Endothelial IL17RD promotes Western diet-induced aortic myeloid cell infiltration.

The Interleukin-17 (IL17) family is a group of cytokines implicated in the etiology of several inflammatory diseases. Interleukin-17 receptor D (IL17RD), also known as Sef (similar expression to fibroblast growth factor) belonging to the family of IL17 receptors, has been shown to modulate IL17A-associated inflammatory phenotypes. The objective of this study was to test the hypothesis that IL17RD promotes endothelial cell activation and consequent leukocyte adhesion. We utilized primary human aortic endothelial cells and demonstrated that RNAi targeting of IL17RD suppressed transcript levels by 83 % compared to non-targeted controls. Further, RNAi knockdown of IL17RD decreased the adhesion of THP-1 monocytic cells onto a monolayer of aortic endothelial cells in response to IL17A. Additionally, we determined that IL17A did not significantly enhance the activation of canonical MAPK and NFκB pathways in endothelial cells, and further did not significantly affect the expression of VCAM-1 and ICAM-1 in aortic endothelial cells, which is contrary to previous findings. We also determined the functional relevance of our findings in vivo by comparing the expression of endothelial VCAM-1 and ICAM-1 and leukocyte infiltration in the aorta in Western diet-fed Il17rd null versus wild-type mice. Our results showed that although Il17rd null mice do not have significant alteration in aortic expression of VCAM-1 and ICAM-1 in endothelial cells, they exhibit decreased accumulation of proinflammatory monocytes and neutrophils, suggesting that endothelial IL17RD induced in vivo myeloid cell accumulation is not dependent on upregulation of VCAM-1 and ICAM-1 expression. We further performed proteomics analysis to identify potential molecular mediators of the IL17A/IL17RD signaling axis. Collectively, our results underscore a critical role for Il17rd in the regulation of aortic myeloid cell infiltration in the context of Western diet feeding.

New evidence of high-speed rail promoting green economic growth in the Yangtze River Economic Belt: empirical analysis based on difference-in-differences.

The Yangtze River Economic Belt (YREB) is an important ecological barrier in China. From new perspectives, this paper explores the mechanism of high-speed rail (HSR) for green economic growth (GEG) in the YREB. This paper constructs 108 city panel data at the prefecture level and above in the YREB from 2003 to 2020. Difference-in-differences (DID) is adopted to research the impact of high-speed rail on GEG in the YREB. (1) HSR has significantly improved the GEG of the YREB. The effect value is 4.88%. The parallel trend test suggests that DID is valid. A time-varying instrumental variable combining average altitude and historical railway network is constructed for the endogeneity test. (2) Propensity score matching (PSM) and DID (PSM-DID) were employed to test the sample selection bias. (3) A battery of robustness tests, including the placebo test, variable replacement, and policy interference exclusion, is carried out. The conclusions are still valid. (4) HSR can promote the GEG of the YREB by encouraging technological innovation, industrial upgrading, and increasing ecological efficiency. The contribution rate from the largest to the smallest is ecological efficiency, industrial upgrading, and technological innovation. (5) Heterogeneity analysis shows that HSR has played an important role in encouraging GEG in the eastern, peripheral cities, and the downstream cities of the YREB. Finally, this paper puts forward policy suggestions for promoting GEG in the YREB.

Notch Signaling Regulates Mouse Perivascular Adipose Tissue Function via Mitochondrial Pathways.

