetosphaeronema kunmingense,Pseudoconlarium punctiforme,Pseudodactylaria camporesiana,Pseudomurilentithecium camporesii,Pseudotetraploa rajmachiensis,Pseudotruncatella camporesii,Rhexocercosporidium senecionis,Rhytidhysteron camporesii,Rhytidhysteron erioi,Septoriella camporesii,Setoapiospora thailandica,Srinivasanomyces kangrensis,Tetraploa dwibahubeeja,Tetraploa pseudoaristata,Tetraploa thrayabahubeeja,Torula camporesii,Tremateia camporesii,Tremateia lamiacearum,Uzbekistanica pruni,Verruconis mangrovei,Wilcoxina verruculosa,Xenoanthostomella chromolaenaeandXenodidymella camporesii. The five new combinations areCamporesiomyces patagoniensis,Camporesiomyces vaccinia,Camposporium lycopodiellae,Paraloratospora gahniaeandRhexocercosporidium microsporum. The 22 new records on host and geographical distribution compriseArthrinium marii,Ascochyta medicaginicola,Ascochyta pisi,Astrocystis bambusicola,Camposporium pellucidum,Dendryphiella phitsanulokensis,Diaporthe foeniculina,Didymella macrostoma,Diplodia mutila,Diplodia seriata,Heterosphaeria patella,Hysterobrevium constrictum,Neodidymelliopsis ranunculi,Neovaginatispora fuckelii,Nothophoma quercina,Occultibambusa bambusae,Phaeosphaeria chinensis,Pseudopestalotiopsis theae,Pyxine berteriana,Tetraploa sasicola,Torula gaodangensisandWojnowiciella dactylidis. In addition, the sexual morphs ofDissoconium eucalyptiandPhaeosphaeriopsis pseudoagavacearumare reported fromLaurus nobilisandYucca gloriosain Italy, respectively. The holomorph ofDiaporthe cynaroidisis also reported for the first time.

Simplicilliumspecies have a wide host range and an extensive distribution. Some species are associated with rusts, as well as other plant pathogenic fungi and play an important role in biological control. In this study, two specimens ofSimplicilliumwere collected from Chiang Mai Province, Thailand.Simplicillium formicaesp. nov. was isolated from an infected ant andS. lanosoniveumfromOphiocordyceps unilateraliswhich is a new host record. Species were initially identified using ITS gene sequences and confirmed using morphology coupled with phylogenetic analyses of a combined nrLSU, nrSSU, TEF and RPB1 dataset.Simplicillium formicaediffers from other species in the genus by the presence of flask-shaped synnemata and phialides with intercalary nodes.Simplicillium lanosoniveumresembles other collections of the species by its completely solitary, tapering phialides and globose to ellipsoidal conidia which adhere in a slimly head. A key to species ofSimplicilliumis also provided.

Construction of a genome-wide transgenic UAS-cDNA/ORF library in Drosophila based on the binary GAL4/UAS system has been severely hampered by technical difficulties, although genome-wide cDNA or ORF resources of Drosophila, human, and mouse have been publicly available for more than a decade. Here, we developed a new method named CRISPR-based modular assembly (CRISPRmass) for the high-throughput construction of a genome-wide UAS-cDNA/ORF library from publicly available cDNA/ORF resources. Through cleavage of shared vector sequences of cDNA/ORF plasmids by CRISPR/Cas9 and subsequent insertion of UAS modules by Gibson assembly, the procedure of construction of such a library by CRISPRmass is standardized as massively parallel two-step test tube reactions before bacterial transformation. Using CRISPRmass, we generated 5551 UAS-cDNA/ORF constructs covering 83% of the Drosophila genes conserved in humans in the Drosophila Genomics Resource Center (DGRC) Gold Collection, and among them, 5518 were generated within 3 mo by three people. Our results show that CRISPRmass allows modulization, simplicity, efficiency, and adaptability in the generation of a genome-wide UAS-cDNA/ORF plasmid library by using publicly available cDNA/ORF resources. CRISPRmass can be applied to editing various genome-wide libraries in general and is an alternative to Gateway technology in high-throughput plasmid library editing. Furthermore, the more than 5500 UAS-cDNA/ORF plasmids of Drosophila genes serve as a powerful resource for gain-of-function (GOF) screening in cultured cells and for generation of a transgenic UAS-cDNA/ORF library in Drosophila.

Summary: Proliferating cells need to evaluate the environment to determine the optimal timing for cell cycle entry. However, how this is achieved is not well understood. Here, we show that, in budding yeast, the G1 inhibitor Whi5 is a key environmental indicator and plays a crucial role in coordinating cell growth and division. We found that, under a variety of nutrient and stress conditions, Whi5 amount in G1 is proportional to the cell’s doubling time in the environment, which in turn influences the timing for the next cell cycle entry. In addition, the coordination between division and environment is further fine-tuned in G1 by environmentally dependent growth rate, G1 cyclin-Cdk1 contribution, and Whi5 threshold at the start. Our results show that the cell stores the past environmental information in Whi5, which works together with other mechanisms sensing the current environmental condition to achieve an adaptive cellular decision making process. : Qu et al. find that the level of the cell cycle inhibitor Whi5 is proportional to the doubling time of the past cell cycle across a variety of nutrient and stress conditions. Thus, both past and current environmental information is utilized in coordinating cell growth and division. Keywords: Whi5, cellular memory, cell cycle control, environment sensing, cellular decision making, cell growth and division

A new species, Colletotrichum artocarpicola, on Artocarpus heterophyllus from Chiang Rai, Thailand, is introduced using both morphological and molecular approaches. Combined phylogenetic analysis of ITS, GAPDH, CHS-1, ACT and TUB2 sequence data demonstrate that Colletotrichum artocarpicola is a distinct species within the gloeosporioides species complex. The new species is illustrated and compared with related taxa, and evidence of its pathogenicity is provided.

One natural recombinant avian leukosis virus (ALV) strain GX14DJ3–18 was isolated from a native gamecock by DF-1 cell culture and identified with Polymerase Chain Reaction (PCR), immunofluorescence assay and the viral genome's nucleotide sequencing. This strain was revealed as a novel recombinant virus with nucleotide sequence similarities of 95.4% Long Terminal Repeated (LTR), 95.8% 5′, UTR, 97.9% gag, and 92.9% 3′untranslated regions (UTR) in ALV-J. Also we found sequence similarities of 99.3% pol and 99.0% gp37 in ALV-E, and 89.9% gp85 in ALV-A. The simulated congenital infection with GX14DJ3–18 in Three-Yellow chickens exhibited a significant negative effect on the development of immune organs (P < 0.05). Also, lower antibody responses were found to vaccinations with the commercial vaccines of Newcastle disease virus and with subtypes H5 and H9 of avian influenza virus (P < 0.05). The incidence of tumor or tumor-like lesions in the challenged birds was 14.28% (5/35), while none were observed in the un-challenged control group (0/35). These results suggested that GX14DJ3–18 is a novel recombinant ALV that can induce pathogenicity in the commercial Three-Yellow chickens. We speculated that cross-provincial sales of gamecocks in which ALVs have not been eradicated thoroughly might be a potential route for the transmission of ALVs to commercial chickens.

