The high diversity of Scedosporium and Lomentospora species and their prevalence in human-disturbed areas in Taiwan.

Scedosporium and Lomentospora are important opportunistic pathogens causing localized or disseminated infection in humans. Understanding their environmental distribution is critical for public hygiene and clinical management. We carried out the first environmental survey in urbanized and natural regions in Taiwan. Overall, Scedosporium and Lomentospora species were recovered in 132 out of 273 soil samples (48.4%) across Taiwan. We morphologically and molecularly identified six Scedosporium and one Lomentospora species. All four major clinical relevant species were isolated with high frequency, i.e., Scedosporium apiospermum (42.4%), S. boydii (21.8%), Lomentosporaprolificans (14.5%), S. aurantiacum (8.5%); two clinically minor species, Pseudallescheria angusta (6.7%) and S. dehoogii (5.6%), and a saprobic species, S. haikouense (0.6%), had moderate to rare incidence. These fungal species had high incidence in urban (48.6%) and hospital (67.4%) soil samples, and had limited distribution in samples from natural regions (5%). Multivariate analysis of the fungal composition revealed strong evidence of the preferential distribution of these fungi in urban and hospital regions compared with natural sites. In addition, strong evidence suggested that the distribution and abundance of these fungal species were highly heterogeneous in the environment; samples in vicinity often yielded varied fungal communities. We concluded that these fungal species were prevalent in soil in Taiwan and their occurrences were associated with human activities. Although, hygiene sensitive sites such as hospitals were not harboring heavier fungal burdens than other urban facilities in our survey, still, aware should be taken for the high frequency of these clinical relevant species around hospital regions.

Scedosporium and Lomentospora are two fungal genera that can cause infections to wildlife and humans. Our experiment demonstrated that these fungi are ubiquitous in the soil in Taiwan. Their proximity to human-dwelling regions raises our awareness of their exposure to those who are susceptible.

Tributyrin Intake Attenuates Angiotensin II-Induced Abdominal Aortic Aneurysm in LDLR-/- Mice.

Abdominal aortic aneurysm (AAA) is a multifactorial cardiovascular disease with a high risk of death, and it occurs in the infrarenal aorta with vascular dilatation. High blood pressure acts on the aortic wall, resulting in rupture and causing life-threatening intra-abdominal hemorrhage. Vascular smooth muscle cell (VSMC) dysregulation and extracellular matrix (ECM) degradation, especially elastin breaks, contribute to structural changes in the aortic wall. The pathogenesis of AAA includes the occurrence of oxidative stress, inflammatory cell infiltration, elastic fiber fragmentation, VSMC apoptosis, and phenotypic transformation. Tributyrin (TB) is decomposed by intestinal lipase and has a function similar to that of butyrate. Whether TB has a protective effect against AAA remains uncertain. In the present study, we established an AAA murine model by angiotensin II (AngII) induction in low-density lipoprotein receptor knockout (LDLR-/-) mice and investigated the effects of orally administered TB on the AAA size, ratio of macrophage infiltration, levels of matrix metalloproteinase (MMP) expression, and epigenetic regulation. TB attenuates AngII-induced AAA size and decreases elastin fragmentation, macrophage infiltration, and MMP expression in the medial layer of the aorta and reduces the levels of SBP (systolic blood pressure, p < 0.001) and MMP-2 (p < 0.02) in the serum. TB reduces the AngII-stimulated expression levels of MMP2 (p < 0.05), MMP9 (p < 0.05), MMP12, and MMP14 in human aortic smooth muscle cells (HASMCs). Moreover, TB and valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, suppress AngII receptor type 1 (AT1R, p < 0.05) activation and increase the expression of acetyl histone H3 by HDAC activity inhibition (p < 0.05). Our findings suggest that TB exerts its protective effect by suppressing the activation of HDAC to attenuate the AngII-induced AT1R signaling cascade.

Fibroblast growth factor 21 reverses high-fat diet-induced impairment of vascular function via the anti-oxidative pathway in ApoE knockout mice.

