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Estradiol (E2) treatment has been known to induce changes in food intake, energy expenditure, and weight gain. However, its direct effects on adipose tissue macrophages (ATM) in vivo are not fully understood. Thus, we aimed to explore this aspect at cellular and molecular levels in ovariectomized obese mice. We examined the changes in ATMs after eight weeks of a high-fat diet (HFD) in male, female, and ovariectomized (OVX) mice. After eight weeks, osmotic pumps were inserted into OVX mice to provide two weeks of E2 treatment. We additionally set up a vehicle Pair-Fed (PF) control group that supplied the same amount of HFD consumed by the E2-treated group. We then investigated the in vivo phenotypic changes of visceral adipose tissue (VAT) macrophages. The percentage of M1-like ATMs decreased by the anorectic effect of E2, while M2-like ATMs increased regardless of the anorexia. E2 treatment increased the expression of anti-inflammatory genes but decreased pro-inflammatory genes in VAT. Monocyte recruitment and local proliferation contributed to M2-like ATMs. Furthermore, M2-like phenotypes were induced by E2 treatment in human macrophages. E2 treatment increases M2-like macrophages and improves the tissue milieu of VAT regardless of the anorectic reaction of E2.

Identifying the mechanisms underlying the early inflammatory phase of aortic valve disease is crucial for disease prevention. Here the authors perform single-cell RNA sequencing to show the immunomodulatory role of PPARγ in valvular endothelial cells during hyperlipidemia.

Lepista sordida is a fairy ring-forming fungus that belongs to the family Tricholomataceae and is widely distributed in the Northern Hemisphere. Here, we report the complete mitochondrial genome sequence of L. sordida. The mitochondrial genome (57,375 bp) contained 20 protein-coding genes, 2 ribosomal RNA genes, and 26 transfer RNA genes. Phylogenetic analysis based on 14 conserved protein sequences from L. sordida and 15 related basidiomycetes showed that L. sordida was located on the outermost branch of the Tricholomataceae clade. This study is the first to report the complete mitochondrial genome sequence of a fairy ring-forming fungus belonging to the genus Lepista.

Background & Aims: Helicobacter pylori has been reported to modulate local immune responses to colonize persistently in gastric mucosa. Although the induced expression of programmed cell death ligand 1 (PD-L1) has been suggested as an immune modulatory mechanism for persistent infection of H pylori, the main immune cells expressing PD-L1 and their functions in Helicobacter-induced gastritis still remain to be elucidated. Methods: The blockades of PD-L1 with antibody or PD-L1–deficient bone marrow transplantation were performed in Helicobacter-infected mice. The main immune cells expressing PD-L1 in Helicobacter-infected stomach were determined by flow cytometry and immunofluorescence staining. Helicobacter felis or H pylori–infected dendritic cell (DC)-deficient mouse models including Flt3–/–, Zbtb46–diphtheria toxin receptor, and BDCA2–diphtheria toxin receptor mice were analyzed for pathologic changes and colonization levels. Finally, the location of PD-L1–expressing DCs and the correlation with H pylori infection were analyzed in human gastric tissues using multiplexed immunohistochemistry. Results: Genetic or antibody-mediated blockade of PD-L1 aggravated Helicobacter-induced gastritis with mucosal metaplasia. Gastric classical DCs expressed considerably higher levels of PD-L1 than other immune cells and co-localized with T cells in gastritis lesions from Helicobacter-infected mice and human beings. H felis– or H pylori–infected Flt3–/– or classical DC-depleted mice showed aggravated gastritis with severe T-cell and neutrophil accumulation with low bacterial loads compared with that in control mice. Finally, PD-L1–expressing DCs were co-localized with T cells and showed a positive correlation with H pylori infection in human subjects. Conclusions: The PD-1/PD-L1 pathway may be responsible for the immune modulatory function of gastric DCs that protects the gastric mucosa from Helicobacter-induced inflammation, but allows persistent Helicobacter colonization.

