Associations of polysocial risk score, lifestyle and genetic factors with incident psoriasis: a larger-scale prospective cohort study.

OBJECTIVES: The impact of polysocial risk score (PsRS), a composite measure of multiple social risk factors, on the development of psoriasis remains unclear. Moreover, the potential modifying effects of lifestyle and genetic susceptibility on the relationship between PsRS and psoriasis risk require further exploration. STUDY DESIGN: This was a prospective cohort study conducted among UK Biobank. METHODS: In this study, we analyzed 331,631 participants enrolled in the UK Biobank cohort. To derive the PsRS, we utilized a summative strategy, amalgamating six social determinants of health derived from three domains: socio-economic status, psychosocial factors, and neighborhood and living environment consistently linked to incident psoriasis. Cox proportional hazard models were used to assess the associations between PsRS and psoriasis incidence. Furthermore, we constructed a lifestyle score and a genetic risk score to explore the potential modifying effects of these factors on the relationship between PsRS and psoriasis risk. RESULTS: Compared with individuals with a low PsRS (≤1), those with intermediate PsRS (2-4) and high PsRS (≥5) had 1.20 (95% confidence interval [CI], 1.06-1.36) and 1.53 (95% CI, 1.31-1.78) times higher risks of developing psoriasis, respectively. Our findings revealed an additive interaction between PsRS and genetic susceptibility. Moreover, it was found that individuals with high PsRS and unhealthier lifestyles had a 2.60 times higher risk of developing psoriasis than those with lower PsRS and healthier ones. CONCLUSIONS: Our study results imply that an elevated PsRS is linked to a heightened risk of psoriasis, which is further influenced by genetic factors. Our results also indicate that greater social vulnerability and unhealthier lifestyle may synergistically contribute to the additional risk of psoriasis.

HBx-induced MiR-1269b in NF-κB dependent manner upregulates cell division cycle 40 homolog (CDC40) to promote proliferation and migration in hepatoma cells.

BACKGROUND: Occurrence and progression of hepatocellular carcinoma (HCC) are associated with hepatitis B virus (HBV) infection. miR-1269b is up-regulated in HCC cells and tissues. However, the regulation of miR-1269b expression by HBV and the mechanism underlying the oncogenic activity of miR-1269b in HCC are unclear. METHODS: Reverse transcription quantitative PCR (RT-qPCR) was used to measure the expression of miR-1269b and target genes in HCC tissues and cell lines. Western blot analysis was used to assess the expression of miR-1269b target genes and related proteins. Using luciferase reporter assays and EMSA, we identified the factors regulating the transcriptional level of miR-1269b. Colony formation, flow cytometry and cell migration assays were performed to evaluate the phenotypic changes caused by miR-1269b and its target in HCC cells. RESULTS: We demonstrated that the expression levels of pre-miR-1269b and miR-1269b in HBV-positive HepG2.2.15 cells were dramatically increased compared with HBV-negative HepG2 cells. HBx was shown to facilitate translocation of NF-κB from the cytoplasm to the nucleus, and NF-κB binds to the promoter of miR-1269b to enhance its transcription. miR-1269b targets and up-regulates CDC40, a cell division cycle 40 homolog. CDC40 increases cell cycle progression, cell proliferation and migration. Rescue experiment indicated that CDC40 promotes malignancy induced by miR-1269b in HCC cells. CONCLUSION: We found that HBx activates NF-κB to promote the expression of miR1269b, which augments CDC40 expression, contributing to malignancy in HCC. Our findings provide insights into the mechanisms underlying HBV-induced hepatocarcinogenesis.

Aphicidal Activity of an Ageraphorone Extract From Eupatorium adenophorum Against Pseudoregma bambucicola (Homoptera: Aphididae, Takahashi).