Circulating endothelial progenitor cells (EPCs), which function in vascular repair, are the markers of endothelial dysfunction and vascular health. Fibroblast growth factor 21 (FGF21), a liver-secreted protein, plays a crucial role in glucose homeostasis and lipid metabolism. FGF21 has been reported to attenuate the progression of atherosclerosis, but its impact on EPCs under high oxidative stress conditions remains unclear. In vitro studies showed that the ß-klotho protein was expressed in cultured EPCs and that its expression was upregulated by FGF21 treatment. Hydrogen peroxide (H2 O2 )-induced oxidative stress impaired EPC function, including cell viability, migration and tube formation. Pretreatment with FGF21 restored the functions of EPCs after the exposure to H2 O2 . Administration of N(ω)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, inhibited the effects of FGF21 in alleviating oxidative injury by suppressing endothelial nitric oxide synthase (eNOS). In an in vivo study, the administration of FGF21 significantly reduced total cholesterol (TC) and blood glucose levels in apolipoprotein E (ApoE)-deficient mice that were fed a high-fat diet (HFD). Endothelial function, as reflected by acetylcholine-stimulated aortic relaxation, was improved after FGF21 treatment in ApoE-deficient mice. Analysis of mRNA levels in the aorta indicated that FGF21 increased the mRNA expression of eNOS and upregulated the expression of the antioxidant genes superoxide dismutase (SOD)1 and SOD2 in ApoE-deficient mice. These data suggest that FGF21 improves EPC functions via the Akt/eNOS/nitric oxide (NO) pathway and reverses endothelial dysfunction under oxidative stress. Therefore, administration of FGF21 may ameliorate a HFD-induced vascular injury in ApoE-deficient mice.

Beneficial effects of an endogenous enrichment in n3-PUFAs on Wnt signaling are associated with attenuation of alcohol-mediated liver disease in mice.

Alcohol-associated liver disease (ALD) is a major human health issue for which there are limited treatment options. Experimental evidence suggests that nutrition plays an important role in ALD pathogenesis, and specific dietary fatty acids, for example, n6 or n3-PUFAs, may exacerbate or attenuate ALD, respectively. The purpose of the current study was to determine whether the beneficial effects of n3-PUFA enrichment in ALD were mediated, in part, by improvement in Wnt signaling. Wild-type (WT) and fat-1 transgenic mice (that endogenously convert n6-PUFAs to n3) were fed ethanol (EtOH) for 6 weeks followed by a single LPS challenge. fat-1 mice had less severe liver damage than WT littermates as evidenced by reduced plasma alanine aminotransferase, hepatic steatosis, liver tissue neutrophil infiltration, and pro-inflammatory cytokine expression. WT mice had a greater downregulation of Axin2, a key gene in the Wnt pathway, than fat-1 mice in response to EtOH and LPS. Further, there were significant differences between WT and fat-1 EtOH+LPS-challenged mice in the expression of five additional genes linked to the Wnt signaling pathway, including Apc, Fosl1/Fra-1, Mapk8/Jnk-1, Porcn, and Nkd1. Compared to WT, primary hepatocytes isolated from fat-1 mice exhibited more effective Wnt signaling and were more resistant to EtOH-, palmitic acid-, or TNFα-induced cell death. Further, we demonstrated that the n3-PUFA-derived lipid mediators, resolvins D1 and E1, can regulate hepatocyte expression of several Wnt-related genes that were differentially expressed between WT and fat-1 mice. These data demonstrate a novel mechanism by which n3-PUFAs can ameliorate ALD.

Melatonin Improves Ischemia-Induced Circulation Recovery Impairment in Mice with Streptozotocin-Induced Diabetes by Improving the Endothelial Progenitor Cells Functioning.

Patients with diabetes mellitus tend to develop ischemia-related complications and have compromised endothelial progenitor cell (EPC) function. Melatonin protects against ischemic injury, possibly via EPC modulation. We investigated whether melatonin pretreatment could restore EPC function impairment and improve circulation recovery in a diabetic critical limb ischemia mouse model. Under 25 mM high-glucose medium in vitro, EPC proliferation, nitric oxide production, tube formation, and endothelial nitric oxide synthase (eNOS) phosphorylation were significantly suppressed. Hyperglycemia promoted EPC senescence and apoptosis as well as increased reactive oxygen species (ROS) production. Melatonin treatment reversed the harmful effects of hyperglycemia on EPC through adenosine monophosphate-activated protein kinase-related mechanisms to increase eNOS phosphorylation and heme oxygenase-1 expression. In an in-vivo study, after a 4-week surgical induction of hindlimb ischemia, mice with streptozotocin (STZ)-induced diabetes showed significant reductions in new vessel formation, tissue reperfusion, and EPC mobilization in ischemic hindlimbs compared to non-diabetic mice. Mice with STZ-induced diabetes that received melatonin treatment (10 mg/kg/day, intraperitoneal) had significantly improved blood perfusion ratios of ischemic to non-ischemic limb, EPC mobilization, and densities of capillaries. In addition, a murine bone marrow transplantation model to support these findings demonstrated that melatonin stimulated bone marrow-originated EPCs to differentiate into vascular endothelial cells in femoral ligation-induced ischemic muscles. In summary, this study suggests that melatonin treatment augments EPC function along with neovascularization in response to ischemia in diabetic mice. We illustrated the protective effects of melatonin on EPC H2O2 production, senescence, and migration through melatonin receptors and modulating eNOS, AMPK, and HO-1 activities at the cellular level. Thus, melatonin might be used to treat the impairment of EPC mobilization and circulation recuperation in response to ischemic injury caused by chronic hyperglycemia. Additional studies are needed to elucidate the applicability of the results in humans.

