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Purpose: To study the effect of individualized treatment strategy based on imaging evaluation in patients with rheumatoid arthritis (RA). Methods: Eighty patients with RA of the wrist treated in the Second Affiliated Hospital of Nanjing Medical University, China from January 2018 to December 2022 were assigned to control and study groups. Conventional methods were used for treating control subjects, based on RA laboratory index results, while the study group received individualized treatment based on RA laboratory index results and results of imaging evaluation. Before and after treatment, serum levels of rheumatoid factor (RF) and C-reactive protein (CRP) were assayed using immunoturbidimetry. Erythrocyte sedimentation rate (ESR) was determined by Wei method. Imaging examination - ultrasound or magnetic resonance imaging (MRI) - was carried out in study group before and after treatment. Disease activity score 28 (DAS28) and score on the visual analogue scale (VAS) were evaluated before and after treatment, and the curative effect in the two groups was compared based on curative effect evaluation. Results: In both groups, post-treatment values of RF, CRP and ESR were lower than the corresponding pre-treatment levels, but were significantly smaller in study group (p < 0.05). The DAS28 and VAS scores of the two groups after treatment were significantly lower (p < 0.05) than the pret-reatment levels, but the DAS28 and VAS scores were significantly lower in study group (p < 0.05). Treatment efficacy in study group (95.0 %) was significantly higher than in control patients (77.5 %, p = 0.0476). The results of imaging indicators showed significantly reduced post-treatment synovial thickness and joint effusion in study group patients when compared with control patients (p < 0.01). Conclusion: Individualized treatment strategy for RA patients based on imaging results enhances curative effectiveness, reduces disease activity, relieves pain, and improves the quality of life of patients. [ABSTRACT FROM AUTHOR]

Four new ent -kaurane diterpenoid maizediterpenes A-D (1 – 4), along with fourteen known compounds were isolated from the roots of Zea mays (maize). Compounds 7 , 15 , 16 were isolated from this genus for the first time. The planar structures of the new compounds were determined by extensive analysis of their NMR and HR-ESI-MS spectra, and the absolute configurations were established on the basis of specific rotation in association with calculated ECD spectra. Compounds 2 , 6 and 18 showed significant antiproliferative effects against five human cancer cell lines (A549, MDA-MB-231, SK-Hep-1, SNU638, HCT116) with IC 50 values ranging from 1.99 ± 0.41 μM to 15.18 ± 1.17 μM. Unlabelled Image [ABSTRACT FROM AUTHOR]

In this study, a new flavonolignan vernicilignan A was isolated from Toxicodendron vernicifluum. The neuroprotective effects of this compound against H 2 O 2 induced cell injury in SH-SY5Y cells were evaluated by MTT assay and LDH release assay. Vernicilignan A dose-dependently attenuated the cell injury and LDH release induced by H 2 O 2 in SH-SY5Y cells. Further study indicated that vernicilignan A reduced cell apoptosis caused by H 2 O 2 treatment via regulation of some apoptotic related proteins including Bax, Bcl-2, caspase 3 and caspase 9. Also, vernicilignan A increase the cell viability of H 2 O 2 treated cells via the activation of Akt and GSK3β. Base on the findings, vernicilignan A exhibited neuroprotective effects through the activation of PI3K/Akt signaling and inhibition of mitochondria apoptosis pathway. Vernicilignan A might be a promising therapeutic agent for oxidative stress induced neurodegenerative diseases. Unlabelled Image [ABSTRACT FROM AUTHOR]

[Display omitted] • Three series of novel 6-(imidazo[1,2-a] pyridin-6-yl)-quinazolin-4(3H)-one derivatives were designed and synthesized. • Compound 12d exhibited potent anti-tumor activity in vitro and in vivo. • Compound 12d induced mitotic catastrophe and cell apoptosis in SH-SY5Y cells. • Compound 12d was identified as a novel dual ROR1/Aurora kinase inhibitor. ROR1 and Aurora kinase were overexpressed in various cancers and essential for cell proliferation, survive and metastasis. Pharmaceutical inhibition of ROR1 and Aurora kinase abrogated the activation of downstream signaling and induced cancer cell apoptosis. Hence, ROR1 and Aurora kinase considered as attractive therapeutic targets for the development of anticancer drugs. In the present work, three series of novel 6-(imidazo[1,2- a ] pyridin-6-yl)-quinazolin-4(3 H)-one derivatives were designed and synthesized via bioisosterism and scaffold-hopping strategies guided by FLF-13, an Aurora kinase inhibitor we discovered earlier. Most of compounds in series 2 and series 3 showed submicromolar to nanomolar inhibitory activity against multiple cancer cell lines. More importantly, compounds 12d and 12f in series 3 showed nanomolar inhibitory activity against all test cancer cells. The most promising compound 12d exhibited potent inhibitory activity against Aurora A and Aurora B with IC 50 values of 84.41 nM and 14.09 nM, respectively. Accordingly, compounds 12d induced G2/M phase cell cycle arrest at 24 h and polyploidy at 48 h. It's worth noting that 12d also displayed inhibitory activity against ROR1 and induce cell apoptosis. Furthermore, 12d could significantly inhibit the tumor growth in SH-SY5Y xenograft model with tumor growth inhibitory rate (IR) up to 46.31 % at 10 mg/kg and 52.66 % at 20 mg/kg. Overall, our data suggested that 12d might serve as a promising candidate for the development of therapeutic agents for cancers with aberrant expression of ROR1 and Aurora kinases by simultaneously targeting ROR1 and Aurora kinase. [ABSTRACT FROM AUTHOR]

[Display omitted] • A series of novel structurally optimized 6-(2-amino-1 H -benzo[ d ]imidazole-6-yl) -quinazolin-4(3 H)-one derivatives were designed and synthesized. • Compound 9a exhibited the most potent antiproliferation activity with IC 50 values of 0.83, 0.26 and 1.02 μM against A549, HCC827 and H1975 cells, respectively. • 9a markedly inhibited the Aurora A and PI3Kα kinase activities with an IC 50 values of 10.19 nM and 13.12 nM. • 9a remarkably down-regulated the p-PI3K, p-Aurora A and BRD4 in a dose-dependent manner in HCC827 cells, which suggested 9a might be a potential multi-targeted inhibitor. • 9a significantly attenuated HCC827 cell growth through promoting intrinsic apoptosis and G2/M phase arrests. Aurora A (Aurora kinase A), a critical regulator of cell mitosis, is frequently overexpressed in many malignant cancers, and has been considered as a promising drug target for cancer therapy. Likewise, Phosphatidylinositol 3-kinase alpha (PI3Kα) is also regarded as one of the most important targets in cancer therapy by mediating the cell growth and angiogenesis of various human cancers. In addition, Bromodomain-containing protein 4 (BRD4) modulates oncogene expressions of Myc, Aurora kinase and various RTKs. Recently, accumulating evidences indicated that hyperactivated or abnormally expressed Aurora A, PI3Kα or BRD4 are closely associated with drug resistance and poor prognosis of non-small cell lung cancer (NSCLC). Hence, simultaneous inhibition of Aurora A, PI3Kα, and BRD4 is expected to be a new strategy for NSCLC therapy. In this study, we performed further structure optimization of 6-(2-amino-1 H -benzo[ d ]imidazole-6-yl)-quinazolin-4(3 H) -one based on previous study to obtain a series of derivatives for discovering potential Aurora A, PI3Kα and BRD4 multi-targeted inhibitors. MTT assay showed that most of the newly synthesized compounds exhibited an evident anticancer activity against the NSCLC cells. Among them, the IC 50 values of the most potent compound 9a were 0.83, 0.26 and 1.02 μM against A549, HCC827 and H1975 cells, respectively. In addition, 9a markedly inhibited the Aurora A and PI3Kα kinase activities with IC 50 values of 10.19 nM and 13.12 nM. Compound 9a induced G2/M phase arrests and apoptosis of HCC827 cells by simultaneous inhibition of Aurora A/PI3K/ BRD4 signaling pathways. Collectively, our studies suggested that 9a might be a potential multi-targeted inhibitor for NSCLC therapy. [ABSTRACT FROM AUTHOR]