The bamboo aphid, Pseudoregma bambucicola, is an important insect pest of bamboo that affects normal bamboo growth and induces sooty molds. The control of P. bambucicola involves the application of chemicals, such as imidacloprid, to which many species are resistant. In this study, we isolate a novel botanical pesticide (9-oxo-10,11-dehydro-ageraphorone) from an Eupatorium adenophorum(Asteraceae: Compositae) petroleum ether extract and test the aphicidal activity of this compound against P. bambucicola in laboratory bioassay and field-based experiments. This ageraphorone compound at a concentration of 2 mg/ml caused 73.33% mortality (corrected mortality [Subtracted the mortality of the negative control]: 70%) of P. bambucicola by laboratory bioassay within 6 h. Even at lower concentrations, this compound caused greater 33% mortality (corrected mortality: 30%) of aphids. Field experiments with naturally infested bamboo plants showed that two applications of 2 mg/ml ageraphorone to infested plants completely cleared infestations within 30 d. These effects were similar to those of the positive control (imidacloprid). These results reveal that 9-oxo-10,11-dehydro-ageraphorone exhibits significant aphicidal activity against bamboo aphids. We suggest that future research be directed at developing this ageraphorone compound from E. adenophorum as an aphicidal agent for biocontrol.

Acaricidal activity of petroleum ether extracts from Eupatorium adenophorum against the ectoparasitic cattle mite, Chorioptes texanus.

In this study, we evaluated the acaricidal efficacy of extracts obtained from the plant Eupatorium adenophorum against the common cattle mite Chorioptes texanus. The results showed that 95% ethanol extracts at concentrations of 1.0, 0.5, and 0.25 g/mL (w/v) were highly toxic to C. texanus in vitro, killing 100% of mites in 4 h. Similarly, petroleum ether extracts of E. adenophorum resulted in between 80 and 100% mortality of mites in vitro at concentrations of 0.1, 0.05, and 0.025 mL/mL (v/v) within 4 h. In clinical trials, all infected individuals completely recovered after two treatments administered at 7-day intervals and remained disease-free at 60 days posttreatment. The clinical effect of treatment with E. adenophorum petroleum ether extracts was similar to that of treatment with the acaricide fenvalerate. These results indicated that E. adenophorum contains novel potential acaricidal compounds that can effectively control mites in livestock.

Acaricidal properties of an Ailanthus altissima bark extract against Psoroptes cuniculi and Sarcoptes scabiei var. cuniculi in vitro.

The potential acaricidal properties of an Ailanthus altissima bark extract were assessed against two common species of animal ectoparasitic mites, Psoroptes cuniculi and Sarcoptes scabiei var. cuniculi, in vitro. A. altissima bark extract was obtained by ethanol thermal circumfluence and tested at four concentrations (1.0, 0.5, 0.25 and 0.125 g/ml) on mites collected from rabbits. Compared to the fenvalerate treatment group, the A. altissima bark exhibited significant acaricidal properties for both mite species treated. The extract of concentrations of 1.0, 0.5 and 0.25 g/ml killed all tested S. scabiei within 7 h, however, only 1.0 and 0.5 g/ml of extract killed all treated P. cuniculi. The median lethal time (LT50) values at 1, 0.5 and 0.25 g/ml were 0.60, 0.78, 1.48 h for S. scabiei and 0.74, 1.29, 3.33 h for P. cuniculi. The median lethal concentration (LC50) for P. cuniculi was approximately 1.6 times that for S. scabiei var. cuniculi at 4 h. The extract showed stronger toxicity against S. scabiei than against P. cuniculi. Mortality rates increased with increasing concentration of extract administered and with increasing time post-treatment, indicating that the acaricidal activity of A. altissima bark extract is both time-dependent and dose-dependent. This is the first report on acaricidal activity of A. altissima against P. cuniculi and S. scabiei var. cuniculi. It indicates that A. altissima contain potential acaricidal compounds. Our study is the first step to develop potentially novel compounds from A. altissima for the effective control of mites in livestock.

Non-invasive efficacy assessment of pulsed dye laser and photodynamic therapy for port-wine stain.