The recombinant human growth hormone (GH) has been used for the treatment of growth hormone deficiency (GHD) and diverse short stature state, and its physiological and therapeutic effects are well documented. However, since the effect of GH treatment on metabolic disorders has not been well characterized, we injected GH to Western diet-fed low-density lipoprotein receptor-deficient (Ldlr−/−) mice to understand the exact effect of GH on metabolic diseases including atherosclerosis, hepatic steatosis, and obesity. Exogenous GH treatment increased plasma IGF-1 concentration and decreased body weight without affecting serum lipid profiles. GH treatment changed neither atherosclerotic lesion size nor collagen and smooth muscle cells accumulation in the lesion. GH treatment reduced macrophage accumulation in adipose tissue. Importantly, GH treatment attenuated hepatic steatosis and inflammation. The hepatic expression IL-1β mRNA were decreased by GH treatment. The mRNA and protein levels of CD36 were markedly decreased in GH treated mice without significant changes in other molecules related to lipid metabolism. Therefore, the treatment of GH treatment could attenuate hepatic steatosis and inflammation with downregulation of CD36 expression in hyperlipidemic condition.

Higher-order deformation theories, such as the couple stress and strain gradient theory, have been widely used to predict the mechanical behavior of micro/nano-scale structures. In this paper, the additional length scale parameter introduced in the couple stress theory is measured by performing bulk-scale tensile and micro-scale cantilever bending experiments. Bulk-scale characterization provided microstructural information of the polycrystalline copper plate along with macroscopic mechanical properties. Micro-scale cantilevers with thicknesses ranging from 1.6 µm to 8.6 µm were fabricated within the copper plate using femtosecond laser machining followed by focused ion beam milling. Line load was applied on these samples utilizing a nanoindenter. Finite element analysis was performed to exclude the effect of substrate deformation. The measured effective elastic modulus increases from 94 GPa to 215 GPa with decreasing thickness. The increase of the bending rigidity is analyzed based on the couple stress theory, and the length scale parameter is measured as 0.78 µm. The physical origin of the length scale parameter is discussed by considering mobile dislocations escaping via the free surfaces during loading.

A novel compound (1) along with two known compounds (2 and 3) were isolated from the culture broth of Chlorophyllum molybdites, and three known compounds (4–6) were isolated from its fruiting bodies. The planar structure of 1 was determined by the interpretation of spectroscopic data. By comparing the specific rotation of the compound with that of the analog compound, the absolute configuration of 1 was determined to be R. This is the first time that compounds 2–4 were isolated from a mushroom-forming fungus. Compound 2 showed significant inhibition activity against Axl and immune checkpoints (PD-L1, PD-L2). In the bioassay to examine growth inhibitory activity against the phytopathogenic bacteria Peptobacterium carotovorum, Clavibacter michiganensis and Burkholderia glumae, compounds 2 and 3 inhibited the growth of P. carotovorum and C. michiganensis. In the bioassay to examine plant growth regulatory activity, compounds 1–4 showed a significant regulatory activity on lettuce growth.

Abstract Pulmonary hypertension (PH) is a pathological state with sustained elevation of pulmonary artery (PA) pressure. Since the pathogenesis of PH is mostly irreversible, the disease often comes up with poor prognosis. Pulmonary arterioles are affected by deteriorative changes, such as development of occlusive lesions of thickening of arterial walls. Such processes increase the pulmonary arterial pressure thus lead to consequent injuries such as right ventricle failure. Proliferation, or resistance to apoptosis of pulmonary artery smooth muscle cells (PASMC) and fibroblasts, are characteristic changes observed in the PA in pulmonary arterial hypertension (PAH) patients. PAH can either occur idiopathically or come with other diseases. Emerging evidences suggest that pro-inflammatory processes are closely related to the development of PAH. Therefore, it is inferred that immune cells could be the key factors in PAH development. In this review, we summarize the way how each types of immune cells participate in PAH. We would also like to list the current rodent models used for PAH study.