Perivascular adipose tissue (PVAT) regulates vascular function by secreting vasoactive substances. In mice, Notch signaling is activated in the PVAT during diet-induced obesity, and leads to the loss of the thermogenic phenotype and adipocyte whitening due to increased lipid accumulation. We used the Adiponectin-Cre (Adipoq-Cre) strain to activate a ligand-independent Notch1 intracellular domain transgene (N1ICD) to drive constitutive Notch signaling in the adipose tissues (N1ICD;Adipoq-Cre). We previously found that constitutive activation of Notch1 signaling in the PVAT phenocopied the effects of diet-induced obesity. To understand the downstream pathways activated by Notch signaling, we performed a proteomic analysis of the PVAT from control versus N1ICD;Adipoq-Cre mice. This comparison identified prominent changes in the protein signatures related to metabolism, adipocyte homeostasis, mitochondrial function, and ferroptosis. PVAT-derived stromal vascular fraction cells were derived from our mouse strains to study the cellular and molecular phenotypes during adipogenic induction. We found that cells with activated Notch signaling displayed decreased mitochondrial respiration despite similar levels of adipogenesis and mitochondrial number. We observed variable regulation of the proteins related to mitochondrial dynamics and ferroptosis, including PHB3, PINK1, pDRP1, and the phospholipid hydroperoxidase GPX4. Mitochondria regulate some forms of ferroptosis, which is a regulated process of cell death driven by lipid peroxidation. Accordingly, we found that Notch activation promoted lipid peroxidation and ferroptosis in PVAT-derived adipocytes. Because the PVAT phenotype is a regulator of vascular reactivity, we tested the effect of Notch activation in PVAT on vasoreactivity using wire myography. The aortae from the N1ICD;Adipoq-Cre mice had increased vasocontraction and decreased vasorelaxation in a PVAT-dependent and age-dependent manner. Our data provide support for the novel concept that increased Notch signaling in the adipose tissue leads to PVAT whitening, impaired mitochondrial function, increased ferroptosis, and loss of a protective vasodilatory signal. Our study advances our understanding of how Notch signaling in adipocytes affects mitochondrial dynamics, which impacts vascular physiology.

Hybrid Metal-Ligand Interfacial Dipole Engineering of Functional Plasmonic Nanostructures for Extraordinary Responses of Optoelectronic Properties.

Programmable manipulation of inorganic-organic interfacial electronic properties of ligand-functionalized plasmonic nanoparticles (NPs) is the key parameter dictating their applications such as catalysis, photovoltaics, and biosensing. Here we report the localized surface plasmon resonance (LSPR) properties of gold triangular nanoprisms (Au TNPs) in solid state that are functionalized with dipolar, conjugated ligands. A library of thiocinnamate ligands with varying surface dipole moments were used to functionalize TNPs, which results in ∼150 nm reversible tunability of LSPR peak wavelength with significant peak broadening (∼230 meV). The highly adjustable chemical system of thiocinnamate ligands is capable of shifting the Au work function down to 2.4 eV versus vacuum, i.e., ∼2.9 eV lower than a clean Au (111) surface, and this work function can be modulated up to 3.3 eV, the largest value reported to date through the formation of organothiolate SAMs on Au. Interestingly, the magnitude of plasmonic responses and work function modulation is NP shape dependent. By combining first-principles calculations and experiments, we have established the mechanism of direct wave function delocalization of electrons residing near the Fermi level into hybrid electronic states that are mostly dictated by the inorganic-organic interfacial dipole moments. We determine that both interfacial dipole and hybrid electronic states, and vinyl conjugation together are the key to achieving such extraordinary changes in the optoelectronic properties of ligand-functionalized, plasmonic NPs. The present study provides a quantitative relationship describing how specifically constructed organic ligands can be used to control the interfacial properties of NPs and thus the plasmonic and electronic responses of these functional plasmonics for a wide range of plasmon-driven applications.

Research on the policy effect and mechanism of green finance to reduce environmental pollution: micro evidence from 285 cities in China.

Based on panel data from 285 Chinese prefecture-level cities from 2003 to 2020, this paper uses the difference-in-difference (DID) method to investigate the policy effect, mechanism, and heterogeneity of green finance (GF) to reduce environmental pollution. (1) Green finance has significant effect on reducing environmental pollution. The parallel trend test demonstrates that DID test results are valid. (2) Following a battery of robustness tests including instrumental variable, propensity score matching (PSM), variable substitution, and changing time-bandwidth, the conclusions are still valid. (3) Mechanism analysis reveals that green finance can reduce environmental pollution by increasing energy efficiency, adjusting industrial structure, and transforming green consumption. (4) Heterogeneity analysis proves that green finance has a substantial impact on reducing the environmental pollution in eastern and western cities, but not in central China. (5) In the "two-control zone" and "low-carbon pilot cities," the results of applying green finance policies are better, and a policy superposition effect exists. To be able to promote environmental pollution control, and green and sustainable development, this paper provides useful enlightenment for environmental pollution control for China and other similar countries.

Sprouty1 has a protective role in atherogenesis and modifies the migratory and inflammatory phenotype of vascular smooth muscle cells.

