Carvedilol ameliorates persistent erythema of erythematotelangiectatic rosacea by regulating the status of anxiety/depression.

The treatment of persistent erythema and rosacea flushing is extremely challenging, especially for patients with anxiety. The aim of this study was to verify the efficacy of carvedilol in rosacea patients with persistent erythema and flushing. A total of 156 patients were randomized to use oral carvedilol 5 mg bid (twice per day) (n = 105) or topical brimonidine (n = 51) for a 10-week period with 6 weeks of follow-up. Both the efficacy of carvedilol and the status of anxiety/depression were analyzed by patient self-assessment (PSA), clinician erythema assessment (CEA), generalized anxiety disorder (GAD-7), and patient health questionnaire-9 (PHQ-9). Our study found that carvedilol exerted a dramatic reduction in CEA/PSA scores and sting/burning sensation scores in comparison to topical brimonidine. Additionally, carvedilol treatment dramatically improved telangiectasia, erythema, and pigmentation with no obvious side effects. Patients with carvedilol treatment showed an improvement of depression/anxiety, as reflected by lower GAD-7 and PHQ-9 scores than patients with topical brimonidine. Notably, we found carvedilol treatment had better outcomes among patients under 30 years of age with rosacea younger than 30 years old. Conclusively, our findings reveal that carvedilol could quickly and effectively improve facial erythema, which might stem from the improved the status of anxiety/depression.

Comprehensive circRNA-microRNA-mRNA network analysis revealed the novel regulatory mechanism of Trichosporon asahii infection.

BACKGROUND: Invasive Trichosporon asahii (T. asahii) infection frequently occurs with a high mortality in immunodeficient hosts, but the pathogenesis of T. asahii infection remains elusive. Circular RNAs (circRNAs) are a type of endogenous noncoding RNA that participate in various disease processes. However, the mechanism of circRNAs in T. asahii infection remains completely unknown. METHODS: RNA sequencing (RNA-seq) was performed to analyze the expression profiles of circRNAs, microRNAs (miRNAs), and mRNAs in THP-1 cells infected with T. asahii or uninfected samples. Some of the RNA-seq results were verified by RT-qPCR. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to analyze the differentially expressed mRNAs. A circRNA-miRNA-mRNA network was constructed and verified by dual-luciferase reporter assay and overexpression experiments. RESULTS: A total of 46 circRNAs, 412 mRNAs and 47 miRNAs were differentially expressed at 12 h after T. asahii infection. GO and KEGG analyses showed that the differentially expressed mRNAs were primarily linked to the leukocyte migration involved in the inflammatory response, the Toll-like receptor signaling pathway, and the TNF signaling pathway. A competing endogenous RNA (ceRNA) network was constructed with 5 differentially expressed circRNAs, 5 differentially expressed miRNAs and 42 differentially expressed mRNAs. Among them, hsa_circ_0065336 was found to indirectly regulate PTPN11 expression by sponging miR-505-3p. CONCLUSIONS: These data revealed a comprehensive circRNA-associated ceRNA network during T. asahii infection, thus providing new insights into the pathogenesis of the T. asahii-host interactions.

The complete mitochondrial genome sequence of Garrulax poecilorhynchus (Aves, Passeriformes, Timaliidae).

The entire mitochondrial genome of Garrulax poecilorhynchus consists of 17 814 bp and containe 13 protein-coding genes, 22 tRNA genes, two rRNA genes, and two control regions. The nucleotide composition of the mitogenome of G. poecilorhynchus is A = 5342 (29.99%), T = 4314 (24.22%), G = 2480 (13.92%), and C = 5678 (31.87%). The genome has an overall A + T content of 54.21%, which has a similar value among known genus Garrulax mitogenomes. All the tRNA genes display a typical clover-leaf structure. Garrulax poecilorhynchus share the closest relationship with other two species, G. perspicillatus and G. sannio. These data could serve to enrich the resource of genus Garrulax in systematic, population genetic, and evolutionary biological studies.

Evidence of adaptive evolution of alpine pheasants to high-altitude environment from mitogenomic perspective.

Adaptive evolutions to high-altitude adaptation have been intensively studied in mammals. However, considering the additional vertebrate groups, new perception regarding selection challenged by high-altitude stress on mitochondrial genome can be gained. To test this hypothesis, we compiled and analyzed the mitochondrial genomes of 5 alpine pheasants and 12 low-altitude species in Phasianidae. The results that evolutionary rates of ATP6 and ND6 showing significant fluctuation among branches when involved with five alpine pheasants revealed both genes might have implications with adapting to highland environment. The radical physico-chemical property changes identified by the modified MM01 model, including composition (C) and equilibrium constant (ionization of COOH) (Pk') in ATP6 and beta-structure tendencies (Pß), Pk', and long-range non-bonded energy (El) in ND6, suggested that minor overall adjustments in size, protein conformation and relative orientation of reaction interfaces have been optimized to provide the ideal environments for electron transfer, proton translocation and generation of adenosine triphosphate (ATP). Additionally, three unique substitution sites were identified under selection in ND6, which could be potentially important adaptive changes contributing to cellular energy production. Our findings suggested that adaptive evolution may occur in alpine pheasants, which are an important complement to the knowledge of genetic mechanisms against the high-altitude environment in non-mammal animals.

