scImmOmics: a manually curated resource of single-cell multi-omics immune data.

Single-cell sequencing technology has enabled the discovery and characterization of subpopulations of immune cells with unique functions, which is critical for revealing immune responses under healthy or disease conditions. Efforts have been made to collect and curate single-cell RNA sequencing (scRNA-seq) data, yet an immune-specific single-cell multi-omics atlas with harmonized metadata is still lacking. Here, we present scImmOmics (https://bio.liclab.net/scImmOmics/home), a manually curated single-cell multi-omics immune database constructed based on high-quality immune cells with known immune cell labels. Currently, scImmOmics documents >2.9 million cell-type labeled immune cells derived from seven single-cell sequencing technologies, involving 131 immune cell types, 47 tissues and 4 species. To ensure data consistency, we standardized the nomenclature of immune cell types and presented them in a hierarchical tree structure to clearly describe the lineage relationships within the immune system. scImmOmics also provides comprehensive immune regulatory information, including T-cell/B-cell receptor sequencing clonotype information, cell-specific regulatory information (e.g. gene/chromatin accessibility/protein/transcription factor states within known cell types, cell-to-cell communication and co-expression networks) and immune cell responses to cytokines. Collectively, scImmOmics is a comprehensive and valuable platform for unraveling the heterogeneity and diversity of immune cells and elucidating the specific regulatory mechanisms at the single-cell level.

Transcriptome and Metabolome Reveal Accumulation of Key Metabolites with Medicinal Properties of Phylloporia pulla.

Phylloporia pulla, a macrofungal species in the Hymenochaetales, Basidiomycota, is known to enhance the nutritional and bioactive properties of rice through co-fermentation; however, its own secondary metabolites are not well understood. In this study, an integrative analysis of transcriptome and metabolome data revealed that the accumulation of steroids, steroid derivatives, and triterpenoids in P. pulla peaks during the mid-growth stage, while the genes associated with these metabolites show higher expression levels from the early to mid-growth stages. Weighted gene co-expression network analysis identified several modules containing candidate genes involved in the synthesis of steroids, steroid derivatives, and triterpenoids. Specifically, six key hub genes were identified, along with their connectivity to other related genes, as potential catalysts in converting the precursor lanosterol to celastrol. This study enhances our understanding of the secondary metabolites of P. pulla and is essential for the selective utilization of these bioactive compounds.

Management of post-radiation carotid blowout syndrome in patients with head and neck cancer: A systematic review.

BACKGROUND AND PURPOSE: Carotid blowout syndrome (CBS) is a rare but potentially life-threatening complication that can occur in patients with head and neck cancer (HNC), especially with a history of radiotherapy. This study aimed to review and initially compare managements for post-radiation CBS in patients with HNC. MATERIALS AND METHODS: A systematic review of published studies was performed. Information including management, survival, and complication were collected. RESULTS: A total of 39 articles and 917 cases were included in the systematic review. The interval between radiation therapy and CBS ranged from 1.2 years to 17.8 years. The managements of CBS included embolization, stent, bypass surgery, surgical ligation, electrocoagulation, flap coverage, arterial repair, and nasopharyngeal packing. The cumulative 30-day, 1-year, and 2-year overall survival rates were 85.2 %, 48.9 %, and 37.0 %, respectively, with a median survival time of 11.3 months. Disease progression and rebleeding were the most common death causes. The lowest rebleeding rate and neurologic complications rate were presented in cases receiving bypass surgery at 1.4 % and 10.8 %, respectively. The highest rebleeding rate of 35.6 % was showed in cases underwent stent, and the highest neurologic complications rate of 32.0 % was showed in cases underwent ligation. CONCLUSION: Post-radiation CBS in patients with HNC had a low survival rate and high complication rate. Rebleeding and neurologic complication were common complications. Endovascular embolization and stent were the mainstream management, and bypass surgery presented a promising outcome in survival and complication for selected patients.

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.

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.

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.

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.

Preliminary species diversity and community phylogenetics of wood-inhabiting basidiomycetous fungi in the Dabie Mountains, Central China reveal unexpected richness.

