SERPINB7 Deficiency Increases Legumain Activity and Impairs the Epidermal Barrier in Nagashima-type Palmoplantar Keratoderma.

Nagashima-type palmoplantar keratoderma (NPPK) is an autosomal recessive genodermatosis caused by loss-of-function variants in SERPINB7 and is the most prevalent form of inherited palmoplantar keratodermas among Asians. However, there is currently no effective therapy for NPPK because its pathogenesis remains unclear. In this study, Serpinb7-/- mice were generated and spontaneously developed a disrupted skin barrier, which was further exacerbated by acetone-ether-water treatment. The skin of these Serpinb7-/- mice showed weakened cytoskeletal proteins. Additionally, SERPINB7 deficiency consistently led to decreased epidermal differentiation in a three-dimensional human epidermal model. We also demonstrated that SERPINB7 was an inhibitory serpin that mainly inhibited the protease legumain. SERPINB7 bound directly with legumain and inhibited legumain activity both in vitro and in vivo. Furthermore, we found that SERPINB7 inhibited legumain in a 'protease-substrate' manner and identified the cleavage sites of SERPINB7 as Asn71 and Asn343. Overall, we found that SERPINB7 showed the nature of a cysteine protease inhibitor, and identified legumain as a key target protease of SERPINB7. Loss of SERPINB7 function led to overactivation of legumain, which might disrupt cytoskeletal proteins, contributing to the impaired skin barrier in NPPK. These findings may lead to the development of therapeutic strategies for NPPK.

Species diversity of pathogenic wood-rotting fungi (Agaricomycetes, Basidiomycota) in China.

Wood-rotting basidiomycetes have been investigated in the Chinese forest ecosystem for the past 30 years. Two hundred and five pathogenic wood-decayers belonging to 9 orders, 30 families, and 74 genera have been found in Chinese native forests, plantations, and gardens. Seventy-two species (accounting for 35% of the total pathogenic species) are reported as pathogenic fungi in China for the first time. Among these pathogens, 184 species are polypores, nine are corticioid fungi, eight are agarics and five are hydnoid basidiomycetes. One hundred and seventy-seven species (accounting for 86%) cause white rot, while 28 species (accounting for 14%) result in brown rot; 157 species grow on angiosperm trees (accounting for 76.5%) and 44 species occur on gymnosperm trees (accounting for 21.5%), only four species inhabit both angiosperms and gymnosperms (accounting for 2%); 95 species are distributed in boreal to temperate forests and 110 in subtropical to tropical forests. In addition, 17 species, including Fomitopsis pinicola, Heterobasidion parviporum, and Phellinidium weirii etc. which were previously treated as pathogenic species in China, do not occur in China according to recent studies. In this paper, the host(s), type of forest, rot type, and distribution of each pathogenic species in China are given.

Two new species of Antrodia (Polyporales, Basidiomycota) in western China.

Two new species of Antrodia, A. aridula and A. variispora, are described from western China. Phylogeny based on a six-gene dataset (ITS + nLSU + nSSU + mtSSU + TEF1 + RPB2) demonstrates that samples of the two species form two independent lineages within the clade of Antrodia s.s. and are different in morphology from the existing species of Antrodia. Antrodia aridula is characterized by its annual and resupinate basidiocarps with angular to irregular pores of 2-3 mm each and oblong ellipsoid to cylindrical basidiospores measuring 9-12 × 4.2-5.3 µm, growing on gymnosperm wood in a dry environment. Antrodia variispora is characterized by its annual and resupinate basidiocarps with sinuous or dentate pores with a size of 1-1.5 mm each and oblong ellipsoid, fusiform, pyriform, or cylindrical basidiospores measuring 11.5-16 × 4.5-5.5 µm, growing on the wood of Picea. The differences between the new species and morphologically similar species are discussed in this article.

A contribution to Porogramme (Polyporaceae, Agaricomycetes) and related genera.

The polypores with shallow pores from tropical Asia and America are studied. Our molecular phylogeny based on the internal transcribed spacer (ITS), the large subunit nuclear ribosomal RNA gene (nLSU), the translation elongation factor 1-α gene (TEF1), and the largest subunit of RNA polymerase II (RPB1) demonstrates six clades are formed among Porogramme and related genera. Two new genera, Cyanoporus and Pseudogrammothele, are established, and the six clades represent Porogramme, Cyanoporus, Grammothele, Epithele, Theleporus, and Pseudogrammothele, respectively. The molecular clock analyses estimate the divergence times of the six clades based on a dataset (ITS + LSU + TEF1 + RPB1 + RPB2), and we recognize the mean stem ages of the six genera are earlier than 50 Mya. Three new species in Porogramme were morphologically and phylogenetically confirmed, and they are described as P. austroasiana, P. cylindrica, and P. yunnanensis. Phylogenetic analysis shows that type species of Tinctoporellus and Porogramme are nested in the same clade, and Tinctoporellus is treated as a synonym of Porogramme. Based on our phylogeny, twelve new combinations are proposed, and the differences between the new species and similar or related species are discussed.