Coumalamide derivatives are one of 2-pyrones derivatives, exerting multifunctional bioactivity. An array of coumalamide derivatives have been developed and presented good antiproliferative properties on cancer cells. However, the synthesis of 5-substituted coumalamide derivatives has not yet been published. Resistance to chemotherapeutic drugs is a major obstacle in hepatocellular carcinoma therapy. Recent evidence suggests that overexpression of constitutively active Akt confers on cancer cells resistance to chemotherapy. In this study, we report the synthesis and biological evaluation of a novel N -substituted coumalamide derivative (NSCA-1). The results indicated that NSCA-1 exerts synergistic cytotoxicity with Adriamycin in HepG2/ADR (HepG2/adriamycin) cells. Furthermore, both of the Akt kinase activity and phosphorylated Akt (Ser473) were found to be inhibited by NSCA-1 and subsequently resulting in decreased phosphorylation of GSK-3β. The intracellular accumulation of Adriamycin was also boosted by NSCA-1 via reducing the expression of p-gp. In addition, we found that combined treatment with NSCA-1 enhance cell apoptosis induced by Adriamycin via p53-dependant apoptotic pathway. [ABSTRACT FROM AUTHOR]

The ent-kaurane diterpenoid enriched fraction (EDEF) of maize root was isolated and purified, and 10 compounds, including 4 ent-kaurane diterpenoids, were isolated and identified. We evaluated their neuroprotective properties in vitro for the first time using an H 2 O 2 -induced oxidative damage model in SH-SY5Y cells. The results showed that pretreatment with maizediterpene D, a new ent-kaurane diterpenoid isolated from the EDEF, significantly attenuated H 2 O 2 -induced apoptosis by improving cell survival, reducing ROS production and increasing mitochondrial membrane potential. Mechanistically, the neuroprotective effect of maizediterpene D was confirmed to be related to the dual activation of IGF-1R and BDNF/TrkB crosstalk pathways. Our findings suggest that the EDEF and its active constituent maizediterpene D had good neuroprotective properties and could serve as potential candidates for the development of therapeutic drugs for oxidative stress-related diseases. [Display omitted] • EDEF and Maizediterpene D were isolated from maize roots. • EDEF showed good antioxidant activity against H 2 O 2 induced oxidative stress. • D showed better cytoprotective activity against H 2 O 2 triggered oxidative stress. • M-D attenuated H 2 O 2 induced oxidative stress by BDNF/TrkB and BDNF/TrkB crosstalk pathways [ABSTRACT FROM AUTHOR]

Eriocaulon sieboldianum (Sieb. & Zucc. ex Steud.), a genus of Eriocaulon in the Eriocaulaceae family, is an edible and medicinal plant used in traditional Chinese medicine. It was processed into healthcare beverages for expelling wind-heat, protecting eyes, and reducing blood fat. Also, it has been used with other herbs as Traditional Chinese herbal compound to treat cancer as adjuvants in tumor therapy in China. However, the active fractions and precise cellular mechanisms of E. sieboldianum extract remain to be illustrated. The goal of this study was to investigate the effects of the active fraction of E. sieboldianum on the growth of K562 cells and understand the possible mechanisms of its action. Our findings suggested that the fraction E3 of E. sieboldianum could effectively inhibit the activity of Aurora kinase and induce apoptosis via blocking cell cycle, up-regulating the expression of proapoptotic proteins including p53 and Bax and reducing the expression of Bcl-2. The levels of Cytochrome C, cleaved caspase-9, cleaved caspase-3 and cleaved PARP were also found to be increased after treatment with fraction E3 of E. sieboldianum . This study could improve the development of E. sieboldianum and raise its application value in cancer adjuvant therapy. Considering it is both a dietary supplement and a traditional Chinese herbal medicine which exhibits anticancer activities, it can be developed into functional food. [ABSTRACT FROM AUTHOR]

Eukaryotic cells store lipids in membrane-encased droplets. The entomopathogenic fungus, Beauveria bassiana, initiates infection via attachment of its spores to the epicuticle or waxy layer of target insects, degrading and assimilating host surface hydrocarbons, carbohydrates and proteins. Caleosins are components of the proteinaceous coat of lipid droplets and a single B. bassiana caleosin homologue, Bbcal1, was identified and characterized. The BbCal1 sequence contained an EF-hand Ca2+ binding domain and potential hydrophobic stretches similar to those found in plant caleosins, along with a proline knot motif defined by only two proline residues. Targeted gene inactivation of Bbcal1 did not appear to affect spore germination, growth on lipid substrates or stress response, but changes in lipid, vacuole and endoplasmic reticulum/multilamellar vesicle-like structures, and altered cellular lipid profiles were seen in conidia grown on a variety of substrates including potato dextrose agar, olive oil, glyceride trioleate, oleic acid and the alkane, C16. The Bbcal1 mutant produced more compact assemblages of conidia, displayed a reduced and delayed spore dispersal phenotype, and showed decreased virulence in insect bioassays using the greater wax moth, Galleria mellonella. Our data indicate novel functions for caleosins in fungal virulence, spore development and the trafficking and/or turnover of lipid-related structures. [ABSTRACT FROM AUTHOR]

The photocatalytic activity of TiO 2 can be mainly improved from three approaches: (1) enhancing surface energy; (2) increasing availability of visible light and (3) improving the separation efficiency of photo-induced electrons and holes. Here, we report a one-step route to obtain nitrogen (N) doped TiO 2 sheets with dominant {001} facets by a hydrothermal process. The XRD patterns confirm the better crystallinity. XPS spectrums show nitrogen acting as interstitial N or an O–Ti–N structure in TiO 2 sheets. Compared with that of TiO 2 sheets, the N doped TiO 2 sheets not only absorb visible light, but also have a large percentage of high reactive {001} facets, so the photocatalytic activities are greatly enhanced, as confirmed by the decomposition of methylene orange. [ABSTRACT FROM AUTHOR]

Abstract: White-line-inducing principle (WLIP), a lipodepsipeptide isolated from Lasiosphaera fenzlii Reich., which is one of the puffballs, for the first time, has been reported to exhibit anti-microbial activity. However, there are no reports regarding the anti-tumor effects of WLIP. In this study, we reported the anti-cancer effects of WLIP on K562 cells, and its potential effect on the PPAR-γ activation pathway. The obtained results showed that WLIP exerted strong anti-proliferative effect on K562 cells. Moreover, WLIP was found to increase apoptosis and induce G0/Gl arrest. Modeling results from the Surflex-Dock program suggested that PPAR-γ might be the potential anti-tumor target of WLIP, which was confirmed by the experiments that WLIP increased the activity in luciferase reporter assay and the expression of PPAR-γ in Western blot. Besides, WLIP was able to down-regulate the expression of Bcl-xL, Cyclin-D1 in K562 cells. In summary, our novel observations suggested that WLIP might have a potential implication in cancer prevention and treatment, and also showed for the first time that the anti-tumor effect of WLIP might be mediated through modulation of the PPAR-γ activation pathway. [Copyright &y& Elsevier]

Highlights: [•] The mechanisms of CF3CHFCF3/CF3CF2CHF2 with halogen are studied theoretically. [•] The reactivity decreases in the order of F>Cl>Br. [•] The dynamics properties are calculated by dual-level (X//Y) direct dynamics methods. [Copyright &y& Elsevier]