Background Brain metastasis (BM) is thought to be related to the mortality and poor prognosis of non-small cell lung cancer (NSCLC). Despite promising development of NSCLC treatment, the treatment of NSCLC BM is still not optimistic due to the existence of the blood-brain barrier (BBB) that prevent drug penetration, as well as the short median survival time of the patients left for treatment. In this context, further development of quick and effective pre-clinical models is needed in NSCLC BM treatment. Here, we report a model system using zebrafish to promote the development of drugs for patients with NSCLC BM. Methods Three different NSCLC cell lines (H1975, A549 and H1299) were used to establish zebrafish BM models. The embryo age and cell number for injection were first optimized. Metastatic cells were observed in the brain blood vessels of zebrafish and were verified by hematoxylin-eosin (HE) staining. Then, the metastasis potentials of H1975 and A549 with manipulated microRNA-330-3p (miR-330-3p) expression were also investigated. Finally, sensitivities of H1975 and A549 to osimertinib and gefitinib were tested. Results This zebrafish BM model could distinguish NSCLC cell lines with different BM potential. Over-expressed miR-330-p significantly improved the BM potential of the A549 cells while knockdown miR-330-p reduced the BM ability of the H1975 cells. Both osimertinib and gefitinib showed inhibition effect in zebrafish BM model with the inhibition rate higher than 50 %. H1975 cell showed much higher sensitivity to osimertinib rather than gefitinib both in vivo and in vitro. Conclusions We established zebrafish brain metastasis model for studying mechanism and treatment of NSCLC BM. This study provided a useful model for NSCLC brain metastasis that could be used to study the mechanism that drive NSCLC cells to the brain as well as identify potential therapeutic options.

Uterine M1/M2 macrophages activation states undergo dynamic changes throughout pregnancy, and inappropriate macrophages polarization can cause adverse pregnancy outcomes, especially during the peri-implantation period. Our previous studies have confirmed that Cytochrome P450 26A1 (CYP26A1) can affect embryo implantation by regulating uterine NK cells and DCs. The aim of this study was to investigate whether CYP26A1 regulates the polarization of uterine macrophages in early pregnancy. Here, we observed that Cyp26a1 was significantly upregulated in M1 as compared with M2 of uterine macrophages, Raw264.7 and iBMDM. Knockdown of CYP26A1 in mice uterine significantly decreased the number of embryo implantation sites and the proportion of CD45+F4/80+CD206− M1-like uterine macrophages. Primary uterine macrophages treated with anti-CYP26A1 antibody expressed significantly lower levels of M1 markers Nos2, Il1b, Il6 and Tnf-a. In CYP26A1 knockout Raw264.7 cells, the protein levels of M1 markers TNF-α, IL-6 and CD86 were significantly decreased as compared with the wild type cells. Moreover, CYP26A1 deficiency decreased the ability to produce nitric oxide and increased the phagocytosis capacity of Raw264.7 cells under M1 stimulation state. The re-introduction of CYP26A1 partially reversed the polarization levels of M1 in CYP26A1 knockout Raw264.7 cells. CYP26A1 may regulate the polarization of uterine macrophages to M1 through Stap1 and Slc7a2. In summary, these results indicate that CYP26A1 plays a significant role in macrophage polarization, and knockdown of CYP26A1 can cause insufficient M1 polarization during the peri-implantation period, which has adverse effects on blastocyst implantation.

Stictidaceae comprises taxa with diverse lifestyles. Many species in this family are drought resistant and important for studying fungal adaptation and evolution. Stictidaceae comprises 32 genera, but many of them have been neglected for decades due to the lack of field collections and molecular data. In this study, we introduce a new species Fitzroyomyces hyaloseptisporus and a new combination Fitzroyomyces&nbsp, pandanicola. We also provide additional morphological and molecular data for Ostropomyces pruinosellus and O. thailandicus based on new collections isolated from an unidentified woody dicotyledonous host in Chiang Rai, Thailand. Taxonomic conclusions are made with the aid of morphological evidence and phylogenetic analysis of combined LSU, ITS and mtSSU sequence data. Characteristics such as the shape and septation of ascospores and conidia as well as lifestyles among genera of Stictidaceae are discussed.

Ischemia-reperfusion injury (IRI) remains as a critical challenge for organ transplantation. Herein, an enzyme therapeutic based on superoxide dismutase and catalase for effective mitigation of IRI and pathogen-induced liver injury is reported, providing a therapeutic for organ transplantation and other diseases.

Novel variant infectious bursal disease virus (nvIBDV) is an emerging pathotype that can cause subclinical disease with severe, prolonged immunosuppression in young chickens. At present, two major pathotypes including vvIBDV and nvIBDV are prevailing in China. In this study, we propose that the nvIBDV is a new genotype (A2dB1b) and also first isolated and characterized a nvIBDV reassortant strain YL160304 (A2dB3) with segments A and B derived respectively from the nvIBDV and the HLJ-0504-like vvIBDV from Yellow-chickens in southern China. The YL160304 causes more extensive cytotropism and can infect SPF chicken embryos with severe subcutaneous hemorrhage. The pathogenicity of YL160304 to 4-week-old Three-Yellow chickens was determined and compared with those of the nvIBDV QZ191002 and the HLJ-0504-like vvIBDV NN1172. Weight gain was significantly reduced in all the challenged birds. No clinical signs and associated mortality were observed in the birds challenged with QZ191002, while the mortalities in the birds challenged with NN1172 and YL160304 were 30% (3/10) and 10% (1/10), respectively. At 7 days post-challenge, the bursa was severely damaged and the percentage of peripheral blood B lymphocyte (PBBL) decreased significantly in all the challenged birds and the quantity of the viral RNA detected in the bursa was in accordance with the results of the histomorphometry and the depletion of PBBL. This study not only confirmed the emerging epidemic of the novel variant and its reassortant strains, but also discovered that the naturally reassortant nvIBDV strain with the segment B of HLJ 0504-like vvIBDV can significantly enhance the pathogenicity to chickens. This article is protected by copyright. All rights reserved.