Wood-inhabiting fungi have important economic values as well as playing a major ecological role in forest ecosystem cycles. The Dabie Mountains, at the junction of Henan, Hubei, and Anhui Provinces, Central China, provide an ideal climate and favorable niches for the speciation and diversification of various forms of life including fungi. We studied the species diversity and community phylogenetics of wood-inhabiting basidiomycetous fungi that revealed 175 wood-inhabiting basidiomycetous species, of which 20 represented unidentified species, based on morphological and phylogenetic analyses of 575 specimens collected from ten sampling sites. These species belonged to two classes, 11 orders, 42 families, and 106 genera of Basidiomycota, and included 12 edible species, 28 medicinal species, four poisonous species, and seven forest pathogens. Four types of fungal distribution pattern at the genus level were recognized for 65 genera, while another 41 genera could not be placed in any known distribution pattern. The five sampling sites in the eastern part of the Dabie Mountains had significantly higher species diversity and phylogenetic diversity of wood-inhabiting basidiomycetous fungi than those in the western part, and thus deserve priority in terms of conservation. The community of wood-inhabiting basidiomycetous fungi in the Dabie Mountains is generally affected by a combination of habitat filtering and competitive exclusion. This study provides a basis on which to build actions for the comprehensive recognition, utilization, and conservation of wood-inhabiting basidiomycetous fungi in the region.

Biodegradation of Benzo[a]pyrene by a White-Rot Fungus Phlebia acerina: Surfactant-Enhanced Degradation and Possible Genes Involved.

Polycyclic aromatic hydrocarbons (PAHs) are persistent environmental pollutants that pose a threat to human health. Among these PAHs, benzo[a]pyrene (BaP), a five-ring compound, exhibits high resistance to biodegradation. White-rot fungus Phlebia acerina S-LWZ20190614-6 has demonstrated higher BaP degradation capabilities compared with Phanerochaete chrysosporium and P. sordida YK-624, achieving a degradation rate of 57.7% after 32 days of incubation under a ligninolytic condition. To further enhance the biodegradation rate, three nonionic surfactants were used, and the addition of 1 or 2 g·L-1 of polyethylene glycol monododecyl ether (Brij 30) resulted in nearly complete BaP biodegradation by P. acerina S-LWZ20190614-6. Interestingly, Brij 30 did not significantly affect the activity of manganese peroxidase and lignin peroxidase, but it did decrease laccase activity. Furthermore, the impact of cytochrome P450 on BaP degradation by P. acerina S-LWZ20190614-6 was found to be relatively mild. Transcriptomic analysis provided insights into the degradation mechanism of BaP, revealing the involvement of genes related to energy production and the synthesis of active enzymes crucial for BaP degradation. The addition of Brij 30 significantly upregulated various transferase and binding protein genes in P. acerina S-LWZ20190614-6. Hence, the bioremediation potential of BaP by the white-rot fungus P. acerina S-LWZ20190614-6 holds promise and warrants further exploration.

Xenasmatellales ord. nov. and Xenasmatellaceae fam. nov. for Xenasmatella (Agaricomycetes, Basidiomycota).

In the era of molecular phylogeny as dominant evidence in fungal taxonomy, the taxonomic framework of fungi adopted from morphological characteristics has been largely updated. Compared with other fungal groups, macrofungi underwent fewer updates at the order and higher level. In this study, the taxonomic placement of a poorly known macro-basidiomycetous genus Xenasmatella is studied. Phylogenetic and molecular clock analyses inferred from a seven-locus dataset support that the genus represents an order rank lineage. Accordingly, a monotypic order Xenasmatellales and a monotypic family Xenasmatellaceae are newly introduced for Xenasmatella within Agaricomycetes. The species diversity and relationships of Xenasmatella are further clarified with the aid of the phylogenetic analysis inferred from a four-locus dataset. In association with morphological characteristics, a new species Xenasmatella hjortstamii is described. Moreover, the distribution of Xenasmatella ailaoshanensis, X. gossypina, and X. wuliangshanensis previously known only from type localities in Yunnan Province, China are expanded. In addition, two unnamed single-specimen lineages of Xenasmatella from Victoria State, Australia and Sichuan, China are revealed, likely representing two potential new species of this genus. In summary, the current study updates the taxonomic framework of Agaricomycetes and provides a crucial supplement for comprehensively understanding the evolutionary history of this fungal class.

