StemDriver: a knowledgebase of gene functions for hematopoietic stem cell fate determination.

StemDriver is a comprehensive knowledgebase dedicated to the functional annotation of genes participating in the determination of hematopoietic stem cell fate, available at http://biomedbdc.wchscu.cn/StemDriver/. By utilizing single-cell RNA sequencing data, StemDriver has successfully assembled a comprehensive lineage map of hematopoiesis, capturing the entire continuum from the initial formation of hematopoietic stem cells to the fully developed mature cells. Extensive exploration and characterization were conducted on gene expression features corresponding to each lineage commitment. At the current version, StemDriver integrates data from 42 studies, encompassing a diverse range of 14 tissue types spanning from the embryonic phase to adulthood. In order to ensure uniformity and reliability, all data undergo a standardized pipeline, which includes quality data pre-processing, cell type annotation, differential gene expression analysis, identification of gene categories correlated with differentiation, analysis of highly variable genes along pseudo-time, and exploration of gene expression regulatory networks. In total, StemDriver assessed the function of 23 839 genes for human samples and 29 533 genes for mouse samples. Simultaneously, StemDriver also provided users with reference datasets and models for cell annotation. We believe that StemDriver will offer valuable assistance to research focused on cellular development and hematopoiesis.

SPASCER: spatial transcriptomics annotation at single-cell resolution.

In recent years, the explosive growth of spatial technologies has enabled the characterization of spatial heterogeneity of tissue architectures. Compared to traditional sequencing, spatial transcriptomics reserves the spatial information of each captured location and provides novel insights into diverse spatially related biological contexts. Even though two spatial transcriptomics databases exist, they provide limited analytical information. Information such as spatial heterogeneity of genes and cells, cell-cell communication activities in space, and the cell type compositions in the microenvironment are critical clues to unveil the mechanism of tumorigenesis and embryo differentiation. Therefore, we constructed a new spatial transcriptomics database, named SPASCER (https://ccsm.uth.edu/SPASCER), designed to help understand the heterogeneity of tissue organizations, region-specific microenvironment, and intercellular interactions across tissue architectures at multiple levels. SPASCER contains datasets from 43 studies, including 1082 sub-datasets from 16 organ types across four species. scRNA-seq was integrated to deconvolve/map spatial transcriptomics, and processed with spatial cell-cell interaction, gene pattern and pathway enrichment analysis. Cell-cell interactions and gene regulation network of scRNA-seq from matched spatial transcriptomics were performed as well. The application of SPASCER will provide new insights into tissue architecture and a solid foundation for the mechanistic understanding of many biological processes in healthy and diseased tissues.

The grapevine miR827a regulates the synthesis of stilbenes by targeting VqMYB14 and gives rise to susceptibility in plant immunity.

Grapevine (Vitis vinifera L.) is an economically important fruit crop cultivated worldwide. In China, grapevine cultivation is very extensive, and a few Vitis grapes have excellent pathogen and stress resistance, but the molecular mechanisms underlying the grapevine response to stress remain unclear. In this study, a microRNA (miRNA; miR827a), which negatively regulates its target gene VqMYB14, a key regulatory role in the synthesis of stilbenes, was identified in Vitis quinquangularis (V. quinquangularis) using transcriptome sequencing. Using overexpression and silencing approaches, we found that miR827a regulates the synthesis of stilbenes by targeting VqMYB14. We used flagellin N-terminal 22-amino-acid peptide (flg22), the representative elicitor in plant basal immunity, as the elicitor to verify whether miR827a is involved in the basal immunity of V. quinquangularis. Furthermore, the promoter activity of miR827a was alleviated in transgenic grape protoplasts and Arabidopsis thaliana following treatment with flg22 and Pseudomonas syringae pv. Tomato DC3000 (Pst DC3000), respectively. In addition, yeast one-hybrid and dual luciferase reporter assay revealed that the ethylene transcription factor VqERF057 acted as a key regulator in the inhibition of miR827a transcription. These results will contribute to the understanding of the biological functions of miR827a in grapevine and clarify the molecular mechanism of the interaction between miR827a and VqMYB14.

Cytokinetic engineering enhances the secretory production of recombinant human lysozyme in Komagataella phaffii.