Infectious bronchitis virus (IBV) poses massive economic losses in the global poultry industry. Here, we firstly report the construction and immunogenicity comparison of virus-like particles (VLPs) carrying the S, M and E proteins (SME-VLPs), VLPs carrying the S and M proteins (SM-VLPs), and VLPs carrying the M and E proteins (ME-VLPs) from the dominant serotype representative strain GX-YL5 in China. The neutralizing antibody response induced by the SME-VLPs was similar to that induced by the inactivated oil vaccine (OEV) of GX-YL5, and higher than those induced by the SM-VLPs, ME-VLPs and commercial live vaccine H120. More importantly, the SME-VLPs elicited higher percentages of CD4+ and CD8+ T lymphocytes than the SM-VLPs, ME-VLPs and OEV of GX-YL5. Compared with the OEV of GX-YL5, higher levels of IL-4 and IFN-γ were also induced by the SME-VLPs. Moreover, the mucosal immune response (sIgA) induced by the SME-VLPs in the tear and oral swabs was comparable to that induced by the H120 vaccine and higher than that induced by the OEV of GX-YL5. In the challenge experiment, the SME-VLPs resulted in significantly lower viral RNA levels in the trachea and higher protection scores than the OEV of GX-YL5 and H120 vaccines, and induced comparable viral RNA levels in the kidneys, and tear and oral swabs to the OEV of GX-YL5. In summary, among the three VLPs, the SME-VLPs carrying the S, M and E proteins of IBV could stimulate the strongest humoral, cellular and mucosal immune responses and provide effective protection, indicating that it would be an attractive vaccine candidate for IB.

Gallid alpha-herpesvirus 1, also known as avian infectious laryngotracheitis virus (ILTV), continues to cause huge economic losses to the poultry industry worldwide. Similar to that of other herpesvirus-encoded proteins, the expression of viral genes encoded by ILTV is regulated by a cascade, and the underlying regulatory mechanism remains largely unclear. The viral immediate-early (IE) gene ICP4 plays a prominent role in the initiation of the transcription of early and late genes during ILTV replication. In this study, we identified AP-1 as the key regulator of the transcription of ILTV genes by bioinformatics analysis of genome-wide transcriptome data. Subsequent functional studies of the key members of the AP-1 family revealed that Fos, but not Jun, regulates ILTV infection through AP-1 since knockdown of Fos, but not Jun, by gene silencing significantly reduced ICP4 transcription and subsequent viral genome replication and virion production. Using several approaches, we identified ICP4 as a bona fide target gene of Fos that regulated Fos and has Fos response elements within its promoter. Neither the physical binding of Jun to the promoter of ICP4 nor the transcriptional activity of Jun was observed. In addition, knockdown of Fos reduced the transcription of MDH1 and ATP5A1, genes encoding two host rate-limiting enzymes essential for the production of the TCA intermediates OAA and ATP. The biological significance of the transcriptional regulation of MDH1 and ATP5A1 by Fos in ILTV infection was supported by the fact that anaplerosis of OAA and ATP rescued both ICP4 transcription and virion production in infected cells under when Fos was silenced. Our study identified the transcription factor Fos as a key regulator of ILTV infection through its transcription factor function on both the virus and host sides, improving the current understanding of both avian herpesvirus–host interactions and the roles of AP-1 in viral infection.

Herein, based on iron oxyhydroxide (FeOOH) as the photoactive material and exonuclease III (exo III)-aided dual recycling signal amplification, a new photoelectrochemical (PEC) biosensor was successfully developed for human papillomavirus-16 (HPV-16) detection with a wide linear range from 0.5 fM to 1 nM and a low detection limit of 0.17 fM.

Pathological TDP‐43 aggregation is characteristic of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD‐TDP); however, how TDP‐43 aggregation and function are regulated remain poorly understood. Here, we show that O‐GlcNAc transferase OGT‐mediated O‐GlcNAcylation of TDP‐43 suppresses ALS‐associated proteinopathies and promotes TDP‐43's splicing function. Biochemical and cell‐based assays indicate that OGT's catalytic activity suppresses TDP‐43 aggregation and hyperphosphorylation, whereas abolishment of TDP‐43 O‐GlcNAcylation impairs its RNA splicing activity. We further show that TDP‐43 mutations in the O‐GlcNAcylation sites improve locomotion defects of larvae and adult flies and extend adult life spans, following TDP‐43 overexpression in Drosophila motor neurons. We finally demonstrate that O‐GlcNAcylation of TDP‐43 promotes proper splicing of many mRNAs, including STMN2, which is required for normal axonal outgrowth and regeneration. Our findings suggest that O‐GlcNAcylation might be a target for the treatment of TDP‐43‐linked pathogenesis.

Reactive Oxygen Species (ROS) are present in high amount in patients with tumors, and these ROS can kill and destroy tumor cells. Thus, tumor cells upregulate ROS-related genes to protect themselves and reduce their destruction. Cancer cells already damaged by ROS can be repaired by expressing DNA repair genes consequently promoting their proliferation. In this work, lung adenocarcinoma (LUAD) transcriptome data in the TCGA database was analyzed and samples were clustered into 5 ROS-related categories and 6 DNA repair categories. Survival analysis revealed a significant difference in patient survival between the two classification methods. In addition, the samples corresponding to the two categories overlap, thus, the gene expression profile of the same sample with different categories and survival prognosis was further explored, and the connection between ROS-related genes and DNA repair genes was investigated. The interactive sample recombination classification was used, revealing that the patient's prognosis was worse when the ROS-related genes and DNA repair genes were expressed at the same time. The further research on the potential regulatory network of the two categories of genes and the correlation analysis revealed that ROS-related genes and DNA repair genes have a mutual regulatory relationship. The ROS-related genes NQO1, TXNRD1, and PRDX4 could establish links with other DNA repair genes through the DNA repair gene NEIL3, thereby increasing the growth of tumor cells and balancing the level of ROS, leading to tumor cell death and constant damage to the tumor cell repair system, thus prolonging patient survival. Thus, targeting ROS-related genes and DNA repair genes might be a promising strategy in the treatment of LUAD. Finally, a survival prognostic model of ROS-related genes and DNA repair genes was established (TERT, PRKDC, PTTG1, SMUG1, TXNRD1, CAT, H2AFX and PFKP), the risk score might be used as an independent prognostic factor in LUAD patients.

