The entomopathogenic fungus Beauveria bassiana is a typical filamentous fungus and has been used for pest biocontrol. Conidia are the main active agents of fungal pesticides; however, we know little ...about conidial developmental mechanisms and less about maturation mechanisms. We found that a Zn
Cys
transcription factor of
bassiana (named BbCmr1) was mainly expressed in late-stage conidia and was involved in conidium maturation regulation. Deletion of
impaired the conidial cell wall and resulted in a lower conidial germination rate under UV (UV), heat shock, H
O
, Congo red (CR) and SDS stresses compared to the wild type. Transcription levels of the genes associated with conidial wall components and trehalose synthase were significantly reduced in the
mutant. Further analysis found that BbCmr1 functions by upregulating BbWetA, a well-known transcription factor in the central development of BrlA-AbaA-WetA. The expression of
was positively regulated by BbBrlA. These results indicated that BbCmr1 played important roles in conidium maturation by interacting with the central development pathway, which provided insight into the conidial development networks in
bassiana.
Conidium maturation is a pivotal event in conidial development and affects fungal survival ability under various biotic/abiotic stresses. Although many transcription factors have been reported to regulate conidial development, we know little about the molecular mechanism of conidium maturation. Here, we demonstrated that the transcription factor BbCmr1 of
bassiana was involved in conidium maturation, regulating cell wall structure, the expression of cell wall-related proteins, and trehalose synthesis. BbCmr1 orchestrated conidium maturation by interplaying with the central development pathway BrlA-AbaA-WetA. BbBrlA positively regulated the expression of
, and the latter positively regulated
expression, which forms a regulatory network mediating conidial development. This finding was critical to understand the molecular regulatory networks of conidial development in
bassiana and provided avenues to engineer insect fungal pathogens with high-quality conidia.
Aim: To decipher the molecular interactions between c-Met and its type I inhibitors and to facilitate the design of novel c-Met inhibitors. Methods: Based on the prototype model inhibitor 1, four ...ligands with subtle differences in the fused aromatic rings were synthesized. Quantum chemistry was employed to calculate the binding free energy for each ligand. Symmetry-adapted perturbation theory (SAPT) was used to decompose the binding energy into several fundamental forces to elucidate the determinant factors. Results: Binding free energies calculated from quantum chemistry were correlated well with experimental data. SAPT calculations showed that the predominant driving force for binding was derived from a sandwich n-n interaction with Tyr-1230. Arg-1208 was the differentiating factor, interacting with the 6-position of the fused aromatic ring system through the backbone carbonyl with a force pattern similar to hydrogen bonding. Therefore, a hydrogen atom must be attached at the 6-position, and changing the carbon atom to nitrogen caused unfavorable electrostatic interactions. Conclusion: The theoretical studies have elucidated the determinant factors involved in the binding of type I inhibitors to c-Met.
Aim: Aberrant c-Met activation plays a critical role in cancer formation, progression and dissemination, as well as in development of resistance to anticancer drugs. Therefore, c-Met has emerged as ...an attractive target for cancer therapy. The aim of this study was to develop new c-Met inhibitors and elaborate the structure-activity relationships of identified inhibitors. Methods: Based on the predicted binding modes of Compounds ,5 and 14 in docking studies, a new series of c-Met inhibitor-harboring 3-((1H-pyrrolo3,2-cpyridin-1-yl)sulfonyl)imidazo1,2-apyridine scaffolds was discovered. Potent inhibitors were identified through extensive optimizations combined with enzymatic and cellular assays. A promising compound was further investigated in regard to its selectivity, its effects on c-Met signaling, cell proliferation and cell scattering in vitro. Results: The most potent Compound 31 inhibited c-Met kinase activity with an ICso value of 12.8 nmol/L, which was 〉78-fold higher than those of a panel of 16 different tyrosine kinases. Compound 31 (8, 40, 200 nmol/L) dose-dependently inhibited the phosphorylation of c-Met and its key downstream Akt and ERK signaling cascades in c-Met aberrant human EBC-1 cancer cells. In 12 human cancer cell lines harboring different background levels of c-Met expression/activation, Compound 31 potently inhibited c-Met- driven cell proliferation. Furthermore, Compound 31 dose-dependently impaired c-Met-mediated cell scattering of MDCK cells. Conclusion: This series of c-Met inhibitors is a promising lead for development of novel anticancer drugs.
Effects of Mo and Mn elements on pitting corrosion resistance of lean duplex stainless steel in C1- media solution have been studied. Gravimetric tests in 6 mass% FeCl3 at 35 ℃ and potentiodynamic ...analysis in 3.5 mass% NaCI were carried out. The corrosion potential (Ecoor) and the pitting potential (Epit) are shifted to a more noble po tential because of the presence of Mo around the pits. While the presence of Mn could sharply reduce the value of pitting resistance equivalent number (PREn) and the pits can be formed more easily. The pits are found generating at the phase with a lower PREn. The identical tendencies between the Epit and PREn of weaker phase are the same. A corrosion mechanism has been proposed to determinate pitting corrosion behavior based on microstructural observations.
