scATAC-Ref: a reference of scATAC-seq with known cell labels in multiple species.

Chromatin accessibility profiles at single cell resolution can reveal cell type-specific regulatory programs, help dissect highly specialized cell functions and trace cell origin and evolution. Accurate cell type assignment is critical for effectively gaining biological and pathological insights, but is difficult in scATAC-seq. Hence, by extensively reviewing the literature, we designed scATAC-Ref (https://bio.liclab.net/scATAC-Ref/), a manually curated scATAC-seq database aimed at providing a comprehensive, high-quality source of chromatin accessibility profiles with known cell labels across broad cell types. Currently, scATAC-Ref comprises 1 694 372 cells with known cell labels, across various biological conditions, >400 cell/tissue types and five species. We used uniform system environment and software parameters to perform comprehensive downstream analysis on these chromatin accessibility profiles with known labels, including gene activity score, TF enrichment score, differential chromatin accessibility regions, pathway/GO term enrichment analysis and co-accessibility interactions. The scATAC-Ref also provided a user-friendly interface to query, browse and visualize cell types of interest, thereby providing a valuable resource for exploring epigenetic regulation in different tissues and cell types.

SEanalysis 2.0: a comprehensive super-enhancer regulatory network analysis tool for human and mouse.

Super-enhancers (SEs) play an essential regulatory role in various biological processes and diseases through their specific interaction with transcription factors (TFs). Here, we present the release of SEanalysis 2.0 (http://licpathway.net/SEanalysis), an updated version of the SEanalysis web server for the comprehensive analyses of transcriptional regulatory networks formed by SEs, pathways, TFs, and genes. The current version added mouse SEs and further expanded the scale of human SEs, documenting 1 167 518 human SEs from 1739 samples and 550 226 mouse SEs from 931 samples. The SE-related samples in SEanalysis 2.0 were more than five times that in version 1.0, which significantly improved the ability of original SE-related network analyses ('pathway downstream analysis', 'upstream regulatory analysis' and 'genomic region annotation') for understanding context-specific gene regulation. Furthermore, we designed two novel analysis models, 'TF regulatory analysis' and 'Sample comparative analysis' for supporting more comprehensive analyses of SE regulatory networks driven by TFs. Further, the risk SNPs were annotated to the SE regions to provide potential SE-related disease/trait information. Hence, we believe that SEanalysis 2.0 has significantly expanded the data and analytical capabilities of SEs, which helps researchers in an in-depth understanding of the regulatory mechanisms of SEs.

Discovery of a novel DDRs kinase inhibitor XBLJ-13 for the treatment of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic fatal lung disease characterized by destruction of lung parenchyma and deposition of extracellular matrix in interstitial and alveolar spaces. But known drugs for IPF are far from meeting clinical demands, validation of drug targets against pulmonary fibrosis is in urgent demand. Tyrosine kinase receptor DDRs has been considered as a potential therapeutic target for pulmonary fibrosis due to its pathological collagen binding property and the roles in regulating extracellular matrix remodeling. In this study we designed and synthesized a new indazole derivative XBLJ-13, and identified XBLJ-13 as a highly specific and potent DDRs inhibitor with anti-inflammation and anti-fibrosis activities. We first demonstrated that DDR1/2 was highly expressed in the lung tissues of IPF patients. Then we showed that XBLJ-13 potently inhibited DDR1 and DDR2 kinases with IC50 values of 17.18 nM and 15.13 nM, respectively. Among a panel of 34 kinases tested, XBLJ-13 displayed relatively high selectivity for DDRs with minimal inhibitory effect on PDGFR family and FGFR1, as well as Abl kinase that had high homology with DDRs. Extensive profiling of XBLJ-13 revealed that the new inhibitor had much lower toxicity than nintedanib and better pharmacokinetic properties in mice. Furthermore, pharmacodynamic evaluation conducted in bleomycin-induced pulmonary fibrosis mice showed that administration of XBLJ-13 (30, 60, 90 mg·kg-1·d-1, i.g.) for 12 days significantly and dose-dependently ameliorated lung inflammation and fibrosis. Together, this study confirms that DDRs kinase is a potential target for PF, Particularly, compound XBLJ-13 is a highly potent and specific DDRs inhibitor, along with good pharmacokinetics profiles, and preferable in vivo efficacy, suggesting that it is a potential candidate for the treatment of PF.