BACKGROUND AND AIMS: Sprouty1 (Spry1) regulates the differentiation of vascular smooth muscle cells (VSMC), and our aim was to determine its role in atherogenesis. A significant proportion of cells within atherosclerotic lesions are derived from migration and pathological adaptation of medial VSMC. METHODS: We used global Spry1 null mouse, and Myh11-CreERT2, ROSA26-STOPfl/fl-tdTomato-Spry1fl/fl mice to allow for lineage tracing and conditional Spry1 deletion in VSMC. Atherosclerosis was induced by injection of a mutant form of mPCSK9D377Y-AAV followed by Western diet. Human aortic VSMC (hVSMC) with shRNA targeting of Spry1 were also analyzed. RESULTS: Global loss of Spry1 increased inflammatory markers ICAM1 and Cox2 in VSMC. Conditional deletion of Spry1 in VSMC had no effect on early lesion development, despite increased Sca1high cells. After 26 weeks of Western diet, mice with VSMC deletion of Spry1 had increased plaque burden, with reduced collagen content and smooth muscle alpha actin (SMA) in the fibrous cap. Lineage tracing via tdTomato marking Cre-recombined cells indicated that VSMC with loss of Spry1 had decreased migration into the lesion, noted by decreased proportions of tdTomato+ and tdTomato+/SMA + cells. Loss-of-function of Spry1 in hVSMC increased mesenchymal and activation markers, including KLF4, PDGFRb, ICAM1, and Cox2. Loss of Spry1 enhanced the effects of PDGFBB and TNFa on hVSMC. CONCLUSIONS: Loss of Spry1 in VSMC aggravated plaque formation at later stages, and increased markers of instability. Our results indicate that Spry1 suppresses the mesenchymal and inflammatory phenotype of VSMC, and its expression in VSMC is protective against chronic atherosclerotic disease.

Does China's Carbon Trading Pilot Policy Reduce Carbon Emissions? Empirical Analysis from 285 Cities.

This article studies the influence of the Carbon Trading Pilot Policy (CTPP) on carbon emissions by constructing the balanced panel data from 2003 to 2020 for 285 cities in China above the prefecture level. Difference-in-Difference (DID) method is used to test the influence and the mechanism. (1) The findings suggested that CTPP has dramatically reduced China's carbon emissions by 6.21%. The parallel trend test shows that the premise of DID is reliable. (2) A variety of robustness tests, such as the instrumental variable method for endogeneity, Propensity Score Matching (PSM) for sample selection bias, variable substitution, time-bandwidth change, and exclusion of policy intervention, show that the conclusion is still robust. (3) The mediation mechanism test indicates that CTPP can promote the reduction in carbon emissions by promoting Green Consumption Transformation (GCT), improving Ecological Efficiency (EE), and promoting Industrial Structure Upgrading (ISU). GCT contributes the most, followed by EE and ISU. (4) The analysis of the heterogeneity reveals that CTPP has a greater effect on carbon emission reduction in central and peripheral cities in China. This study provides policy implications for China and similar developing countries in the face of carbon reduction.

CASP8 Is a Potential Therapeutic Target and Is Correlated with Pyroptosis in Traumatic Brain Injury.

BACKGROUND: Traumatic brain injury (TBI) is a major cause of neurological and psychological problems, especially long-term disability. The purpose of this article is to explore molecular mechanisms linking TBI and pyroptosis with the aim of providing a promising target for future therapeutic interventions. METHODS: GSE104687 microarray dataset was downloaded from the Gene Expression Omnibus database to obtain differential expressed genes. Meanwhile, pyroptosis-related genes were screened from GeneCards database, and the overlapped genes were considered as the pyroptosis-related genes in TBI. The immune infiltration analysis was conducted to quantify lymphocyte infiltration levels. Moreover, we researched the relevant microRNAs (miRNAs) and transcription factors and investigated the interactions and functions of miRNAs. In addition, the validation set and in vivo experiment further verified the expression of hub gene. RESULTS: Altogether, we found 240 differential expressed genes in GSE104687 and 254 pyroptosis-related genes in the GeneCards database, and the overlapped gene was caspase 8 (CASP8). Immune Infiltration Analysis suggested the abundance of Tregs cells was significantly higher in TBI group. The NKT and CD8+ Tem were positively correlated with the expression levels of CASP8. The most significant term regarding CASP8 in Reactome pathways analysis was related to NF-kappaB. A total of 20 miRNAs and 25 transcription factors associated with CASP8 were obtained. After investigating the interactions and functions of miRNAs, the NF-kappaB-related signaling pathway was still enriched with a relatively low P-value. The validation set and in vivo experiment further verified the expression of CASP8. CONCLUSIONS: Our study showed the potential role of CASP8 in pathogenesis of TBI, which may provide a new target for individualized therapy and drug development.