Characteristic of complete mitochondrial genome and phylogenetic relationship of Garrulax sannio (Passeriformes, Timaliidae).

Garrulax sannio (Passeriformes, Timaliidae) was the medium-sized bird, whose plumage color was similar for both sexes. The complete sequence of the mitochondrial DNA genome from G. sannio used the polymerase chain reaction method. The genome (17 840 bp in length) contained 13 protein-coding genes, 2 rRNA (12S and 16S) genes, 22 tRNA genes and 2 control regions (D-loop). The base composition of G. sannio mitogenome A + T percentage was 52.22%. It is slightly higher than G + C 47.78% which was similar with other vertebrates. Through constructed phylogenetic tree, we could identify its taxonomic status. Therefore, mitochondrial genome was a best way to preserve genetic resources of species.

Characterization of the complete mitochondrial genome and phylogenetic relationship of Pomatorhinus ruficollis (Passeriformes, Timaliinae).

In our study, we first report complete mitogenome for P. ruficollis and obtain basic genetic information. The genome of P. ruficollis is 17 009 bp which contained 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes and two control regions. Overall bases composition of the complete mitochondrial genome is 29.70%A, 14.47%G, 23.31% T, 32.52%C. Twelve PCGs and 14 tRNA genes are distributed on the H-strand, ND6 and eight tRNA genes are encoded on the L-strand.

Genetic diversity and differentiation of the rhesus macaque (Macaca mulatta) population in western Sichuan, China, based on the second exon of the major histocompatibility complex class II DQB (MhcMamu-DQB1) alleles.

BACKGROUND: Rhesus macaques living in western Sichuan, China, have been separated into several isolated populations due to habitat fragmentation. Previous studies based on the neutral or nearly neutral markers (mitochondrial DNA or microsatellites) showed high levels of genetic diversity and moderate genetic differentiation in the Sichuan rhesus macaques. Variation at the major histocompatibility complex (MHC) loci is widely accepted as being maintained by balancing selection, even with a low level of neutral variability in some species. However, in small and isolated or bottlenecked populations, balancing selection may be overwhelmed by genetic drift. To estimate microevolutionary forces acting on the isolated rhesus macaque populations, we examined genetic variation at Mhc-DQB1 loci in 119 wild rhesus macaques from five geographically isolated populations in western Sichuan, China, and compared the levels of MHC variation and differentiation among populations with that previously observed at neutral microsatellite markers. RESULTS: 23 Mamu-DQB1 alleles were identified in 119 rhesus macaques in western Sichuan, China. These macaques exhibited relatively high levels of genetic diversity at Mamu-DQB1. The Hanyuan population presented the highest genetic variation, whereas the Heishui population was the lowest. Analysis of molecular variance (AMOVA) and pairwise FST values showed moderate genetic differentiation occurring among the five populations at the Mhc-DQB1 locus. Non-synonymous substitutions occurred at a higher frequency than synonymous substitutions in the peptide binding region. Levels of MHC variation within rhesus macaque populations are concordant with microsatellite variation. On the phylogenetic tree for the rhesus and crab-eating macaques, extensive allele or allelic lineage sharing is observed between the two species. CONCLUSIONS: Phylogenetic analyses confirm the apparent trans-species model of evolution of the Mhc-DQB1 genes in these macaques. Balancing selection plays an important role in sharing allelic lineages between species, but genetic drift may share balancing selection dominance to maintain MHC diversity. Great divergence at neutral or adaptive markers showed that moderate genetic differentiation had occurred in rhesus macaque populations in western Sichuan, China, due to the habitat fragmentation caused by long-term geographic barriers and human activity. The Heishui population should be paid more attention for its lowest level of genetic diversity and relatively great divergence from others.

Genetic variation and phylogenetic relationship between three serow species of the genus Capricornis based on the complete mitochondrial DNA control region sequences.

The molecular evidence of phylogenetic status regarding the Formosan serow (Capricornis swinhoei) is not robust and little is known about the genetic diversity of the Sumatran serow (Capricornis sumatraensis), which partly is due to the hardness in sample collection. Here we determined the sequences of the complete mitochondrial DNA control region (1,014 bp) of 19 Sumatran-serow individuals. Nine new haplotypes were defined based on 78 variable sites. Combined analysis with other 32 haplotypes downloaded from the public database, including 1 Sumatran-serow, 11 Formosan-serow and 20 Japanese-serow (Capricornis crispus) haplotypes, a relatively high level of nucleotide diversity was first observed in Sumatran serow (π = 0.0249). By comparative analysis with structural consensus sequences from other mammals, we have identified central, left and right domains and depicted the putative functional structure, including extend termination associated sequences and conserve sequence blocks, in mtDNA control region. The alignment of mtDNA control region revealed that both Sumatran and Japanese serow have two tandem repeats (TRs), but three TRs in Formosan serow. Phylogenetic analyses revealed that the Formosan serow is distinct species with the Japanese serow, but a sister group with the Sumatran serow. The divergence time estimated among three serow species revealed that Pleistocene climate changes and the uplift of Qinghai-Tibetan plateau might play an important role in the genetic differentiation of the serows. These results mainly provide the convinced evidence on the genetic relationship between three serow species.