Species Diversification of the Coniferous Pathogenic Fungal Genus Coniferiporia (Hymenochaetales, Basidiomycota) in Association with Its Biogeography and Host Plants.

Coniferiporia, belonging to Hymenochaetaceae and now segregated from Phellinidium, is a wood-inhabiting fungal genus with three species, each having a specific geographic distribution and a strong host specificity as a forest pathogen of coniferous trees. In this study, the species diversity of Coniferiporia is further clarified with the aid of a wider sampling and multilocus-based phylogenetic analysis, which reveals a new species Coniferiporia uzbekistanensis. The molecular clock and ancestral geographic origin analyses indicate that the ancestor of Coniferiporia emerged in one of the Pinaceae and Cupressaceae, then jumped to the other plant family originated in eastern Eurasia 17.01 million years ago (Mya; 95% highest posterior density: 9.46 to 25.86 Mya), and later extended its distribution to western North America, Central Asia, and eastern Europe. Coniferiporia sulphurascens speciated on Pinaceae in eastern Eurasia 8.78 Mya (9.46 to 25.86 Mya) and then extended its distribution to western North America and eastern Europe. Coniferiporia qilianensis and C. uzbekistanensis speciated on Juniperus przewalskii in eastern Eurasia 3.67 Mya (0.36 to 8.02 Mya) and on Juniperus polycarpos in Central Asia 4.35 Mya (0.94 to 8.37 Mya), respectively. The speciation event of Coniferiporia weirii occurred 4.45 Mya (0.77 to 9.33 Mya) right after the emergence of its host, the endemic Cupressaceae species Thuja plicata, and soon after, this fungus evolved to also inhabit another endemic Cupressaceae species Calocedrus decurrens. In summary, this study for the first time unambiguously clarified and timed the adaptive evolutionary event of Coniferiporia in association with its biogeography and host plants.

[Complete chloroplast genome of Ligustrum lucidum and highly variable marker identification for Ligustrum].

Ligustri Lucidi Fructus, the sun-dried mature fruit of Ligustrum lucidum, is cool, plain, sweet, and bitter, which can be used as both food and medicine, with the effects of improving vision, blacking hair, and tonifying liver and kidney. It takes effect slowly. However, little is known about the genetic information of the medicinal plant and it is still a challenge to distinguish Ligustrum species. In this study, the complete chloroplast genome of L. lucidum was obtained by genome skimming and then compared with that of five other Ligustrum species, which had been reported. This study aims to evaluate the interspecific variation of chloroplast genome within the genus and develop molecular markers for species identification of the genus. The result showed that the chloroplast genome of L. lucidum was 162 162 bp with a circular quadripartite structure of two single-copy regions separated by a pair of inverted repeats. The Ligustrum chloroplast genomes were conserved with small interspecific difference. Comparative analysis of six Ligustrum chloroplast genomes revealed three variable regions(rbcL-accD, ycf1a, and ycf1b), and ycf1a and ycf1b can be used as the species-specific DNA barcode for Ligustrum. Phylogeny analysis provided the best resolution of Ligustrum and supported that L. lucidum was sister to L. gracile. This study clarified the genetic diversity of L. lucidum from provenance, which can serve as a reference for further analysis of pharmacological differences and breeding of excellent varieties with stable drug effects.

SEanalysis: a web tool for super-enhancer associated regulatory analysis.

Super-enhancers (SEs) have prominent roles in biological and pathological processes through their unique transcriptional regulatory capability. To date, several SE databases have been developed by us and others. However, these existing databases do not provide downstream or upstream regulatory analyses of SEs. Pathways, transcription factors (TFs), SEs, and SE-associated genes form complex regulatory networks. Therefore, we designed a novel web server, SEanalysis, which provides comprehensive SE-associated regulatory network analyses. SEanalysis characterizes SE-associated genes, TFs binding to target SEs, and their upstream pathways. The current version of SEanalysis contains more than 330 000 SEs from more than 540 types of cells/tissues, 5042 TF ChIP-seq data generated from these cells/tissues, DNA-binding sequence motifs for ∼700 human TFs and 2880 pathways from 10 databases. SEanalysis supports searching by either SEs, samples, TFs, pathways or genes. The complex regulatory networks formed by these factors can be interactively visualized. In addition, we developed a customizable genome browser containing >6000 customizable tracks for visualization. The server is freely available at http://licpathway.net/SEanalysis.