The impact and mechanism of high-speed rail on energy efficiency: an empirical analysis based on 285 cities of China.

Improving energy efficiency is an important measure of environmental governance. At present, studies on the impact of high-speed rail on energy efficiency need to be further studied. This paper constructs panel data of 285 cities at prefecture-level and above in China from 2003 to 2017, and uses the difference-in-difference (DID) to study the impact of high-speed railway on urban energy efficiency. Based on the theories of "factor flow," "knowledge spillover," and "center-periphery," this paper discusses the influence mechanism and heterogeneity of high-speed railway on energy efficiency. The empirical results show that high-speed railway can significantly improve energy efficiency, and the conclusion is still valid after parallel trend test, propensity score matching and difference-in-difference (PSM-DID) test, and instrumental variable method. The results remained true after a series of robustness tests. Mechanism analysis shows that high-speed railway can improve energy efficiency by promoting industrial structure upgrading, technological innovation, and market integration. Analysis of heterogeneity shows that the promotion effect of high-speed railway on energy efficiency is greater in central and western cities and core cities. This study provides useful enlightenment for optimizing China's high-speed rail construction planning and seizing the opportunity of high-speed rail development to improve energy efficiency.

Drive soil nitrogen transformation and improve crop nitrogen absorption and utilization - a review of green manure applications.

Green manure application presents a valuable strategy for enhancing soil fertility and promoting ecological sustainability. By leveraging green manures for effective nitrogen management in agricultural fields can significantly reduce the dependency of primary crops on chemical nitrogen fertilizers, thereby fostering resource efficiency. This review examines the current advancements in the green manure industry, focusing on the modulation of nitrogen transformation in soil and how crops absorb and utilize nitrogen after green manure application. Initially, the influence of green manure on soil nitrogen transformation is delineated, covering processes such as soil nitrogen immobilization, and mineralization, and losses including NH3, N2O, and NO3 --N leaching. The review then delves into the effects of green manure on the composition and function of soil microbial communities, highlighting their role in nitrogen transformation. It emphasizes the available nitrogen content in the soil, this article discussing nitrogen uptake and utilization by plants, including aspects such as nitrogen translocation, distribution, the root system, and the rhizosphere environment of primary crops. This provides insights into the mechanisms that enhance nitrogen uptake and utilization when green manures are reintroduced into fields. Finally, the review anticipates future research directions in modulating soil nitrogen dynamics and crop nitrogen uptake through green manure application, aiming to advance research and the development of the green manure sector.

Integrated genetic analysis of leaf blast resistance in upland rice: QTL mapping, bulked segregant analysis and transcriptome sequencing.

Elite upland rice cultivars have the advantages of less water requirement along with high yield but are usually susceptible to various diseases. Rice blast caused by Magnaporthe oryzae is the most devastating disease in rice. Identification of new sources of resistance and the introgression of major resistance genes into elite cultivars are required for sustainable rice production. In this study, an upland rice genotype UR0803 was considered an emerging source of blast resistance. An F2 mapping population was developed from a cross between UR0803 and a local susceptible cultivar Lijiang Xintuan Heigu. The individuals from the F2 population were evaluated for leaf blast resistance in three trials 7 days after inoculation. Bulked segregant analysis (BSA) by high-throughput sequencing and SNP-index algorithm was performed to map the candidate region related to disease resistance trait. A major quantitative trait locus (QTL) for leaf blast resistance was identified on chromosome 11 in an interval of 1.61-Mb genomic region. The candidate region was further shortened to a 108.9-kb genomic region by genotyping the 955 individuals with 14 SNP markers. Transcriptome analysis was further performed between the resistant and susceptible parents, yielding a total of 5044 differentially expressed genes (DEGs). There were four DEGs in the candidate QTL region, of which, two (Os11g0700900 and Os11g0704000) were upregulated and the remaining (Os11g0702400 and Os11g0703600) were downregulated in the susceptible parent after inoculation. These novel candidate genes were functionally annotated to catalytic response against disease stimulus in cellular membranes. The results were further validated by a quantitative real-time PCR analysis. The fine-mapping of a novel QTL for blast resistance by integrative BSA mapping and transcriptome sequencing enhanced the genetic understanding of the mechanism of blast resistance in upland rice. The most suitable genotypes with resistance alleles would be useful genetic resources in rice blast resistance breeding.

