Effects of multiple cations and sintering temperature on microstructure and dielectric properties in Na1/2Ln1/2Cu3Ti4O12 (Ln = Sm and Eu) ceramic materials.

Na1/2Eu1/2Cu3Ti4O12 and Na1/2Sm1/2Cu3Ti4O12 dielectric ceramics were synthesized at different sintering temperatures (950, 975 and 1000 °C) by a solid-state reaction method. Phase structure, cation valence state, and dielectric properties of all sintered ceramics were systematically investigated. When the preparation temperature was changed, the Cu+ ion concentration of (Na+, Eu3+) co-doped ceramics changed faster than that of (Na+, Sm3+) co-doped ceramics. Abnormally high dielectric constants of ~ 3.17 × 104 and ~ 1.06 × 104 (at 10 Hz and 303 K) were achieved in Na1/2Sm1/2Cu3Ti4O12 and Na1/2Eu1/2Cu3Ti4O12 ceramics prepared at 950 °C, respectively. However, Na1/2Sm1/2Cu3Ti4O12 and Na1/2Eu1/2Cu3Ti4O12 prepared in high sintering temperature (1000 °C) exhibited a good frequency stability of dielectric permittivity. It was demonstrated that an increasing number of charge carriers induced by the increase of sintering temperature could lead to a competitive coexistence of two polarization mechanisms (surface barrier layer capacitor and internal barrier layer capacitor), further changing the dielectric properties of CaCu3Ti4O12-based ceramics.

Effect of alirocumab and evolocumab on all-cause mortality and major cardiovascular events: A meta-analysis focusing on the number needed to treat.

Aims: The efficacy of anti-proprotein convertase subtilisin/Kexin type 9 (PCSK9) monoclonal antibodies in patients with atherosclerotic cardiovascular disease (ASCVD) remains unclear. Therefore, this study aims to assess the effect of PCSK9 inhibitors (alirocumab and evolocumab) on ASCVD patients considering the number needed to treat (NNT). Methods: We reviewed randomized controlled trials (RCTs) which compared the effects of alirocumab or evolocumab and placebo or standards of care. All articles were published in English up to May 2022. Using random effect models, we estimated risk ratios (RRs), NNT, and 95% confidence intervals (CI). Results: We incorporated 12 RCTs with 53 486 patients total, of which 27 674 received PCSK9 inhibitors and 25 812 received placebos. The mean follow-up duration was 1.56 years. The effect of PCSK9 inhibitors on major adverse cardiovascular events (MACE) was statistically significant, and the corresponding mean NNT was 36. Alirocumab reduced the risk of MACE, stroke, and coronary revascularization; the corresponding mean NNT were 37, 319, and 107, respectively. Evolocumab positively affected MACE, myocardial infarction, stroke, and coronary revascularization; the corresponding mean NNT were 32, 78, 267, and 65, respectively. The effects of alirocumab or evolocumab on all-cause mortality and cardiovascular mortality were not statistically significant. Conclusion: This study suggests that preventing one patient from MACE needed to treat 36 patients with ASCVD with PCSK9 inhibitors for 1.56 years. Both alirocumab and evolocumab reduced MACE, stroke, and coronary revascularization. Evolocumab had a positive effect on myocardial infarction, but no effects were noted for alirocumab. In addition, alirocumab may not be as effective as evolocumab. NNT visualizes the magnitude of efficacy to assist in clinical decisions. Systematic review registration: [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=344908], identifier [CRD42022344908].

Aureoverticillactam, a Potent Antifungal Macrocyclic Lactam from Streptomyces aureoverticillatus HN6, Generates Calcium Dyshomeostasis-Induced Cell Apoptosis via the Phospholipase C Pathway in Fusarium oxysporum f. sp. cubense Race 4.