Phylogenomic Analysis of a 55.1-kb 19-Gene Dataset Resolves a Monophyletic Fusarium that Includes the Fusarium solani Species Complex.

Scientific communication is facilitated by a data-driven, scientifically sound taxonomy that considers the end-user's needs and established successful practice. In 2013, the Fusarium community voiced near unanimous support for a concept of Fusarium that represented a clade comprising all agriculturally and clinically important Fusarium species, including the F. solani species complex (FSSC). Subsequently, this concept was challenged in 2015 by one research group who proposed dividing the genus Fusarium into seven genera, including the FSSC described as members of the genus Neocosmospora, with subsequent justification in 2018 based on claims that the 2013 concept of Fusarium is polyphyletic. Here, we test this claim and provide a phylogeny based on exonic nucleotide sequences of 19 orthologous protein-coding genes that strongly support the monophyly of Fusarium including the FSSC. We reassert the practical and scientific argument in support of a genus Fusarium that includes the FSSC and several other basal lineages, consistent with the longstanding use of this name among plant pathologists, medical mycologists, quarantine officials, regulatory agencies, students, and researchers with a stake in its taxonomy. In recognition of this monophyly, 40 species described as genus Neocosmospora were recombined in genus Fusarium, and nine others were renamed Fusarium. Here the global Fusarium community voices strong support for the inclusion of the FSSC in Fusarium, as it remains the best scientific, nomenclatural, and practical taxonomic option available.

First Report of Binucleate Rhizoctonia AG-L Causing Root and Stem Rot of Wishbone Flower (Torenia fournieri) in Taiwan.

Wishbone flower (Torenia fournieri L.) is a common ornamental plant for flower bed in Taiwan. In August 2018, root and stem rot of wishbone flower occurred on the flower bed in the campus of National Chung Hsing University, Taichung city, with 100% incidence. Symptoms were dark brown discoloration of basal stems and brown necrosis of roots. Lesions from base of stems were excised into 5 mm long fragments, which were then surface sterilized in 1% sodium hydrochloride for 1 min, rinsed in sterile distilled water, dried on filter paper and thereafter placed onto 2% water agar. After 24 h, hyphae characteristic of Rhizoctonia (Sneh et al. 1991) appeared and dominated in every isolation. Hyphal tips were transferred to potato dextrose agar (PDA). After 5 days of incubation at 28°C, characteristic brown colonies of Rhizoctonia (Sneh et al. 1991) were observed. Hyphal width was 4.29±0.52 µm. No sclerotia were visibly present after 21 days of growth on PDA at 28°C. Hyphae were stained by 0.3% safranin-O and 1% KOH. There were two nuclei in each hyphal compartment, suggesting a binucleate Rhizoctonia fungus. ITS sequence has been used as the best tool to identify specific anastomosis group (AG) of Rhizoctonia as shown by Sharon et al. (2006, 2008). ITS sequence was amplified using the primers Bd1a and ITS4 (Goka et al. 2009; White et al. 1990). Blast search analysis of this acquired sequence (acc. no. LC498494) revealed the highest similarity (98.75 to 99.83%) with the reference sequences (acc. nos. AB286934, AB286933, and AB196653) of binucleate Rhizoctonia AG-L, namely Ceratobasidium sp. AG-L. Pathogenicity test was carried out using seedlings of 4-week-old wishbone flower each grown in a pot of 6.35 cm diameter. To prepare the inoculum, a PDA agar block (6 mm in diameter) excised from the growing front of 5-day-old colony was transferred into a flask with 200 ml of potato dextrose broth (PDB) incubated in a shaker at 26°C and 120 rpm for 6 days. The PDB broth was then blended into slurry. Ten pots each with a seedling were inoculated by pouring 50 ml of slurry onto the potting medium. Five pots were served as the controls by pouring PDB only. Pots were maintained in a greenhouse (26 to 33°C). Three days after inoculation, all inoculated plants exhibited symptom of root and stem rot. The same fungus was reisolated and confirmed by sequencing rDNA-ITS. This is the first report of root and stem rot of wishbone flower caused by binucleate Rhizoctonia AG-L in Taiwan and in the world. Although this is the second cases, since Wang and Hsieh (1993), for binucleate Rhizoctonia AG-L to be pathogenic, this study shows that this fungus has the potential to cause damages and is worth of further investigations.