Exploring the pathogenesis linking traumatic brain injury and epilepsy via bioinformatic analyses.

Traumatic brain injury (TBI) is a serious disease that could increase the risk of epilepsy. The purpose of this article is to explore the common molecular mechanism in TBI and epilepsy with the aim of providing a theoretical basis for the prevention and treatment of post-traumatic epilepsy (PTE). Two datasets of TBI and epilepsy in the Gene Expression Omnibus (GEO) database were downloaded. Functional enrichment analysis, protein-protein interaction (PPI) network construction, and hub gene identification were performed based on the cross-talk genes of aforementioned two diseases. Another dataset was used to validate these hub genes. Moreover, the abundance of infiltrating immune cells was evaluated through Immune Cell Abundance Identifier (ImmuCellAI). The common microRNAs (miRNAs) between TBI and epilepsy were acquired via the Human microRNA Disease Database (HMDD). The overlapped genes in cross-talk genes and target genes predicted through the TargetScan were obtained to construct the common miRNAs-mRNAs network. A total of 106 cross-talk genes were screened out, including 37 upregulated and 69 downregulated genes. Through the enrichment analyses, we showed that the terms about cytokine and immunity were enriched many times, particularly interferon gamma signaling pathway. Four critical hub genes were screened out for co-expression analysis. The miRNA-mRNA network revealed that three miRNAs may affect the shared interferon-induced genes, which might have essential roles in PTE. Our study showed the potential role of interferon gamma signaling pathway in pathogenesis of PTE, which may provide a promising target for future therapeutic interventions.

Kinetic and molecular insight into immunoglobulin G binding to immobilized recombinant protein A of different orientations.

Mechanistic understanding of immunoglobulin G (IgG) binding to protein A is crucial for the design and development of high-performance protein A chromatography. In this work, the IgG binding domain (Z) of protein A from Staphylococcus aureus was genetically modified by introducing a cysteine residue at the N-terminus (Cys-Z) or a cysteine-lysine dipeptide at the C-terminus (Z-Cys), and the two ligands were used to unravel the IgG binding mechanism by means of binding kinetics and different single molecule measurements. Surface plasma resonance (SPR) measurement of the binding kinetics of mouse myeloma IgG2a (mIgG2a) to the two ligands indicated that oriented ligand immobilization significantly increased the association rate constant of mIgG2a, and Z-Cys had the highest binding affinity to mIgG2a among the three ligands (Cys-Z, Z-Cys and Z). This was attributed to the synergistic contribution of the high association rate constant and low dissociation rate constant to mIgG2a. Furthermore, quartz crystal microbalance with energy dissipation monitoring (QCM-D) measurement provided the maximum adsorption densities of IgGs on the Z-Cys-immobilized chip as zeta potentials of IgGs were nearly zero. The QCM-D investigation revealed that the adsorbed layer was dependent on ligand type and density, and IgG. Moreover, Z-Cys and Cys-Z induced IgG binding in flipped orientations, as evidenced by the antigen-antibody reaction. Finally, rectangular DNA origami tiles were introduced to analyze the molecular orientation of adsorbed IgG. Single-molecule imaging showed that mIgG2a was associated with flexible Z-Cys on the tiles predominantly in side-on and end-on orientations. The research has provided molecular insight into the binding mechanism of IgG molecules at liquid-solid interfaces and would help design new protein A-based ligands and high-capacity adsorbents.

Liquiritin reduces lipopolysaccharide-aroused HaCaT cell inflammation damage via regulation of microRNA-31/MyD88.