BACKGROUND: Human lysozyme (hLYZ) is a natural antibacterial protein with broad applications in food and pharmaceutical industries. Recombinant production of hLYZ in Komagataella phaffii (K. phaffii) has attracted considerable attention, but there are very limited strategies for its hyper-production in yeast. RESULTS: Here through Atmospheric and Room Temperature Plasma (ARTP)-based mutagenesis and transcriptomic analysis, the expression of two genes MYO1 and IQG1 encoding the cytokinesis core proteins was identified downregulated along with higher hLYZ production. Deletion of either gene caused severe cytokinesis defects, but significantly enhanced hLYZ production. The highest hLYZ yield of 1,052,444 ± 23,667 U/mL bioactivity and 4.12 ± 0.11 g/L total protein concentration were obtained after high-density fed-batch fermentation in the Δmyo1 mutant, representing the best production of hLYZ in yeast. Furthermore, O-linked mannose glycans were characterized on this recombinant hLYZ. CONCLUSIONS: Our work suggests that cytokinesis-based morphology engineering is an effective way to enhance the production of hLYZ in K. phaffii.

Pterostilbene improves neurological dysfunction and neuroinflammation after ischaemic stroke via HDAC3/Nrf1-mediated microglial activation.

BACKGROUND: Stroke is a type of acute brain damage that can lead to a series of serious public health challenges. Demonstrating the molecular mechanism of stroke-related neural cell degeneration could help identify a more efficient treatment for stroke patients. Further elucidation of factors that regulate microglia and nuclear factor (erythroid-derived 2)-like 1 (Nrf1) may lead to a promising strategy for treating neuroinflammation after ischaemic stroke. In this study, we investigated the possible role of pterostilbene (PTS) in Nrf1 regulation in cell and animal models of ischaemia stroke. METHODS: We administered PTS, ITSA1 (an HDAC activator) and RGFP966 (a selective HDAC3 inhibitor) in a mouse model of middle cerebral artery occlusion-reperfusion (MCAO/R) and a model of microglial oxygen‒glucose deprivation/reperfusion (OGD/R). The brain infarct size, neuroinflammation and microglial availability were also determined. Dual-luciferase reporter, Nrf1 protein stability and co-immunoprecipitation assays were conducted to analyse histone deacetylase 3 (HDAC3)/Nrf1-regulated Nrf1 in an OGD/R-induced microglial injury model. RESULTS: We found that PTS decreased HDAC3 expression and activity, increased Nrf1 acetylation in the cell nucleus and inhibited the interaction of Nrf1 with p65 and p65 accumulation, which reduced infarct volume and neuroinflammation (iNOS/Arg1, TNF-α and IL-1ß levels) after ischaemic stroke. Furthermore, the CSF1R inhibitor PLX5622 induced elimination of microglia and attenuated the therapeutic effect of PTS following MCAO/R. In the OGD/R model, PTS relieved OGD/R-induced microglial injury and TNF-α and IL-1ß release, which were dependent on Nrf1 acetylation through the upregulation of HDAC3/Nrf1 signalling in microglia. However, the K105R or/and K139R mutants of Nrf1 counteracted the impact of PTS in the OGD/R-induced microglial injury model, which indicates that PTS treatment might be a promising strategy for ischaemia stroke therapy. CONCLUSION: The HDAC3/Nrf1 pathway regulates the stability and function of Nrf1 in microglial activation and neuroinflammation, which may depend on the acetylation of the lysine 105 and 139 residues in Nrf1. This mechanism was first identified as a potential regulatory mechanism of PTS-based neuroprotection in our research, which may provide new insight into further translational applications of natural products such as PTS.

Biosynthetic mechanisms of isoflavone accumulation affected by different growth patterns in Astragalus mongholicus products.

