Discovery of GOT1 Inhibitors from a Marine-Derived Aspergillus terreus That Act against Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a devastating digestive system carcinoma with high incidence and death rates. PDAC cells are dependent on the Gln metabolism, which can preferentially utilize glutamic oxaloacetate transaminase 1 (GOT1) to maintain the redox homeostasis of cancer cells. Therefore, small molecule inhibitors targeting GOT1 can be used as a new strategy for developing cancer therapies. In this study, 18 butyrolactone derivatives (1–18) were isolated from a marine-derived Aspergillus terreus, and asperteretone B (5), aspulvinone H (AH, 6), and (+)-3′,3′-di-(dimethylallyl)-butyrolactone II (12) were discovered to possess significant GOT1-inhibitory activities in vitro, with IC₅₀ values of (19.16 ± 0.15), (5.91 ± 0.04), and (26.38 ± 0.1) µM, respectively. Significantly, the molecular mechanism of the crystal structure of GOT1–AH was elucidated, wherein AH and the cofactor pyrido-aldehyde 5-phosphate competitively bound to the active sites of GOT1. More importantly, although the crystal structure of GOT1 has been discovered, the complex structure of GOT1 and its inhibitors has never been obtained, and the crystal structure of GOT1–AH is the first reported complex structure of GOT1/inhibitor. Further in vitro biological study indicated that AH could suppress glutamine metabolism, making PDAC cells sensitive to oxidative stress and inhibiting cell proliferation. More significantly, AH exhibited potent in vivo antitumor activity in an SW1990-cell-induced xenograft model. These findings suggest that AH could be considered as a promising lead molecule for the development of anti-PDAC agents.     

软X射线对柑桔愈伤组织和原生质体的影响

研究了软Ｘ射线对丹西红桔愈伤组织和原生质体的影响。结果表明,辐照１ｈ和１．５ｈ都在不同程度上抑制了愈伤组织的生长,辐照１．５ｈ表现更为明显;原生质体经辐照１．５ｈ后分裂的很少,在培养过程中发生质壁分离,辐射１ｈ的原生质体受抑制的作用不一些。     

Physical aspects of the biopolymer matrix in wheat bran and its dissected layers

The objectives of this work were to 1) determine the physical structure of untreated wheat bran and the differences in physical structure between its dissected layers; 2) evaluate how bran hydration affected bran crystallinity and polymer order; and 3) determine how enzymatic treatment of wheat bran affected its physical structure. For the first time, X-ray diffraction (XRD), small angle X-ray scattering (SAXS), solid-state ¹³C cross-polarization magic-angle spinning nuclear magnetic resonance (¹³C CP/MAS NMR), and polarized light microscopy with a waveplate were used to study the physical structure of wheat bran and its dissected layers. The XRD and solid-state ¹³C CP/MAS NMR both confirmed the presence of crystalline cellulose in untreated bran, enzymatically treated bran, and dissected bran layers. The outer pericarp had the highest crystallinity of the dissected bran layers and showed negative birefringence. The aleurone layer was low in cellulose content and completely amorphous, yet the cell walls in the aleurone layer showed strong positive birefringence. The treatment of destarched and deproteinated bran with the Updegraff reagent removed amorphous material, leaving its crystalline cellulose structure intact. Hydration of the outer pericarp increased its crystallinity index and CP/MAS NMR resonance intensity, which indicated a possible increase in polymer order. The SAXS also confirmed that cell wall polymers, possibly aggregated cellulose microfibrils, increased in order as a result of hydration.     

Study of the microstructure of durum wheat endosperm using X-ray micro-computed tomography

Durum wheat grains are used for producing food, such as pasta or couscous. The grain mechanical properties which are linked to its internal micro-structure (i.e. endosperm porosity) are known to determine its ability to produce semolina during milling. The proportion of grains having porous endosperm in a batch appears therefore as a critical quality factor for the durum wheat value chain. Our objective was to investigate the ability of X-ray micro-tomography (μCT) method to describe the porous or vitreous counterpart structures in the endosperm of durum wheat grains. We selected two different durum wheat samples displaying vitreous or partially porous endosperms. The grains were analyzed using μCT at two pixel sizes (1 μm or 7 μm). The μCT data collected at 7 μm pixel size were used for qualitative classification of grains according to apparent distribution curve of the porosity parameters. Analysis of μCT images at 1 μm pixel size allowed us to propose pore size classification in the vitreous and porous parts of the endosperm in three durum wheat grain. Results are used to better describe the durum-wheat endosperm microstructure, but requires long scanning periods.     