Taxonomy of Hyphodermella: a case study to show that simple phylogenies cannot always accurately place species in appropriate genera.

The genus is a special and crucial taxonomic rank compared with others above the species level, because a species has to be placed in a certain genus instead of any other higher ranks. With more and more new species being described, the placements of their generic position are sometimes incorrect due to the simple phylogenies resulting from inappropriate sampling. Here, we focus on the taxonomy of a small wood-inhabiting fungal genus Hyphodermella. With the most comprehensive sampling to date, the phylogenetic position of Hyphodermella within Phanerochaetaceae is rearranged by employing the same ITS and nLSU regions as in previous studies and also the ITS, nLSU, rpb1, rpb2 and tef1α regions. Three species are excluded from Hyphodermella: H. poroides is placed in a newly introduced monotypic genus Pseudohyphodermella, while H. aurantiaca and H. zixishanensis are transferred to Roseograndinia. Hyphodermella suiae is described as a new species from South China and Vietnam. Keys to eight species in Hyphodermella and five in Roseograndinia are provided. Beyond solving the taxonomic issue of Hyphodermella itself, the current study also aims to suggest that all fungal taxonomists especially beginners should keep in mind to sample as many comprehensive taxa as possible in phylogenetic analyses.

Genome Re-Annotation and Transcriptome Analyses of Sanghuangporus sanghuang.

Sanghuangporus sanghuang, the generic type of Sanghuangporus belonging to Hymenochaetaceae, is a precious medicinal wood-inhabiting macrofungus with high commercial potential. To facilitate the medicinal utilization of this fungal resource, transcriptome sequences are newly generated from S. sanghuang strain MS2. In association with the previously generated genome sequences from the same strain by our lab and all available fungal homologous protein sequences in the UniProtKB/Swiss-Prot Protein Sequence Database, a new methodology was employed for genome assembly and annotation. A total of 13,531 protein-coding genes were identified from the new version of the genome of S. sanghuang strain MS2 with a complete BUSCOs of 92.8%, which indicates a remarkable improvement in the accuracy and completeness of the genome assembly. In general, more genes involved in medicinal functions were annotated compared with the original version of the genome annotation, and most of these genes were also found in the transcriptome data of the currently sampled growth period. Given the above, the current genomic and transcriptomic data provides valuable insights into the evolution and metabolites analysis of S. sanghuang.

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.

Fungal taxonomy: current status and research agendas for the interdisciplinary and globalisation era.

Fungal taxonomy is a fundamental discipline that aims to recognise all fungi and their kinships. Approximately 5% of a practical estimate of 2.2-3.8 million species globally are currently known, and consequently the Fungal Tree of Life (FTOL) is very incompletely reconstructed. With the advances of new technologies, mycology is marching into the interdisciplinary and globalisation era. To make fungal taxonomy relevant, innovative sampling methods and phylogenomics analyses should be performed to reconstruct a much more comprehensive FTOL. In association with this densely sampled FTOL, multiomics will reveal what drives fungal species diversification and how fungal traits evolve to adapt to various environments, while metagenomics will facilitate the understanding and protection of the ecological functions of fungi. A coordinated approach to pursuing these research agendas that includes conceiving of and costing a mission to describe all the fungi on the planet will unlock potential of fungi to support sustainable development of our society.

Umbellaceae fam. nov. (Hymenochaetales, Basidiomycota) for Umbellus sinensis gen. et sp. nov. and Three New Combinations.