Avian leukosis virus subgroup J (ALV-J) has infected a variety of birds, causing major economic losses in China. Understanding the comprehensive criteria of classification and nomenclature of ALV-J would be useful for the investigation of the viral evolution and also for the prevention and control of this infection. An in-depth analysis of the genetic diversity of ALV-J was performed in the present study. Four hundred and seventy-five sequences of the gp85 gene, including thirteen of avian endogenous retrovirus designated ev/J and 462 of ALV-J, were used in the phylogenetic and the evolutionary distance analysis for this classification. The study identified that the current ALV-J strains were divided into two first-order clades (Clades 1 and 2) and three second-order clades (Clades 1.1, 1.2 and 1.3). The current Chinese ALV-J strains are predominantly in Clade 1.3, and the Chinese and Egyptian chicken flocks have been facing the emerging Clade 2 viruses. This system pioneers the classification efforts for ALV-J, which uses Pilot tree for rapid classification of the new isolates and also the addition of possible new clades. The proposed unified classification system will facilitate future studies of ALV-J epidemiology and genetic evolution and of the comparison of sequences obtained across the world.

Taylor’s power law and Iwao’s patchiness regression were used to describe the dispersion patterns for overwintering and wandering stages of Corythucha ciliata on the London plane trees, Platanus x acerifolia (Ait.) Willd. Both Taylor’s and Iwao’s tests fit the distribution data for the overwintering stage. The overwintering adults were spatially aggregated. In the wandering stage, Taylor’s power law consistently fit the data, whereas the fit of Iwao’s patchiness regression was erratic. Both Iwao’s and Taylor’s indices indicated a clumped distribution pattern for eggs, nymphs, and wandering adults. Trunk was identified as the best sampling target for the overwintering stage whereas twig was the best for the wandering stage. In order to determine the sample size for evaluating whether the population has reached the control threshold, the sampling of 35 and 7 trunks for the overwintering stage and 32 and 8 twigs per tree for the wandering stage would provide 0.5- and 0.25-precision levels, respectively.

Adenosine, which is produced mainly by microbial fermentation, plays an important role in the therapy of cardiovascular disease and has been widely used as an antiarrhythmic agent. In this study, guanosine 5′-monophosphate (GMP) synthetase gene (guaA) was inactivated by gene-target manipulation to increase the metabolic flux from inosine 5′-monophosphate (IMP) to adenosine in B. subtilis A509. The resulted mutant M3-3 showed an increased adenosine production from 7.40 to 10.45 g/L, which was further enhanced to a maximum of 14.39 g/L by central composite design. As the synthesis of succinyladenosine monophosphate (sAMP) from IMP catalysed by adenylosuccinate synthetase (encoded by purA gene) is the rate-limiting step in adenosine synthesis, the up-regulated transcription level of purA was the potential underlying mechanism for the increased adenosine production. This work demonstrated a practical strategy for breeding B. subtilis strains for industrial nucleoside production.

Cytochrome P450 26A1 (CYP26A1) plays important roles in the mice peri‐implantation period. Inhibiting its expression or function leads to pregnancy failure. However, little is known about the underlying mechanisms involved, especially the relationship between CYP26A1 and immune cells. In this study, using Cyp26a1‐specific antisense morpholigos (Cyp26a1‐MO) knockdown mice model and pCR3.1‐Cyp26a1 vaccine mice model, we found that the number of uterine CD45+CD11c+MHCIIlo‐hiF4/80− dendritic cells (DCs) was significantly decreased in the treated mice. The percentage of mature DCs (CD86hi) was obviously lower and the percentage of immature DCs (CD86lo) was remarkably higher in uterine DCs in the treatment group than that of the control group. Further experiments found that ID2, a transcription factor associated with DCs development, and CD86, a DC mature marker molecule, were both significantly reduced in mice uteri in the treated group. In vitro, ID2 and CD86 also decreased in bone marrow‐derived DCs under Cyp26a1‐MO treatment. These findings provide novel information that CYP26A1 might affect the embryo implantation via modulating the differentiation and maturation of uterine DCs.

This article is the tenth series of the Fungal Diversity Notes, where 114 taxa distributed in three phyla, ten classes, 30 orders and 53 families are described and illustrated. Taxa described in the present study include one new family (viz. Pseudoberkleasmiaceae in Dothideomycetes), five new genera (Caatingomyces, Cryptoschizotrema, Neoacladium, Paramassaria and Trochilispora) and 71 new species, (viz. Acrogenospora thailandica, Amniculicola aquatica, A. guttulata, Angustimassarina sylvatica, Blackwellomyces lateris, Boubovia gelatinosa, Buellia viridula, Caatingomyces brasiliensis, Calophoma humuli, Camarosporidiella mori, Canalisporium dehongense, Cantharellus brunneopallidus, C. griseotinctus, Castanediella meliponae, Coprinopsis psammophila, Cordyceps succavus, Cortinarius minusculus, C. subscotoides, Diaporthe italiana, D. rumicicola, Diatrypella delonicis, Dictyocheirospora aquadulcis, D. taiwanense, Digitodesmium chiangmaiense, Distoseptispora dehongensis, D. palmarum, Dothiorella styphnolobii, Ellisembia aurea, Falciformispora aquatic, Fomitiporia carpinea, F. lagerstroemiae, Grammothele aurantiaca, G. micropora, Hermatomyces bauhiniae, Jahnula queenslandica, Kamalomyces mangrovei, Lecidella yunnanensis, Micarea squamulosa, Muriphaeosphaeria angustifoliae, Neoacladium indicum, Neodidymelliopsis sambuci, Neosetophoma miscanthi, N. salicis, Nodulosphaeria aquilegiae, N. thalictri, Paramassaria samaneae, Penicillium circulare, P. geumsanense, P. mali-pumilae, P. psychrotrophicum, P. wandoense, Phaeoisaria siamensis, Phaeopoacea asparagicola, Phaeosphaeria penniseti, Plectocarpon galapagoense, Porina sorediata, Pseudoberkleasmium chiangmaiense, Pyrenochaetopsis sinensis, Rhizophydium koreanum, Russula prasina, Sporoschisma chiangraiense, Stigmatomyces chamaemyiae, S. cocksii, S. papei, S. tschirnhausii, S. vikhrevii, Thysanorea uniseptata, Torula breviconidiophora, T. polyseptata, Trochilispora schefflerae and Vaginatispora palmae). Further, twelve new combinations (viz. Cryptoschizotrema cryptotrema, Prolixandromyces australi, P. elongatus, P. falcatus, P. longispinae, P. microveliae, P. neoalardi, P. polhemorum, P. protuberans, P. pseudoveliae, P. tenuistipitis and P. umbonatus), an epitype is chosen for Cantharellus goossensiae, a reference specimen for Acrogenospora sphaerocephala and new synonym Prolixandromyces are designated. Twenty-four new records on new hosts and new geographical distributions are also reported (i.e. Acrostalagmus annulatus, Cantharellus goossensiae, Coprinopsis villosa, Dothiorella plurivora, Dothiorella rhamni, Dothiorella symphoricarposicola, Dictyocheirospora rotunda, Fasciatispora arengae, Grammothele brasiliensis, Lasiodiplodia iraniensis, Lembosia xyliae, Morenoina palmicola, Murispora cicognanii, Neodidymelliopsis farokhinejadii, Neolinocarpon rachidis, Nothophoma quercina, Peroneutypa scoparia, Pestalotiopsis aggestorum, Pilidium concavum, Plagiostoma salicellum, Protofenestella ulmi, Sarocladium kiliense, Tetraploa nagasakiensis and Vaginatispora armatispora).