Extensive efforts have been made to discover new biofungicides of high efficiency for control of Fusarium oxysporum f. sp. cubense race 4, a catastrophic soilborne phytopathogen causing banana Fusarium wilt worldwide. We confirmed for the first time that aureoverticillactam (YY3) has potent antifungal activity against F. oxysporum f. sp. cubense race 4, with effective dose for 50% inhibition (EC50) of 20.80 µg/ml against hyphal growth and 12.62 µg/ml against spore germination. To investigate its mechanism of action, we observed the cellular ultrastructures of F. oxysporum f. sp. cubense race 4 with YY3 treatment and found that YY3 led to cell wall thinning, mitochondrial deformities, apoptotic degradation of the subcellular fractions, and entocyte leakage. Consistent with these variations, increased permeability of cell membrane and mitochondrial membrane also occurred after YY3 treatment. On the enzymatic level, the activity of mitochondrial complex III, as well as the ATP synthase, was significantly suppressed by YY3 at a concentration >12.50 µg/ml. Moreover, YY3 elevated the cytosolic Ca2+ level to promote mitochondrial reactive oxygen species (ROS) production. Cell apoptosis also occurred as expected. On the transcriptome level, key genes involved in the phosphatidylinositol signaling pathway were significantly affected, with the expression level of Plc1 increased approximately fourfold. The expression levels of two apoptotic genes, casA1 and casA2, were also significantly increased by YY3. Of note, phospholipase C activation was observed with YY3 treatment in F. oxysporum f. sp. cubense race 4. These findings indicate that YY3 exerts its antifungal activity by activating the phospholipase C calcium-dependent ROS signaling pathway, which makes it a promising biofungicide.

Dual Functional Eudragit® S100/L30D-55 and PLGA Colon-Targeted Nanoparticles of Iridoid Glycoside for Improved Treatment of Induced Ulcerative Colitis.

AIM: Iridoid glycosides (IG) as the major active fraction of Syringa oblata Lindl. has a proven anti-inflammatory effect for ulcerative colitis (UC). However, its current commercial formulations are hampered by low bioavailability and unable to reach inflamed colon. To overcome the limitation, dual functional IG-loaded nanoparticles (DFNPs) were prepared to increase the residence time of IG in colon. The protective mechanism of DFNPs on DSS-induced colonic injury was evaluated in rats. MATERIALS AND METHODS: We prepared DFNPs using the oil-in-water emulsion method. PLGA was selected as sustained-release polymer, and ES100 and EL30D-55 as pH-responsive polymers. The morphology and size distribution of NPs were measured by SEM and DLS technique. To evaluate colon targeting of DFNPs, DiR, was encapsulated as a fluorescent probe into NPs. Fluorescent distribution of NPs were investigated. The therapeutic potential and in vivo transportation of NPs in gastrointestinal tract were evaluated in a colitis model. RESULTS: SEM images and zeta data indicated the successful preparation of DFNPs. This formulation exhibited high loading capacity. Drug release results suggested DFNPs released less than 20% at the first 6 h in simulated gastric fluid (pH1.2) and simulated small intestine fluid (pH6.8). A high amount of 84.7% sustained release from NPs in simulated colonic fluid (pH7.4) was beyond 24 h. DiR-loaded NPs demonstrated a much higher colon accumulation, suggesting effective targeting due to functionalization with pH and time-dependent polymers. DFNPs could significantly ameliorate the colonic damage by reducing DAI, macroscopic score, histological damage and cell apoptosis. Our results also proved that the potent anti-inflammatory effect of DFNPs is contributed by decrease of NADPH, gene expression of COX-2 and MMP-9 and the production of TNF-α, IL-17, IL-23 and PGE2. CONCLUSION: We confirm that DFNPs exert protective effects through inhibiting the inflammatory response, which could be developed as a potential colon-targeted system.

Perturbation of the lipid metabolism and intestinal inflammation in growing pigs with low birth weight is associated with the alterations of gut microbiota.