Deletion of the FHL2 gene attenuates intima-media thickening in a partially ligated carotid artery ligated mouse model.

The four and a half LIM domain protein 2 (FHL2) is a member of the four and a half LIM domain (FHL) gene family, and it is associated with cholesterol-enriched diet-promoted atherosclerosis. However, the effect of FHL2 protein on vascular remodelling in response to hemodynamic alterations remains unclear. Here, we investigated the role of FHL2 in a model of restricted blood flow-induced atherosclerosis. To promote neointimal hyperplasia in vivo, we subjected FHL2+/+ and FHL2-/- mice to partial ligation of the left carotid artery (LCA). The expression of p-ERK and p-AKT was decreased in FHL2-/- mice. FHL2 bound to AKT regulated AKT phosphorylation and led to Rac1-GTP inactivation. FHL2 silencing in human aortic smooth muscle cells down-regulated the PDGF-induced phosphorylation of ERK and AKT. Furthermore, FHL2 silencing reduced cytoskeleton conformational changes and caused cell cycle arrest. We concluded that FHL2 is essential for the regulation of arterial smooth muscle cell function. FHL2 modulates proliferation and migration via mitogen-activated protein kinase (MAPK) and PI3K-AKT signalling, leading to arterial wall thickening and thus neointimal hyperplasia.

Brown Root Rot Disease of Phyllanthus myrtifolius: The Causal Agent and Two Potential Biological Control Agents.

Brown root rot (BRR), caused by Phellinus noxius (Corner) G. Cunningham, occurs on over 200 species of plants, especially woody trees and shrubs. Ceylon myrtle (Phyllanthus myrtifolius [Wight] Müll.Arg.), a common hedge plant, was recently observed to be infected with BRR. Disease diagnosis was performed by completing Koch's postulates, and Ceylon myrtle was confirmed to be a new host of P. noxius. Typical symptoms of BRR were observed, including reduction in leaf size, dieback of branches, and suspended growth of young leaves. A disease severity index was used to quantify BRR in this study. Compared with Malabar chestnut, Ceylon myrtle was relatively resistant to BRR. Surprisingly, phylogenetic analysis of the ITS and 28S sequences revealed that isolates identified as P. noxius from Taiwan and many other countries were clustered in the same clade but separate from the clade comprising isolates from China, which were designated Pyrrhoderma noxium based on P. noxius. Therefore, to temporarily distinguish these pathogens, the former clade was designated GPN (global P. noxius), whereas the latter clade was designated CPN (China Py. noxium). In biocontrol assays, Streptomyces padanus and Bacillus sp. were selected for BRR control of Ceylon myrtle. Disease severity was reduced from 0.51 to 0.37 by S. padanus and to 0.14 by Bacillus sp. in greenhouse trials. In addition, the two biocontrol agents, especially S. padanus, exhibited good growth-promoting effects on cuttings of Ceylon myrtle. With these double advantages, S. padanus and Bacillus sp. have great potential to control BRR in practical applications.

Two Novel Fungal Symbionts Fusarium kuroshium sp. nov. and Graphium kuroshium sp. nov. of Kuroshio Shot Hole Borer (Euwallacea sp. nr. fornicatus) Cause Fusarium Dieback on Woody Host Species in California.