Background Building brain reserves before dementia onset could represent a promising strategy to prevent Alzheimer’s disease (AD), while how to initiate early cognitive stimulation is unclear. Given that the immature brain is more sensitive to environmental stimuli and that brain dynamics decrease with ageing, we reasoned that it would be effective to initiate cognitive stimulation against AD as early as the fetal period. Methods After conception, maternal AD transgenic mice (3 × Tg AD) were exposed to gestational environment enrichment (GEE) until the day of delivery. The cognitive capacity of the offspring was assessed by the Morris water maze and contextual fear-conditioning tests when the offspring were raised in a standard environment to 7 months of age. Western blotting, immunohistochemistry, real-time PCR, immunoprecipitation, chromatin immunoprecipitation (ChIP) assay, electrophysiology, Golgi staining, activity assays and sandwich ELISA were employed to gain insight into the mechanisms underlying the beneficial effects of GEE on embryos and 7–10-month-old adult offspring. Results We found that GEE markedly preserved synaptic plasticity and memory capacity with amelioration of hallmark pathologies in 7–10-m-old AD offspring. The beneficial effects of GEE were accompanied by global histone hyperacetylation, including those at bdnf promoter-binding regions, with robust BDNF mRNA and protein expression in both embryo and progeny hippocampus. GEE increased insulin-like growth factor 1 (IGF1) and activated its receptor (IGF1R), which phosphorylates Ca2+/calmodulin-dependent kinase IV (CaMKIV) at tyrosine sites and triggers its nuclear translocation, subsequently upregulating histone acetyltransferase (HAT) and BDNF transcription. The upregulation of IGF1 mimicked the effects of GEE, while IGF1R or HAT inhibition during pregnancy abolished the GEE-induced CaMKIV-dependent histone hyperacetylation and BDNF upregulation. Conclusions These findings suggest that activation of IGF1R/CaMKIV/HAT/BDNF signaling by gestational environment enrichment may serve as a promising strategy to delay AD progression. Electronic supplementary material The online version of this article (10.1186/s40035-019-0149-9) contains supplementary material, which is available to authorized users.