Hymenochaetales, belonging to Agaricomycetes, Basidiomycota, comprises most polypores and corticioid fungi and, also, a few agarics. The latest taxonomic framework accepts 14 families in this order. When further exploring species diversity of Hymenochaetales, two corticioid specimens collected from China producing cystidia with large umbrella-shaped crystalline heads attracted our attention. This kind of cystidia was reported only in three unsequenced species, viz. Tubulicrinis corneri, T. hamatus and T. umbraculus, which were accepted in Tubulicrinaceae, Hymenochaetales. The current multilocus-based phylogeny supports that the two Chinese specimens formed an independent lineage from Tubulicrinaceae as well as the additional 13 families and all sampled genera in Hymenochaetales. Therefore, a monotypic family, Umbellaceae, is newly described with the new genus Umbellus as the type genus to represent this lineage. The two Chinese specimens are newly described as U. sinensis, which differs from T. corneri, T. hamatus, and T. umbraculus in a combination of a smooth to grandinioid hymenophoral surface, not flattened, broadly ellipsoid basidiospores with a tiny apiculus, and growth on angiosperm wood. Due to the presence of the unique cystidia, the three species of Tubulicrinis, even though they lack available molecular sequences, are transferred to Umbellus as U. corneri, U. hamatus, and U. umbraculus. Hereafter, all known species with large umbrella-shaped crystalline-headed cystidia are in a single genus. In summary, the current study provides a supplement to the latest taxonomic framework of Hymenochaetales and will help to further explore species diversity and the evolution of this fungal order.

Modeling current geographic distribution and future range shifts of Sanghuangporus under multiple climate change scenarios in China.

The genus Sanghuangporus is well-known for its edible and medicinal values. In this study, the most comprehensive occurrence records of Sanghuangporus with accurate species identification are subjected to MaxEnt, to model the current geographic distribution and future range shifts under multiple climate change scenarios in China. The current potential distribution model of Sanghuangporus is excellently predicted as indicated by the value of Area Under Receiver Operator Characteristic Curve. The current potential distribution basically corresponds to the known occurrence records of Sanghuangporus, and provides clues to new suitable habitats. The critical environmental variables to the distribution are annual precipitation, host plant, annual mean temperature and elevation. Host plant is not the most critical contribution to the model, but it indeed plays a decisive role in restricting the distribution of Sanghuangporus. This role is further confirmed by the distribution area of the highly suitable habitat increasing by 155.468%, when excluding host plant from environmental variables. For future scenarios, generally the area of highly suitable habitat for Sanghuangporus extremely increases, but the locations do not change a lot. In conclusion, this study provides important ecological information for the utilization and conservation of the edible and medicinal fungus Sanghuangporus.

Alloexidiopsis gen. nov., A Revision of Generic Delimitation in Auriculariales (Basidiomycota).

Auriculariales is a fungal order with highly diverse morphological traits of basidiomes, which partially leads to a poor understanding of its taxonomic system at the generic level. To identify our recently collected specimens of Auriculariales to a species level, we perform a comprehensive phylogenetic analysis of the generic relationships in Auriculariales. In association with morphological characteristics, a new genus Alloexidiopsis belonging to Auriculariaceae is erected with two new species, namely, A. australiensis and A. schistacea. Moreover, Exidiopsis calcea separated from the generic type E. effusa and Heteroradulum niveum and H. yunnanense recently inaccurately described as members of Heteroradulum are recovered in the clade of Alloexidiopsis. These three species are thus transferred to this new genus. One collection of Exidiopsis grisea also falls in the clade of Alloexidiopsis, whereas another collection of this species is separated far from Alloexidiopsis and E. effusa. Since we have no collection to confirm the species identity of E. grisea, its generic position is uncertain. The main taxonomic morphological differences among Alloexidiopsis and related corticioid genera in Auriculariales are summarized. A key to all the five accepted species of Alloexidiopsis is provided. As two unnamed lineages exist in Alloexidiopsis besides the abovementioned five species, it is assumed that more new species will be revealed from this genus under its current circumscription.

[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.

Redelimitation of Heteroradulum (Auriculariales, Basidiomycota) with H.australiense sp. nov.

Auriculariales accommodates species with diverse basidiomes and hymenophores. From morphological and phylogenetic perspectives, we perform a taxonomic study on Heteroradulum, a recently validated genus within the Auriculariales. The genus Grammatus is merged into Heteroradulum, and thus its generic type G.labyrinthinus is combined with Heteroradulum and G.semis is reaccepted as a member of Heteroradulum. Heteroradulumaustraliense is newly described on the basis of three Australian specimens. Heteroradulumyunnanense is excluded from this genus and its taxonomic position at the generic level is considered uncertain. Accordingly, the circumscription of Heteroradulum is re-delimited and the concept of this genus is adjusted by including irpicoid to poroid hymenophores and a hyphal system with clamp connections or simple septa. A key to all nine accepted species of Heteroradulum is presented.

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.