Low birth weight (LBW) is accompanied by metabolic dysfunction, chronic inflammation and gut microbiota perturbation in piglets during early life. Regulating gut microbiota structure can indirectly or directly affect gut health and the host's metabolism. However, whether gut microbiota dysbiosis impact lipid metabolism and inflammation progression in the LBW pigs later in life is unclear. In the present study, we investigated the role of gut microbiota on homeostasis in organisms using young pigs as a model. The plasma concentrations of High-density lipoproteins (HDLC) and pro-inflammatory cytokines such as Interleukin 6 (IL-6), Tumor necrosis factor alpha (TNF-α) and Interleukin 18 (IL-18) were increased in LBW pigs. The bacterial composition was modified dramatically in LBW group in association with an increase in propionate, butyrate and Short-chain fatty acids (SCFAs) in the ileal digesta. LBW impaired intestine results in damaged Fatty acid-binding protein 1 (FABP2) and Fatty acid-binding protein 4 (FABP4) expressions, and the inhibition of Free fatty acid receptor 1 (FFAR1), Free fatty acid receptor 2 (FFAR2) and G protein-coupled receptor 119 (GPR119) expressions, causing inefficient SCFAs absorption. Meanwhile, the physical barrier and chemical barrier related to functional gene expressions of Occludin, Claudin-1, Mucin 1 (MUC1) and Mucin 2 (MUC2) in both ileum and colon were decreased in the LBW pigs. The genera of Blautia, Bifidobacterium, Subdoligranulum and Coprococcus 3 in the ileum were correlated positively with lipid metabolic dysfunction and pro-inflammatory response in LBW pigs. Collectively, the gut microbiota is critical for perturbation of lipid metabolism and inflammatory progression in LBW pigs, which suggests the interventions for modulating bacterial communities may be therapeutically beneficial for metabolic diseases and chronic inflammation.

Improvement of Heterojunction Nanomaterials Photoelectrochemical Properties by Sol-Gel Synthesis and Hydrothermal Reaction.

The ZnO nanorod arrays (NRs)/CuAlO2 laminar crystal thin films (LFs)/Ni heterojunctions with delafossite structure were prepared by sol-gel synthesis for LFs and hydrothermal for NRs. X-ray diffraction analysis demonstrates the typical delafossite structure CuAlO2 and pure ZnO of R¯3m space group. Compared with a traditional CuAlO2/Ni laminar films (LFs) nanostructure, the photocurrent of this heterojunction nanostructure is significantly increased. Note that a significant blue-shift of the absorption edge and a favorable forward current to reverse current ratio at applied voltages of -0.75 to +2 V were observed in this heterojunction with the increase of Zn2+ ion concentration in the hydrothermal reaction. Moreover, the photoelectrochemical characteristics recorded under AM 1.5 illumination with 100 mW/cm2 light intensity at 0 V (vs. Ag/AgCl), while the highest photocurrent density arrive at 3.59 mA/cm2. This study demonstrates that heterojuction nanostructure, which is easily adapted to other chemical systems, is a promising technique for improving photoelectro-chemical properties of low-cost solar cells.

Jujuboside A attenuates norepinephrine-induced apoptosis of H9c2 cardiomyocytes by modulating MAPK and AKT signaling pathways.

Cardiomyocyte apoptosis is closely associated with the pathogenesis of heart failure. Jujuboside A (JUA) is a type of saponin isolated from the seeds of Zizyphus jujuba. In traditional Chinese medicine, it is believed that JUA possesses multiple biological effects, including antianxiety, antioxidant and anti­inflammatory activities. The present study aimed to evaluate the effects of JUA on norepinephrine (NE)­induced apoptosis of H9c2 cells and to investigate its underlying mechanisms. Rat H9c2 cardiomyocytes were pretreated with JUA and were then exposed to NE as an in vitro model of myocardial apoptosis. A cell viability assay, scanning electron microscopy, transmission electron microscopy, flow cytometry assay, acridine orange/ethidium bromide staining, reverse transcription­quantitative polymerase chain reaction and western blotting, all revealed that NE induced H9c2 cell apoptosis. The results demonstrated that NE inhibited cell viability, and enhanced cell damage and apoptosis of H9c2 cells. Conversely, pretreatment with JUA was able to reverse NE­induced decreased cell viability and increased apoptosis. Furthermore, JUA suppressed upregulation of the B­cell lymphoma 2 (Bcl­2)­associated X protein/Bcl­2 ratio, and inhibited the increased protein expression levels of cleaved caspase­3 and cleaved caspase­9 following NE exposure. However, the protein expression levels of cleaved caspase­12 and cleaved caspase­8 were not significantly altered following exposure to NE or JUA pretreatment. In addition, in JUA­pretreated cells, the protein expression levels of phosphorylated (p)­p38 and p­c­Jun N­terminal kinase were downregulated compared with in NE­treated cells. Furthermore, JUA regulated the activation of extracellular signal­regulated kinase (ERK) in NE­treated cells and significantly increased the expression levels of p­AKT. Taken together, these data suggested that JUA may protect against NE­induced apoptosis of cardiomyocytes via modulation of the mitogen­activated protein kinase and AKT signaling pathways. Therefore, JUA may be considered a potential therapeutic strategy for the treatment of heart disease.