Phellinopsis lonicericola and P. tibetica spp. nov. (Hymenochaetales, Basidiomycota), from Tibet, with a key to worldwide species.

Phellinopsis (Hymenochaetaceae) was recently segregated from Phellinus. Phellinopsis differs from other genera segregated from Phellinus in a combination of hymenial setae, if present, mostly originating from tramal hyphae and hyaline basidiospores becoming pale yellowish with age. In this study, two new species of Phellinopsis, P. lonicericola and P. tibetica, from Tibet in southwestern China were described and illustrated. Morphological data and sequences of the nuc rDNA ITS1-5.8S-ITS2 region (internal transcribed spacer [ITS] barcode) support the recognition of these taxa as distinct. They are morphologically compared with other species of Phellinopsis. Notably, P. lonicericola was often found on Lonicera together with Sanghuangporus alpinus, which was originally described from the same locality. In addition, Phellinopsis helwingiae, known from a single collection from Sichuan Province in midwestern China, is reported from Tibet. Eight accepted species of Phellinopsis worldwide, each forming a terminal lineage, grouped together as a strongly supported clade distinct from the clade representing Phellinus. A key to the eight species of Phellinopsis is provided.

Phylogeny and diversity of Fomitiporella (Hymenochaetales, Basidiomycota).

Fomitiporella accommodates polypores producing annual to perennial basidiocarps with an indistinct subiculum (very thin to almost lacking), mostly a dimitic hyphal structure, lacking any kind of setae, with brownish, thick-walled basidiospores, and causing a white rot. Previously, only a few samples of Fomitiporella were studied on the basis of morphological and nuc 28S rDNA (28S)-based phylogenetic analyses. In this study, we made a comprehensive study on Fomitiporella on the basis of collections from Central America, USA, Europe, and China. The phylogenetic analysis, including 28 nuc 28S rDNA and 29 nuc rDNA ITS1-5.8S-ITS2 (internal transcribed spacer [ITS]) sequences newly generated, discovered 14 new lineages. Combined with morphological evidence, 4 new lineages are described and illustrated as new species, viz., Fomitiporella americana, F. micropora, F. sinica, and F. subinermis; 10 other new lineages, each with a single collection, are still treated as unidentified taxa; three new combinations, viz., Fomitiporella tenuissima, F. chinensis, and F. resupinata, are proposed. In addition, F. inermis is redescribed. A key to the 12 known species of Fomitiporella is provided.

Global diversity and phylogeny of Onnia (Hymenochaetaceae) species on gymnosperms.

Onnia includes white rotting polypores with annual basidiocarps, a duplex context, monomitic hyphal structure, hymenial setae, and hyaline, thin-walled, smooth basidiospores. Specimens of Onnia, originating mainly from East Asia, Europe, and North America, were studied using both morphology and phylogenetic analyses. Our concatenated data set was derived from 25 collections and included (i) 25 nuc rDNA internal transcribed spacer region sequences (ITS1-5.8S-ITS2 = ITS), 17 generated in this study; and (ii) 14 nuc rDNA 28S rDNA sequences, including the D1-D2 domains, 11 of them generated in this study. The resulting maximum likelihood and Bayesian phylogenies recovered all sampled collections of Onnia as a well-supported clade. In this clade, three previously accepted species, viz., Onnia leporina, O. tomentosa, and O. triquetra, received strong support, whereas three additional lineages with strong support represent the new species described in this paper, O. subtriquetra, O. microspora, and O. tibetica. Of the six Onnia species occurring on gymnosperms, O. tomentosa and O. leporina grow mainly on Picea and have circumboreal distribution in the Northern Hemisphere. In contrast, other species that mostly grow on Pinus are geographically restricted to limited regions, viz., O. triquetra in Europe, O. subtriquetra in North America, and O. microspora and O. tibetica in Asia.