BACKGROUND: At present, Astragalus mongholicus products on the market represent two growth patterns: imitative wild A. mongholicus (WAM) and cultivated A. mongholicus (CAM). The 6-year-old WAM (A6) and 2-year-old CAM (B2) products are often sold as commodities. This study aimed to explore the effects of the abovementioned growth patterns on the biosynthetic mechanisms of isoflavone accumulation in A. mongholicus products. RESULTS: In this paper, the content of calycosin-7-O-ß-D-glucoside in 6-year-old WAM (A6) was significantly higher than that in 2-year-old CAM (B2) based on high-performance liquid chromatography. Tissue anatomy indicated that A6 has developed phloem fibers, thickened secondary walls, and a more well-developed vascular system than B2. Thirteen differentially accumulated metabolites were found in A6 and B2 by UHPLC-ESI-Q-TOF-MS/MS, of which isoflavones were highly and significantly enriched in A6. By combining transcriptomics and metabolomics analysis, we found that the metabolomics profile was the same as the transcriptomics profile in both A6 and B2. In total, 11 novel isoflavone-related genes were isolated using BLAST and functional annotation through RNA-Seq and Iso-Seq. The results of integrated analysis, Short Time-series Expression Miner analysis, and Pearson correlation analysis showed that the regulation of four key enzymes, cinnamate 4-hydroxylase, 6-deoxychalcone synthase, chalcone reductase, and chalcone isomerase, led to the high accumulation of isoflavones in A6. In addition, AmUFGT (c778119) and AmUCGT (c303354) were predicted to be 7-O-glycosyltransferases by phylogenetic analysis; these genes catalyze formononetin and calycosin, respectively. CONCLUSIONS: The findings of this work will clarify the differences in the biosynthetic mechanism of isoflavone accumulation between A6 and B2, which will guide the cultivation of A. mongholicus.

Accumulation and conversion of ß-carotene and astaxanthin induced by abiotic stresses in Schizochytrium sp.

Astaxanthin is a kind of ketone carotenoid belonging to tetraterpenoids with an excellent antioxidant activity and it is widely used in nutrition and health-care industries. This study aimed to explore the effect of different abiotic stresses on carotenoid production in Schizochytrium sp. Firstly, the characteristics of carotenoid accumulation were studied in Schizochytrium sp. by monitoring the change of carotenoid yields and gene expressions. Then, different abiotic stresses were systematically studied to regulate the carotenoid accumulation. Results showed that low temperature could advance the astaxanthin accumulation, while ferric ion could stimulate the conversion from carotene to astaxanthin. The glucose and monosodium glutamate ratio of 100:5 was helpful for the accumulation of ß-carotene. In addition, micro-oxygen supply conditions could increase the yield of ß-carotene and astaxanthin by 25.47% and 14.92%, respectively. This study provided the potential regulation strategies for carotenoid production which might be used in different carotenoid-producing strains.

[Molecular mechanism underlying difference of astragaloside â £ content in imitating wild and cultivated Astragalus mongholicus].

The difference of astragaloside Ⅳ content and the expression of its biosynthesis related genes in imitating wild Astragalus mongolicus(IWA) and cultivated A.mongolicus(CA) under different growth years were systematically compared and analyzed.Then the key enzyme genes affected the difference of astragaloside Ⅳ content in the above two A.mongolicus were screened.High-perfo-rmance liquid chromatography(HPLC)was used to determine the content of astragaloside Ⅳ in A.mongolicusunderthe above two diffe-rent growth patterns.Based on the Illumina HiSeq and PacBio high-throughput sequencing platforms, thesecond-and third-generation transcriptome sequencing(RNA-Seq)databaseof the two A.mongolicuswas constructed.The related enzyme genes in the biosynthetic pathway of astragaloside Ⅳ were screened and verified byquantitative reverse transcriptase polymerase chain reaction(RT-qPCR).The RNA-sequencing(RNA-Seq) and RT-qPCR data of each gene were subjected to correlation analysis and trend analysis.The results showed that the variation trend of astragaloside Ⅳ contentby HPLC wasthe same as that of genes by RNA-Seq and RT-qPCR in 1-4 year IWA and 1-2 year CA.The trend level of astragaloside Ⅳ contentwas lower in 2-year IWA than 1-year IWA.Compared with 2-year IWA, 3-year IWA had an upward trend, while 4-year IWA hada downward trend versus 3-year IWA.Additionally, 1-year CA had increased trendthan 2-year CA.However, the content of astragaloside Ⅳ in 5-year IWA was higher than that of 6-year IWA, which wasinconsistent with the findings of RNA-Seq and RT-qPCR.This study preliminarily clarifiedthat the difference of astragaloside Ⅳ contentin 1-4 year IWA and 1-2 year CA wasclosely related to the expression of the upstream and midstream genes(MVK, CMK, PMK, MVD, SS) in the biosynthetic pathway.The results facilitate the production and planting of Radix Astragali seu Hedysari.

Identification of candidate biomarkers and pathways associated with psoriasis using bioinformatics analysis.