Background: Adult and larval mosquitoes regulate food digestion in their gut with trypsin modulating oostatic factor (TMOF), a decapeptide hormone synthesized by the ovaries and the neuroendocrine system. TMOF is currently being developed as a mosquitocide, however, delivery of the peptide to the mosquito remains a significant challenge. Entomopathogenic fungi offer a means for targeting mosquitoes with TMOF. Findings: The efficacy of wild type and transgenic Beauveria bassiana strains expressing Aedes aegypti TMOF (Bb-Aa1) were evaluated against larvae and sugar- and blood-fed adult Anopheles gambiae mosquitoes using insect bioassays. Bb-Aa1 displayed increased virulence against larvae, and sugar and blood fed adult A. gambiae when compared to the wild type parent strain. Median lethal dose (LD50) values decreased by ∼20% for larvae, and ∼40% for both sugar and blood-fed mosquitoes using Bb-Aa1 relative to the wild type parent. Median lethal time (LT50) values were lower for blood-fed compared to sugar-fed mosquitoes in infections with both wild type and Bb-Aa1. However, infection using Bb-Aa1 resulted in 15% to 25% reduction in LT50 values for sugar- and blood fed mosquitoes, and ∼27% for larvae, respectively, relative to the wild type parent. In addition, infection with Bb-Aa1 resulted in a dramatic reduction in fecundity of the target mosquitoes. Conclusions: B. bassiana expressing Ae. aegypti TMOF exhibited increased virulence against A. gambiae compared to the wild type strain. These data expand the range and utility of entomopathogenic fungi expressing mosquito-specific molecules to improve their biological control activities against mosquito vectors of disease. [ABSTRACT FROM AUTHOR]

Abstract: Fe3O4/SiO2/TiO2 nanocomposites with well-defined core-shell structures were successfully prepared by a facile hydrothermal synthetic method for titania coating on Fe3O4/SiO2 magnetic core. The as-prepared Fe3O4/SiO2/TiO2 composite particles were characterized by X-ray diffraction (XRD),transmission electron microscopy (TEM),Fourier transform infrared spectroscopy (FT-IR). The results showed that Fe3O4/SiO2/TiO2 was well crystallized at 140°C with well-defined core-shell structures. Fe3O4/SiO2/TiO2 nanocomposites as well as pure TiO2 showed good photocatalytic performance in the decolorization of methyl orange aqueous solution. Magnetic core coated by SiO2 and TiO2 layer still retained the good magnetic properties (Ms:3.04emug-1) to facilitate catalyst recovery using external magnetic field. [Copyright &y& Elsevier]

Abstract: The entomopathogenic fungus Beauveria bassiana displays a broad insect host range and serves as a model for examining host-pathogen interactions. Rapid construction and screening of random-insertion mutants of B. bassiana provides a powerful tool to dissect the molecular mechanisms of fungal virulence. LiAc/DMSO treated B. bassiana blastospores were found to be highly competent to transformation using linear DNA and a polyethylene glycol-based method. Selection on cellophane-layered Czapek-Dox agar at a lowered pH (from 7.5 to 6.3) greatly decreased background growth of non-transformed cells and improved screening of transformants. Optimization of the protocol using integration of the bar phosphinothricin resistance gene resulted in high transformation rates (200–250transformants/μgDNA/108 cells). A collection of ∼4000 insertion mutants was examined via high-throughput screens for hydrocarbon utilization. One mutant was isolated that grew poorly on both n-hexadecane and tributyrin. The random insertion site was mapped to a gene that displayed homology to vitamin H (biotin)/tartrate transporters. Insect bioassays using Galleria mellonella as the target host revealed decreased virulence in the mutant. This system provides a simple and rapid method for the generation and screening of insertion mutants and should expand our ability to genetically analyze the B. bassiana lifestyle. [ABSTRACT FROM AUTHOR]

Abstract: Insect cuticles consist mainly of interlinked networks of proteins and the highly insoluble polysaccharide, chitin. Entomopathogenic fungi, such as Beauveria bassiana, invade insects by direct penetration of host cuticles via the action of diverse hydrolases including proteases and chitinases coupled to mechanical pressure. In order to better target cuticle protein-chitin structures and accelerate penetration speed, a hybrid protease (CDEP-BmChBD) was constructed by fusion of a chitin binding domain BmChBD from Bombyx mori chitinase to the C-terminal of CDEP-1, a subtilisin-like protease from B. bassiana. Compared to the wild-type, the hybrid protease was able to bind chitin and released greater amounts of peptides/proteins from insect cuticles. The insecticidal activity of B. bassiana was enhanced by including proteases, CDEP-1 or CDEP:BmChBD produced in Pichia pastoris, as an additive, however, the augment effect of CDEP:BmChBD was significantly higher than that of CDEP-1. Expression of the hybrid protease in B. bassiana also significantly increased fungal virulence compared to wild-type and strains overexpressing the native protease. These results demonstrate that rational design virulence factor is a potential strategy for strain improvement by genetic engineering. [ABSTRACT FROM AUTHOR]

Abstract: Ba0.7−x Sr0.3Mn x TiO3 (x =0, 0.025, 0.05) thin films have been prepared on copper foils using sol–gel method. The films were processed in an atmosphere with low oxygen pressure so that the substrate oxidation is avoided and the formation of the perovskite phase is allowed. XRD and SEM results showed that Mn doping enhanced the crystallization of the perovskite phase in the films. The Mn substitution prevents the reduction of Ti4+ to Ti3+, which is supported by XPS analysis. The Ba0.7−x Sr0.3Mn x TiO3 film with x =0.025 (BSMT25) exhibits preferred dielectric behavior and a lower leakage current density among the three thin films. The dielectric constant and loss of the BSMT25 film are 1213.5 and 0.065 at 1MHz and around zero field, which are mostly desired for embedded capacitor applications. The mechanism of Mn doping on improving the electrical properties of barium strontium titanate (BST) thin films was investigated. [Copyright &y& Elsevier]

A new binary cocrystal [C26H20N6][C14H10O4S2]1 has been synthesized and characterized by IR, elemental analysis, TG technique and X-ray crystallography with N',N'-bis[1-(pyridin-4-yl)methylidene]benzil dihydrazone and 2,2-dithiosalicylic acid. Analysis of the crystal packing of 1 suggests that there are classical intermolecular O-H···N hydrogen bonds between acid and base components and obvious six types of C-H···π interactions involving aromatic rings of adjacent molecules in the crystal packing. The luminescent properties of the compound 1 were investigated. [ABSTRACT FROM AUTHOR]

Beauveria bassiana is a filamentous ascomycete that is pathogenic towards a broad host range of insect targets and is increasingly serving as a model for examining fungal development and host-pathogen interactions. B. bassiana displays a prohibitive level of resistance against many current fungal and/or yeast selection markers including hygromycin, neomycin, and zeocin. A genetic transformation system for B. bassiana based upon the use of a sulfonylurea resistance cassette derived from the Magnaporthe grisea, acetolactate synthase gene ( sur) was developed. The transformation frequency ranged from 100–150 transformants per microgram DNA/108 cells and Southern blot analysis indicated that the plasmid vector was randomly integrated into the genome of B. bassiana. In addition, a construct bearing the sur gene and the enhanced green fluorescent protein gene egfp as a visual marker was used to successfully transform B. bassiana. Over 95% of the transformants retained the sulfonylurea resistance phenotype under non-selective conditions. The described transformation method increases opportunities for the genetic manipulation of B. bassiana. [ABSTRACT FROM AUTHOR]

Two new organic-inorganic composite sandwich-type arsenotungstates [H2dap]6H8[Ni4(H2O)2(B-α-AsW9O34)2]2 · 33H2O (1) and {[Ni(dap)2(H2O)]2[Ni(dap)2]2[Ni4(Hdap)2(B-α-AsW9O34)2]} · 4H2O (2) (dap = 1,2-diaminopropane) have been hydrothermally synthesized by reaction of Na8[A-α-HAsW9O34] · 11H2O with NiCl2 · 6H2O in the presence of 1,2-diaminopropane and characterized by elemental analysis, IR spectra, X-ray single-crystal diffraction, and thermogravimetric analysis. 1 crystallizes in the triclinic P1 space group with a = 16.351(6) Å, b = 16.423(6) Å, c = 19.894(7) Å, α = 110.630(6)°, β = 92.684(7)°, γ =104.946(7)°, V = 4774(3) Å3, Z = 1, GOOF = 1.033, R1 = 0.0517, wR2 = 0.1086. 2 also crystallizes in the triclinic P1 space group with a = 13.305(4) Å, b = 13.882(4) Å, c = 17.031(5) Å, α = 68.109(5)°, β = 71.511(4)°, γ = 88.407(5)°, V = 2753.5(14) Å3, Z = 1, GOOF = 1.051, R1 = 0.0491, wR2 = 0.1150. Notably, 1 is a discrete structure, composed of two tetra-NiII substituted sandwich-type polyoxoanions [Ni4(H2O)2(B-α-AsW9O34)2]10- with different spatial orientation, whereas 2 displays a organic-inorganic composite 2-D sheet architecture constructed by tetra-NiII sandwiched [Ni4(H2O)2(B-α-AsW9O34)2]10- units by means of [Ni(dap)2]2+ bridges. Some previously reported transition-metal-substituted sandwich-type polyoxotungstates have been summarized. [ABSTRACT FROM AUTHOR]