Port wine stain (PWS) is a congenital vascular malformation that commonly occurs on the face and neck. Currently, the main treatments for port wine stain are pulsed dye laser (PDL) and photodynamic therapy (PDT). However, the efficacy evaluation of PWS mostly relies on the subjective judgement of clinicians, and it is difficult to accurately respond to many small changes after treatment. Therefore, some non-invasive and efficient efficacy assessment methods are also needed. With the continuous development of technology, there are currently many visualisation instruments to evaluate PWS, including dermoscopy, VISIA-CR™ system, reflectance confocal microscopy (RCM), high-frequency ultrasound (HFUS), optical coherence tomography (OCT), Photoacoustic imaging (PAI), laser speckle imaging (LSI) and laser Doppler imaging (LDI). Among them, there are simple and low-cost technologies such as dermoscopy and the VISIA-CR™ system, but they may not be able to observe the deeper structures of PWS. At this time, combining techniques such as HFUS and OCT to increase penetration depth is crucial to evaluate PWS. In the future, the combination of these different technologies could help overcome the limitations of a single technology. This article provides a systematic overview of non-invasive methods for evaluating treatment efficacy in port wine stains and summarises their advantages and disadvantages.

Deficiency of N6-Methyladenosine Demethylase ALKBH5 Alleviates Ultraviolet B Radiation-Induced Chronic Actinic Dermatitis via Regulating Pyroptosis.

Pyroptosis is an inflammatory programmed cell death (PCD) and is reported to be associated with N6-methyladenosine (m6A) modification. This study aimed to investigate the mechanism of m6A demethylase AlkB homolog 5 (ALKBH5) in pyroptosis in the process of chronic actinic dermatitis (CAD). Changes of m6A-related genes were evaluated between CAD and normal samples using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Human keratinocytes (HaCaT cells) exposed to ultraviolet B (UVB; 10, 20, and 30 mJ/cm2), followed by evaluation of cell proliferation, cell apoptosis, inflammatory cytokines (interleukin (IL)-1ß, IL-18, and tumor necrosis factor (TNF-α)), and pyroptosis-related proteins (gasdermin D (GSDMD), Caspase-1, and Caspase-4). Small interfering RNA (siRNA) targeting ALKBH5 was transfected into HaCaT cells to assess the effect of si-ALKBH5 on CAD. A CAD mice model was induced after exposure to UVB (250 mJ/cm2 per day) to confirm the role of ALKBH5 in CAD. AKKBH5 was highly expressed in CAD patients. UVB also promoted ALKBH5 expression, increased cell apoptosis, and induced the release of inflammatory cytokines (IL-1ß, IL-18, and TNF-α) as well as pyroptosis-related proteins (GSDMD, Caspase-1, and Caspase-4). Silencing ALKBH5 repressed cell apoptosis and suppressed UVB-induced pyroptosis and inflammatory response. Meanwhile, silencing ALKBH5 attenuated UVB-induced skin damage of CAD mice, accompanied with the reduction in expression of inflammatory cytokines and pyroptosis-related proteins. This study helps to further understand the mechanism of ALKBH5 in CAD-induced pyroptosis and provides novel ideas for the research and management of CAD.

Analysis of codon usage patterns in Taenia pisiformis through annotated transcriptome data.

Taenia pisiformis (Cestoidea; Cyclophyllidea; Taeniidae) tapeworms infect the small intestine of canids and felines, such as dogs and foxes. Synonymous codon usage in T. pisiformis was examined through 8118 reconstructed annotations of transcriptome sequences. The mean value of GC content for the reconstructed genes was 49.48%. Twenty-four codons were determined as "optimal codons". Approximately all translational optimal codons (except CGU) ended on G or C. The gene positions on the primary axis were strongly positively correlated with GC content at the third codon positions and GC content of individual genes. At the same time, the gene expression level assessed by the CAI, the hydrophobicity and aromaticity of encoded proteins were correlated with the GC content at the third codon positions and the effective number of codons (ENC), respectively. We infer that the gene expression level, the hydrophobicity and the aromaticity of the encoded proteins also influenced codon usage in T. pisiformis. Knowledge of the codon usage pattern in T. pisiformis can improve our understanding of the mechanisms of biased usage of synonymous codons and can help in selecting appropriate host expression systems for potential vaccine genes of T. pisiformis.