Shot hole borer (SHB)-Fusarium dieback (FD) is a new pest-disease complex affecting numerous tree species in California and is vectored by two distinct, but related ambrosia beetles (Euwallacea sp. nr. fornicatus) called polyphagous shot hole borer (PSHB) and Kuroshio shot hole borer (KSHB). These pest-disease complexes cause branch dieback and tree mortality on numerous wildland and landscape tree species, as well as agricultural tree species, primarily avocado. The recent discovery of KSHB in California initiated an investigation of fungal symbionts associated with the KSHB vector. Ten isolates of Fusarium sp. and Graphium sp., respectively, were recovered from the mycangia of adult KSHB females captured in three different locations within San Diego County and compared with the known symbiotic fungi of PSHB. Multigene phylogenetic analyses of the internal transcribed spacer region (ITS), translation elongation factor-1 alpha (TEF1-α), and RNA polymerase II subunit (RPB1, RPB2) regions as well as morphological comparisons revealed that two novel fungal associates Fusarium kuroshium sp. nov. and Graphium kuroshium sp. nov. obtained from KSHB were related to, but distinct from the fungal symbionts F. euwallaceae and G. euwallaceae associated with PSHB in California. Pathogenicity tests on healthy, young avocado plants revealed F. kuroshium and G. kuroshium to be pathogenic. Lesion lengths from inoculation of F. kuroshium were found to be significantly shorter compared with those caused by F. euwallaceae, while no difference in symptom severity was detected between Graphium spp. associated with KSHB and PSHB. These findings highlight the pest disease complexes of KSHB-FD and PSHB-FD as distinct, but collective threats adversely impacting woody hosts throughout California.

Ectopic expression of specific GA2 oxidase mutants promotes yield and stress tolerance in rice.

A major challenge of modern agricultural biotechnology is the optimization of plant architecture for enhanced productivity, stress tolerance and water use efficiency (WUE). To optimize plant height and tillering that directly link to grain yield in cereals and are known to be tightly regulated by gibberellins (GAs), we attenuated the endogenous levels of GAs in rice via its degradation. GA 2-oxidase (GA2ox) is a key enzyme that inactivates endogenous GAs and their precursors. We identified three conserved domains in a unique class of C20 GA2ox, GA2ox6, which is known to regulate the architecture and function of rice plants. We mutated nine specific amino acids in these conserved domains and observed a gradient of effects on plant height. Ectopic expression of some of these GA2ox6 mutants moderately lowered GA levels and reprogrammed transcriptional networks, leading to reduced plant height, more productive tillers, expanded root system, higher WUE and photosynthesis rate, and elevated abiotic and biotic stress tolerance in transgenic rice. Combinations of these beneficial traits conferred not only drought and disease tolerance but also increased grain yield by 10-30% in field trials. Our studies hold the promise of manipulating GA levels to substantially improve plant architecture, stress tolerance and grain yield in rice and possibly in other major crops.

Simvastatin pretreatment enhances ischemia-induced neovascularization and blood flow recovery in streptozotocin-treated mice.

OBJECTIVE: In contrast to statins, ezetimibe belongs to a new class of cholesterol-lowering agent not known to mediate pleiotropic effects. Here we investigate whether ezetimibe or simvastatin can help recover blood flow and reduce tissue damage after hindlimb ischemia surgery in diabetic mice. METHODS: Diabetic mice were created by intraperitoneal streptozotocin injection in male FVB/NJ mice. All diabetic mice were subsequently divided into three groups: diabetic control, diabetic with simvastatin (0.2 mg/kg), and diabetic with ezetimibe (0.1 mg/kg). All experimental mice received hindlimb ischemia surgery after 2 weeks of drug treatment. Circulating endothelial progenitor cell number was determined by flow cytometry (Sca-1+/C-kit+/Flk-1+) in peripheral blood. RESULTS: In comparison to the mice in the diabetic control group (n = 6), wild-type mice (n = 6) and diabetic mice that received simvastatin (n = 6) had significantly increased ischemic/nonischemic limb blood perfusion ratio, higher capillary density (P < .05, respectively), and reduced ischemic limb damage (diabetic control, 80%; diabetic with simvastatin, 40%; diabetic with ezetimibe, 80%). However, these proangiogenic effects were not observed in diabetic mice that had been treated with ezetimibe. In addition, the number of ischemia-triggered endothelial progenitor cells in peripheral blood was significantly enhanced in the wild-type mice and in the diabetic mice being treated with simvastatin, but not in those being treated with ezetimibe, after ischemic surgery. Endothelial nitric oxide synthase activity as determined by acetylcholine-stimulated vasorelaxation recovered notably in diabetic mice that were treated with simvastatin but was not improved by ezetimibe (n = 6, each group). Moreover, simvastatin led to a significant upregulation of endothelial nitric oxide synthase phosphorylation; vascular endothelial growth factor protein levels in ischemic tissues were also increased. By contrast, administration of ezetimibe did not produce these effects. CONCLUSIONS: Simvastatin helped recover blood flow and reduce tissue damage in ischemic hindlimbs and also promoted new vessel formation in streptozotocin-treated mice, whereas ezetimibe did not. These results may help explain why statins and ezetimibe decrease cholesterol levels, whereas their pleiotropic effects on vasoprotective functions independent of low-density lipoprotein cholesterol lowering are different.