Abstract: Ba0.7Sr0.3(Ti1 − x Zr x )O3 (x =0, 0.1, 0.2) (BSZT) thin films have been prepared on copper foils using sol–gel method. The films were annealed in an atmosphere with low oxygen pressure so that the substrate oxidation was avoided and the formation of the perovskite phase was allowed. The X-ray diffraction results show a stable polycrystalline perovskite phase, with the diffraction peaks of the BSZT films shifting toward the smaller 2θ with increasing Zr content. Scanning electron microscopy images show that the grain size of the BSZT thin films decreases with increasing Zr content. High resolution transmission electron microscopy shows the clear lattice and domain structure in the film. The dielectric peaks of the BSZT thin films broaden with increasing Zr content. Leakage current density of Ba0.7Sr0.3(Ti1 − x Zr x )O3 (x =0.1) thin film is the lowest over the whole applied voltage. [Copyright &y& Elsevier]

Abstract: Ba0.5Sr0.5TiO3 (BST) thin films were deposited on copper foils via sol–gel method with La2O3 as a buffer layer. The films were processed in almost inert atmosphere so that the substrate oxidation was avoided while allowing the perovskite film phase to crystallize. The existence of a La2O3 buffer layer between the BST thin film and Cu foil improved the dielectric constant and reduced the leakage current density of the BST thin film. Meanwhile, the BST thin film exhibited ferroelectric character at room temperature, which was contrast to the para-electric behavior of the film without the buffer layer. Effects of La2O3 buffer layer on the crystallizability and microstructure of BST thin films were also investigated. [Copyright &y& Elsevier]

Abstract: Beauveria bassiana chitinase (Bbchit1) is an important cuticle degrading enzyme involved in pathogenesis of fungi against insect. To obtain enough active chitinase for performing in vitro functional analysis, Bbchit1 gene was expressed in Escherichia coli and Pichia pastoris, respectively. The high-level production of recombinant Bbchit1 was detected in E. coli expression system, however mainly located in inclusion bodies. Refolding of solubilized inclusion body proteins was achieved by dialysis. In P. pastoris expression system, Bbchit1 was secreted into the culture medium under the induction of methanol. Active Bbchit1 was purified to near 90% purity from culture medium by desalting chromatography and anion exchange chromatography. The yield of Bbchit1 produced by P. pastoris was estimated at 153mg/L, significantly higher than that of the refolded Bbchit1 from E. coli inclusion bodies (50mg/L). Additionally, the specific activity of Bbchit1 from P. pastoris was also higher than that from E. coli (3.9U/mg versus 2.8U/mg). These results indicated P. pastoris was a convenient expression system for the efficient production of Bbchit1. [Copyright &y& Elsevier]

Background: To obtain a more detailed description of the stress-free state of the intestinal wall, longitudinal residual strain measurements are needed. Furthermore, data on longitudinal stressstrain relations in visceral organs are scarce. The present study aims to investigate the longitudinal residual strain and the longitudinal stress-strain relationship in the rat small intestine. Methods: The longitudinal zero-stress state was obtained by cutting tissue strips parallel to the longitudinal axis of the intestine. The longitudinal residual stress was characterized by a bending angle (unit: degrees per unit length and positive when bending outwards). Residual strain was computed from the change in dimensions between the zero-stress state and the no-load state. Longitudinal stresses and strains were computed from stretch experiments in the distal ileum at luminal pressures ranging from 0-4 cmH2O. Results: Large morphometric variations were found between the duodenum and ileum with the largest wall thickness and wall area in the duodenum and the largest inner circumference and luminal area in the distal ileum (p < 0.001). The bending angle did not differ between the duodenum and ileum (p > 0.5). The longitudinal residual strain was tensile at the serosal surface and compressive at the mucosal surface. Hence, the neutral axis was approximately in the mid-wall. The longitudinal residual strain and the bending angle was not uniform around the intestinal circumference and had the highest values on the mesenteric sides (p < 0.001). The stress-strain curves fitted well to the mono-exponential function with determination coefficients above 0.96. The a constant increased with the pressure, indicating the intestinal wall became stiffer in longitudinal direction when pressurized. Conclusion: Large longitudinal residual strains reside in the small intestine and showed circumferential variation. This indicates that the tissue is not uniform and cannot be treated as a homogenous material. The longitudinal stiffness of the intestinal wall increased with luminal pressure. Longitudinal residual strains must be taken into account in studies of gastrointestinal biomechanical properties. [ABSTRACT FROM AUTHOR]

The topic of this study is to obtain the constitutive equations for two layers in the oesophagus from inflation experiment of each layer in the in vivo state and to calculate the corresponding stress distribution referenced to a new stress-free state for multi-layered tissue. The oesophagus is treated as a two-layered structure consisting of an inner submucosa layer and an outer muscle layer. An anisotropic exponential pseudo-strain energy density function is used as the constitutive equation to fit the experimental loading curve and for the calculation of the stress distribution in each layer. Significant differences in the constitutive parameters and zero-stress parameter were found between the submucosa layer and the muscle layer. The stress in the submucosa layer was higher than that in the muscle layer and intact (non-separated) wall under the same loading conditions. The submucosa layer was stiffer than the muscle layer and the intact wall. The zero-stress state of the intact oesophagus and the zero-stress state after separation were used as a reference to compare the stress–strain distributions. The residual strain was discontinuous when using the zero-stress state after separation as a reference. Furthermore, the circumferential stress when using the zero-stress state of the intact wall as a reference was about 100 times higher than that referenced to the zero-stress state after separation. Hence, it is important to use the zero-stress state obtained after the layer separation as the stress-free state in the study of multi-layered tissue. [Copyright &y& Elsevier]

[Display omitted] • Bbetfs and Bbetfdh are involved in growth. • Bbetfs and Bbetfdh participate in conidiation and conidial germination. • Bbetfs and Bbetfdh contribute to infection structure formation. Electron-transferring flavoprotein (Etf) and its dehydrogenase (Etfdh) are integral components of the electron transport chain in mitochondria. In this study, we characterize two putative etf genes (Bbetfa and Bbetfb) and their dehydrogenase gene Bbetfdh in the entomopathogenic fungus Beauveria bassiana. Individual deletion of these genes caused a significant reduction in vegetative growth, conidiation, and delayed conidial germination. Lack of these genes also led to abnormal metabolism of fatty acid and increasing lipid body accumulation. Furthermore, the virulence of Bbetfs and Bbetfdh deletion mutants was severely impaired due to decreasing infection structure formation. Additionally, all deletion strains showed reduced ATP synthesis compared to the wild-type strain. Taken together, Bbetfa and Bbetfb, along with Bbetfdh , play principal roles in fungal vegetative growth, conidiation, conidial germination, and pathogenicity of B. bassiana due to their essential functions in fatty acid metabolism. [ABSTRACT FROM AUTHOR]

Beauveria bassiana is an entomopathognic fungus, which is widely employed in the biological control of pests. Gene disruption is a common method for studying the functions of genes involved in fungal development or its interactions with hosts. However, generating gene deletion mutants was a time‐consuming work. The transcriptional factor OpS3 has been identified as a positive regulator of a red secondary metabolite oosporein in B. bassiana. In this study, we have designed a new screening system by integrating a constitutive OpS3 expression cassette outside one of the homologous arms of target gene. Ectopic transformants predominantly exhibit a red colour with oosporein production, while knockout mutants appear as white colonies due to the loss of the OpS3 expression cassette caused by recombinant events. This screening strategy was used to obtain the deletion mutants of both tenS and NRPS genes. Correct mutants were obtained by screening fewer than 10 mutants with a positive efficiency ranging from 50% to 75%. This system significantly reduces the workload associated with DNA extraction and PCR amplification, thereby enhancing the efficiency of obtaining correct transformants in B. bassiana. [ABSTRACT FROM AUTHOR]