Potential of recombinant inorganic pyrophosphatase antigen as a new vaccine candidate against Baylisascaris schroederi in mice.

The intestinal nematode Baylisascaris schroederi is an important cause of death for wild and captive giant pandas. Inorganic pyrophosphatases (PPases) are critical for development and molting in nematode parasites and represent potential targets for vaccination. Here, a new PPase homologue, Bsc-PYP-1, from B. schroederi was identified and characterized, and its potential as a vaccine candidate was evaluated in a mouse challenge model. Sequence alignment of PPases from nematode parasites and other organisms show that Bsc-PYP-1 is a nematode-specific member of the family I soluble PPases. Immunohistochemistry revealed strong localization of native Bsc-PYP-1 to the body wall, gut epithelium, ovary and uterus of adult female worms. Additionally, Bsc-PYP-1 homologues were found in roundworms infecting humans (Ascaris lumbricoides), swine (Ascaris suum) and dogs (Toxocara canis). In two vaccine trials, recombinant Bsc-PYP-1 (rBsc-PYP-1) formulated with Freund complete adjuvant induced significantly high antigen-specific immunoglobulin (Ig)G but no IgE or IgM responses. Analysis of IgG-subclass profiles revealed a greater increase of IgG1 than IgG2a. Splenocytes from rBsc-PYP-1/FCA-immunized mice secreted low levels of T helper (Th)1-type cytokines, interferon-γ and interleukin (IL)-2, while producing significantly high levels of IL-10 and significantly elevated levels of IL-4 (Th2 cytokines) after stimulation with rBsc-PYP-1 in vitro. Finally, vaccinated mice had 69.02-71.15% reductions (in 2 experiments) in larval recovery 7 days post-challenge (dpc) and 80% survival at 80 dpc. These results suggest that Th2-mediated immunity elicited by rBsc-PYP-1 provides protection against B. schroederi, and the findings should contribute to further development of Bsc-PYP-1 as a candidate vaccine against baylisascariasis.

Characterisation and analysis of thioredoxin peroxidase as a potential antigen for the serodiagnosis of sarcoptic mange in rabbits by dot-ELISA.

BACKGROUND: Scabies caused by Sarcoptes scabiei is a widespread but a neglected tropical zoonosis. In this study, we characterised a S. scabiei thioredoxin peroxidase (SsTPx) and evaluated a recombinant SsTPx as a diagnostic antigen in rabbits. METHODS: The open reading frame of the gene encoding SsTPx-2 was amplified and the recombinant protein was expressed in Escherichia coli cells and purified. SsTPx was localized in mite tissue by immunolocalisation using the purified recombinant protein. Serodiagnosis assays were carried out in 203 New Zealand White rabbit serum samples by dot-ELISA. RESULT: The open reading frame (489 bp) of the gene encodes an 18.11 kDa protein, which showed highly homology to that of Psoroptes cuniculi (98.77% identity) and belongs to the 2-Cys family of peroxiredoxins. SsTPx was mainly distributed in muscle tissues of mites, integument of the epidermis and the anterior end of S. scabiei. Although SsTPx cross-reactivity with psoroptic mites was observed, the SsTPx dot-ELISA showed excellent diagnostic ability, with 95.3% sensitivity and 93.8% specificity in mange-infected and uninfected groups. CONCLUSIONS: This study showed that the purified SsTPx is a highly sensitive antigen for the diagnosis of mange infection by dot-ELISA. This technique is a rapid and convenient method that can be used worldwide for the clinical diagnosis of sarcoptic mange in rabbits, and is especially useful in developing regions.

Evaluation acaricidal efficacy of botanical extract from Eupatorium adenophorum against the hard tick Haemaphysalis longicornis (Acari: Ixodidae).

