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.

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.

Biogenic manganese oxides promote metal(loid) remediation by shaping microbial communities in biological aqua crust.

Biological aqua crust (biogenic aqua crust-BAC) is a potentially sustainable solution for metal(loid) bioremediation in global water using solar energy. However, the key geochemical factors and underlying mechanisms shaping microbial communities in BAC remain poorly understood. The current study aimed at determining the in situ metal(loid) distribution and the key geochemical factors related to microbial community structure and metal(loid)-related genes in BAC of a representative Pb/Zn tailing pond. Here we showed that abundant metal(loid)s (e.g. Pb, As) were co-distributed with Mn/Fe-rich minerals (e.g. biogenic Mn oxide, FeOOH) in BAC. Biogenic Mn oxide (i.e. Mn) was the most dominant factor in shaping microbial community structure in BAC and source tailings. Along with the fact that keystone species (e.g. Burkholderiales, Haliscomenobacter) have the potential to promote Mn ion oxidization and particle agglomeration, as well as Mn is highly associated with metal(loid)-related genes, especially genes related to As redox (e.g. arsC, aoxA), and Cd transport (e.g. zipB), biogenic Mn oxides thus effectively enhance metal(loid) remediation by accelerating the formation of organo-mineral aggregates in biofilm-rich BAC system. Our study indicated that biogenic Mn oxides may play essential roles in facilitating in situ metal(loid) bioremediation in BAC of mine drainage.

The effectiveness of sewage sludge biochar amendment with Boehmeria nivea L. in improving physicochemical properties and rehabilitating microbial communities in mine tailings.

Biochar amendment can be adopted to improve soil substrate, in turn facilitated phytoremediation. However, improvements to the properties of tailings following different feedstocks of biochar amendment in phytoremediation, particularly the impacts on nitrogen cycle and the related nitrogen-fixing microorganisms remain unclear. In this study, a 100-day pot experiment was designed to determine the co-effects of different combinations of woody and non-woody biochar, namely hibiscus cannabinus core biochar (HB), sewage sludge biochar (SB), chicken manure biochar (MB) and two crops (Cassia alata L., Boehmeria nivea L.). It was found that, on the one hand, biochar amendment directly immobilized heavy metal (loid) contamination in the tailings; on the other hand, biochar amendment, particularly non-woody SB, improved soil properties (i.e., the combination of SB with crops increased the total nitrogen content by 4.7-7.5 times). This indirectly improved phytostabilization (i.e., SB increased crop height 1.5-1.8 fold, root length 3.3-3.7 fold, decreased NH4NO3-extractable Pb, Cu, Cd and also increased the relative abundance of nitrogen-fixing bacteria such as Mesorhizobium, Bradyrhizobium, and Rhizobium). Besides this, redundant analysis shown that the carbon, nitrogen sources, and pH provided by the biochar were identified as the key factors associated with the nitrogen-fixing bacteria. Through the comprehensive evaluation of different biochar amendment in phytoremediation, it was found that the non-woody SB got higher comprehensive score (3.1-3.6) in biochar amendment in phytoremediation, especially in Boehmeria nivea L. Thus, the combination of non-woody SB and Boehmeria nivea L. improved microbial function, while the microorganisms in turn promoted crop growth. Our results revealed the prospect of using non-woody SB assisted Boehmeria nivea L. for phytoremediation in multi-metal mine tailings.

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.

Mechanism of arsenic immobilization and biotransformation in the biological aqua crust of mine drainage.