BACKGROUND: The aim of this study was to identify the candidate biomarkers and pathways associated with psoriasis. GSE13355 and GSE14905 were extracted from the Gene Expression Omnibus (GEO) database. Then the differentially expressed genes (DEGs) with |logFC| > 2 and adjusted P < 0.05 were chosen. In addition, the Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses for DEGs were performed. Then, the GO terms with P < 0.05 and overlap coefficient greater than 0.5 were integrated by EnrichmentMap. Additionally, risk subpathways analysis for DEGs was also conducted by using the iSubpathwayMiner package to obtain more psoriasis-related DEGs and pathways. Finally, protein-protein interaction (PPI) network analysis was performed to identify the hub genes, and the DGIdb database was utilized to search for the candidate drugs for psoriasis. RESULTS: A total of 127 DEGs which were mostly associated with keratinization, keratinocyte differentiation, and epidermal cell differentiation biological processes were identified. Based on these GO terms, 3 modules (human skin, epidermis and cuticle differentiation, and enzyme activity) were constructed. Moreover, 9 risk subpathways such as steroid hormone biosynthesis, folate biosynthesis, and pyrimidine metabolism were screened. Finally, PPI network analysis demonstrated that CXCL10 was the hub gene with the highest degree, and CXCR2, CXCL10, IVL, OASL, and ISG15 were the potential gene targets of the drugs for treating psoriasis. CONCLUSION: Psoriasis may be mostly caused by keratinization, keratinocyte differentiation, and epidermal cell differentiation; the pathogeneses were more related with pathways such as steroid hormone biosynthesis, folate biosynthesis, and pyrimidine metabolism. Besides, some psoriasis-related genes such as SPRR genes, HSD11B1, GGH, CXCR2, IVL, OASL, ISG15, and CXCL10 may be important targets in psoriatic therapy.

The Epigenetic Regulation of Scleroderma and Its Clinical Application.

Scleroderma (systemic sclerosis; SSc) is a complex and highly heterogeneous multisystem rheumatic disease characterized by vascular abnormality, immunologic derangement, and excessive deposition of extracellular matrix (ECM) proteins. To date, the etiology of this life-threatening disorder remains not fully clear. More and more studies show epigenetic modifications play a vital role. The aberrant epigenetic status of certain molecules such as Fli-1, BMPRII, NRP1, CD70, CD40L, CD11A, FOXP3, KLF5, DKK1, SFRP1, and so on contributes to the pathogenesis of progressive vasculopathy, autoimmune dysfunction, and tissue fibrosis in SSc. Meanwhile, numerous miRNAs including miR-21, miR-29a, miR-196a, miR-202-3p, miR-150, miR-let-7a, and others are involved in the process. In addition, the abnormal epigenetic biomarker levels of CD11a, Foxp3, HDAC2, miR-30b, miR-142-3p, miR-150, miR-5196 in SSc are closely correlated with disease severity. In this chapter, we not only review new advancements on the epigenetic mechanisms involved in the pathogenesis of SSc and potential epigenetic biomarkers, but also discuss the therapeutic potential of epigenetic targeting therapeutics such as DNA methylation inhibitors, histone acetylase inhibitors, and miRNA replacement.

The Effect of Transcription Factor MYB14 on Defense Mechanisms in Vitis quinquangularis-Pingyi.

In the current study, we identified a transcription factor, MYB14, from Chinese wild grape, Vitis quinquangularis-Pingyi (V. quinquangularis-PY), which could enhance the main stilbene contents and expression of stilbene biosynthesis genes (StSy/RS) by overexpression of VqMYB14. The promoter of VqMYB14 (pVqMYB14) was shown to be induced as part of both basal immunity (also called pathogen-associated molecular pattern (PAMP)-triggered immunity, PTI) and effector-triggered immunity (ETI), triggered by the elicitors flg22 and harpin, respectively. This was demonstrated by expression of pVqMYB14 in Nicotiana benthamiana and Vitis. We identified sequence differences, notably an 11 bp segment in pVqMYB14 that is important for the PTI/ETI, and particularly for the harpin-induced ETI response. In addition, we showed that activation of the MYB14 promoter correlates with differences in the expression of MYB14 and stilbene pattern induced by flg22 and harpin. An experimental model of upstream signaling in V. quinquangularis-PY is presented, where early defense responses triggered by flg22 and harpin partially overlap, but where the timing and levels differ. This translates into a qualitative difference with respect to patterns of stilbene accumulation.