Neomensularia duplicata gen. et sp. nov. (Hymenochaetales, Basidiomycota) and two new combinations.

Neomensularia (Hymenochaetaceae) is a new genus introduced for N. duplicata sp. nov. (generic type), N. crocitincta and N. kanehirae combs. nov., based on a combination of distinct morphological characters and phylogenetic analyses inferred from nuc rDNA partial 28S and ITS datasets. The new genus is characterized by annual, pileate, brown to fuscous basidiocarps, duplex context, dimitic hyphal structure, ventricose, and hooked hymenial setae, golden yellow, thick-walled, smooth basidiospores that are negative in both Melzer's reagent and Cotton Blue and a growth habit in tropical forests. Neomensularia duplicata closely resembles Mensularia radiata by hooked hymenial setae, but M. radiata has a homogenous context, larger pores (5-7 per mm), monomitic hyphal structure, hyphoid setae, larger cyanophilic basidiospores and occurs in temperate forests. Central American specimens labeled as Inonotus crocitinctus and Asian specimens identified as Fulvifomes kanehirae were re-examined. The duplex context, hooked hymenial setae and colored basidiospores are similar to N. duplicata Phylogenetic inferences based on 28S and ITS sequence data confirm their affinities with N. duplicata and result in the proposal of new combinations, Neomensularia crocitincta and N. kanehirae.

Global diversity and phylogeny of the Phellinus igniarius complex (Hymenochaetales, Basidiomycota) with the description of five new species.

The Phellinus igniarius complex corresponds to Phellinus s.s., a well supported clade in the polyphyletic Phellinus s.l. studied worldwide. Recently a molecular phylogeny of this complex was performed for the European and North American species. In this study we expand the taxon samplings of the P. igniarius complex to include 59, seven and 12 additional collections originating from China, Czech Republic and USA, respectively. We generated 78 nuc rDNA ITS1-5.8S-ITS2 (ITS) and 42 translation elongation factor 1-α gene (tef1α) sequences. Based on the morphological and phylogenetic (combined ITS and tef1α dataset) analyses, Phellinus monticola, P. orientoasiaticus, P. padicola, P. parmastoi and P. pomaceoides are newly described and illustrated from China and USA. Phellinus pseudoigniarius is treated as a later synonym of P. igniarius, whereas Phellinus betulinus subsp. betulinus is accepted as P. betulinus. A total of 15 species are accepted in the P. igniarius complex worldwide. Of them, 10 species are distributed in eastern Asia, eight in Europe and six in North America. The taxonomy, phylogeny, host associations and geographic distributions of these 15 species are briefly discussed.

Colivelin ameliorates amyloid ß peptide-induced impairments in spatial memory, synaptic plasticity, and calcium homeostasis in rats.

Amyloid ß peptide (Aß) has been thought to be neurotoxic and responsible for the impairment of learning and memory in Alzheimer's disease (AD). Humanin (HN), a 24 amino acid polypeptide first identified from the unaffected occipital lobe of an AD patient, is believed to be neuroprotective against the AD-related neurotoxicity. In this study, we investigated the neuroprotective effects of Colivelin (CLN), a novel HN derivative, against Aß by using behavioral test, in vivo electrophysiological recording, and intracellular calcium imaging. Our results showed that intrahippocampal injection of CLN (0.2 nmol) effectively prevented Aß25-35 (4 nmol)-induced deficits in spatial learning and memory of rats in Morris water maze test; the suppression of in vivo hippocampal long term potentiation (LTP) by Aß25-35 was nearly completely prevented by CLN; in addition, CLN pretreatment also effectively inhibited Aß25-35-induced calcium overload in primary cultured hippocampal neurons. These results indicate that CLN has significant neuroprotective properties against Aß, and CLN may holds great promise for the treatment and prevention of AD.

Four new species of Phylloporia (Hymenochaetales, Basidiomycota) from tropical China with a key to Phylloporia species worldwide.