Biological aqua crust (BAC), as a novel biological crust with high arsenic (As) immobilization capacity, might be an ideal nature-based solution for As removal in mine drainage. This study examined the As speciation, binding fraction and biotransformation genes in the BACs to find out the underlying mechanism of As immobilization and biotransformation. Results showed that the BACs could immobilize As from mine drainage up to 55.8 g/kg, and their As immobilization concentrations were 1.3-6.9 times higher than that of sediments. Extremely high As immobilization capacity was attributed to the processes of bioadsorption/absorption and biomineralization driven by Cyanobacteria. The high abundance of As(III) oxidation genes (27.0 %) enhanced microbial As(III) oxidation, resulting in >90.0 % of As(V) with low toxicity and mobility in the BACs. The increase in abundances of aioB, arsP, acr3, arsB, arsC and arsI with As was the key process for microbiota in the BACs for resistance to the As toxicity. In conclusion, our findings innovatively confirmed the potential mechanism of As immobilization and biotransformation mediated by the microbiota in the BACs and highlighted the important role of BACs for As remediation in mine drainage.

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.

Novel biological aqua crust enhances in situ metal(loid) bioremediation driven by phototrophic/diazotrophic biofilm.

BACKGROUND: Understanding the ecological and environmental functions of phototrophic biofilms in the biological crust is crucial for improving metal(loid) (e.g. Cd, As) bioremediation in mining ecosystems. In this study, in combination with metal(loid) monitoring and metagenomic analysis, we systematically evaluated the effect of biofilm in a novel biological aqua crust (biogenic aqua crust-BAC) on in situ metal(loid) bioremediation of a representative Pb/Zn tailing pond. RESULTS: We observed strong accumulation of potentially bioavailable metal(loid)s and visible phototrophic biofilms in the BAC. Furthermore, dominating taxa Leptolyngbyaceae (10.2-10.4%, Cyanobacteria) and Cytophagales (12.3-22.1%, Bacteroidota) were enriched in biofilm. Along with predominant heterotrophs (e.g. Cytophagales sp.) as well as diazotrophs (e.g. Hyphomonadaceae sp.), autotrophs/diazotrophs (e.g. Leptolyngbyaceae sp.) in phototrophic biofilm enriched the genes encoding extracellular peptidase (e.g. family S9, S1), CAZymes (e.g. CBM50, GT2) and biofilm formation (e.g. OmpR, CRP and LuxS), thus enhancing the capacity of nutrient accumulation and metal(loid) bioremediation in BAC system. CONCLUSIONS: Our study demonstrated that a phototrophic/diazotrophic biofilm constitutes the structured communities containing specific autotrophs (e.g. Leptolyngbyaceae sp.) and heterotrophs (e.g. Cytophagales sp.), which effectively control metal(loid) and nutrient input using solar energy in aquatic environments. Elucidation of the mechanisms of biofilm formation coupled with metal(loid) immobilization in BAC expands the fundamental understanding of the geochemical fate of metal(loid)s, which may be harnessed to enhance in situ metal(loid) bioremediation in the aquatic ecosystem of the mining area. Video Abstract.

The interplay between microalgae and toxic metal(loid)s: mechanisms and implications in AMD phycoremediation coupled with Fe/Mn mineralization.

Acid mine drainage (AMD) is low-pH with high concentration of sulfates and toxic metal(loid)s (e.g. As, Cd, Pb, Cu, Zn), thereby posing a global environmental problem. For decades, microalgae have been used to remediate metal(loid)s in AMD, as they have various adaptive mechanisms for tolerating extreme environmental stress. Their main phycoremediation mechanisms are biosorption, bioaccumulation, coupling with sulfate-reducing bacteria, alkalization, biotransformation, and Fe/Mn mineral formation. This review summarizes how microalgae cope with metal(loid) stress and their specific mechanisms of phycoremediation in AMD. Based on the universal physiological characteristics of microalgae and the properties of their secretions, several Fe/Mn mineralization mechanisms induced by photosynthesis, free radicals, microalgal-bacterial reciprocity, and algal organic matter are proposed. Notably, microalgae can also reduce Fe(III) and inhibit mineralization, which is environmentally unfavorable. Therefore, the comprehensive environmental effects of microalgal co-occurring and cyclical opposing processes must be carefully considered. Using chemical and biological perspectives, this review innovatively proposes several specific processes and mechanisms of Fe/Mn mineralization that are mediated by microalgae, providing a theoretical basis for the geochemistry of metal(loid)s and natural attenuation of pollutants in AMD.