A new contribution to Megasporoporia sensu lato: Six new species and three new combinations.

Megasporoporia sensu lato has recently been intensively studied in China and South America, and four independent clades representing four genera have been recognized phylogenetically. In this study, more samples, mostly from subtropical and tropical Asia, Oceania, and East Africa, are analyzed. A phylogeny based on a 4-gene dataset of sequences (ITS + nLSU + mtSSU + tef) has confirmed the presence of four genera in Megasporoporia sensu lato: Jorgewrightia, Mariorajchenbergia, Megasporia, and Megasporoporia sensu stricto. Six new species, Jorgewrightia austroasiana, Jorgewrightia irregularis, Jorgewrightia tenuis, Mariorajchenbergia subleucoplaca, Megasporia olivacea, and Megasporia sinuosa, are described based on morphology and phylogenetic analysis. Three new combinations are proposed, viz. Jorgewrightia kirkii, Mariorajchenbergia epitephra, and Mariorajchenbergia leucoplaca. To date, 36 species of Megasporoporia sensu lato are accepted and an identification key to these species is provided. In addition, the identification of Dichomitus amazonicus, Dichomitus cylindrosporus, and Megasporoporia hexagonoides is discussed.

Two new forest pathogens in Phaeolus (Polyporales, Basidiomycota) on Chinese coniferous trees were confirmed by molecular phylogeny.

Phaeolus schweinitzii (Fr.) Pat. was originally described in Europe and is considered a common forest pathogen on conifers in the Northern Hemisphere. Our molecular phylogeny based on samples from China, Europe, and North America confirms that P. schweinitzii is a species complex, including six taxa. P. schweinitzii sensu stricto has a distribution in Eurasia; the samples from Northeast and Southwest China are distantly related to P. schweinitzii sensu stricto, and two new species are described after morphological, phylogenetic, and geographical analyses. The species growing on Larix, Picea, and Pinus in Northeast China is described as Phaeolus asiae-orientalis. Another species mostly occurring on Pinus yunnanensis in Southwest China is Phaeolus yunnanensis. In addition, three taxa distributed in North America differ from P. schweinitzii sensu stricto. Phaeolus tabulaeformis (Berk.) Pat. is in Southeast North America, "P. schweinitzii-1" in Northeast North America, and "P. schweinitzii-2" in western North America.

Outline, Divergence Times, and Phylogenetic Analyses of Trechisporales (Agaricomycetes, Basidiomycota).

Phylogenetic analyses inferred from the nuc rDNA ITS1-5.8S-ITS2 (ITS) data set and the combined 2-locus data set [5.8S + nuc 28S rDNA (nLSU)] of taxa of Trechisporales around the world show that Sistotremastrum family forms a monophyletic lineage within Trechisporales. Bayesian evolutionary and divergence time analyses on two data sets of 5.8S and nLSU sequences indicate an ancient divergence of Sistotremastrum family from Hydnodontaceae during the Triassic period (224.25 Mya). Sistotremastrum family is characterized by resupinate and thin basidiomata, smooth, verruculose, or odontoid-semiporoid hymenophore, a monomitic hyphal structure, and generative hyphae bearing clamp connections, the presence of cystidia and hyphidia in some species, thin-walled, smooth, inamyloid, and acyanophilous basidiospores. In addition, four new species, namely, Trechispora dentata, Trechispora dimitiella, Trechispora fragilis, and Trechispora laevispora, are described and illustrated. In addition, three new combinations, namely, Brevicellicium daweishanense, Brevicellicium xanthum, and Sertulicium limonadense, are also proposed.

Two new brown rot polypores from tropical China.

Brown-rot fungi are types of fungi that selectively degrade cellulose and hemicellulose from wood and are perhaps the most important agents involved in the degradation of wood products and dead wood in forest ecosystem. Two new brown-rot species, collected from southern China, are nested within the clades of Fomitopsis sensu stricto and Oligoporus sensu stricto, respectively. Their positions are strongly supported in the Maximum Likelihood phylogenetic tree of the concatenated the internal transcribed spacer (ITS) regions, the large subunit of nuclear ribosomal RNA gene (nLSU), the small subunit of nuclear ribosomal RNA gene (nuSSU), the small subunit of mitochondrial rRNA gene (mtSSU), the largest subunit of RNA polymerase II (RPB1), the second largest subunit of RNA polymerase II (RPB2) and the translation elongation factor 1-α gene (TEF1) sequences. Fomitopsisbambusae, only found on bamboo, is characterised by its resupinate to effused-reflexed or pileate basidiocarps, small pores (6-9 per mm), the absence of cystidia, short cylindrical to oblong-ellipsoid basidiospores measuring 4.2-6.1 × 2-2.3 µm. Oligoporuspodocarpi is characterised by white to pale cream pore surface, round or sometimes angular pores (5-6 per mm), broadly ellipsoid to reniform basidiospores measuring 3.8-4.2 × 2-2.3 µm and growing on Podocarpus. Illustrated descriptions of these two novel species, Fomitopsisbambusae and Oligoporuspodocarpi, are provided.