Distribution of yeast isolates from invasive infections and their in vitro susceptibility to antifungal agents: evidence from 299 cases in a 3-year (2010 to 2012) surveillance study.

Invasive yeast infections cause significant morbidity and mortality. Surveillance for the infection is necessary to detect trends in species distribution and antifungal resistance. We performed this retrospective study of yeast infection at Jinling Hospital, Nanjing in China, from year of 2010 to 2012. A total of 341 yeast isolates were obtained from patients with invasive infections in the period. Among these isolates, Candida spp. comprised of the highest percentage of yeast strains (91.8 %), followed by Cryptococcus neoformans (5.9 %) and other non-Candida yeast strains (2.3 %). Bloodstream isolates made up 41.3 % of yeast strains and the isolates from CVC made up 17.3 %. Among Candida spp., C. albicans was the most common species identified from non-blood clinical specimens (42.9 %), but appeared in only 20.8 % of blood isolates (P < 0.001). C. tropicalis was the most prevalent Candida species in the blood samples (28.5 %). Candida spp. was mainly isolated from specimens of the ICU patients, while C. neoformans was mainly isolated from specimens in medical wards. Resistance to FLC occurred in 3.7 % of C. albicans, 9.9 % of C. tropicalis, 74.0 % of C. glabrata, and 4.4 % of C. parapsilosis. Most (>92 %) isolates of C. albicans, C. tropicalis, C. parapsilosis, and C. neoformans strains were susceptible to VRC; However, 26.7 % of isolates of C. glabrata were VRC resistant.

Fluoxetine protects against monocrotaline-induced pulmonary arterial remodeling by inhibition of hypoxia-inducible factor-1α and vascular endothelial growth factor.

The selective serotonin re-uptake inhibitor fluoxetine has been shown to protect against monocrotaline (MCT)-induced pulmonary hypertension in rats. To investigate the possible role of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in mediating this protective effect, MCT-treated rats were administered fluoxetine by gavage, at doses of 2 mg/kg body mass or 10 mg/kg once daily for 3 weeks. Changes in pulmonary hemodynamic parameters, pulmonary artery morphologies, and expressions of HIF-1α and VEGF were assessed. Fluoxetine at the 10 mg/kg dose, but not at the 2 mg/kg dose, attenuated the effects of MCT on pulmonary artery pressure, right ventricle index, and medial wall thickness. In addition, 10 mg/kg fluoxetine mitigated the MCT-induced up-regulation of HIF-1α and VEGF protein and reactive oxygen species (ROS) in the lungs. This dosage also decreased pERK1/2 levels and inhibited proliferation of pulmonary arterial smooth muscle cells in MCT-treated rats. In conclusion, fluoxetine can protect against MCT-induced pulmonary arterial remodeling, which linked to reduced ROS generation and decreased HIF-1α and VEGF protein levels via the ERK1/2 phosphorylation pathway.

Downregulation of osteopontin is associated with fluoxetine amelioration of monocrotaline-induced pulmonary inflammation and vascular remodelling.