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.

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.

bFGF stimulated plasminogen activation factors, but inhibited alkaline phosphatase and SPARC in stem cells from apical Papilla: Involvement of MEK/ERK, TAK1 and p38 signaling.

INTRODUCTION: Basic fibroblast growth factor (bFGF) plays a critical role in odontoblast differentiation and dentin matrix deposition, thereby aiding pulpo-dentin repair and regeneration. OBJECTIVES: The purpose of this study was to clarify the effects of bFGF on plasminogen activation factors, TIMP-1), ALP; and SPARC (osteonectin) expression/production of stem cells from apical papilla (SCAP) in vitro; and the involvement of MEK/ERK, p38, Akt, and TAK1 signaling. METHODS: SCAP were exposed to bFGF with/without pretreatment and co-incubation with various signal transduction inhibitors (U0126, SB203580, LY294002, and 5Z-7-oxozeaenol). The expression of FGF receptors (FGFRs), PAI-1, uPA, p-ERK, p-TAK1, and p-p38 was analyzed via immunofluorescent staining. The gene expression and protein secretion of SCAP were determined via real-time PCR and ELISA. ALP activity was evaluated via ALP staining. RESULTS: SCAP expressed FGFR1, 2, 3, and 4. bFGF stimulated the PAI-1, uPA, uPAR, and TIMP-1 mRNA expression (p < 0.05). bFGF induced PAI-1, uPA, and soluble uPAR production (p < 0.05) but suppressed the ALP activity and SPARC production (p < 0.05) of SCAP. bFGF stimulated ERK, TAK1, and p38 phosphorylation of SCAP. U0126 (a MEK/ERK inhibitor) and 5Z-7-oxozeaenol (a TAK1 inhibitor) attenuated the bFGF-induced PAI-1, uPA, uPAR, and TIMP-1 expression and production of SCAP, but SB203580 (a p38 inhibitor) did not. LY294002, SB203580, and 5Z-7oxozeaenol could not reverse the inhibition of ALP activity caused by bFGF. Interestingly, U0126 and 5Z-7-oxozeaenol prevented the bFGF-induced decline of SPARC production (p < 0.05). CONCLUSION: bFGF may regulate fibrinolysis and matrix turnover via modulation of PAI-1, uPA, uPAR, and TIMP-1, but bFGF inhibited the differentiation (ALP, SPARC) of SCAP. These events are mainly regulated by MEK/ERK, p38, and TAK1. Combined use of bFGF and SCAP may facilitate pulpal/root repair and regeneration via regulation of the plasminogen activation system, migration, matrix turnover, and differentiation of SCAP.

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.

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.

Sitagliptin attenuates arterial calcification by downregulating oxidative stress-induced receptor for advanced glycation end products in LDLR knockout mice.

Diabetes is a complex disease characterized by hyperglycemia, dyslipidemia, and insulin resistance. Plasma advanced glycation end products (AGEs) activated the receptor for advanced glycation end products (RAGE) and the activation of RAGE is implicated to be the pathogenesis of type 2 diabetic mellitus (T2DM) patient vascular complications. Sitagliptin, a dipeptidyl peptidase-4 (DPP4) inhibitor, is a new oral hypoglycemic agent for the treatment of T2DM. However, the beneficial effects on vascular calcification remain unclear. In this study, we used a high-fat diet (HFD)-fed low-density lipoprotein receptor deficiency (LDLR-/-) mice model to investigate the potential effects of sitagliptin on HFD-induced arterial calcification. Mice were randomly divided into 3 groups: (1) normal diet group, (2) HFD group and (3) HFD + sitagliptin group. After 24 weeks treatment, we collected the blood for chemistry parameters and DPP4 activity measurement, and harvested the aorta to evaluate calcification using immunohistochemistry and calcium content. To determine the effects of sitagliptin, tumor necrosis factor (TNF)-α combined with S100A12 was used to induce oxidative stress, activation of nicotinamide adenine dinucleotide phosphate (NADPH), up-regulation of bone markers and RAGE expression, and cell calcium deposition on human aortic smooth muscle cells (HASMCs). We found that sitagliptin effectively blunted the HFD-induced artery calcification and significantly lowered the levels of fasting serum glucose, triglyceride (TG), nitrotyrosine and TNF-α, decreased the calcium deposits, and reduced arterial calcification. In an in-vitro study, both S100A12 and TNF-α stimulated RAGE expression and cellular calcium deposits in HASMCs. The potency of S100A12 on HASMCs was amplified by the presence of TNF-α. Sitagliptin and Apocynin (APO), an NADPH oxidase inhibitor, inhibited the TNF-α + S100A12-induced NADPH oxidase and nuclear factor (NF)-κB activation, cellular oxidative stress, RAGE expression, osteo transcription factors expression and calcium deposition. In addition, treatment with sitagliptin, knockdown of RAGE or TNF-α receptor blunted the TNF-α + S100A12-induced RAGE expression. Our findings suggest that sitagliptin may suppress the initiation and progression of arterial calcification by inhibiting the activation of NADPH oxidase and NF-κB, followed by decreasing the expression of RAGE.