The aim of this study was to evaluate the acaricidal activity of a botanical extract from Eupatorium adenophorum against the hard tick Haemaphysalis longicornis. This could result in developing effective extracts of E. adenophorum as a source of natural, low-toxicity plant-based acaricidal drugs. Adult engorged females of H. longicornis were collected from naturally infected goats. The engorged females were reared in the laboratory and their offspring (larvae and nymphs) were used as test ectoparasites. The toxic effects of botanical extracts from E. adenophorum against larvae and nymphs of H. longicornis were evaluated. The results showed that the extracts with 1.5 and 1.0g/ml (w/v) concentrations were toxic for H. longicornis, comparable to a toxic effect of 2% chlorpyrifos (positive control). The median lethal time (LT50) for larval and nymphal ticks with 1.5g/ml (w/v) concentration of extract were 0.790 (LT99=1.065) and 1.018 (LT99=10.608) hours, respectively, whereas the LT50 of 1.0g/ml (w/v) concentration were 1.445 (LT99=6.047) and 1.313 (LT99=29.932) hours for larval and nymphal ticks, respectively. At a concentration of 1.5g/ml (w/v), an acaricidal effect of 100% was achieved for both larval and nymphal ticks, while a concentration of 1.0g/ml (w/v) resulted in 100% (for larvae) and 93% (for nymphs) within a 6h period. In additional, we found that the relatively low concentration (0.5g/ml) also obtained a good acaricidal effect during the short experimental period, with 2.22 and 2.651h LT50 for larval and nymphal ticks, respectively. These results indicate that E. adenophorum contains potent acaricidal ingredients against the hard tick H. longicornis.

Genetic variation of Taenia pisiformis collected from Sichuan, China, based on the mitochondrial cytochrome B gene.

Taenia pisiformis is one of the most important parasites of canines and rabbits. T. pisiformis cysticercus (the larval stage) causes severe damage to rabbit breeding, which results in huge economic losses. In this study, the genetic variation of T. pisiformis was determined in Sichuan Province, China. Fragments of the mitochondrial cytochrome b (cytb) (922 bp) gene were amplified in 53 isolates from 8 regions of T. pisiformis. Overall, 12 haplotypes were found in these 53 cytb sequences. Molecular genetic variations showed 98.4% genetic variation derived from intra-region. FST and Nm values suggested that 53 isolates were not genetically differentiated and had low levels of genetic diversity. Neutrality indices of the cytb sequences showed the evolution of T. pisiformis followed a neutral mode. Phylogenetic analysis revealed no correlation between phylogeny and geographic distribution. These findings indicate that 53 isolates of T. pisiformis keep a low genetic variation, which provide useful knowledge for monitoring changes in parasite populations for future control strategies.

[Screening for virulence strains of Metarhizium against Dorysthenes hydropicus pascoes].

OBJECTIVE: The aim of the present study was to screen the Metarhizium strains with high virulence against the larvae of Dorysthenes hydropicus, a serious pest of Citrus grandis. METHOD: Thirty six strains of Metarhiziums were isolated from the soil of C. grandis GAP base and collected from other institutions, and the pathogenicity of these strains against 1st instar larvae of D. hydropicus was detected at concentration of 1 x 10(8) conidia/g. The high violence strains against D. hydropicus were cultivated in sabouraud dextrose yeast medium at first, then transfer to rice grain. And the sporulations of these violent strains against D. hydropicus were detected. RESULT: Twenty-eight strains showed virulence against D. hydropicus by preliminary study, and 7 strains of them were collected for further study, 6 of the 7 showed high virulence, the highest cadaver rate was higher than 74%. The conidia production of strain 1 and strain 4 were 2.35 +/- 0. 25 (1 x 10(9) conidia/g), 2.21 +/- 0.27 (1 x 10(9) conidia/g), respectively, showed significantly higher than other strains. CONCLUSION: Strain 1 and strain 4 of the 36 Metarhiziums strains showed high virulence against D. hydropicus, and the highest sporulation ability, so they have a best application prospect.