There are various potential practical uses of fairy chemicals (FCs) in the fields of agriculture, cosmetics, and medicine; however, the production costs of FCs are very high. To enable the practical use of FCs, more efficient and inexpensive methods of culturing the mycelia of FCs-producing fungi and producing FCs need to be developed. The purpose of the present study was to determine methods of reducing the production costs of FCs and mycelia of the FCs-producing fungus Lepista sordida. We investigated the effects of four food industrial by-products, i.e., corn steep liquor (CSL), rice bran, wheat bran, and Japanese liquor lees, as nutritional additives in the liquid culture medium of the fungus. We found that CSL was more effective than the other tested additives in increasing the production of FCs and mycelia. Medium containing 1% CSL was optimal for increasing the mycelial yield while medium containing 6% CSL was optimal for increasing the production of FCs. The reason for this difference in the optimal CSL concentration was considered to be related to the stress on the mycelia caused by the amount of nutrients in the liquid medium. These results are expected to facilitate the practical use of FCs and the mycelia of FCs-producing fungi.

Two compounds 1 and 2 were isolated from the culture broth of Lepista luscina. This is the first time that compound 1 was isolated from a natural source. The structure of compound 1 was identified via 1D and 2D NMR and HRESIMS data. Compounds 1 and 2 along with 8-nitrotryptanthrin (4) were evaluated for their biological activities using the A549 lung cancer cell line. As a result, 1 and 2 inhibited the expression of Axl and immune checkpoint molecules. In addition, compounds 1, 2 and 4 were tested for HIF inhibitory activity. Compound 2 demonstrated statistically significant HIF inhibitory effects on NIH3T3 cells and 1 and 2 against ARPE19 cells.

Calcific aortic valve disease (CAVD) is the most common degenerative heart valve disease. Among the many risk factors for this disease are age, hypercholesterolemia, hypertension, smoking, type-2 diabetes, rheumatic fever, and chronic kidney disease. Since many of these overlap with risk factors for atherosclerosis, the molecular and cellular mechanisms of CAVD development have been presumed to be similar to those for atherogenesis. Thus, attempts have been made to evaluate the therapeutic efficacy of statins, representative anti-atherosclerosis drugs with lipid-lowering and anti-inflammatory effects, against CAVD. Unfortunately, statins have shown little or no effect on CAVD development. But some reports suggest that statins may prevent or reduce the development of early stage CAVD in which having calcification is absent or minimal. These results suggest that therapeutic approaches should differ according to the stage of disease, and that a precise understanding of the mechanism of aortic valve calcification is required to identify novel therapeutic targets for advanced CAVD. Given the involvement of inflammatory processes in the development and progression of CAVD, current therapeutic approaches for chronic inflammatory cardiovascular disease like atherosclerosis may help to prevent or minimize the early development of CAVD. In this review, we focus on several inflammatory cellular and molecular components involved in CAVD that might be considered drug targets for preventing CAVD.

Stropharia rugosoannulata (Strophariaceae, Basidiomycota) is an edible mushroom distributed in northern temperate zones throughout the world. In this study, the complete mitochondrial genome sequence of S. rugosoannulata was determined. This mitochondrial genome is 60,551 bp in length with a GC content of 31.0% and encodes 14 conserved proteins, 2 ribosomal RNAs, 29 transfer RNAs, and 12 further ORFs. Phylogenetic relationships based on the mitochondrial genome between S. rugosoannulata and other basidiomycetes are inconsistent with those based on nuclear genes. This is the first report of the mitochondrial genome of mushrooms belonging to the family Strophariaceae.

Summary: CD137, a potent costimulatory receptor for CD8+ T cells, is expressed in various non-T cells, but little is known about its regulatory functions in these cells. In this study, we show that CD137 signaling, specifically in intestinal CD11b−CD103+ dendritic cells (DCs), restricts acute colitis progression. Mechanistically, CD137 engagement activates TAK1 and subsequently stimulates the AMPK-PGC-1α axis to enhance expression of the Aldh1a2 gene encoding the retinoic acid (RA) metabolizing enzyme RALDH2. RA can act on CD11b+CD103− DCs and induce SOCS3 expression, which, in turn, suppresses p38MAPK activation and interleukin-23 (IL-23) production. Administration of RA in DC-specific CD137−/− mice represses IL-23-producing CD11b+CD103− DCs and TH17 cells, indicating that RA is a major inhibitory effector molecule against intestinal CD11b+CD103− DCs. Additionally, the therapeutic effect of the anti-CD137 antibody is abrogated in DC-specific CD137−/− mice. Taken together, our results define a mechanism of paracrine immunoregulation operating between adjacent DC subsets in the intestine. : Jin et al. demonstrate that CD137 signaling functions as an immune checkpoint by controlling the survival and function of regulatory intestinal CD11b−CD103+ dendritic cells to coordinate the balance between regulatory T cells and pathogenic IL-23 during acute colitis. Keywords: CD137, regulatory CD11b−CD103+ DC, Foxp3+ Treg, acute colitis, retinoic acid, RALDH2, IL-23, TH17, immune checkpoint, immune tolerance