This article is the ninth in the series of Fungal Diversity Notes, where 107 taxa distributed in three phyla, nine classes, 31 orders and 57 families are described and illustrated. Taxa described in the present study include 12 new genera, 74 new species, three new combinations, two reference specimens, a re-circumscription of the epitype, and 15 records of sexual-asexual morph connections, new hosts and new geographical distributions. Twelve new genera comprise Brunneofusispora, Brunneomurispora, Liua, Lonicericola, Neoeutypella, Paratrimmatostroma, Parazalerion, Proliferophorum, Pseudoastrosphaeriellopsis, Septomelanconiella, Velebitea and Vicosamyces. Seventy-four new species are Agaricus memnonius, A. langensis, Aleurodiscus patagonicus, Amanita flavoalba, A. subtropicana, Amphisphaeria mangrovei, Baorangia major, Bartalinia kunmingensis, Brunneofusispora sinensis, Brunneomurispora lonicerae, Capronia camelliae-yunnanensis, Clavulina thindii, Coniochaeta simbalensis, Conlarium thailandense, Coprinus trigonosporus, Liua muriformis, Cyphellophora filicis, Cytospora ulmicola, Dacrymyces invisibilis, Dictyocheirospora metroxylonis, Distoseptispora thysanolaenae, Emericellopsis koreana, Galiicola baoshanensis, Hygrocybe lucida, Hypoxylon teeravasati, Hyweljonesia indica, Keissleriella caraganae, Lactarius olivaceopallidus, Lactifluus midnapurensis, Lembosia brigadeirensis, Leptosphaeria urticae, Lonicericola hyaloseptispora, Lophiotrema mucilaginosis, Marasmiellus bicoloripes, Marasmius indojasminodorus, Micropeltis phetchaburiensis, Mucor orantomantidis, Murilentithecium lonicerae, Neobambusicola brunnea, Neoeutypella baoshanensis, Neoroussoella heveae, Neosetophoma lonicerae, Ophiobolus malleolus, Parabambusicola thysanolaenae, Paratrimmatostroma kunmingensis, Parazalerion indica, Penicillium dokdoense, Peroneutypa mangrovei, Phaeosphaeria cycadis, Phanerochaete australosanguinea, Plectosphaerella kunmingensis, Plenodomus artemisiae, P. lijiangensis, Proliferophorum thailandicum, Pseudoastrosphaeriellopsis kaveriana, Pseudohelicomyces menglunicus, Pseudoplagiostoma mangiferae, Robillarda mangiferae, Roussoella elaeicola, Russula choptae, R. uttarakhandia, Septomelanconiella thailandica, Spencermartinsia acericola, Sphaerellopsis isthmospora, Thozetella lithocarpi, Trechispora echinospora, Tremellochaete atlantica, Trichoderma koreanum, T. pinicola, T. rugulosum, Velebitea chrysotexta, Vicosamyces venturisporus, Wojnowiciella kunmingensis and Zopfiella indica. Three new combinations are Baorangia rufomaculata, Lanmaoa pallidorosea and Wojnowiciella rosicola. The reference specimens of Canalisporium kenyense and Tamsiniella labiosa are designated. The epitype of Sarcopeziza sicula is re-circumscribed based on cyto- and histochemical analyses. The sexual-asexual morph connection of Plenodomus sinensis is reported from ferns and Cirsium for the first time. In addition, the new host records and country records are Amanita altipes, A. melleialba, Amarenomyces dactylidis, Chaetosphaeria panamensis, Coniella vitis, Coprinopsis kubickae, Dothiorella sarmentorum, Leptobacillium leptobactrum var. calidus, Muyocopron lithocarpi, Neoroussoella solani, Periconia cortaderiae, Phragmocamarosporium hederae, Sphaerellopsis paraphysata and Sphaeropsis eucalypticola., Rungtiwa Phookamsak thanks CAS President’s International Fellowship Initiative (PIFI) for Young Staff 2019–2021 (grant number 2019FY0003), the Research Fund from China Postdoctoral Science Foundation (Grant No. Y71B283261), the Yunnan Provincial Department of Human Resources and Social Security (Grant No. Y836181261), and National Science Foundation of China (NSFC) project code 31850410489 for financial research support. Kevin D. Hyde thanks the Foreign Experts Bureau of Yunnan Province, Foreign Talents Program (2018; Grant No. YNZ2018002), Thailand Research grants entitled Biodiversity, phylogeny and role of fungal endophytes on above parts of Rhizophora apiculata and Nypa fruticans (Grant No: RSA5980068), the future of specialist fungi in a changing climate: baseline data for generalist and specialist fungi associated with ants, Rhododendron species and Dracaena species (Grant No: DBG6080013), Impact of climate change on fungal diversity and biogeography in the Greater Mekong Subregion (Grant No: RDG6130001). Jianchu Xu thanks the Key Research Program of Frontier Sciences of the Chinese Academy of Sciences (Grant No. QYZDY-SSW-SMC014). Peter E Mortimer would like to thank the National Science Foundation of China and the Chinese Academy of Sciences for financial support under the following grants: 41761144055, 41771063 and Y4ZK111B01. Olivier Raspé is grateful to the Fonds de la Recherche Scientifique-FNRS (Belgium) for travel grants. Samantha C. Karunarathna thanks CAS President’s International Fellowship Initiative (PIFI) for funding his postdoctoral research (Grant No. 2018PC0006) and the National Science Foundation of China (NSFC, project code 31750110478). Dhanushaka N. Wanasinghe would like to thank CAS President’s International Fellowship Initiative (PIFI) for funding his postdoctoral research (Grant No. 2019PC0008). E.B. Gareth Jones is supported under the Distinguished Scientist Fellowship Program (DSFP), King Saud University, Kingdom of Saudi Arabia., Aniket Ghosh, Kanad Das, Priyanka Uniyal, Rajendra P. Bhatt, Tahir Mehmood, and Upendra Singh are grateful to the Head, Department of Botany & Microbiology & USIC Dept. HNB Garhwal University, Srinagar Garhwal and thank to the Director, Botanical Survey of India, Kolkata for providing all kinds of facilities during the present study and UGC for providing fellowship to Aniket Ghosh, Priyanka Uniyal and Tahir Mehmood. K. P. Deepna Latha acknowledge the Kerala State Council for Science, Technology and Environment (KSCSTE) in the form of a PhD fellowship (Grant No. 001/FSHP/2011/CSTE) and the Principal Chief Conservator of forests, Kerala State, for granting permission (No. WL10- 4937/2012, dated 03-10-2013) to collect agarics from the forests of Kerala. K. N. Anil Raj thanks the Council of Scientific & Industrial Research (CSIR), New Delhi, India, in the form of an award of CSIR Research Associateship (09/043(0178) 2K17 dated: 31/03/2017). Mao-Qiang He and Rui-Lin Zhao thank the National Natural Science Foundation of China (Project ID: 31470152 and 31360014) and the Foundation of Innovative Group of Edible Mushrooms Industry of Beijing (Project ID:BAIC05-2017). Mingkwan Doilom would like to thank the 5th batch of Postdoctoral Orientation Training Personnel in Yunnan Province and the 64th batch of China Postdoctoral Science Foundation., Tatiana Baptista Gibertoni and Renato Lu´cio Mendes Alvarenga acknowledge Dr. Viacheslav Spirin for the taxonomic and morphological advises, CNPq for the Ph.D scholarship of RLMA (140283/ 2016-1), Po´s-Graduac¸a˜o em Biologia de Fungos (UFPE, Brazil), Capes (Capes-SIU 008/13), CNPq (PQ 307601/2015-3) and FACEPE (APQ 0375-2.03/15) for funding the research. Margarita Duen˜as, M. Teresa Telleria and Marı´a P. Martı´n acknowledge financial support from the Agreement ENDESA and San Ignacio de Huinay Foundations and Consejo Superior de Investigaciones Cientı´ficas, CSIC (Projects No. 2011HUIN10, 2013CL0012, 2014CL0011), the AECID (Agencia Espan˜ola de Cooperacio´n Internacional para el Desarrollo) and Plan Nacional I ? D?i project no. CGL2015–67459–P; to Reinhard Fitzek (San Ignacio del Huinay Foundation, Chile) for his invaluable help during fieldwork, and M. Glenn (Seton Hall University, US) for revising the text and Miguel Jerez and Yolanda Ruiz Leo´n for SEM technical assistance. Sandra Nogal-Prata was supported by a Predoctoral Grant from the Ministerio de Economı´a y Competitividad (Spain) (BES-2016-077793). Armin Mesˇic´ and Zdenko Tkalcˇec thank Croatian Science Foundation for their partial support under the project HRZZ-IP-2018-01-1736 (ForFungiDNA) and are grateful to Milan Cˇ erkez for collecting specimens of coprinoid taxa for this study. Hyang Burm Lee was supported by the Graduate Program for the Undiscovered Taxa of Korea, and the Project on Survey and Discovery of Indigenous Fungal Species of Korea funded by NIBR and Project on Discovery of Fungi from Freshwater and Collection of Fungarium funded by NNIBR of the Ministry of Environment (MOE), and in part carried out with the support of Cooperative Research Program for Agriculture Science and Technology Development (PJ013744), Rural Development Administration, and BK21 PLUS program funded by Ministry of Education, Republic of Korea., Mubashar Raza would like to thank the CASTWAS for the PhD Fellowship. Sanjay K. Singh, Paras Nath Singh, Shiwali Rana and Frank Kwekucher Ackah thank Director, MACS, Agharkar Research Institute, Pune, India for providing facilities. Shiwali Rana and Frank Kwekucher Ackah thank UGC (Junior Research Fellowship) and DST, Govt. of India (CV Raman Fellowship for African Researchers), respectively. Gen-Nuo Wang, Huang Zhang, Wei Dong and Xian-Dong Yu thank the National Natural Science Foundation of China (Project ID: NSF 31500017). Bandarupalli Devadatha and V. Venkateswara Sarma thank The Ministry of Earth sciences, Govt. of India (Sanction order: MOES/36/OO1S/ Extra/40/2014/PC-IV dt.14.1.2015) for a funding of the project, T, District Forest Office, Tiruvarur, Tamil Nadu and PCCF (Head of Forest Force), Chennai, Tamil Nadu Forest Department for providing permission to collect samples from Muthupet mangroves, and Department of Biotechnology, Pondicherry University is thanked for providing the facilities. Myung Soo Park, Seung-Yoon Oh and Young Woon Lim thank the Marine Bio Resource Bank Program of the Ministry of Ocean & Fisheries, Korea. Olinto Pereira thanks the CAPES, CNPq and FAPEMIG for financial support. Neven Matocˇec, Ivana Kusˇan and Margita Jadan express their gratitude to Livio Lorenzon, Enrico Bizio and Raffaella Trabucco (MCVE) for their kind help with loan of Sarcopeziza sicula type material; parts of their, research were financed by Public Institutions Sjeverni Velebit National Park and Paklenica National Park. Dong-Qin Dai and LiZhou Tang thank the National Natural Science Foundation of China (No. NSFC 31760013, NSFC 31260087, NSFC 31460561), the Scientific Research Foundation of Yunnan Provincial Department of Education (2017ZZX186) and utilization of endophytes and the Thousand Talents Plan, Youth Project of Yunnan Provinces. Ting-Chi Wen, Chada Norphanphoun and Shi-Ke Huang are grateful to the National Natural Science Foundation of China (No. 31760014) and the Science and Technology Foundation of Guizhou Province (No. [2017]5788). Monika C. Dayarathne thanks to Thailand Research Fund (TRF) Grant No MRG6080089 for financial research support. Napalai Chaiwan thanks The Royal Golden Jubilee Ph. D. Program (PHD60K0147) under Thailand Research Fund, for financial research supports on project entitle ‘‘Fungi on limestone outcrops from southern Thailand to lower himalyas’’. Saranyaphat Boonmee and Sirinapa Konta would like to thank the National Research Council of Thailand (Grant No. 61215320023, 61215320013) and the Thailand Research Fund (Grant No. TRG6180001) for research financial support. Saisamorn Lumyong would like to thank the Thailand Research Fund (RTA 5880006) and Chiang Mai University for partially support this research work. Itthyakorn Promputtha would like to thank Chiang Mai University for partially supported this research work. Lei Cai acknowledges China-Thailand Joint Lab on Microbial Biotechnology (Most KY201701011) for financial support. PhD students from Mae Fah Laung and Chiang Mai Universities thank the Mushroom Research Foundation for research financial support and PhD Fellowships.