Evaluation of the up-to-7 criterion for determining the treatment of hepatocellular carcinoma in Barcelona Clinic Liver Cancer stage B: a single-center retrospective cohort study.

Background: At present, there are still disputes on the treatment of surgery for patients with stage B hepatocellular carcinoma (HCC). This study sought to investigate whether the up-to-7 criterion could be used to decide the treatment for HCC in Barcelona Clinic Liver Cancer stage B (BCLC-B). Methods: We analyzed 340 patients with HCC in BCLC-B who treated with hepatectomy or transcatheter arterial chemoembolization (TACE). Of the 285 HCC patients who underwent hepatectomy, 108 met the up-to-7 criterion and 177 exceeded it. All 55 patients in the TACE group met the up-to-7 criterion. We obtained the tumor status of the patients through inpatient medical records, outpatient medical records, and telephone follow-up of the hospital. We compared overall survival (OS) and progression-free survival (PFS) were compared between patients who met the up-to-7 criterion and who underwent either hepatectomy or TACE. OS and recurrence time were also compared between the patients who were treated with hepatectomy and who either met or exceeded the up-to-7 criterion. Across BCLC-B patients, we compared the OS of patients after surgical treatment between subgroups stratified by tumor number and diameter. Results: Patients who met the up-to-7 criterion had significantly higher OS rates after hepatectomy than TACE (P<0.001). However, the 2 groups did not differ in terms of PFS (P=0.758). Among the patients treated by hepatectomy, the OS rates were significantly higher in patients who met the up-to-7 criterion than in those who exceeded it (P=0.001). The recurrence rates did not differ between patients who met or exceeded the criterion (P=0.662). OS was significantly higher in patients with ≤3 tumors than those with >3 tumors (P=0.001). When we stratified patients with ≤3 tumors based in whether they met or exceeded the up-to-8 to up-to-15 criterion, OS was significantly better among those who met the criterion in all cases. Conclusions: Hepatectomy appears to be associated with better survival than TACE in patients with BCLC-B HCC who meet the up-to-7 criterion, but this criterion is not a strict indication for deciding whether to treat patients with BCLC-B surgically. Tumor number strongly affects the prognosis of BCLC-B patients after hepatectomy.

Combination of high-frequency electric with 5-ALA photodynamic therapy in cellular angiofibroma of vulva: A case report.

Cellular angiofibroma is a rare benign tumor and difficult to diagnose. Surgery was used in most cases of prior treatment. However, due to the individual differences, this method may be limited, and there is a risk of recurrence. After signing informed consent for treatment, we treated an 18-year-old female with cellular angiofibroma successfully by using the High-Frequency electric pretreatment combined with 5-Aminolevulinic Acid (5-ALA) photodynamic therapy. The tumor was numerous and irregularly shaped on the right labia majora. The specific treatment process was as follows:5-Aminolevulinic Acid (5-ALA) photodynamic therapy was administered after pretreatment with high-frequency electric ion. We did five treatments in total, 10 days apart. And the therapeutic effect was satisfactory for patients. The wound healed well and no recurrence during 12 months follow-up, and the follow-up is continuing. For similar cases, our experience can be taken into account.

Effects from supplementary feeding of bamboo powder in perinatal period on farrowing process, serum biochemical indexes, and fecal microbes of sows and offspring piglets.