Phylloporia (Hymenochaetaceae) is a monophyletic and cosmopolitan genus with diverse morphology. In a nuc 28S rDNA-based phylogeny specimens collected from tropical China were recovered as four new lineages within the Phylloporia clade. Based on morphological evidence and host relationships, these four lineages are described and illustrated as four new species: Phylloporia clausenae, P. cylindrispora, P. flacourtiae and P. homocarnica. The distinctive morphological characters of the four new species of Phylloporia are discussed. In addition, the phylogenetic position of P. tiliae, which was recently described from China, was confirmed in the Phylloporia clade. A key is provided for all 30 accepted species of Phylloporia.

A Novel Phellinidium sp. Causes Laminated Root Rot on Qilian Juniper (Sabina przewalskii) in Northwest China.

A laminated root rot on Qilian juniper (Sabina przewalskii) caused by a species of Phellinidium (Basidiomycota) was observed in northwest China. Seventeen fungal samples collected from Qinghai Province during 2012 and 2013 were used for taxonomic and pathogenicity tests. The fungal pathogen was identified by morphological characters and phylogenetic analyses based on nLSU sequences. A new fungus is described herein as Phellinidium qilianense sp. nov. One-year-old Qilian juniper seedlings were wound-inoculated under controlled conditions to test pathogenicity of the fungal species. The fungus was successfully reisolated from decayed tissue of tested seedlings. P. qilianense is a new forest pathogen on coniferous trees in China.

Medium composition optimization and characterization of polysaccharides extracted from Ganoderma boninense along with antioxidant activity.

Ganoderma is a well-known medicinal macrofungal genus, of which several species have been thoroughly studied from the medicinal perspective, but most species are rarely involved in. In this study, we focus on the polysaccharides extracted from Ganoderma boninense and their antioxidant activity. Ganoderma boninense is a serious pathogen of oil palms that are cultivated commercially in Southeast Asia. Response surface methodology was conducted to optimize the liquid medium composition, and the mycelia biomass reached 7.063 g/L, that is, 1.4-fold compared with the seed medium. The crude and purified polysaccharides extracted from the fermentation broth showed well 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid radical scavenging abilities, and the scavenging abilities of purified polysaccharides reached 94.47 % and 99.88 %, respectively. Six fractions of polysaccharides were extracted and purified from fruiting bodies, mycelia and fermentation broth separately with the elution buffers of distilled water and 0.1 M NaCl solution. Generally, the polysaccharides from fruiting bodies showed stronger protective effect on H2O2-induced HepG2 cell oxidative damage than other fractions. A total of five to seven monosaccharides were identified in the six fractions of polysaccharides. The correlation analysis revealed that the content of fucose was significantly correlated with the antioxidant activity of polysaccharides, while xylose showed negative correlation results. In summary, the polysaccharides from G. boninense have a potential to be used as natural antioxidants.

Metabolomics analysis of rice fermented by medicinal fungi providing insights into the preparation of functional food.

Rice, a primary staple food, may be improved in value via fermentation. Here, ten medicinal basidiomycetous fungi were separately applied for rice fermentation. After preliminary screening, Ganoderma boninense, Phylloporia pulla, Sanghuangporus sanghuang and Sanghuangporus weigelae were selected for further LC-MS based determination of the changes in metabolic profile after their fermentation with rice, and a total of 261, 296, 312, and 355 differential compounds were identified, respectively. Most of these compounds were up-regulated and involved in the metabolic pathways of amino acid metabolism, lipid metabolism, carbohydrate metabolism and the biosynthesis of other secondary metabolites. Sanghuangporus weigelae endowed the rice with the highest nutritional and bioactive values. The metabolic network of the identified differential compounds in rice fermented by S. weigelae illustrated their close relationships. In summary, this study provides insights into the preparation and application of potential functional food via the fermentation of rice with medicinal fungi.

scBlood: A comprehensive single-cell accessible chromatin database of blood cells.