In the ever‐evolving AI‐driven education, integrating AI technologies into teaching practices has become increasingly imperative for aspiring STEM educators. Yet, there remains a dearth of studies exploring pre‐service STEM teachers' readiness to incorporate AI into their teaching practices. This study examined the factors influencing teachers' willingness to integrate AI (WIAI), especially from the perspective of pre‐service STEM teachers' attitudes towards the application of AI in teaching. In the study, a comprehensive survey was conducted among 239 pre‐service STEM teachers, examining the influences and interconnectedness of Technological Pedagogical Content Knowledge (TPACK), Perceived Usefulness (PU), Perceived Ease of Use (PE), and Self‐Efficacy (SE) on WIAI. Structural Equation Modeling (SEM) was employed for data analysis. The findings illuminated direct influences of TPACK, PU, PE, and SE on WIAI. TPACK was found to directly affect PE, PU, and SE, while PE and PU also directly influenced SE. Further analysis revealed significant mediating roles of PE, PU, and SE in the relationship between TPACK and WIAI, highlighting the presence of a chain mediation effect. In light of these insights, the study offers several recommendations on promoting pre‐service STEM teachers' willingness to integrate AI into their teaching practices. Practitioner notes What is already known about this topic? The potential of AI technologies to enrich learning experiences and improve outcomes in STEM education has been recognized. Pre‐service teachers' willingness to integrate AI into teaching practice is crucial for shaping the future learning environment. The TAM and TPACK frameworks are used to analyse teacher factors in technology‐supported learning environments. Few studies have been conducted for examining factors of pre‐service teachers' willingness to integrate AI into teaching practices in the context of STEM education. What this paper adds? A survey was designed and developed for exploring pre‐service STEM teachers' WIAI and its relationships with factors including TPACK, PE, PU, and SE. TPACK, SE, PU, and PE have direct impact on pre‐service STEM teachers' WIAI. SE, PU, and PE have been identified as mediating variables in the relationship between TPACK and WIAI. Two sequential mediation effects, TPACK → PE → SE → WIAI and TPACK → PU → SE → WIAI, among pre‐service STEM teachers were further identified. Implications of this study for practice and/or policy Pre‐service STEM teachers are encouraged to explore and utilize AI technology to enhance their confidence and self‐efficacy in integrating AI into teaching practices. Showcasing successful cases and practical experiences is essential for fostering awareness of AI integration in STEM education. It is recommended to introduce AI education courses in teacher training programs. Offering internship and practicum opportunities related to AI technologies can enhance their practical skills in integrating AI into education. What is already known about this topic? The potential of AI technologies to enrich learning experiences and improve outcomes in STEM education has been recognized. Pre‐service teachers' willingness to integrate AI into teaching practice is crucial for shaping the future learning environment. The TAM and TPACK frameworks are used to analyse teacher factors in technology‐supported learning environments. Few studies have been conducted for examining factors of pre‐service teachers' willingness to integrate AI into teaching practices in the context of STEM education. What this paper adds? A survey was designed and developed for exploring pre‐service STEM teachers' WIAI and its relationships with factors including TPACK, PE, PU, and SE. TPACK, SE, PU, and PE have direct impact on pre‐service STEM teachers' WIAI. SE, PU, and PE have been identified as mediating variables in the relationship between TPACK and WIAI. Two sequential mediation effects, TPACK → PE → SE → WIAI and TPACK → PU → SE → WIAI, among pre‐service STEM teachers were further identified. Implications of this study for practice and/or policy Pre‐service STEM teachers are encouraged to explore and utilize AI technology to enhance their confidence and self‐efficacy in integrating AI into teaching practices. Showcasing successful cases and practical experiences is essential for fostering awareness of AI integration in STEM education. It is recommended to introduce AI education courses in teacher training programs. Offering internship and practicum opportunities related to AI technologies can enhance their practical skills in integrating AI into education. [ABSTRACT FROM AUTHOR]

The article discusses a novel technique to insect control, in which expression of host molecules in an insect pathogen is utilized for augmentation of virulence. With this approach, the increase in virulence can be exploited to be host specific depending on the chosen host molecule. Minimization of resistance development is possible as the host peptide hormones regulate developmental processes that are species- and tissue-specific.

Anhua dark tea known as the earliest produced Chinese dark tea, has been commercially available and famous for its unique flavor and health care effect. NMDA receptors are glutamate-coupled ion channels that critically involved in survival of neuronal cells and neurodegenerative diseases. Thus, it is considered a promising target for the therapy of neurodegenerative disease. In this study, four catechins including two new catechins derivatives (1 – 2), together with thirteen known flavonoids were isolated from Anhua dark tea. The structures of compounds 1 – 2 [2 S ,3 R -6-methoxycarbonylgallocatechin (1) and 2 R ,3 R -6-methoxycarbonylgallocatechin (2)] were determined on the basis of their spectroscopic data. The preliminary bioassay indicated that compound 1 showed the best neuroprotective effects via N -methyl- d -aspartate (NMDA) receptors inhibition. Compound 1 protected SH-SY5Y cells against NMDA-induced injury and cell apoptosis via the modulation of NR2B expression, the activation of PI3K/Akt signaling and caspase-dependent pathway. The results suggested compound 1 would be a potent dietary therapy reagent for prevention of excitable brain injury. Unlabelled Image [ABSTRACT FROM AUTHOR]

Background: MAPK/ERK kinases transmit signals from many growth factors/kinase receptors during normal cell growth/differentiation, and their dysregulation is a hallmark of diverse types of cancers. A plethora of drugs were developed to block this kinase pathway for clinical application. With the exception of a recently identified agent, EQW, most of these inhibitors target upstream factors but not ERK1/2; no activator of ERK1/2 is currently available.Method: A library of compounds isolated from medicinal plants of China was screened for anti-cancer activities. Three limonoid compounds, termed A1541-43, originally isolated from the plant Melia azedarach, exhibiting strong anti-leukemic activity. The anti-neoplastic activity and the biological target of these compounds were explored using various methods, including western blotting, flow cytometry, molecular docking and animal model for leukemia.Results: Compounds A1541-43, exhibiting potent anti-leukemic activity, was shown to induce ERK1/2 phosphorylation. In contrast, the natural product Cedrelone, which shares structural similarities with A1541-43, functions as a potent inhibitor of ERK1/2. We provided evidence that A1541-43 and Cedrelone specifically target ERK1/2, but not the upstream MAPK/ERK pathway. Computational docking analysis predicts that compounds A1541-43 bind a region in ERK1/2 that is distinct from that to which Cedrelone and EQW bind. Interestingly, both A1541-43, which act as ERK1/2 agonists, and Cedrelone, which inhibit these kinases, exerted strong anti-proliferative activity against multiple leukemic cell lines, and induced robust apoptosis as well as erythroid and megakaryocytic differentiation in erythroleukemic cell lines. These compounds also suppressed tumor progression in a mouse model of erythroleukemia.Conclusions: This study identifies for the first time activators of ERK1/2 with therapeutic potential for the treatment of cancers driven by dysregulation of the MAPK/ERK pathway and possibly for other disorders. [ABSTRACT FROM AUTHOR]

Aberrant activation of hepatocyte growth factor (HGF)/c-Met signaling pathway caused by gene amplification or mutation plays an important role in tumorigenesis. Therefore, c-Met is considered as an attractive target for cancer therapy and c-Met inhibitors have been developed with great interests. However, cancers treated with c-Met inhibitors inevitably develop resistance commonly caused by the activation of PI3K/Akt signal transduction pathway. Therefore, the combination of c-Met and PI3Kα inhibitors showed synergistic activities, especially, in c-Met hyperactivated and PIK3CA-mutated cells. In our previous study, we rationally designed and synthesized DFX117(6-(5-(2,4-difluorophenylsulfonamido)-6-methoxypyridin-3-yl)-N-(2-morpholinoethyl) imidazo[1,2-a]pyridine-3-carboxamide) as a novel PI3Kα selective inhibitor. Herein, the antitumor activity and underlying mechanisms of DFX117 against non-small cell lung cancer (NSCLC) cells were evaluated in both in vitro and in vivo animal models. Concurrent targeted c-Met and PI3Kα by DFX117 dose-dependent inhibited the cell growth of H1975 cells (PIK3CA mutation and c-Met amplification) and A549 cells (KRAS mutation). DFX117 subsequently induced G0/G1 cell cycle arrest and apoptosis. These data highlight the significant potential of DFX117 as a feasible and efficacious agent for the treatment of NSCLC patients. [ABSTRACT FROM AUTHOR]