Phylogenetically divergent bacteria consortium from neutral activated sludge showed heightened potential on bioleaching spent lithium-ion batteries.

Recycling of spent lithium-ion batteries (LIBs) has become a global issue because of the potential environment risks raised by spent LIBs as well as high valuable metal content remaining in them. Although bioleaching is an environmentally friendly method to recover metals from spent LIBs, the commonly utilized bioleaching bacterial consortia or strains enriched/isolated from acidic environments cannot be applied at large scales owing to their long leaching cycle and poor tolerance to organic compounds. Here, two bioleaching consortia were enriched in 60 days from neutral activated sludge and were identified phylogenetically divergent from the documented bioleaching bacteria. The results showed that the novel consortia shortened the leaching cycle almost by half when compared to the previous reported consortia or strains, of which one consortium dominated by Acidithiobacillus ferrooxidans displayed high bioleaching efficiency on LiMn2O4, as 69.46% lithium (Li) and 67.60% manganese (Mn) were leached out in seven days. This consortium was further domesticated using cathodic materials for 100 days and proved consisted of three mixotrophs and two chemoautotrophs, three of which were novel species from the genera Sulfobacillus and Leptospirillum. More genes coding for proteins that utilize organic compounds were annotated in the metagenomic assembled genomes (MAGs) than previously reported. A mutualistic relationship between mixotrophs and chemoautotrophs was suggested to help the consortium surviving under either organic- rich or shortage environments. The results discovered that novel bioleaching bacteria with shorter leaching cycle and higher tolerance to organics could be enriched from non-acidic environments, which showed high potential for the metal recovering from spent LIBs or other organic-rich environments.

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.

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.

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.

Phylogeny and taxonomy of Ceriporia and other related taxa and description of three new species.

Species of Ceriporia (Irpicaceae, Basidiomycota) are saprotrophs or endophytes in forest ecosystems. To evaluate the taxonomy and generic relationships of Ceriporia and other related taxa, we used morphology and multigene phylogenetic analyses based on sequence data from nuc rDNA internal transcribed spacer ITS1-5.8S-ITS2 (ITS) region, nuc 28S rDNA (28S), and RNA polymerase II largest subunit (rpb1). Our results show that Ceriporia sensu lato is polyphyletic and distributed across multiple clades in the Irpicaceae, Phanerochaetaceae, and Meruliaceae. Some species previously considered in Ceriporia are now recovered in Meruliopsis, resulting in four new combinations: M. albomellea, M. crassitunicata, M. nanlingensis, and M. pseudocystidiata. Two new species of Meruliopsis are described: M. leptocystidiata from northeast China and South Korea and M. parvispora from Taiwan. Ceriporia arbuscula is described as a new species from Taiwan. Ceriporia mellita and Meruliopsis nanlingensis are newly recorded from Japan and Taiwan, and M. taxicola is recorded from Taiwan for the first time.