Introduction: This study was conducted to explore the effects of supplementary feeding of bamboo powder on the physical parameters of sows during the perinatal period of 7 days ± in parturition, including farrow duration, serum biochemical indexes, fecal physicochemical indexes, and microbial flora. Methods: Thirty pregnant sows were randomly divided into three groups: the control group was fed a basal diet, TRE1 group and TRE2 group were fed a basal diet supplemented with 30 g d-1 and 60 g d-1 bamboo powder, respectively. Multiple parameters of sows and offspring piglets were determined. Results: The contents of serum total cholesterol and triglyceride of sows in TRE2 group were significantly lower than those in the control group. The contents of serum malondialdehyde of sows in TRE2 and TRE1 groups were significantly lower than that in control group. The water content of sow feces in TRE2 group was significantly higher than that in control group, and the pH values of sows in TRE2 and TRE1 groups were significantly higher than that in control group. The richness index (Chao) of sow fecal bacterial community in TRE2 group was significantly lower than that of the control group, and the Ace and Sobs indexes tended to be lower than those of the control group. At the phylum level, the relative abundance of Actinobacteriota in the feces of sows in TRE2 group was significantly lower than that of the control group, while that of Fusobacteriota in the feces of suckling piglets in TRE2 group tended to be lower than that of the control group. At the genus level, among the Top10 dominant bacteria, the relative abundance of Tissierella in the feces of sows in TRE2 group was significantly lower than that of the control group while that of Fusobacterium in the feces of suckling piglets in TRE2 group tended to be lower than that of the control group. The relative abundance of Clostridium_sensu_stricto_1, Terrisporobacter, Turicibacter, and Tissierella in the feces of sows in TRE2 group was significantly lower than that of TRE1 group (p < 0.05), while Lactobacillus tended to be higher than that of TRE1 group (p < 0.10). Discussion: The results suggested that supplementary feeding 60 g d-1 bamboo powder could increase the water content in the feces of sows, reduce the oxidative damage, and tend to reduce the relative abundance of opportunistic pathogenic Fusobacterium for suckling piglets, while it reduced the fecal microbial diversity of sows.

Endophytic Fungi Isolated from Ageratina adenophora Exhibits Potential Antimicrobial Activity against Multidrug-Resistant Staphylococcus aureus.

Multidrug-resistant bacteria such as Staphylococcus aureus (MRSA) cause infections that are difficult to treat globally, even with current available antibiotics. Therefore, there is an urgent need to search for novel antibiotics to tackle this problem. Endophytes are a potential source of novel bioactive compounds; however, the harnessing of novel pharmacological compounds from endophytes is infinite. Therefore, this study was designed to identify endophytic fungi (from Ageratina adenophora) with antibacterial activity against multidrug-resistant bacteria. Using fungal morphology and ITS-rDNA, endophytic fungi with antibacterial activities were isolated from A. adenophora. The results of the ITS rDNA sequence analysis showed that a total of 124 morphotype strains were identified. In addition, Species richness (S, 52), Margalef index (D/, 7.3337), Shannon-Wiener index (H/,3.6745), and Simpson's diversity index (D, 0.9304) showed that A. adenophora have abundant endophytic fungi resources. Furthermore, the results of the agar well diffusion showed that the Penicillium sclerotigenum, Diaporthe kochmanii, and Pestalotiopsis trachycarpicola endophytic fungi's ethyl acetate extracts showed moderate antibacterial and bactericidal activities, against methicillin-resistant Staphylococcus aureus (MRSA) SMU3194, with a MIC of 0.5-1 mg/mL and a MBC of 1-2 mg/mL. In summary, A. adenophora contains endophytic fungi resources that can be pharmacologically utilized, especially as antibacterial drugs.

GWAS of Chronic Spontaneous Urticaria Reveals Genetic Overlap with Autoimmune Diseases, Not Atopic Diseases.

Although chronic spontaneous urticaria (CSU) is a common disease, GWASs of CSU are lacking. We aimed to identify susceptibility SNPs by performing a GWAS in Chinese Han adults with CSU. The discovery cohort included 430 CSU cases and 482 healthy controls. The GWAS findings were validated in 800 CSU cases and 900 healthy controls. Genetic, functional enrichment, and bioinformatic analyses of genome-wide significant SNPs were performed to assess the association between CSU and autoimmunity or atopy. Five genome-wide significant SNPs were identified: rs434124/LILRA3, rs61986182/IGHG1/2, rs73075571/TDGF1, rs9378141/HLA-G, and rs3789612/PTPN22. The first four SNPs were in linkage disequilibrium with autoimmune-related diseases‒associated SNPs and were cis-expression quantitative trait loci in immune cells. The five SNPs-annotated genes were significantly enriched in immune processes. Higher polygenic risk scores and allele frequencies of rs3789612∗T, rs9378141∗C, and rs73075571∗G were significantly associated with autoimmune-related CSU phenotypes, including positive antithyroglobulin IgG, positive anti-FcεRIα IgG, total IgE <40 IU/ml, and positive antithyroid peroxidase IgG but not with atopic or allergic sensitized CSU phenotypes. This GWAS of CSU identifies five risk loci and reveals that CSU shares genetic overlap with autoimmune diseases and that genetic factors predisposing to CSU mainly manifest through associations with autoimmune traits.