Dual-ligand targeting drug delivery nanoplatforms are considered a promising tool for enhancing the specificity of chemotherapy. However, serious off-target delivery has been observed in current dual-ligand targeting nanoplatforms, as each ligand can independently recognize receptors on the cell membrane surface and guide drug nanocarriers to different cells. To overcome this barrier, a dual-ligand synergistic targeting (DLST) nanoplatform is developed, which can guide chemotherapy treatment specifically to cancer cells simultaneously overexpressing two receptors. This nanoplatform consists of a singlet oxygen (1O2) photosensitizer-loaded nanocarrier and a drug-loaded nanocarrier with 1O2 responsiveness, which were, respectively, decorated with a pair of complementary DNA sequences and two different ligands. For cancer cells overexpressing both receptors, two nanocarriers can be internalized in larger quantities to cause DNA hybridization-induced nanocarrier aggregation, which further activates 1O2-triggered drug release under light irradiation. For cells overexpressing a single receptor, only one type of nanocarrier can be internalized in a large quantity, leading to blocked drug release due to the ultrashort action radius of 1O2. In vivo evaluation showed this DLST nanoplatform displayed highly specific tumor treatment with minimized long-term toxicity. This is a highly efficient drug delivery system for DLST chemotherapy, holding great potential for clinical applications. [ABSTRACT FROM AUTHOR]

Thirty-three 1,3-dihydro-2H-indolin-2-one derivatives bearing α, β-unsaturated ketones were designed and synthesized via the Knoevenagel condensation reaction. The cytotoxicity, in vitro anti-inflammatory ability, and in vitro COX-2 inhibitory activity of all the compounds were evaluated. Compounds 4a, 4e, 4i-4j, and 9d exhibited weak cytotoxicity and different degrees of inhibition against NO production in LPS-stimulated RAW 264.7 cells. The IC50 values of compounds 4a, 4i, and 4j were 17.81 ± 1.86 μM, 20.41 ± 1.61 μM, and 16.31 ± 0.35 μM, respectively. Compounds 4e and 9d showed better anti-inflammatory activity with IC50 values of 13.51 ± 0.48 μM and 10.03 ± 0.27 μM, respectively, which were lower than those of the positive control ammonium pyrrolidinedithiocarbamate (PDTC). Compounds 4e, 9h, and 9i showed good COX-2 inhibitory activities with IC50 values of 2.35 ± 0.04 µM, 2.422 ± 0.10 µM and 3.34 ± 0.05 µM, respectively. Moreover, the possible mechanism by which COX-2 recognized 4e, 9h, and 9i was predicted by molecular docking. The results of this research suggested that compounds 4e, 9h, and 9i might be new anti-inflammatory lead compounds for further optimization and evaluation. [ABSTRACT FROM AUTHOR]

Sanguinarine (1) is a natural product with significant pharmacological effects. However, the application of sanguinarine has been limited due to its toxic side effects and a lack of clarity regarding its molecular mechanisms. To reduce the toxic side effects of sanguinarine, its cyanide derivative (1a) was first designed and synthesized in our previous research. In this study, we confirmed that 1a presents lower toxicity than sanguinarine but shows comparable anti-leukemia activity. Further biological studies using RNA-seq, lentiviral transfection, Western blotting, and flow cytometry analysis first revealed that both compounds 1 and 1a inhibited the proliferation and induced the apoptosis of leukemic cells by regulating the transcription of c-MET and then suppressing downstream pathways, including the MAPK, PI3K/AKT and JAK/STAT pathways. Collectively, the data indicate that 1a, as a potential anti-leukemia lead compound regulating c-MET transcription, exhibits better safety than 1 while maintaining cytostatic activity through the same mechanism as 1. [ABSTRACT FROM AUTHOR]

Aberrant expression of the phosphatidylinositol 3-kinase (PI3K) signalling pathway is often associated with tumourigenesis, progression and poor prognosis. Hence, PI3K inhibitors have attracted significant interest for the treatment of cancer. In this study, a series of new 6-(imidazo[1,2-a]pyridin-6-yl)quinazoline derivatives were designed, synthesized and characterized by 1H NMR, 13C NMR and HRMS spectra analyses. In the in vitro anticancer assay, most of the synthetic compounds showed submicromolar inhibitory activity against various tumour cell lines, among which 13k is the most potent compound with IC50 values ranging from 0.09 μΜ to 0.43 μΜ against all the tested cell lines. Moreover, 13k induced cell cycle arrest at G2/M phase and cell apoptosis of HCC827 cells by inhibition of PI3Kα with an IC50 value of 1.94 nM. These results suggested that compound 13k might serve as a lead compound for the development of PI3Kα inhibitor. [ABSTRACT FROM AUTHOR]

[Display omitted] • A series of novel 3-(6-aminopyridin-3-yl)benzamide derivatives were synthesized. • Compound 7l displayed the optimal activity as an antiproliferative agent, with an IC 50 value of 0.04 ± 0.01 μM in A549 cells in vitro. • Compound 7l induced G2/M phase arrest by AURKB transcription inhibition and resulted in cell apoptosis via the p53 signaling pathway. • Compound 7l significantly inhibited the tumor growth in A549 xenograft model with tumor growth inhibitory rate (IR) up to 51.11 % at 15 mg/kg and 76.60 % at 30 mg/kg. Here, a series of 3-(6-aminopyridin-3-yl) benzamide derivatives were designed and synthesized. Cell viability assay indicated that most compounds exhibited potent antiproliferative activity against all the tested cancer cells. Among them, compound 7l displayed the best antiproliferative activity particularly in A549 cells, with an IC 50 value of 0.04 ± 0.01 μM. RNA-seq analysis was employed to explore the potential pathways related to the antiproliferative activity of compound 7l. The data revealed that 7l exerted antiproliferative activity mainly by regulating cell cycle, DNA replication and p53 signaling pathway. Indeed, compound 7l induced G2/M phase arrest by AURKB transcription inhibition and resulted in cell apoptosis via p53 signaling pathway. Most importantly, compound 7l demonstrated potent antitumor activity in A549 xenograft tumor model. Collectively, 7l might be a promising lead compound for the development of new therapeutic agents for AURKB overexpressed or mutated cancers. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) is the most common lung cancer subtype. Although chemotherapy and targeted therapy are used for the treatment of patients with NSCLC, the survival rate remains very low. Recent findings suggested that aurora kinase A (AKA), a cell cycle regulator, is a potential target for NSCLC therapy. Previously, we reported that a chemical entity of quinazolin-4(3H)-one represents a new template for AKA inhibitors, with antiproliferative activity against cancer cells. A quinazolin-4(3H)-one derivative was further designed and synthesized in order to improve the pharmacokinetic properties and antiproliferation activity against NSCLC cell lines. The derivative, BIQO-19 (Ethyl 6-(4-oxo-3-(pyrimidin-2-ylmethyl)-3,4-dihydroquinazolin-6-yl)imidazo [1,2-a]pyridine-2-carboxylate), exhibited improved solubility and antiproliferative activity in NSCLC cells, including epidermal growth factor receptor–tyrosine kinase inhibitor (EGFR-TKI)-resistant NSCLC cells. BIQO-19 effectively inhibited the growth of the EGFR-TKI-resistant H1975 NSCLC cells, with the suppression of activated AKA (p-AKA) expression in these cells. The inhibition of AKA by BIQO-19 significantly induced G2/M phase arrest and subsequently evoked apoptosis in H1975 cells. In addition, the combination of gefitinib and BIQO-19 exhibited synergistic antiproliferative activity in NSCLC cells. These findings suggest the potential of BIQO-19 as a novel therapeutic agent for restoring the sensitivity of gefitinib in EGFR-TKI-resistant NSCLC cells. [ABSTRACT FROM AUTHOR]