The transcription factor MYB15 is essential for basal immunity (PTI) in Chinese wild grape.

MAIN CONCLUSION: MYB15 promoter of Vitis quinquangularis has potential as a target for disease resistance breeding, and its involvement in PTI is associated with a range of defense mechanisms. China is a center of origin for Vitis and is home to diverse wild Vitis genotypes, some of which show superior pathogen resistance, although the underlying molecular basis for this has not yet been elucidated. In the current study, we identified a transcription factor, MYB15, from the Chinese wild grape, Vitis quinquangularis, whose promoter region (pVqMYB15) was shown to be induced by basal immunity (also called PAMP-triggered immunity, PTI) triggered by flg22, following heterologous expression in Nicotiana benthamiana and homologous expression in grapevine. By analyzing the promoter structure and activity, we identified a unique 283 bp sequence that plays a key role in the activation of basal immunity. In addition, we showed that activation of the MYB15 promoter correlates with differences in the expression of MYB15 and RESVERATROL SYNTHASE (RS) induced by the flg22 elicitor. We further tested whether the MYB15 induction triggered by flg22 was consistent with MYB15 and RS expression following inoculation with Plasmopara viticola in grape (V. quinquangularis and Vitis vinifera) leaves. Mapping upstream signals, we found that calcium influx, an RboH-dependent oxidative burst, an MAPK cascade, and jasmonate and salicylic acid co-contributed to flg22-triggered pVqMYB15 activation. Our data suggest that the MYB15 promoter has potential as a target for disease resistance breeding, and its involvement in PTI is associated with a range of defense mechanisms.

A specific allele of MYB14 in grapevine correlates with high stilbene inducibility triggered by Al3+ and UV-C radiation.

KEY MESSAGE: The structural differences of MYB14 promoter in two grapevine genotypes affect the expression of MYB14 and stilbene synthesis in response to Al3+ and UV-C radiation. Grapevines provide an important fruit crop worldwide, but production is often limited by pathogen infection. Stilbenes, a class of secondary metabolite, represent phytoalexins that contribute to defence against pathogens in many plants, including grapevine. It is known that the transcription factors MYB14 and MYB15 are required for the activation of the promoters of resveratrol synthase to regulate stilbene biosynthesis. In the current study, we observed that stilbene levels were more highly induced by Al3+ and UV-C radiation treatments in the cultivar Vitis labrusca 'Concord' than in the cultivar V. vinifera 'Cabernet Sauvignon'. We investigated whether genetic/structural variations in the MYB14 and MYB15 promoters between these two representative genotypes are responsible for the differences in stilbene accumulation. Significant differences in the structure and activity of the promoter of MYB14, but not MYB15 were identified between the two genotypes, following heterologous expression in Nicotiana benthamiana system and treatments with Al3+ and UV-C. Hydrogen peroxide (H2O2) was detected in Concord soon after the stress treatments, but after diphenyleneiodonium chloride pre-treatment, the expressing level of VlMYB14, the promoter activity of VlMYB14 and the accumulation of stilbenes was significantly reduced. A model is presented where the induction of MYB14 contributes to stilbene accumulation in Concord following Al3+ and UV-C treatments involving reactive oxygen species (ROS) production as an early signal.

[Unexpected cutaneous purpura in an infant].

A two-month-old boy visited the hospital due to unexpected cutaneous purpura and thrombocytopenia for 2 days. The physical examination revealed a purple mass on the back. The soft tissue color Doppler ultrasound showed rich blood signals in the tissue, and the results of bone marrow puncture indicated an increased number of megakaryocytes. After the treatment with hormone and gamma globulin, the platelet count rapidly increased and maintained at a normal level. Meanwhile, the boy was given oral administration of propranolol. He was followed up for 4 months and the volume of the mass on the back was reduced significantly. He had a definite diagnosis of hemangioma and immune thrombocytopenia. As for the patients with hemangioma complicated by thrombocytopenia, knowledge of Kasabach-Merritt syndrome should be enhanced and there should be a clarification of the association between thrombocytopenia and hemangioma. There should also be an alertness for thrombocytopenia of other causes.

Epidemiological monitoring and genetic variation analysis of pathogens associated with porcine viral diarrhea in southern China from 2021 to 2023.