The Genetic Structure, Virulence, and Fungicide Sensitivity of Fusarium fujikuroi in Taiwan.

The rice disease bakanae, caused by Fusarium fujikuroi Nirenberg, has been present in Taiwan for over a century. To better understand the genetic diversity and structure of F. fujikuroi, a set of 16 polymorphic simple sequence repeat (SSR) markers were newly developed and used to analyze 637 F. fujikuroi isolates collected in 14 cities or counties around Taiwan from 1996 to 2013. On the basis of Bayesian clustering, the isolates were classified into four highly differentiated clusters: cluster B likely derived from the more widespread and genetically diversified clusters A or C, and cluster D was restricted to four cities or counties and may have been introduced from unknown sources genetically distinct from clusters A, B, and C. The coexistence of both mating types (MAT1-1:MAT1-2 = 1:1.88) and the highly diversified vegetative compatibility groups (VCG) (16 VCG among the 21 assessed isolates) suggest the likelihood of sexual reproduction in the field. However, the biased mating type ratios and linkage disequilibrium in the population suggest nonrandom mating between individuals. A significant pattern of isolation by distance was also detected, which implies a geographical restricted gene flow and low dissemination ability of F. fujikuroi. Evaluation of 24 representative isolates on eight rice varieties revealed differential levels of virulence, however no clear pattern of specific variety x isolate interaction was observed. Investigations of the differences in virulence and fungicide sensitivity between 8 early isolates (1998 and 2002) and 52 recent isolates (2012) indicate the evolution of increased resistance to the fungicide prochloraz in F. fujikuroi in Taiwan.

Deletion of FHL2 gene impaired ischemia-induced blood flow recovery by modulating circulating proangiogenic cells.

OBJECTIVE: The four and a half Lin11, Isl-1 and Mec-3 (LIM) domain protein 2 (FHL2) is a member of the four and a half LIM domain-only (FHL) gene family, and has been shown to play an important role in inhibiting inflammatory angiogenesis. Here, we tested the hypothesis that impaired ischemia-induced neovascularization in mice lacking FHL2 is related to a defect in proangiogenic cell mobilization and functions in vasculogenesis. APPROACH AND RESULTS: Unilateral hindlimb ischemia surgery was conducted in FHL2(-/-) mice and wild-type (FHL2(+/+)) mice. After hindlimb ischemia surgery, expression of FHL2 protein was noted in ischemic tissues of wild-type mice. All FHL2-null mice (100%) suffered from spontaneous foot amputation, but only 20% of wild-type mice had ischemia-induced foot amputation after ischemic surgery. Blood flow recovery was significantly impaired in FHL2(-/-) mice when compared with that in wild-type mice as determined by laser Doppler imaging. Histological analysis revealed that the capillary density in the ischemic limb was increased in wild-type mice, whereas no such increase was noted in FHL2(-/-) mice. Flow cytometry demonstrated that the number of CD34(+) or CD34(+)/Sca-1(+)/Flk-1(+) in peripheral blood after ischemic surgery significantly decreased in FHL2-null mice than those in wild-type mice after hindlimb ischemia surgery. FHL2 deficiency impaired ex vivo angiogenesis in mouse aortic-ring culture assay, which revealed that the mean density of the microvessels was significantly higher in the wild-type aorta than in the FHL2(-/-) aorta. Western blot analysis showed that vascular endothelial growth factor (VEGF), interleukin-6, matrix metalloproteinase-2, matrix metalloproteinase-9, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 levels were significantly downregulated in ischemic muscles in FHL2-null mice compared with wild-type mice. Deletion of FHL2 protein by FHL2 small interfering RNA impaired VEGF production under hypoxia conditions, and also suppressed endothelial progenitor cell angiogenic functions, but these effects could be recovered by administration of VEGF. CONCLUSIONS: Deficiency of FHL2 impairs ischemia-induced neovascularization, and these suppressive effects may occur through a reduction in proangiogenic cell mobilization, migration, and vasculogenesis functions.