Lipid assimilation, storage, and turnover impact growth, development, and virulence in many microbial pathogens including fungi. Perilipins are proteins associated with lipid droplets (LDs) that mediate their assembly and turnover. Here, we characterized the Beauveria bassiana (BbPlin1) perilipin. BbPlin1 expression was higher in minimal media than in rich media, and, using a BbPlin1::eGFP fusion protein, the protein was shown to be co–localized to LDs, with the high expression seen during infection and proliferation within the insect (Galleria mellonella) host that dramatically decreased to almost no expression during fungal outgrowth on cadavers including in conidia, but that BbPlin1 production resumed in the conidia once placed in nutrient–containing media allowing for germination and growth. Characterization of a targeted gene deletion strain (ΔBbPlin1) revealed a dramatic (>30%) reduction in cellular LD content, promotion of aerial hyphal growth, and a small decrease in virulence, with little to no effects on vegetative growth and stress responses. However, in the ΔBbPlin1 strain, expression of the complementary LD–associated caleosin gene, BbCal1, was enhanced under nutrient–poor conditions, although no changes in BbPlin1 expression were seen in a ΔBbCal1 strain and the expression of BbPlin1 in the ΔBbCal1 strain did not change LD patterns in cells. Transcriptome and RT–PCR analyses indicated increased expression of lipid metabolism–related genes, including triacylglyercol lipase 3, enoyl–CoA isomerase, and diacylglycerol–O–acetyl transferase in the BbPlin1 deletion mutant. Lipid profile analyses confirmed that the loss of BbPlin1 significantly reduced the cellular levels of contents of triacylglycerol, diacylglycerol, and phosphatidylethanolamine as compared to the wild–type strain. These results demonstrate the involvement of the B. bassiana perilipin in mediating lipid homeostasis, fungal aerial hyphal growth, and virulence, revealing critical cycling from high expression during nutrient utilization within host cadavers to low expression during growth on the surface of the cadaver during the infection process. [ABSTRACT FROM AUTHOR]

SUMMARY: Verticillium wilt caused by Verticillium dahliae is a major disease of cotton. Acidic protein–lipopolysaccharide complexes are thought to be the toxins responsible for its symptoms. Here, we determined that the sphingolipid biosynthesis inhibitor fumonisin B1 (FB1) acts as a toxin and phenocopies the symptoms induced by V. dahliae. Knocking out genes required for FB1 biosynthesis reduced V. dahliae pathogenicity. Moreover, we showed that overexpression of a FB1 and V. dahliae both downregulated gene, GhIQD10, enhanced verticillium wilt resistance by promoting the expression of brassinosteroid and anti‐pathogen genes. Our results provide a new strategy for preventing verticillium wilt in cotton. [ABSTRACT FROM AUTHOR]

[Display omitted] • Bbhox2 is involved in conidiation. • Bbhox2 contributes to appressorium formation. • Bbhox2 is required for the propagation of entomopathogenic fungi in the host. Beauveria bassiana , a well-known filamentous biocontrol fungus, is the main pathogen of numerous field and forest pests. To explore the potential factors involved in the fungal pathogenicity, Bbhox2, an important and conserved functional transcription factor containing homeodomain was carried out by functional analysis. Homologous recombination was used to disrupt the Bbhox2 gene in B.bassiana. The conidia yield of the deletant fungal strain was significantly reduced. The conidial germination was faster, and stress tolerance to Congo red and high osmotic agents were decreased compared with that in the wildtype. Additionally, ΔBbhox2 showed a dramatic reduction in virulence no matter in topical inoculations or in intra-hemolymph injections against Galleria mellonella larvae, which is likely due to the failure of appressorium formation and the defect in producing hyphal body. These results indicate that the Bbhox2 gene markedly contributes to conidiation and pathogenicity in B. bassiana. [ABSTRACT FROM AUTHOR]

The phase equilibria in the magnesium (Mg) rich corner of the Mg-Er-Sn ternary system at 300, 400 and 500 °C have been determined through key alloy method by means of x-ray diffraction and scanning electron microscopy with assistance of energy dispersive spectroscopy. The results show that in the composition range of our studied, each isothermal section consists of five single-phase regions, seven two-phase regions, and three three-phase regions, four compounds, i.e. MgSn, ErMgSn, ErSn and ErMg are found in equilibrium with the Mg solid solution. The homogeneity ranges of Mg solid solution as well as the solid solubilities of the intermediate phases at different temperatures are reported. [ABSTRACT FROM AUTHOR]

Abstract: Entomopathogenic fungi, such as Beauveria bassiana and Metarhizium anisopliae are being developed as alternatives to chemical insecticides. They infect insects by direct penetration of the cuticle using a combination of physical pressure and extracellular hydrolytic enzymes such as proteases and chitinases. Previously we found that overexpression of a subtilisin-like protease (Pr1A) or a chitinase (Bbchit1) resulted in increased virulence of M. anisopliae and B. bassiana, respectively. In this study, we found that a mixture of the B. bassiana Pr1A homolog (CDEP1) and Bbchit1 degraded insect cuticle in vitro more efficiently than either CDEP1 or Bbchit1 alone. Based on this we produced three plasmid constructs; (1) Bbchit1, (2) CDEP1, and (3) a fusion gene of Bbchit1 linked to CDEP1 each under the control of the constitutive gpd promoter from Aspergillus nidulans. B. bassiana transformants secreting the fusion protein (CDEP1:Bbchit1) penetrated the cuticle significantly faster than the wild type or transformants overexpressing either Bbchit1 or CDEP1. Compared to the wild type, the transformant overexpressing CDEP1 showed a 12.5% reduction in LT50, without a reduction in LC50. The LT50 of the transformant expressing CDEP1:Bbchit1 was reduced by 24.9%. Strikingly, expression of CDEP1:Bbchit1 resulted in a 60.5% reduction in LC50, more than twice the reduction obtained by overexpression of Bbchit1 (28.5%). This work represents a significant step towards the development of hypervirulent insect pathogens for effective pest control. [Copyright &y& Elsevier]

Analysis of oesophageal mechanoreceptor-dependent responses requires knowledge about the distribution of stresses and strains in the layers of the organ. A two-layered and a one-layered quasi-3D finite element model of the rat oesophagus were used for simulation. An exponential pseudo-strain energy density function was used as the constitutive equation in each model. Stress and strain distributions at the distension pressures 0.25 and 1.0 kPa were studied. The stress and strain distributions depended on the wall geometry. In the one-layered model, the stress ranged from -0.24 to 0.38 kPa at a pressure of 0.25 kPa and from -0.67 to 2.57 kPa at a pressure of 1.0 kPa. The stress in the two-layered model at the pressure of 0.25 and 1.0 kPa varied from -0.52 to 0.64 kPa and from -1.38 to 3.84 kPa. In the two-layered model, the stress was discontinuous at the interface between the muscle layer and the mucosa–submucosa layer. The maximum stress jump was 1.67 kPa at the pressure of 1.0 kPa. The present study provides a numerical simulation tool for characterising the mechanical behaviour of a multi-layered, complex geometry organ. [Copyright &y& Elsevier]

Summary: Entomopathogenic fungi such as Metarhizium rileyi and Beauveria bassiana are widely used insect biological control agents. Little, however, is known concerning genetic or enzymatic factors that differentiate the mechanisms employed by these two fungal pathogens to infect target hosts. Infection by either of these organisms is known to increase levels of the growth and molting hormone, ecdysone, which also regulates the expression of a number of innate immune pathways. M. rileyi, but not B. bassiana, has apparently evolved an ecdysteroid‐22‐oxidase (MrE22O) that inactivate ecdysone. We show that deletion of MrE22O impaired virulence compared with the wild‐type strain, with an increase in ecdysone titer seen in hosts that was coupled to an increase in the expression of antimicrobial genes. An M. rileyi strain engineered to overexpress MrE22O (MrE22OOE), as well as trans‐expression in B. bassiana (Bb::MrE220OE) resulted, in strains displaying enhanced virulence and dampening of host immune responses compared with their respective wild‐type parental strains. These results indicate that ecdysone plays an important role in mediating responses to fungal infection and that some insect pathogenic fungi have evolved mechanisms for targeting this hormone as a means for facilitating infection. [ABSTRACT FROM AUTHOR]