Large-scale outbreaks of virus-associated severe diarrhea have occurred in pig populations since 2010. To investigate the prevalence and genetic evolution of the diarrhea-associated viruses responsible for the outbreaks, we tested 1,791 diarrhea samples collected from 213 pig farms in five provinces in southern China between 2021 and 2023. The test results showed that porcine epidemic diarrhea virus (PEDV) was the most frequently detected virus. The prevalence rates ranged from 47.40 to 52.22% in samples and 76.06% (162/213) in pig farms. Porcine rotavirus (PoRV) was the second common virus, with prevalence rates ranging from 25.81 to 50.81% in samples and 72.77%(155/213) in pig farms. Porcine delta coronavirus (PDCoV) was the third common virus, with prevalence rates ranging from 16.33 to 17.48% in samples and 38.50% (82/213) in pig farms. The detection rates of both transmissible gastroenteritis virus (TGEV) and porcine acute diarrheal syndrome coronavirus (SADS-CoV) were very low, less than 1.01% in samples and less than 3.76% in pig farms. In this study, we found SADS-CoV only in piglet diarrhea samples from Jiangxi, Guangdong, and Guangxi provinces in China, with a prevalence rate of 5.16% (11/213) in pig farms. Co-infection with these diarrhea-associated viruses is a common occurrence. The most common co-infections were PEDV and PoRV, with a prevalence rate of 6.64% (119/1,791), followed by PDCoV and PoRV, with a prevalence rate of 4.19% (75/1,791). Phylogenetic analyses showed that PEDV and PEDV variants prevalent in southern China during the past three years clustered into genotype GIIb and recombinant PEDV subtypes. Among the currently endemic PEDV, the most common mutations occurred in the collagenase equivalent (COE) and epitope regions of the spike gene. PoRV strains were mainly dominated by the G9 subtype, followed by the G5, G3 and G4 subtypes. Our results suggest that variant PEDV, PDCoV and PoRV are the main pathogens of swine diarrhea, and singular- or co-infection with pathogenic enteric CoV is common in pig herds in southern China. Therefore, prevention and control of porcine viral diarrhea should be given high attention.

Research Note: Pathogenetic characteristics of avian encephalomyelitis virus in Guangdong and Jiangxi Provinces, China.

In recent years, the infection rate of avian encephalomyelitis virus (AEV) infection in chickens has risen significantly, seriously endangering the development of the chicken industry. In order to study the current epidemiological status of AEV in China as well as the genetic and evolutionary patterns of the virus, we conducted a survey and genomic analysis of chicken AEV. The results showed that 46.26% (136/294) of the tissue samples tested (n = 294) were positive for AEV, with the highest positivity rate of 62.24% (61/98) among tissue samples from chickens aged 13 to 18 wk. The complete genomes of 2 representative AEV strains were determined, and the VP1 evolutionary tree results revealed that the 2 representative strains belonged to a novel AEV strain. Multiple alignment analysis showed that the ORF1 genes of the 2 representative strains differed by 82.3 to 99.9% at the amino acid level compared with the reference AEV strain, and the mutations at the key amino acid loci of VP2 and VP3 were the same as those in the chick embryo-adapted strain. The analysis makes up for the molecular epidemiological data and genetic variation of the 2 representative strains. The analysis makes up for the molecular epidemiological data and genetic variation of AEV and provides a basis for further understanding the spread of AEV in China.

Prevalence and phylogenetic analysis of Gyrovirus galga 1 in southern China from 2020 to 2022.

Since 2011, the Gyrovirus galga 1 (GyVg1, previously recognized as avian gyrovirus 2) strain has extensively been detected worldwide. However, because there are no up-to-date reports of examining the distribution of GyVg1 in flocks in southern China, the epidemiology of this virus is unknown. To investigate the prevalence and genetic evolution of GyVg1, a total of 2,077 field samples collected from 113 chicken farms in 6 provinces in southern China during 2020 to 2022 were tested. Among them, 315 samples (315/2,077, 15.17%) were positive for GyVg1 by PCR. The positive rate of GyVg1 detection between different regions of southern China ranged from 11.69% (Guangdong) to 22.46% (Yunnan). The correlation between GyVg1 prevalence and sample source groups was analyzed, the results showing that the highest seroprevalence of GyVg1 was observed in visceral tissues (27.34%, 187/684), significantly higher (P < 0.05) than that of feather shafts (17.22%, 31/180), serums (8.85%, 78/881), and fecal (5.72%, 19/332). Additionally, the complete genomes of 10 GyVg1 strains were sequenced and analyzed, which showed nucleotide identities of 96.2 to 99.9%, 97.0 to 100.0%, 95.2 to 100.0%, and 95.7 to 99.8% in the complete genome, ORF1, ORF2, and ORF3, respectively, and 94.4 to 100.0%, 91.3 to 100.0%, and 98.7 to 100.0% amino acid similarity in the VP2, VP3, and VP1 proteins, respectively. Phylogenetic analysis of the whole genome showed that 10 GyVg1 strains belong to genotype I, and one strain belongs to genotype III. Sequence analysis showed several amino acid substitutions in both the VP1, VP2, and VP3 proteins. Our results enhance the understanding of the molecular characterization of GyVg1 infection in southern China. In conclusion, this study reveals the high prevalence and high genetic differentiation of GyVg1 in Chinese chickens and suggests that the potential impact of GyVg1 on the chicken industry may be of concern.