Silica films were grown on polyimide substrate using surface sol–gel reaction, and the film growth process was characterized by ellipsometry, atomic force microscopy, and X-ray photoelectron ...spectroscopy. On the activated polyimide surface, silica film was grown by sequential immersion in SiCl
4
solution and H
2
O. The thickness of silica films is linear with the depositing cycle, about 5.0 nm per cycle. The silica films present an island-like growth type and are not a strict equilibrium SiO
2
structure. Moreover, the result of the tensile test suggests that the silica films have a good adhesion to the polyimide substrate.
Establishment of a highly efficient regeneration system for the mature embryo of wheat will provide a convenient tool for wheat tissue culture and transformation, thereby facilitating the ...transformation of foreign genes into wheat. By using the mature embryos derived from 20 different wheat lines including Shi 4185, Yumai 66, Lunxuan 987, CB037, Yangmai 6, Xinchun 9, Bobwhite, Han 6172, Zheng 9023, Jimai 20, Ningchun 4, and Jing 411, the effects of some factors including inoculation methods, initiating culture media, organic additives, antioxidants, and auxins on the regeneration from the explants were evaluated. The results indicated that the scraping embryo culture was better than the whole embryo culture, the Aa medium was better than the SD2 medium and dicamba was better than 2,4-D in increasing the regeneration frequency. An Adi medium was established in this study by adding silver nitrate, cysteine, ascorbic acid, dicamba, glutamine into the Aa medium at the concentration of 4,40, 100, 2, and 5 mg L^-1, respectively. By using the Adi medium and the scraping technique, the regeneration frequencies of the mature embryos of CB037, Lunxuan 987, Hart 6172, Yangmai 6, Bobwhite, Zheng 9023, Shi 4 185, and Jimai 20 became 85.6, 60,1, 46.0, 42.1,42.0, 34.0, 33.0, and 32.0%, respectively, which were about 5-8 times higher than that obtained from the conventional culture mediums and techniques. This novel regeneration system could be helpful in wheat transformation.
Effects of Mo and Mn elements on pitting corrosion resistance of lean duplex stainless steel in Cl-media solution have been studied.Gravimetric tests in 6 mass% FeCl3 at 35 ℃ and potentiodynamic ...analysis in 3.5 mass% Na Cl were carried out.The corrosion potential( Ecoor) and the pitting potential( Epit) are shifted to a more noble potential because of the presence of Mo around the pits.While the presence of Mn could sharply reduce the value of pitting resistance equivalent number( PREn) and the pits can be formed more easily.The pits are found generating at the phase with a lower PREn.The identical tendencies between the Epitand PREn of weaker phase are the same.A corrosion mechanism has been proposed to determinate pitting corrosion behavior based on microstructural observations.
The clinical features and immune responses of asymptomatic individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been well described. We studied 37 ...asymptomatic individuals in the Wanzhou District who were diagnosed with RT-PCR-confirmed SARS-CoV-2 infections but without any relevant clinical symptoms in the preceding 14 d and during hospitalization. Asymptomatic individuals were admitted to the government-designated Wanzhou People's Hospital for centralized isolation in accordance with policy
. The median duration of viral shedding in the asymptomatic group was 19 d (interquartile range (IQR), 15-26 d). The asymptomatic group had a significantly longer duration of viral shedding than the symptomatic group (log-rank P = 0.028). The virus-specific IgG levels in the asymptomatic group (median S/CO, 3.4; IQR, 1.6-10.7) were significantly lower (P = 0.005) relative to the symptomatic group (median S/CO, 20.5; IQR, 5.8-38.2) in the acute phase. Of asymptomatic individuals, 93.3% (28/30) and 81.1% (30/37) had reduction in IgG and neutralizing antibody levels, respectively, during the early convalescent phase, as compared to 96.8% (30/31) and 62.2% (23/37) of symptomatic patients. Forty percent of asymptomatic individuals became seronegative and 12.9% of the symptomatic group became negative for IgG in the early convalescent phase. In addition, asymptomatic individuals exhibited lower levels of 18 pro- and anti-inflammatory cytokines. These data suggest that asymptomatic individuals had a weaker immune response to SARS-CoV-2 infection. The reduction in IgG and neutralizing antibody levels in the early convalescent phase might have implications for immunity strategy and serological surveys.
花椒挥发油作为天然经皮促透剂的细胞毒性及促透活性 YiLAN Ying-qiu MAO Qiong WANG Jing AN Yan-yan CHEN Wen-ping WANG Bo-chen ZHAO Na LIU Ye-wen ZHANG
浙江大学学报:B卷英文版,
2014, Volume:
15, Issue:
2
Journal Article