1. Osteopontin (OPN) has emerged as a key factor in inflammatory activation and cardiovascular remodelling. The aim of the present study was to investigate the involvement of OPN in fluoxetine amelioration of monocrotaline (MCT)-induced pulmonary inflammation and vascular remodelling in rats. 2. Wistar rats were divided into control, MCT and two fluoxetine-treated groups. Pulmonary arterial hypertension (PAH) was induced by a single injection of MCT (60 mg/kg, i.p.). Fluoxetine (2 and 10 mg/kg) was administered via the intragastric route once a day for 21 days. On Day 22, pulmonary haemodynamic measurements were undertaken, followed by ELISA, western blotting and immunohistochemistry. 3. Monocrotaline caused pulmonary inflammation and vascular remodelling and significantly enhanced OPN expression in the plasma, lungs and pulmonary arteries. Fluoxetine decreased pulmonary arterial pressure and ameliorated pulmonary inflammation and pulmonary vascular remodelling. At 10 mg/kg, fluoxetine significantly inhibited MCT-induced increases in the expression of serotonin transporter (SERT) and phosphorylated extracellular signal-regulated kinase 1/2 and downregulated the expression of OPN, macrophage inflammatory protein-1ß and matrix metalloproteinase 2/tissue inhibitor of metalloproteinase 2. Although 2 mg/kg fluoxetine tended to ameliorate some MCT-induced changes in the lung, the differences did not always reach statistical significance. Linear regression analysis showed that there was a positive correlation between plasma OPN concentrations and mean pulmonary arterial pressure, as well as percentage medial wall thickness and percentage wall area in the pulmonary artery. 4. In conclusion, the amelioration by fluoxetine of MCT-induced pulmonary inflammation and vascular remodelling is associated with downregulation of OPN expression in rats.

Fluoxetine inhibited extracellular matrix of pulmonary artery and inflammation of lungs in monocrotaline-treated rats.

AIM: To investigate the effects of the selective serotonin reuptake inhibitor (SSRI) fluoxetine on extracellular matrix (ECM) remodeling of the pulmonary artery and inflammation of the lungs in pulmonary arterial hypertension (PAH) induced by monocrotaline in rats. METHODS: MCT-induced chronic PAH was established in Wistar rats. After treatment with fluoxetine for 3 weeks, pulmonary hemodynamic measurement and morphological investigation of lung tissues were undertaken. The main components of the ECM, elastin and collagen, were detected using Van Gieson stain and Orcein stain, respectively, or using Victoria-ponceau's double stain. The ECM proteolytic enzymes matrix metalloproteinase (MMP)-2 and MMP-9, and the tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2, were detected by Western blot. Inflammation of lung tissue was assayed using lung morphology and inflammatory cytokine expression. RESULTS: Fluoxetine (2 and 10 mg/kg) significantly inhibited MCT-induced PAH, attenuated pulmonary arterial muscularization and ECM remodeling, and decreased MMP/TIMP expression. Fluoxetine also suppressed inflammatory responses in lung tissue and inhibited the expression of the inflammatory cytokines interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), monocyte chemotactic protein (MCP-1) and intercellular adhesion molecule-1 (ICAM-1). CONCLUSION: Fluoxetine inhibited MCT-induced ECM remodeling of the pulmonary artery and inflammation of lung tissue. These effects were related to its inhibition on MMPs/TIMPs and cytokine productions.

Bis(µ-pyridine-2,4-dicarboxyl-ato)-κN,O:O;κO:N,O-bis-[triaqua-magnesium(II)].

In the title centrosymmetric Mg(II) complex, [Mg(2)(C(7)H(3)NO(4))(2)(H(2)O)(6)], each Mg cation is N,O-chelated by a pyridine-2,4-dicarboxyl-ate dianion and is coordinated by three water mol-ecules. A carboxyl-ate O atom from the neighboring pyridine-2,4-dicarboxyl-ate dianion bridges the Mg cation to complete the MgNO(5) distorted octa-hedral coordination geometry. The dinuclear complex mol-ecules are linked by inter-molecular O-H⋯O hydrogen bonding, forming a three-dimensional supra-molecular structure.

[Study on the interaction between brucine and bovine serum albumin].

The interaction between brucine and bovine serum albumin (BSA) was investigated using fluorescence spectroscopy (FS) and ultraviolet spectroscopy (UV). The experimental results showed that the brucine quenches the inner fluorescence by forming a brucine-BSA complex. It was found that both static quenching and non-radiation energy transfer were the main reasons for the fluorescence quenching. The apparent binding constants (K(A)) between brucine and BSA were 6. 3 x 10(3) (27 degrees C) and 7.7 x 10(3) (37 degrees C), and the binding sites (n) were 0.94 (27 degrees C) and 0.97 (37 degrees C). According to the Förster theory of non-radiation energy transfer, the binding distances (r) were also obtained. The process of binding was a spontaneous molecular interaction in which entropy increased and Gibbs free energy decreased, indicating that the interaction between brucine and BSA was driven mainly by hydrophobic force.