Sediment oxygen demand (SOD) and benthic nutrient fluxes (BNFs) were measured using an in situ benthic chamber at a fish farm (FF), oyster farm (OF), and controls (FF-C and OF-C) to assess the impact of aquaculture activities on organic carbon (OC) and nutrients cycles in coastal waters of Korea. The SOD at FF and OF ranged from 60 ± 2 to 157 ± 3 mmol m−2 d−1 and from 77 ± 14 to 84 ± 16 mmol m−2 d−1, respectively, more than five times those of the control sites. The SOD at farm sites is highly correlated with fish stock and food input, suggesting that excess feed input is an important control factor for OC remineralization. The combined analysis of sediment trap and SOD indicates that most of the deposited OC oxidized in the sediment and/or was laterally transported by the current before being buried in the sediment. The benthic nutrient fluxes at farms ranged from 5.45 to 8.95 mmol N m−2 d−1 for nitrogen and from 0.51 to 1.67 mmol P m−2 d−1 for phosphate, respectively, accounting for 37–270% and 52–804% of the N and P required for primary production in the water column. These results indicate that aquaculture farming may profoundly impact biogeochemical cycles in coastal waters.

A Ka-band circularly polarized (CP) waveguide slot antenna with a cross iris is proposed. To achieve the CP characteristic (LHCP) in the antenna, a hexagonal shaped cavity is used. The impedance matching is improved by adjusting the sizes of the hexagonal cavity and a rectangular matching cavity. To enhance the axial ratio bandwidth, a cross iris is used with two arms of different lengths. From experimental results, the proposed antenna has a 3 dB axial ratio bandwidth of 6810 MHz (31.72 GHz–38.53 GHz). The −10 dB reflection coefficient bandwidth of the proposed antenna ranges from 31.51 GHz to 39.21 GHz (7700 MHz).

The dowel bone graft fusion technique for the ankle is a well-known and useful method. However, clinical results of dowel bone graft for small joint fusion are unknown. The objective of the present study is to evaluate the effects of dowel bone graft technique for small joint arthrodesis in an in vivo arthrodesis of rabbit elbow model compared with the conventional arthrodesis technique (open, joint surface debridement, and internal fixation method). We assigned 28 young adult New Zealand white rabbits to one of two groups: Group 1, the conventional fusion technique group; Group 2, the dowel bone graft fusion technique group. We performed arthrodesis surgery in two different ways for each group. Eight weeks after the operation, specimens were harvested, radiographed, mechanically tested for torque to failure and stiffness, and evaluated for histology. Fusion rates were 77% (10/13) in Group 1 and 93% (13/14) in Group 2 (p = 0.326). Torque to failure showed a mean of 0.86 Nm in Group 1 and 0.77 Nm in Group 2 (p = 0.464). The mean value of stiffness was 0.11 Nm/deg in Group 1 and 0.11 Nm/deg in Group 2 (p = 0.832). In Group 2, histological examination showed residual cartilage absorption and inflammatory response in all cases. In this model, we have been unable to show a difference in either the union rate or strength of fusion between the two methods. However, the dowel bone graft technique is an easy and less invasive method and has some advantages over the conventional method.

A low-profile wideband monocone antenna with bent shorting strips, and parasitic and circular sleeves is proposed. By loading the bent shorting strips, parasitic sleeves, and circular sleeves, miniaturization of the antenna is achieved. Along with bent shorting strips from the monocone hat to the ground plane, parasitic sleeves, and circular sleeves are mounted to enhance the impedance bandwidth. From the experimental results, the −10 dB reflection coefficient bandwidth of the proposed antenna ranges from 810 MHz to 5340 MHz. In addition to the wide bandwidth characteristics, the proposed antenna has highly desirable omnidirectional radiation properties for wireless communication systems.