Ruxolitinib associated psoas muscle tuberculosis abscess in a primary myelofibrosis woman: A case report and literature review.

RATIONALE: Primary myelofibrosis is a subtype of myeloproliferative neoplasm that leads to bone marrow fibrosis. Historically, the only curative option for primary myelofibrosis was allogeneic hematopoietic stem cell transplant. Ruxolitinib, a Janus kinase inhibitor, is now used for the treatment of primary myelofibrosis and polycythemia vera. It effectively improves symptoms related to splenomegaly and anemia. However, its association with the development of opportunistic infections has been observed in clinical studies and practical application. PATIENT CONCERNS: A 64-year-old female with primary myelofibrosis and chronic hepatitis B infection who received ruxolitinib treatment. She was admitted for spiking fever and altered consciousness. DIAGNOSIS: Tuberculosis meningitis was suspected but cerebrospinal fluid can't identify any pathogens. An abdominal computed tomography scan revealed a left psoas abscess and an enlarged spleen. A computed tomography-guided pus drainage procedure was performed, showing a strong positive acid-fast stain and a positive Mycobacterium tuberculosis polymerase chain reaction result. INTERVENTIONS: antituberculosis medications were administered. The patient developed a psoas muscle abscess caused by tuberculosis and multiple dermatomes of herpes zoster during antituberculosis treatment. OUTCOMES: The patient was ultimately discharged after 6 weeks of treatment without apparent neurological sequelae. LESSONS: This case underscores the importance of clinicians evaluating latent infections and ensuring full vaccination prior to initiating ruxolitinib-related treatment for primary myelofibrosis.

GDF-15 Attenuates the Epithelium-Mesenchymal Transition and Alleviates TGFß2-Induced Lens Opacity.

Purpose: We sought to evaluate the efficacy of growth differentiation factor (GDF)-15 treatment for suppressing epithelial-mesenchymal transition (EMT) and alleviating transforming growth factor ß2 (TGFß2)-induced lens opacity. Methods: To test whether GDF-15 is a molecule that prevents EMT, we pretreated the culture with GDF-15 in neural progenitor cells, retinal pigment epithelial cells, and lens epithelial cells and then treated with factors that promote EMT, GDF-11, and TGFß2, respectively. To further investigate the efficacy of GDF-15 on alleviating lens opacity, we used mouse lens explant culture to mimic secondary cataracts. We pretreated the lens culture with GDF-15 and then added TGFß2 to develop lens opacity (n = 3 for each group). Western blot and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to measure EMT protein and gene expression, respectively. Results: In cell culture, GDF-15 pretreatment significantly attenuated EMT marker expression in cultured cells induced by treatment with GDF-11 or TGFß2. In the lens explant culture, GDF-15 pretreatment also reduced mouse lens opacity induced by exposure to TGFß2. Conclusions: Our results indicate that GDF-15 could alleviate TGFß2-induced EMT and is a potential therapeutic agent to slow or prevent posterior capsular opacification (PCO) progression after cataract surgery. Translational Relevance: Cataracts are the leading cause of blindness worldwide, with the only current treatment involving surgical removal of the lens and replacement with an artificial lens. However, PCO, also known as secondary cataract, is a common complication after cataract surgery. The development of an adjuvant that slows the progression of PCO will be beneficial to the field of anterior complications.

Ophiodiaporthe cyatheae gen. et sp. nov., a diaporthalean pathogen causing a devastating wilt disease of Cyathea lepifera in Taiwan.

The scaly tree fern, Cyathea lepifera, in Taiwan has been devastated by an ascomycetous pathogen in recent years. This fungus resembles species of Diaporthe, but unlike anamorphs of Diaporthe that produce two types of conidia, its anamorph produces one conidium type. It is described herein as Ophiodiaporthe cyatheae gen. et sp. nov. Through pathogenicity tests, O. cyatheae was demonstrated to be the causal agent of the C. lepifera wilt disease. Of interest, sporulating structures of O. cyatheae have not been found on C. lepifera plants but in culture thus far. The mating system is homothallic. Phylogenetic analyses based on combined sequences of nSSU-rDNA, nLSU-rDNA, EF1-α-1 and RPB2 placed O. cyatheae in Diaporthaceae. Combined sequences of EF1-α-2 and TUB indicated that O. cyatheae had its origin within Diaporthe.