BACKGROUND: Pressure ulcers are a common issue for people who have limited mobility. This study tested the impact of liquiritin on human keratinocyte HaCaT cell inflammatory damage aroused by lipopolysaccharide (LPS). METHODS: HaCaT cells were underwent LPS and/or liquiritin incubation. Cell viability, apoptosis and inflammatory molecules interleukin 6 (IL-6), tumor necrosis factor α (TNF-α) and cyclooxygenase-2 (Cox-2) expressions, along with nuclear factor kappa B (NF-κB) and c-Jun N-terminal kinase (JNK) pathways activities were tested by MTT assay, Guava Nexin assay, ELISA and western blotting, respectively. qRT-PCR was done for measuring microRNA-31 (miR-31) expression. miR-31 inhibitor was transfected to silence miR-31. Animal pressure ulcers was established on the dorsal skin of adult rats. The effects of liquiritin on wound healing were analyzed by measuring wound closure rates. RESULTS: LPS aroused HaCaT cell inflammatory damage, as evidenced by the decrease of cell viability, increase of cell apoptosis and enhanced expressions of IL-6, TNF-α and Cox-2. Liquiritin protected HaCaT cells against LPS-aroused inflammatory damage through increasing cell viability, decreasing cell apoptosis, and reducing IL-6, TNF-α and Cox-2 expressions. Liquiritin attenuated the LPS-aroused NF-κB and JNK pathways activation in HaCaT cells. Rat pressure ulcers model also confirmed that liquiritin promoted wound healing. In mechanism, miR-31 expression was boosted by liquiritin in HaCaT cells. Silencing miR-31 weakened the impacts of liquiritin on LPS-irritated HaCaT cells. Myeloid differentiation factor 88 (MyD88) was a target of miR-31 in HaCaT cells. CONCLUSION: This research affirmed the beneficial impact of liquiritin on pressure ulcers. Liquiritin reduced LPS-aroused HaCaT cell inflammatory damage might be implemented via raising miR-31 expression, lowering MyD88 expression, and repressing NF-κB and JNK pathways.

Sprouty1 regulates gonadal white adipose tissue growth through a PDGFRα/ß-Akt pathway.

Expansion of visceral white adipose tissue (vWAT) occurs in response to nutrient excess, and is a risk factor for metabolic disease. SPRY1, a feedback inhibitor of receptor tyrosine kinase (RTK) signaling, is expressed in PDGFRa+ adipocyte progenitor cells (APC) in vivo. Global deficiency of Spry1 in mice results in disproportionate postnatal growth of gonadal WAT (gWAT), while iWAT and BAT were similar in size between Spry1KO and WT mice. Spry1 deficiency increased the number of PDGFRa+ stromal vascular fraction (SVF) cells in gWAT and showed increased proliferation and fibrosis. Spry1KO gWAT had increased collagen deposition and elevated expression of markers of inflammation. In vitro, SPRY1 was transiently down regulated during early adipocyte differentiation of SVF cells, with levels increasing at later stages of differentiation. SPRY1 deficiency enhances PDGF-AA and PDGF-BB induced proliferation of SVF cells. Increased proliferation of SVF from Spry1KO gWAT accompanies an increase in AKT activation. PDGF-AA stimulated a transient down regulation of SPRY1 in wild type SVF, whereas PDGF-BB stimulated a sustained down regulation of SPRY1 in wild type SVF. Collectively, our data suggest that SPRY1 is critical for regulating postnatal growth of gWAT by restraining APC proliferation and differentiation in part by regulation of PDGFRa/b-AKT signaling.

Key Amino Acids for Pepper Vein Yellows Virus P0 Protein Pathogenicity, Gene Silencing, and Subcellular Localization.