Allergic rhinitis (AR) is the most common allergic disease but little is known about the difference of local immune responses in children and adults with AR.To compare local immune responses between children and adults with AR and nonallergic rhinitis (NAR), and to investigate whether the association of local and systemic immune responses is different between the two age groups.Fifty-one patients with chronic rhinitis were enrolled and grouped into children (N = 27, mean age 7.2 years) and adults (N = 24, mean age 29.9 years). Diagnosis of AR was based on symptoms, skin prick tests and serum specific IgEs. Nasal lavage (NAL) fluids were collected from all subjects and used to measure the levels of total IgE, specific IgEs to house dust mites (Dp and Df), and cytokines (TNF-α, IL-4, IL-10, IL-17A and IFN-γ). Flow cytometry was used to measure inflammatory cell types in NAL fluids.AR had significantly increased local levels of total IgE and specific IgEs to Dp and Df compared with NAR in both age groups (P < 0.05). Nasal eosinophils % (P = 0.01) was significantly increased only in children with AR. Local-systemic correlations of total IgE (r = 0.662, P = 0.000) and eosinophil % (r = 0.461, P = 0.015) between the peripheral blood and NAL fluids were found only in children. Moreover, children had correlations between total IgE and eosinophil % in the peripheral blood (r = 0.629, P = 0.001) and in NAL fluids (r = 0.373, P = 0.061).Elevated local IgE is a common feature of AR in children and adults. Local measures in NAR showed naïve state of immune response which disagree with the hypothesis of local allergic rhinitis. Children showed intense local inflammation and close local-systemic interactions compared to adults supporting pediatric AR as a distinct feature.

Resistin-like molecule alpha (Retnla), also known as 'Found in inflammatory zone 1', is a secreted protein that has been found in bronchoalveolar lavage (BAL) fluid of ovalbumin (OVA)-induced asthmatic mice and plays a role as a regulator of T helper (Th)2-driven inflammation. However, the role of Retnla in the progress of Th2-driven airway inflammation is not yet clear. To better understand the function of Retnla in Th2-driven airway inflammation, we generated Retnla-overexpressing (Retnla-Tg) mice. Retnla-Tg mice showed increased expression of Retnla protein in BAL fluid and airway epithelial cells. Retnla overexpression itself did not induce any alteration in lung histology or lung function compared to non-Tg controls. However, OVA-sensitized/challenged Retnla-Tg mice had decreased numbers of cells in BAL and inflammatory cells accumulating in the lung. They also showed a reduction in mucus production in the airway epithelium, concomitant with a decreased Muc5ac level. These results were accompanied by reduced levels of Th2 cytokines, including interleukin (IL)-4, IL-5, and IL-13, with no effect on levels of OVA-specific immunoglobulin isotypes. Furthermore, phosphorylation of ERK was markedly reduced in the lungs of OVA-challenged Retnla-Tg mice. Taken together, these results indicates that Retnla protects against Th2-mediated inflammation in an experimental mouse model of asthma, suggesting that therapeutic approaches to enhance the production of Retnla or Retnla-like molecules could be valuable for preventing allergic lung inflammation.

Recently, it has been demonstrated that high cholesterol diet induced hypercholesterolemia and vascular lipid oxidation and accumulation in zebrafish larvae, suggesting that zebrafish is a new promising atherosclerosis model in addition to mouse models. However, up to date, there was no report regarding inflammatory cytokine expression during the lipid accumulation in zebrafish larva and adult fish. In this study, we first demonstrated the expression levels of IL-1β and TNF-α in high cholesterol diet (HCD)-fed zebrafish larvae, and found that although HCD induced vascular lipid accumulation, the cytokine expressions in the larvae were not changed by HCD. Furthermore, there was no significant difference in leukocyte accumulation in vessels between control and HCD fed group. But prolonged HCD induced IL-1β expression in spleen and liver compared to those of control zebrafish, and produced very early stage of fatty streak lesion in dorsal aorta of 19 week HCD-fed zebrafish. These results indicate that HCD induced hypercholesterolemia and atherosclerotic changes in zebrafish are very early stage, and suggest the necessity of the generation of mutant zebrafish having a disruption in a lipid metabolism-related gene leading to severe hypercholesterolemia and advanced atherosclerosis.