The advent of single cell transposase-accessible chromatin sequencing (scATAC-seq) technology enables us to explore the genomic characteristics and chromatin accessibility of blood cells at the single-cell level. To fully make sense of the roles and regulatory complexities of blood cells, it is critical to collect and analyze these rapidly accumulating scATAC-seq datasets at a system level. Here, we present scBlood (https://bio.liclab.net/scBlood/), a comprehensive single-cell accessible chromatin database of blood cells. The current version of scBlood catalogs 770,907 blood cells and 452,247 non-blood cells from ∼400 high-quality scATAC-seq samples covering 30 tissues and 21 disease types. All data hosted on scBlood have undergone preprocessing from raw fastq files and multiple standards of quality control. Furthermore, we conducted comprehensive downstream analyses, including multi-sample integration analysis, cell clustering and annotation, differential chromatin accessibility analysis, functional enrichment analysis, co-accessibility analysis, gene activity score calculation, and transcription factor (TF) enrichment analysis. In summary, scBlood provides a user-friendly interface for searching, browsing, analyzing, visualizing, and downloading scATAC-seq data of interest. This platform facilitates insights into the functions and regulatory mechanisms of blood cells, as well as their involvement in blood-related diseases.

Taxonomy and phylogeny of wood-inhabiting hydnoid species in Russulales: two new genera, three new species and two new combinations.

Russulales comprises a highly diverse group of species with respect to basidiocarp morphology and hymenophore type. We reconstructed evolutionary histories of Russulales using ITS and nLSU rDNA sequence data with an emphasis on phylogeny of wood-inhabiting hydnoid species in this order. Based on the combination of morphological and molecular evidence, two new genera, three new species and two new combinations are proposed. Dentipellis microspora and D. coniferarum, newly described, were placed outside Hericiaceae but are provisionally treated in Dentipellis due to their morphological similarity to the generic type. Dentipellis leptodon and D. taiwaniana are transferred to the new genus Dentipellicula as D. leptodon and D. taiwaniana, which is designated as the generic type. The new genus Dentipellopsis was erected to accommodate a newly described species D. dacrydicola. Characters are provided in a generic key to distinguish Dentipellicula, Dentipellis and Dentipellopsis that morphologically are highly similar in addition to a key to the current species in Dentipellis. A new species of Gloeodontia was described based on both molecular and morphological data, and a key to this genus also is provided.

Phylogeny and taxonomy of the recently proposed genus Phellinopsis (Hymenochaetales, Basidiomycota).

Phellinopsis, a recently proposed genus, differs from other genera in Hymenochaetaceae in having setae arising from tramal hyphae and hyaline basidiospores that become pale yellowish with age. The monophyly of 11 taxa, including seven from China, was strongly supported in our phylogeny of ITS sequences. Two species, Phellinopsis junipericola and P. resupinata, are newly described and illustrated from Chinese specimens based on morphological and phylogenetic evidence, bringing the number of known Phellinopsis species worldwide to four. Phylogeny and genetics showed that the North American species, Phellinopsis occidentalis, had an earlier divergence from the other three species. Phellinopsis conchata is distributed in China, Europe and North America, with the Chinese and North American specimens having a closer relationship. An identification key to the four species of Phellinopsis is provided.

Phylogeny and taxonomy of poroid and lamellate genera in the Auriculariales (Basidiomycota).

The phylogeny of taxa with poroid and lamellate hymenophores in Auriculariales as yet has not been well studied. Here we sequenced the nLSU and ITS regions of poroid and lamellate representatives from the genera Elmerina, Protodaedalea and Protomerulius to establish the phylogenetic position of these morphologically similar taxa. Our analyses suggest that (i) Elmerina foliacea is divergent from all other Elmerina species sampled; (ii) Protodaedalea hispida (the type of monotypic genus Protodaedalea) and Protomerulius efibulatus should be transferred to Elmerina as E. hispida and E. efibulata respectively; (iii) after exclusion of P. efibulatus, Protomerulius becomes monophyletic and represents the core of a "Protomerulius family" clade that potentially includes species from Tremellodendropsis, Heterochaetella and Protodontia; and (iv) the presence or absence of gloeocystidia serves as the most reliable morphological feature in delimiting Elmerina s.l. and Protomerulius. Concepts of Elmerina s.l. and Protomerulius are redefined, and diagnostic keys for these two genera are provided.