Two new species of Hymenochaetaceae on Dracaena cambodiana from tropical China.

Two new wood-rotting fungi in the family Hymenochaetaceae, Fulvifomes dracaenicola sp. nov. and Hymenochaete dracaenicola sp. nov., are described and illustrated from tropical China based on morphological characteristics and molecular data. It is worth to mention that both of them grow on Dracaena cambodiana which is a kind of angiosperm tree distributed in tropical regions. F. dracaenicola is characterised by perennial, pileate, triquetrous basidioma with yellowish brown fresh pores which becoming honey yellow with silk sheening upon drying, a dimitic hyphal system in trama and monomitic in context, and subglobose basidiospores measuring 4.8-5 × 4-4.1 µm. H. dracaenicola is characterised by annual, resupinate basidioma with a clay buff hymenophore, a dimitic hyphal system, absence of tomentum and cortex, presence of subulate setae, absence of cystidia, presence of cystidioles and simple hyphidia, and oblong ellipsoid basidiospores measuring 5.2-5.8 × 2.5-2.8 µm. The phylogenetic analyses based on ITS + nLSU rDNA sequences confirm the placement of two new species respectively in Fulvifomes and Hymenochaete. Phylogenetically closely related species to the two new species are discussed.

Nicastrin/miR-30a-3p/RAB31 Axis Regulates Keratinocyte Differentiation by Impairing EGFR Signaling in Familial Acne Inversa.

Nicastrin (NCSTN) mutations are associated with familial acne inversa (AI), and emerging evidence suggests that microRNAs (miRNAs) are involved in various skin diseases. However, whether NCSTN mutations affect miRNA levels and their subsequent signaling pathways in familial AI patients has not been studied. We aimed to elucidate the relationship between NCSTN mutations and familial AI pathogenesis by investigating differential miRNA expression and their related pathways. Combined with miRNA microarray data from familial AI patients, Ncstn keratinocyte-specific-knockout (NcstnΔKC) mice and bioinformatics predictions showed that NCSTN mutations led to decreased miR-30a-3p levels, which negatively regulated RAB31 expression. Moreover, enhanced RAB31 levels accelerated degradation of activated EGFR, leading to abnormal differentiation in keratinocytes. The impaired EGFR signaling and its effects on epidermal differentiation were also observed in familial AI patients and NcstnΔKC mice. Thus, our study showed that miR-30a-3p/RAB31/EGFR signaling pathway may play a key role in the pathogenesis of familial AI with NCSTN mutations.

Accumulation of inhibitory kappaB-alpha as a mechanism contributing to the anti-inflammatory effects of surfactant protein-A.

The collectin surfactant protein (SP)-A has been implicated in multiple immunoregulatory functions of innate pulmonary host defense via modulating immune responses both in vitro and in vivo. The aim of the present study was to investigate mechanisms responsible for the anti-inflammatory effects of human (hu) SP-A on the inhibitory kappaB (IkappaB)/nuclear factor (NF)-kappaB signaling pathway in alveolar macrophages (AMs). Initial CD25 expression analysis by flow cytometry of CD14/hu Toll-like receptor 4-transfected Chinese hamster ovary reporter cells demonstrated that SP-A alone does not induce any NF-kappaB-dependent CD25 expression in these cells. In AMs, SP-A pretreatment caused a marked inhibition of lipopolysaccharide (LPS)-induced NF-kappaB activation independent of the LPS chemotype used as determined by electrophoretic mobility shift assay. Western blot analysis revealed that SP-A by itself increased the protein expression of IkappaB-alpha, the predominant regulator for rapidly induced NF-kappaB, in a dose- and time-dependent manner without enhancing IkappaB-alpha messenger RNA as determined by reverse transcription-polymerase chain reaction. SP-A did not interfere with LPS-induced serine(32) phosphorylation of IkappaB-alpha but significantly enhanced IkappaB-alpha abundance under LPS-coupled conditions. The data suggest that anti-inflammatory effects of SP-A on LPS-challenged AMs are associated with a SP-A-mediated direct modulation of the IkappaB-alpha turnover in these cells.