The chloroplast genome characteristics, comparative genomics and gene resource mining of Celtis sinensis (Persoon, 1805).

Celtis is a large genus in Cannabaceae family, with more than 70 species in the world. However, the intraspecific variabilities of morphological features make it difficult for some species to be distinguished based on their morphological characteristics. To supply the chloroplast (cp) genome resources of Celtis for species identification, the plastome of Celtis sinensis Persoon 1805 was newly sequenced and comparative genomics was analyzed. The chloroplast genome was 159,085 bp in length and had a quadripartite structure consisting of two inverted repeats (IRs) separated by a small single copy (SSC) and a large single copy (LSC) region. A total of 133 genes were annotated, including 88 protein-coding genes, eight rRNA genes, and 37 tRNA genes. Among the protein-coding genes, the frequency of the leucine codon is the highest and that of the cysteine codon is the lowest. Comparative genomic analysis showed that the IRS region was more conservative than the LSC and SSC regions, with most sequence variations located in the intergenic spacer rather than the protein-coding region. Moreover, sixteen highly divergent hotspots were identified. The ML phylogenetic tree showed that all involved Celtis species were clustered together, and the plastome reported in this paper has high enough resolution to distinguish C. sinensis (Pers.) from other Celtis plants. This study provides useful genetic resources for the identification of C. sinensis (Pers.) and is also of great significance for the phylogeny study of Celtis plants in the future.

Antibacterial Activity of Two Metabolites Isolated From Endophytic Bacteria Bacillus velezensis Ea73 in Ageratina adenophora.

Ageratina adenophora, as an invasive and poisonous weed, seriously affects the ecological diversity and development of animal husbandry. Weed management practitioners have reported that it is very difficult to control A. adenophora invasion. In recent years, many researchers have focused on harnessing the endophytes of the plant as a useful resource for the development of pharmacological products for human and animal use. This study was performed to identify endophytes with antibacterial properties from A. adenophora. Agar well diffusion method and 16S rRNA gene sequencing technique were used to screen and identify endophytes with antibacterial activity. The response surface methodology and prep- high-performance liquid chromatography were used to determine the optimizing fermentation conditions and isolate secondary metabolites, respectively. UV-visible spectroscopy, infrared spectroscopy, nuclear magnetic resonance, and high-resolution mass spectrum were used to determine the structures of the isolated metabolites. From the experiment, we isolated a strain of Bacillus velezensis Ea73 (GenBank no. MZ540895) with broad-spectrum antibacterial activity. We also observed that the zone of inhibition of B. velezensis Ea73 against Staphylococcus aureus was the largest when fermentation broth contained 6.55 g/L yeast extract, 6.61 g/L peptone, 20.00 g/L NaCl at broth conditions of 7.95 pH, 51.04 h harvest time, and a temperature of 27.97°C. Two antibacterial peptides, Cyclo (L-Pro-L-Val) and Cyclo (L-Leu-L-Pro), were successfully extracted from B. velezensis Ea73. These two peptides exhibited mild inhibition against S. aureus and Escherichia coli. Therefore, we isolated B. velezensis Ea73 with antibacterial activity from A. adenophora. Hence, its metabolites, Cyclo (L-Pro-L-Val) and Cyclo (L-Leu-L-Pro), could further be developed as a substitute for human and animal antibiotics.