基于广角X射线散射技术的竹材纤维素晶型研究

纤维素Ⅰ是自然界中纤维素晶体的主要存在形式,它具有三斜晶体结构的I_α和单斜晶体结构的I_β。为进一步研究竹材中的纤维素晶型,利用同步辐射广角X射线散射(SR—WAXS)技术对毛竹竹壁纤维素晶型进行了初步研究,通过已知的纤维素晶胞模型计算晶面间距并预测衍射峰的峰位,再根据实验所得的实际峰位,判定竹材中纤维素的晶型。结果表明,竹材的衍射峰位与纤维素I_α的理论计算值相近,证明竹材中的纤维素I_β是绝大多数甚至是唯一品型。相比核磁共振技术而言,利用同步辐射广角X射线散射研究竹材中纤维素晶型是一个较为简单的方法。     

采用变温X射线衍射技术对六方钛酸钡陶瓷材料的结构监控

对于由冷压陶瓷技术所开发的纯六方Ba（Ti0.95Fe0.05）O3-δ陶瓷，采用变温XRD技术测量该陶瓷在不同温度下的XRD谱，鉴定晶体结构．澄清了六方钛酸钡（BaTiO3）介电陶瓷材料的晶体结构是否在BaTiO3的居里温度（n=130℃）发生结构相变，并验证开发的变温X射线衍射（XRD）技术在无机粉体材料结构监控的可行性．结果表明：BaTiO3陶瓷在Tc发生四方-立方的结构相变，以45°附近两个分立的（002）／（200）衍射峰演变为单一对称的（200）衍射峰为标志；而六方Ba（Ti0.95Fe0.05）O3-δ陶瓷直到300℃都不发生结构相变．对于六方Ba（Ti0.95Fe0.05）O3-δ陶瓷，升高温度并不能导致吸附环境氧来填充氧空位，Fe3＋Vo-Fe3＋缺陷复合体所维持的晶格电中性仍占据统治地位，六方-立方结构相变不发生．该项研究为变温XRD技术在工业生产上对无机粉体材料的监控应用提供了技术依据．     

应用软X射线辐射育成香晚粳新品系SX0832

本实验使用 Mo 靶软 x 射线仪,35kV 的发射电压,10000R 的剂量,照射处理21个香稻品种(处在萌芽期的种子)。从武香203亲本品种辐射后代中选育出优异的新品系 SX0832,具有原品种的香味、优质,还具有矮秆,抗病、高产等特点。     

X－射线微区分析不同浓度Ce(NO_3)_3处理下铈及其它离子在I－69杨茎尖分生组织及叶中的分布

Ｉ－６９杨插穗分别培养在含有不同浓度Ｃｅ（ＮＯ３）３的营养液中，经快速冷冻、冷冻干燥、无水塑料包埋及干刀薄切片法，用Ｘ－射线能谱微区分析测定Ｃｅ及其它无机离子在茎尖分生组织和叶的不同组织中细胞壁、细胞质、细胞核及叶绿体中的含量及分布。在１０ｐｐｍＣｅ（ＮＯ３）３处理下，茎尖中Ｃｅ的含量比对照组和１００ｐｐｍＣｅ（ＮＯ３）３处理组高出近１倍，叶的亚细胞中的Ｋ、Ｐ、Ｓ、Ｆｅ的含量也呈增加的趋势。特别是Ｍｇ的含量增加显著，在保卫细胞的细胞质中Ｍｇ的含量比对照组高出３．５倍，而在表皮细胞的细胞核和液泡中的含量则比对照组高出近１３倍。但在１００ｐｐｍＣｅ（ＮＯ３）３处理下，无机离子在叶中亚细胞微区间的含量则显著下降     

Microfibril angle of Norway spruce [Picea abies (L.) Karst.] compression wood: comparison of measuring techniques

The structure of cellulose, especially the microfibril angles (MFAs), in compression wood of Norway spruce [Picea abies (L.) Karst.] was studied by wide- and small-angle X-ray scattering and polarizing microscopy. On the basis of the X-ray scattering experiments the average MF As of the cell wall layers S₂ and S₁ of the studied sample are 39 and 89, respectively; and the average diameter and length of the cellulose crystallites are 2.9 and 20.0nm, respectively. The average of the whole MFA distribution is shown to agree with the one obtained by polarizing microscopy of macerated fibers.