Pepper vein yellows virus (PeVYV) is a newly recognized Polerovirus extracted from Chinese pepper. The symptoms of PeVYV-infested pepper plants comprise intervein yellow staining, leaf curl formation and other malformations, and leaf internodal shrinkage, but the roles of the viral proteins remain undetermined. The P0 protein of the genus Polerovirus has established post-transcriptional gene silencing (PTGS) activity. This investigation focused on the PeVYV-encoded P0 protein and assessed its potential virulence capacity, PTGS activity, and tendencies to localize in the nucleus. This study revealed that P0 influenced the pathogenic properties of a specific heterologous potato virus X. In addition, P0 proteins impaired local gene silencing, although they did not regulate generalized gene silencing within Nicotiana benthamiana 16c plants. Furthermore, P0 proteins localized mainly in the nucleus, particularly in the nucleolus. P0 deletion mutagenesis demonstrated that the F-box motif (56-72 amino acids, AAs) of P0 was essential for symptom determination, inhibition of PTGS, and subcellular localization. Mutation analysis of the F-box motif of P0 protein indicated that AA 57 of the P0 protein was a pivotal site in symptom development and that AA 56 of the P0 protein was indispensable for inhibiting PTGS and subcellular localization. The outcomes obtained here suggest that further studies should be conducted on the molecular mechanisms of amino acids of the F-box domain of P0 protein in the interaction of PeVYV with plants.

Molecular mechanisms of esophageal epithelial regeneration following repair of surgical defects with acellular silk fibroin grafts.

Constructive remodeling of focal esophageal defects with biodegradable acellular grafts relies on the ability of host progenitor cell populations to repopulate implant regions and facilitate growth of de novo functional tissue. Intrinsic molecular mechanisms governing esophageal repair processes following biomaterial-based, surgical reconstruction is largely unknown. In the present study, we utilized mass spectrometry-based quantitative proteomics and in silico pathway evaluations to identify signaling cascades which were significantly activated during neoepithelial formation in a Sprague Dawley rat model of onlay esophagoplasty with acellular silk fibroin scaffolds. Pharmacologic inhibitor and rescue experiments revealed that epithelialization of neotissues is significantly dependent in part on pro-survival stimuli capable of suppressing caspase activity in epithelial progenitors via activation of hepatocyte growth factor receptor (c-MET), tropomyosin receptor kinase A (TrkA), phosphoinositide 3-kinase (PI3K), and protein kinase B (Akt) signaling mechanisms. These data highlight the molecular machinery involved in esophageal epithelial regeneration following surgical repair with acellular implants.

Interleukin-17 receptor D (Sef) is a multi-functional regulator of cell signaling.

Interleukin-17 receptor D (IL17RD or IL-17RD) also known as Sef (similar expression to fibroblast growth factor), is a single pass transmembrane protein that is reported to regulate several signaling pathways . IL17RD was initially described as a feedback inhibitor of fibroblast growth factor (FGF) signaling during zebrafish and frog development. It was subsequently determined to regulate other receptor tyrosine kinase signaling cascades as well as several proinflammatory signaling pathways including Interleukin-17A (IL17A), Toll-like receptors (TLR) and Interleukin-1α (IL1α) in several vertebrate species including humans. This review will provide an overview of IL17RD regulation of signaling pathways and functions with emphasis on regulation of development and pathobiological conditions. We will also discuss gaps in our knowledge about IL17RD function to provide insight into opportunities for future investigation. Video Abstract.

Evaluation of Bilayer Silk Fibroin Grafts for Tubular Esophagoplasty in a Porcine Defect Model.

Surgical reconstruction of tubular esophageal defects with autologous gastrointestinal segments is the gold standard treatment to replace damaged or diseased esophageal tissues. Unfortunately, this approach is associated with adverse complications, including dysphagia, donor-site morbidity, and in some cases patient death. Bilayer silk fibroin (BLSF) scaffolds were investigated as alternative, acellular grafts for tubular esophagoplasty in a porcine defect model for 3 months of implantation. Adult Yucatan mini-swine (n = 5) were subjected to esophageal reconstruction with tubular BLSF grafts (2 cm in length) in combination with transient esophageal stenting for 2 months followed by a 1-month period, where the graft site was unstented. All animals receiving BLSF grafts survived and were capable of solid food consumption, however strictures were noted at graft regions in 60% of the experimental cohort between 2 and 3 months postop and required balloon dilation. In addition, fluoroscopic analysis showed peristaltic function in only 1/5 neotissues. Following swine harvest at 3 months, ex vivo tissue bath evaluations revealed that neoconduits exhibited contractile responses to carbachol, electric field stimulation, and KCl, whereas sodium nitroprusside and isoproterenol induced relaxation effects. Histological (Masson's Trichrome) and immunohistochemical analyses of regenerated tissue conduits showed a stratified, squamous epithelium expressing pan-cytokeratins buttressed by a vascularized lamina propria containing a smooth muscle-rich muscularis mucosa surrounded by a muscularis externa. Neuronal density, characterized by the presence of synaptophysin-positive boutons, was significantly lower in neotissues in comparison to nonsurgical controls. BLSF scaffolds represent a promising platform for the repair of tubular esophageal defects, however improvements in scaffold design are needed to reduce the rate of complications and improve the extent of constructive tissue remodeling. Impact statement The search for a superior "off-the-shelf" scaffold capable of repairing tubularesophageal defects as well as overcoming limitations associated with conventional autologous gastrointestinal segments remains elusive. The purpose of this study was to investigate the performance of an acellular, bilayer silk fibroin graft (BLSF) for tubular esophagoplasty in a porcine model. Our results demonstrated that BLSF scaffolds supported the formation of tubular neotissues with innervated, vascularized epithelial and muscular components capable of contractile and relaxation responses. BLSF scaffolds represent a promising platform for esophageal tissue engineering.