The CDK4/6 inhibitor palbociclib reduces tumor growth by decreasing retinoblastoma (RB) protein phosphorylation and inducing cell cycle arrest at the G1/S phase transition. Palbociclib in combination with anti-hormonal therapy brings significant benefit to breast cancer patients. In this study, novel combination approaches and underlying molecular/cellular mechanisms for palbociclib were explored in squamous cell lung cancer (SqCLC), the second most common subtype of non-small cell lung cancer. While approximate 20% lung patients benefit from immunotherapy, most SqCLC patients who receive platinum-doublet chemotherapy as first-line treatment, which often includes a taxane, are still in need of more effective combination therapies. Our results demonstrated enhanced cytotoxicity and anti-tumor effect with palbociclib plus taxanes at clinically achievable doses in multiple SqCLC models with diverse cancer genetic backgrounds. Comprehensive gene expression analysis revealed a sustained disruption of pRB-E2F signaling by combination that was accompanied with enhanced regulation of pleiotropic biological effects. These included several novel mechanisms such as abrogation of G2/M and mitotic spindle assembly checkpoints, as well as impaired induction of hypoxia-inducible factor 1 alpha (HIF-1α). The decrease in HIF-1α modulated a couple key angiogenic and anti-angiogenic factors, resulting in an enhanced anti-angiogenic effect. This preclinical work suggests a new therapeutic opportunity for palbociclib in lung and other cancers currently treated with taxane based chemotherapy as standard of care.

Endometriosis affects 6-10% of healthy women of reproductive age. Therefore, it is important to study the molecular mechanism by which endometriosis develops. This study examined whether aberrant expression of LINC01541 contributes to the pathogenesis of endometriosis. Human endometrial stromal cells (ESCs) were stimulated with 10 nmol/L of 17β-Estradiol (17β-E2) to simulate ectopic cells found in endometriosis. Next, the levels of proteins related to the epithelial-mesenchymal transition (EMT), cell invasion, and metastasis were investigated. The effects of LINCO1541 silencing and overexpression were also examined in ESCs. Cell proliferation and apoptosis were detected by cell counting kit-8 and flow cytometry assays, respectively. ESCs stimulated with 17β-E2 displayed increased levels of N-Cadherin and vimentin expression, but decreased levels of E-Cadherin expression. 17β-E2 promoted the migration and invasion of ESCs, and those affects were partially reversed by overexpression of LINC01541. Furthermore, silencing of LINC01541 attenuated apoptosis and promoted the EMT of ESCs, while overexpression of LINC01541 stimulated cell apoptosis, increased the levels of caspase 3 protein, and decreased the levels of B cell leukemia/lymphoma 2 protein. Overexpression of LINC01541 also decreased the expression of vascular endothelial growth factor A (VEGFA) by repressing the Wnt/β-catenin pathway. Our, results suggest that LINC01541 can inhibit the EMT process, metastasis of ESCs, and VEGFA expression by regulating the Wnt/β-catenin pathway, which may play an important role in the pathogenesis of endometriosis.

This paper is the second in a series focused on providing a stable platform for the taxonomy of phytopathogenic fungi. It focuses on 25 phytopathogenic genera: Alternaria, Bipolaris, Boeremia, Botryosphaeria, Calonectria, Coniella, Corticiaceae, Curvularia, Elsinoe, Entyloma, Erythricium, Fomitiporia, Fulviformes, Laetisaria, Limonomyces, Neofabraea, Neofusicoccum, Phaeoacremonium, Phellinotus, Phyllosticta, Plenodomus, Pseudopyricularia, Tilletia, Venturia and Waitea, using recent molecular data, up to date names and the latest taxonomic insights. For each genus a taxonomic background, diversity aspects, species identification and classification based on molecular phylogeny and recommended genetic markers are provided. In this study, varieties of the genus Boeremia have been elevated to species level. Botryosphaeria, Bipolaris, Curvularia, Neofusicoccum and Phyllosticta that were included in the One Stop Shop 1 paper are provided with updated entries, as many new species have been introduced to these genera.

The Brassica rapa (B. rapa) species displays enormous phenotypic diversity, with leafy vegetables, storage root vegetables and oil crops. These different crops all have different flowering time, which determine their growing season and cultivation area. Little is known about the effects of diverse temperature and day-lengths on flowering time QTL associated with FLC paralogues. We phenotyped the flowering time of a doubled haploid population, established from a cross between Yellow sarson and Pak choi under diverse environmental conditions. We identified flowering-time QTL (fQTL) in different photoperiod and temperature regimes in the greenhouse, and studied their colocation with known flowering time genes. As several fQTL colocalized with FLC paralogues, we studied the expression patterns of four FLC paralogues during the course of vernalization in parental lines. Under all environmental conditions tested the major fQTL that mapped to the BrFLC2_A02 locus was detected, however its effect decreased when plants were grown at low temperatures. Another fQTL that mapped to the FLC paralogue, BrFLC5_A03 was also identified under all tested environments, while no fQTL colocated with BrFLC1_A10 or BrFLC3_A03. Furthermore, the vernalization treatment decreased expression of all BrFLC paralogues in the parental lines, and showed the lowest transcript level after 28 days of vernalization. Transcript abundance stayed low after returning the plants for seven days to normal growth temperature. Interestingly, transcript abundance of BrFLC3_A03 and BrFLC5_A03 was repressed much stronger and already reached lowest levels after 14d in the early-flowering type YS-143. This study improves understanding of the effects of daylength and vernalization on flowering time in B. rapa and the role of the different BrFLC paralogues therein.