Aberrant histone modification in peripheral blood B cells from patients with systemic sclerosis.

OBJECTIVES: To investigate alterations in histone modifications in B cells and their role in the pathogenesis of systemic sclerosis (SSc). METHODS: Global histone H3/H4 acetylation and H3K4/H3K9 methylation in B cells of SSc were tested by EpiQuik™ assay kits. Related histone modifier enzymes were measured by RT-PCR and Western blot. RESULTS: Global histone H4 hyperacetylation and global histone H3K9 hypomethylation were observed in SSc B cells compared with controls. Expression of JHDM2A was significantly increased but HDAC2, HDAC7, and, SUV39H2 were significantly down-regulated in SSc B cells relative to controls. Global histone H4 acetylation and the expression of HDAC2 were negatively correlated. Global histone H3K9 methylation and the expression of SUV39H2 protein were positively correlated. Global H4 acetylation was positively correlated with disease activity and expression of HDAC2 protein was negatively correlated with skin thickness. CONCLUSIONS: Histone modifications were altered in B cells in SSc correlating with skin thickness and disease activity.

Systemic sclerosis: genetics and epigenetics.

Systemic sclerosis (SSc) is an autoimmune disease characterized by immune abnormalities, vascular obliteration, excessive extracellular matrix deposition, and fibrosis of the skin and/or internal organs. To date, the exact etiology of this complicated disease remains unknown. Over the past few years, however, the role of genetic susceptibility and epigenetic modifications caused by environmental factors have been intensively studied in relation to the pathogenesis of this disease, and important advances have been made. This review focuses on the recent progress in the field of SSc research, including HLA and non-HLA susceptibility genes identified in genome-wide association studies (GWAS), and aberrant epigenetic modifications of gene loci associated with SSc. HLA genes most closely linked with SSc susceptibility include HLA-A, -B, -C, -DR, -DP and -DQ. A large number of non-HLA genes were also reported. It has also been noted that different genetic variants can be linked to specific clinical patterns. Finally, DNA demethylation of regulatory genes (eNOS, CD40L and CD70), therapeutic effects associated with Trichostatin A (TSA) treatment, and abnormal expression of a large spectrum of microRNAs (miR-21, -31, -146, -503, -145, -29b, etc.) are all observed in SSc. Overall, the findings presented in this review illustrate how both genetic and epigenetic aberrations play important roles in the development of SSc; however, several unanswered questions continue to impede our understanding of this complex disease. Future research should focus on the identification of new biomarkers for early diagnosis and prognosis, which will help improve the clinical outcome of patients with SSc.

NK-/T-cell lymphoma resembling hydroa vacciniforme with positive CD4 marker expression: a diagnostic difficulty.

A 35-year-old Chinese woman presented with a 2.5-year history of facial swelling in the left lower quadrant and a 10-month history of relapsing red papules and vesicles in the perioral area resembling hydroa vacciniforme. Histologically, a tissue biopsy showed a dense infiltration of medium-sized atypical lymphocytic cells expressing CD4 and CD56. A diagnosis of cutaneous NK-/T-cell lymphoma was made. The patient was treated with alpha-interferon, valaciclovir hydrochloride, and low-dose prednisone for 2 months. Her skin lesions and lymphoadenopathy resolved initially, but she succumbed to the disease shortly after starting chemotherapy treatment 11 months later. To our knowledge, this is the first case of CD4CD56 NK-/T-cell lymphoma with clinical features resembling hydroa vacciniforme.