First Report of Stem Rot of Huangjing (Polygonatum sibiricum) Caused by Sclerotium rolfsii.

Huangjing (Polygonatum sibiricum) is a medicinal plant widely distributed in China, Japan, and Korea. The dried rhizome of Huangjing has been reported to have many pharmacological applications and biological activities, such as antioxidants, immunity enhancement, anti-fatigue, anti-osteoporosis, and anti-aging activity (Cui et al., 2018). In June 2018, we observed some wilted Huangjing plants in commercial plantings in Shuicheng, Guizhou, China (26.22 N, 104.76 E). Symptoms began as moderate to severe wilting of stems and necrosis of leaves, followed by the death of plants. The collar rot appeared on the stem near to the soil. When incubated at 28°C and 100% relative humidity (RH) for 8 to 10 days, the infected stem produced brown sclerotia. We picked the sclerotia and cultured them on potato dextrose agar (PDA) supplemented with 50 µg/ml of streptomycin. The hyphal tips generated by the sclerotia was isolated under microscopic field and transferred to the fresh PDA. Three isolates (HJ-1, HJ-6 and HJ-10) came from the hyphal tips formed the typical clamp connection structure at 6-7 days post-incubation and the sclerotia of them were white and the late ones turned dark brown. The matured sclerotia were globular, 1.5 to 3.3 mm (avg. 2.2) in diameter. The morphologic observation revealed that three isolates were consistent with Athelia rolfsii (Paul et al., 2017). To further confirm the fungal species, the ribosomal internal transcribed spacer (ITS) sequences were amplified and sequenced. Primers and PCR amplification were referenced as previously described (Paul et al., 2017). The sequences were compared to type sequences in GenBank. The ITS sequences (GenBank accession MT478452, MT949696 and MT949697) of the isolates (HJ-10, HJ-1 and HJ-6) were 99% identical with strain 13M-0091 (GenBank accession KT222898) of A. rolfsii, respectively (Paul et al., 2017). A maximum likelihood tree was constructed using MEGA-X version 10.1.6 (Kumar et al., 2018) based on the ITS sequences of the three strains (HJ-10, HJ-1 and HJ-6) and that of Athelia spp. previously deposited in GenBank (Paul et al., 2017). Phylogenetic analysis showed that the isolates (HJ-10, HJ-1 and HJ-6) belong to the A. rolfsii clade. Based on morphology and DNA sequencing, the isolates (HJ-10, HJ-1 and HJ-6) were identified as A. rolfsii. To verify pathogenicity, Huangjing seedlings were inoculated with colonized agar discs of the isolates. Additional Huangjing plants inoculated with uncolonized agar discs were used as the control. After inoculation, Huangjing seedlings were moved to the inoculation chamber under high humidity and 28°C for 3 days and then transferred to a greenhouse. The typical wilting symptoms appeared 8 days after inoculation and were similar to those observed in the field, while control plants remained symptomless. The causing agents were isolated from the lesions and the ITS sequences of them were sequenced again. The alignment analysis of the ITS sequences showed the causing agents are consistent with the original isolates. These studies fulfilled Koch's postulates. To our knowledge, this is the first report of A. rolfsii causing stem rot on Huangjing.