Summary: Increasing the targeting ability of antifungal proteins towards specific components of fungal cells has the potential to improve their antifungal activity and reduce harmful effects to nontarget cells. To obtain effective disease resistance genes against cotton Verticillium wilt, we constructed several fusion genes, in which binding domains targeting chitin, sphingolipid or ergosterol in the fungal cell wall or cell membrane were individually fused to the antifungal peptide BbAFP1 from entomopathogenic fungus Beauveria bassiana. Transient expression of fusion genes in cotton cotyledons indicated that the BbAFP1::ErBD fusion peptide with an ergosterol binding domain exhibited better disease resistance against V. dahliae than wild‐type BbAFP1 and other fusion genes. BbAFP1::ErBD and BbAFP1 transgenic cotton were obtained and verified by Southern and Western blotting. Compared with BbAFP1‐expressing cotton, BbAFP1::ErBD‐expressing cotton showed higher disease resistance against V. dahliae, with smaller lesion areas (0.07 cm2 vs. 0.16 cm2) on the leaves and a lower disease index (23.9 vs. 34.5). Overexpression of BbAFP1::ErBD by transgenic tobacco also showed enhanced disease resistance against V. dahliae compared with that of the wild‐type gene. These results indicated that construction of fusion antifungal peptides that target fungal cells is a powerful strategy to obtain new anti‐disease genes, and the obtained fusion gene BbAFP1::ErBD has the potential to defend against plant fungal diseases. [ABSTRACT FROM AUTHOR]

• A one-pot protocol for the preparation of (E)-3-benzylideneflavanones. • Moderate to good yields of the products. • Experimentally simple procedure working under air. • Simple starting materials. An efficient and practical PPA/H 2 SO 4 promoted synthesis of (E)-3-benzylideneflavanones from 2-hydroxyacetophenones and aromatic aldehydes was developed. Various (E)-3-benzylideneflavanones were produced in good to excellent yields. [ABSTRACT FROM AUTHOR]

Ultraviolet B (UVB) induces inflammation and causes skin aging. The signs of skin aging, such as wrinkles, discolored spots, loss of skin moisture, and disruption of the skin barrier, are mostly caused by inflammatory signaling among various skin layers. The cells on the outermost surface of the skin are keratinocytes; these cells protect the skin against environmental stress and play an important role in immunomodulation by secreting cytokines in response to environmental stress. In the present study, we found that UVB activates STAT1 to mediate inflammatory signaling, yet STAT1 (S272) and STAT (Y702) shows different responses against UVB exposure. Anhua drak tea is a post-fermented dark tea produced in Anhua and Xinhua country in Hunan province of China. Treatment with 2S,3R-6-methoxycarbonylgallocatechin (MCGE), an epigallocatechin gallate derivative isolated from black tea (Anhua dark tea), effectively suppresses STAT1 activation and inflammatory cytokines, and activates Nrf2 pathway to protect cells from reactive oxygen species production in UVB exposed keratinocyte cells (HaCaT). Interestingly, the effects of MCGE were independent on MAPK signaling pathway. Moreover, MCGE regulates inflammatory cytokines in monocyte-keratinocyte (THP-1, HaCaT) co-culture and macrophage differentiation models. These results suggest that MCGE potentially can be used as a photoprotective agent against UVB-induced inflammatory responses. Unlabelled Image • STAT1 plays a key role in UVB-damaged keratinocytes • MCGE selectively targets p-STAT at the tyrosine 701 residue. • MCGE protects keratinocytes from ROS via Nrf2 activation. • MCGE effectively suppresses cytokine production in M1 macrophage cells. • MCGE suppresses MMP1 and IL6 in a monocyte-keratinocyte co-culture model. [ABSTRACT FROM AUTHOR]

Competition is one of the fundamental driving forces of natural selection. Beauveria bassiana is a soil and plant phylloplane/root fungus capable of parasitizing insect hosts. Soil and plant environments are often enriched with other fungi against which B. bassiana competes for survival. Here, we report an antifungal peptide (BbAFP1), specifically expressed and localized to the conidial cell wall and is released into the surrounding microenvironment inhibiting growth of competing fungi. B. bassiana strains expressing BbAFP1, including overexpression strains, inhibited growth of Alternaria brassicae in co-cultured experiments, whereas targeted gene deletion of BbAFP1 significantly decreased (25%) this inhibitory effect. Recombinant BbAFP1 showed chitin and glucan binding abilities, and growth inhibition of a wide range of phytopathogenic fungi by disrupting membrane integrity and eliciting reactive oxygen species (ROS) production. A phenylalanine residue (F50) contributes to chitin binding and antifungal activity, but was not required for the latter. Expression of BbAFP1 in tomato resulted in transgenic plants with enhanced resistance to plant fungal pathogens. These results highlight the importance of fungal competition in shaping primitive competition strategies, with antimicrobial compounds that can be embedded in the spore cell wall to be released into the environment during the critical initial phases of germination for successful growth in its environmental niche. Furthermore, these peptides can be exploited to increase plant resistance to fungal pathogens. Author summary: Microbial competition exerts powerful selective pressures for the development of defensive and offensive methods of suppressing potential competitors. One of the most vulnerable stages for any fungi is the initial germination of resting spores in potentially hostile environments. Currently, we know little about how fungi defend other microbial competitors during the beginning stage of conidial germination. Here, we report on an antifungal peptide from B. bassiana (BbAFP1) that is specifically expressed in mature aerial conidia, with the protein localized exclusively to the conidial cell wall. The "pre-loaded" BbAFP1 is released into the surrounding microenvironment where it can act to inhibit the growth of competing fungi during the initial stages of fungal germination, i.e. largely before actual germ tubes are apparent, thus conferring an advantage to B. bassiana in out-competing susceptible competitors in the microenvironment surrounding the spore. The effects of BbAFP1 on membrane integrity were characterized and a key amino acid (F50) was shown to function in chitin binding and antifungal activity. Transgenic tomato overexpressing BbAFP1 were shown to exhibit enhanced resistance to plant fungal pathogens. Our study provides new insights into the microbial competition and genes involved in this process that can be exploited to increase plant disease resistance. [ABSTRACT FROM AUTHOR]

Eleven undescribed derivatives of flavan, including flavan-3,4-diols vernicinosides A-H and profisetinidin-type-4-arylflavan-3-ols verniciflavanols A-C, together with eight known compounds were purified from the heartwood of Toxicodendron vernicifluum. The chemical structures of the undescribed compounds were characterized by spectroscopic data interpretation, including NMR (1H and 13C NMR HSQC and HMBC) and HRESIMS analysis. CD data analysis was conducted to assign the absolute configurations of the undescribed compounds and the active compound verniciflavanol A was also confirmed by ECD experiment. The absolute configuration of the sugar moiety was identified by GC analysis of chiral derivatives in the hydrolysate. MTT assay was applied to test these compounds against H 2 O 2 -induced oxidative stress in human neuroblastoma SH-SY5Y cells. Results found that verniciflavanol A demonstrated the best potential in protecting SH-SY5Y cells against H 2 O 2 -induced oxidative stress by inhibiting cell apoptosis and attenuate reactive oxygen species (ROS) level and mitochondrial dysfunction. And the underlying mechanism was confirmed to be associated with Nrf2-antioxidant response element signaling and IL-6 cell survival pathways. [Display omitted] • Eleven undescribed flavanols were isolated from Toxicodendron vernicifluum. • Verniciflavanol A showed the best antioxidant effect. • The mechanism of verniciflavanol A on antioxidant was discussed. • Profisetinidin-4-arylflavan-3-ol was investigated on neuroprotective effect firstly. [ABSTRACT FROM AUTHOR]