The genus Corydalis is recognized as one of the most taxonomically challenging plant taxa. It is mainly distributed in the Himalaya–Hengduan Mountains, a global biodiversity hotspot. To date, no effective solution for species discrimination and taxonomic assignment in Corydalis has been developed. In this study, five nuclear and chloroplast DNA regions, ITS, ITS2, matK, rbcL, and psbA‐trnH, were preliminarily assessed based on their ability to discriminate Corydalis to eliminate inefficient regions, and the three regions showing good performance (ITS, ITS2 and matK) were then evaluated in 131 samples representing 28 species of 11 sections of four subgenera in Corydalis using three analytical methods (NJ, ML, MP tree; K2P‐distance and BLAST). The results showed that the various approaches exhibit different species identification power and that BLAST shows the best performance among the tested approaches. A comparison of different barcodes indicated that among the single barcodes, ITS (65.2%) exhibited the highest identification success rate and that the combination of ITS + matK (69.6%) provided the highest species resolution among all single barcodes and their combinations. Three Pharmacopoeia‐recorded medicinal plants and their materia medica were identified successfully based on the ITS and ITS2 regions. In the phylogenetic analysis, the sections Thalictrifoliae, Sophorocapnos, Racemosae, Aulacostigma, and Corydalis formed well‐supported separate lineages. We thus hypothesize that the five sections should be classified as an independent subgenus and that the genus should be divided into three subgenera. In this study, DNA barcoding provided relatively high species discrimination power, indicating that it can be used for species discrimination in this taxonomically complicated genus and as a potential tool for the authentication of materia medica belonging to Corydalis.

The transcriptional co-activator PGC-1α is a key regulator of mitochondrial function and muscle fiber specification in the skeletal muscle. The E3 ubiquitin ligase RNF34 ubiquitinates PGC-1α and negatively regulates mammalian brown fat cell metabolism. However, the functional importance of RNF34 in the skeletal muscle and its impact on energy metabolism remain unknown. The Drosophila PGC-1 homolog dPGC-1 and its mammalian counterparts have conserved functions in mitochondria and insulin signaling. Here, we showed that the Drosophila RNF34 (dRNF34) ubiquitinates the Drosophila PGC-1α (dPGC-1) and promotes its degradation in HEK293T cells by immunoprecipitation and western blot analysis. This allows us to use Drosophila as a powerful model system to study the physiological role of RNF34 in mitochondrial function and metabolism. In the in vivo studies, by separately expressing two independent UAS-dRNF34 RNAi transgenes driven by the muscle-specific 24B-Gal4 driver, we found that knockdown of dRNF34 specifically in muscle promotes mitochondrial biogenesis, improves negative geotaxis, extends climbing time to exhaustion in moderate aged flies and counteracts high-fat-diet-induced high triglyceride content. Furthermore, we showed that knockdown of dPGC-1 reversed the effects of the dRNF34 knockdown phenotypes described above. Our results reveal that dRNF34 plays an important role in regulating mitochondrial biogenesis in muscle and lipid metabolism through dPGC-1. Thus, inhibition of RNF34 activity provides a potential novel therapeutic strategy for the treatment of age-related muscle dysfunction.

Background Hypoxic conditions area key feature of allergic rhinitis (AR), however, the role of hypoxia in AR remains to be fully understood. The aim of this study was to survey the effect of hypoxia on the Th17 response in AR patients by investigating the action of hypoxia-influenced signaling pathways on Th17 differentiation. Methods 23 AR patients and 15 healthy controls were recruited for this study. Under normoxia and hypoxic conditions, the expression of HIF-1α, AhR, CYP1A1 and CYP1B1 and the presence of Th17 cells in CD4+T cells were measured. Furthermore, the amount of ARNT combined with either HIF-1α or AhR was determined after the exposure of 2-(1H-Indol-3-ylcarbonyl)-4-thiazolecarboxylic acid methyl easter (ITE) with normoxia and hypoxia. Results HIF-1α and AhR expression were higher in CD4+T cells from AR patients than in those from healthy controls. In a hypoxic environment, the expression of HIF-1α was elevated in CD4+T cells of both AR patients and healthy controls. Meanwhile, the suppressive effects of a non-toxic AhR ligand (ITE) on the Th17 response and its positive effects on IL-10 production were suppressed in the cells of AR patients and healthy controls under hypoxia. These effects were arisen from HIF-1α out-competing AhR for ARNT binding which limited the activity of the AhR pathway. Conclusions The present results suggest that hypoxia is capable of promoting the Th17 response by reducing AhR activity via HIF-1α activity. Thus hypoxia may be intimately involved in the pathogenesis of AR.

Background Para-coumaric acid methyl ester (pCAME) is one of the bioactive components of Costus speciosus (Koen) Sm. (Zingiberaceae). This plant is traditionally used in Asia to treat catarrhal fevers, worms, dyspepsia, and skin diseases. Purpose To investigate the anti-angiogenic activity of pCAME and its molecular mechanism of action. Study design We investigated the anti-angiogenic activity of pCAME on human umbilical vein endothelial cells (HUVECs) in vitro and zebrafish (Danio rerio) in vivo. Methods In vitro cell proliferation, would healing, migration and tube formation assays were used, along with in vivo physiological angiogenic vessel formation, tumor-induced angiogenic vessel formation assays on zebrafish model. qRT-PCR and RNA-seq were also used for the target investigation. Results pCAME could inhibit the proliferation, would healing, migration and tube formation of HUVECs, disrupt the physiological formation of intersegmental vessels (ISVs) and the subintestinal vessels (SIVs) of zebrafish embryos, and inhibit tumor angiogenesis in the zebrafish cell-line derived xenograft (zCDX) model of SGC-7901 in a dose-dependent manner. Mechanistic studies revealed that pCAME inhibited vegf/vegfr2 and ang/tie signaling pathways in zebrafish by quantitative RT-PCR analysis, and regulated multi-signaling pathways involving immune, inflammation and angiogenesis in SGC-7901 zCDX model by RNA-seq analysis. Conclusion pCAME may be a multi-target anti-angiogenic drug candidate and hold great potential for developing novel therapeutic strategy for cancer treatment.