Body size of fungus-growing termites infers on the volume and density of their fungal cultivar.

The body size of an animal plays a crucial role in determining its trophic level and position within the food web, as well as its interactions with other species. In the symbiosis between Termitomyces and fungus-growing termites, termites rely on nutrition of fungal nodules produced by Termitomyces. To understand whether the size of termites and fungal nodules are related to their partner specificity, we quantified the size of termite farmer caste, and the size and density of nodules in termite nests of four genera of fungus-growing termites, and identified their cultivated Termitomyces fungus species based on internal transcribed spacer regions and partial large subunit ribosomal RNA gene sequences. The results showed that the size and density of fungal nodules were different among Termitomyces clades and revealed a constant trade-off between size and density among clades. The nodule size of each clade has low variation and fits normal distribution, indicating that size is a stabilized trait. Moreover, we found larger termite genera cultivated Termitomyces with larger but less numerous nodules. Based on these results, we concluded that there is a size specificity between Termitomyces and fungus-growing termites, which may lead to diversification of Termitomyces as adaptations to different termite genera.

Inhibition of Trimethylamine N-Oxide Attenuates Neointimal Formation Through Reduction of Inflammasome and Oxidative Stress in a Mouse Model of Carotid Artery Ligation.

Aims: Trimethylamine-N-oxide (TMAO) is a metabolite generated from dietary choline, betaine, and l-carnitine, after their oxidization in the liver. TMAO has been identified as a novel independent risk factor for atherosclerosis through the induction of vascular inflammation. However, the effect of TMAO on neointimal formation in response to vascular injury remains unclear. Results: This study was conducted using a murine model of acutely disturbed flow-induced atherosclerosis induced by partial carotid artery ligation. 3,3-Dimethyl-1-butanol (DMB) was used to reduce TMAO concentrations. Wild-type mice were divided into four groups [regular diet, high-TMAO diet, high-choline diet, and high-choline diet+DMB] to investigate the effects of TMAO elevation and its inhibition by DMB. Mice fed high-TMAO and high-choline diets had significantly enhanced neointimal hyperplasia and advanced plaques, elevated arterial elastin fragmentation, increased macrophage infiltration and inflammatory cytokine secretion, and enhanced activation of nuclear factor (NF)-κB, the NLRP3 inflammasome, and endoplasmic reticulum (ER) stress relative to the control group. Mice fed high-choline diets with DMB treatment exhibited attenuated flow-induced atherosclerosis, inflammasome expression, ER stress, and reactive oxygen species expression. Human aortic smooth muscle cells (HASMCs) were used to investigate the mechanism of TMAO-induced injury. The HASMCs were treated with TMAO with or without an ER stress inhibitor to determine whether inhibition of ER stress modulates the TMAO-induced inflammatory response. Innovation: This study demonstrates that TMAO regulates vascular remodeling via ER stress. Conclusion: Our findings demonstrate that TMAO elevation promotes disturbed flow-induced atherosclerosis and that DMB administration mitigates vascular remodeling, suggesting a rationale for a TMAO-targeted strategy for the treatment of atherosclerosis. Antioxid. Redox Signal. 38, 215-233.

Gaming control using a wearable and wireless EEG-based brain-computer interface device with novel dry foam-based sensors.

A brain-computer interface (BCI) is a communication system that can help users interact with the outside environment by translating brain signals into machine commands. The use of electroencephalographic (EEG) signals has become the most common approach for a BCI because of their usability and strong reliability. Many EEG-based BCI devices have been developed with traditional wet- or micro-electro-mechanical-system (MEMS)-type EEG sensors. However, those traditional sensors have uncomfortable disadvantage and require conductive gel and skin preparation on the part of the user. Therefore, acquiring the EEG signals in a comfortable and convenient manner is an important factor that should be incorporated into a novel BCI device. In the present study, a wearable, wireless and portable EEG-based BCI device with dry foam-based EEG sensors was developed and was demonstrated using a gaming control application. The dry EEG sensors operated without conductive gel; however, they were able to provide good conductivity and were able to acquire EEG signals effectively by adapting to irregular skin surfaces and by maintaining proper skin-sensor impedance on the forehead site. We have also demonstrated a real-time cognitive stage detection application of gaming control using the proposed portable device. The results of the present study indicate that using this portable EEG-based BCI device to conveniently and effectively control the outside world provides an approach for researching rehabilitation engineering.