Effect of microwave heating time on the gel properties of chicken myofibrillar proteins and their formation mechanism

The present work was conducted to illustrate the mechanism of gel formation of myofibrillar proteins (MPs) under different microwave heating times. The results showed that the denaturation enthalpy (ΔH) of the MPs significantly decreased when the heating time increased from 3 to 9 s and then completely disappeared as the heating time progressed, indicating that the MPs gradually denatured and subsequently aggregated with increasing heating time, which was further verified by the changes in the secondary structure, electrophoretic bands, and gel properties (e.g., water holding capacity and textural profiles) of the MPs. Microstructural images indicated that the MP gel formed under 12 s had the most compact network, indicating that extended microwave heating time could induce quality deterioration of MP gels. Moreover, the hydrophobic forces, electrostatic forces, and disulphide bonds of the MPs gradually intensified with increasing microwave heating time, suggesting that both non-covalent and covalent bonds could promote molecular denaturation and subsequent aggregation of MPs. In addition, correlation analysis revealed that the changes in the molecular conformation of MPs induced by different microwave heating times could effectively regulate the formation of MP gels and their related properties.     

安徽地区汉族心血管疾病患者SLCO1B1与ApoE基因多态性分布及其在他汀类药物临床个体化应用中的意义

目的：探讨脂质及药物代谢相关基因SLCO1B1和ApoE的基因多态性在安徽地区汉族心血管疾病患者中的分布，以评估他汀类药物个体化用药的效益/风险比。方法：利用PCR-荧光探针法技术检测2019年1月至2020年8月合肥市第二人民医院736例心血管疾病患者外周血基因组中SLCO1B1基因的rs2306283（388A>G）和rs4149056（521T>C）位点和ApoE基因的rs429358（388T>C）和rs7412（526C>T）位点的基因多态性分布特点，并与已报道的中国其他地区汉族心血管疾病患者的数据进行比较，分析不同地区间的基因型分布差异。结果：检测到安徽地区汉族心血管疾病患者中SLCO1B1基因型有6种，分别为*1a/*1a型（6.11%）、*1a/*1b型（29.08%）、*1b/*1b型（44.57%）、*1a/*15型（4.08%）、*1b/*15型（15.49%）、*15/*15型（0.68%），未检测到*1a/*5型、*5/*5型和*5/*15型；ApoE基因有6种表型，分别为E2/E2型（0.41%）、E2/E3型（11.96%）、E2/E4型（1.09%）、E3/E3型（67.66%）、E3/E4型（17.93%）、E4/E4型（0.95%）。两种基因的基因多态性频率分布满足Hardy-Weinberg遗传平衡，具有群体代表性。本研究人群中携带SLCO1B1正常肌病风险型的比例最高，约占79.76%；SLCO1B1中度肌病风险型和高度肌病风险型的人群比例较低，分别为19.57%和0.68%。ApoE大众类基因型比例最高，约占68.75%；ApoE保护类基因型及风险类基因型的人群比例分别为12.37%和18.88%。不同性别间SLCO1B1和ApoE基因表型患者差异无统计学意义。与华南地区心血管疾病患者相比，安徽地区ApoE基因多态性分布差异有统计学意义（P<0.05）。结论：安徽地区736例心血管疾病患者SLCO1B1和ApoE基因型分别以他汀药物剂量耐受性较高的正常肌病风险型和对他汀药物敏感的大众类基因型为主，服用他汀类药物诱发肌病的风险较低，降脂疗效较好；且两种基因的多态性分布均不受性别的影响，但ApoE基因多态性分布特征可能在地域上存在差异。因此，检测SLCO1B1和APOE基因多态性对于临床评估效益/风险比有重要的指导意义。     

Form selection of concomitant polymorphs: A case study informed by crystallization kinetics modeling

Molecular mechanisms and process kinetics of crystallizing concomitant polymorphs remain poorly understood. Solvent-mediated phase transformation and concomitant crystallization are difficult to be distinguished in practice, as multiple forms can be detected at the same time. Herein, we developed a population balance model to simulate a concomitant crystallization process of two polymorphs of tolfenamic acid. Our kinetic modeling aims to understand concomitant crystallization and help guide form selection of such a molecular system. Crystallization kinetics of ethanolic solutions were uncovered from induction time measurements, as well as seeded and unseeded crystallization experiments. Experimental and simulation results demonstrate that the stable form I crystallizes concomitantly with the metastable form II. The faster growing form II results in an intermediate decline in the composition of form I in crystallized samples, a characteristic feature of the concomitantly crystallized system. A four-quadrant scheme of attainable polymorph outcome was simulated under various crystallization conditions.     

Heteroalleles in Common Wheat: Multiple Differences between Allelic Variants of the Gli-B1 Locus

The Gli-B1-encoded γ-gliadins and non-coding γ-gliadin DNA sequences for 15 different alleles of common wheat have been compared using seven tests: electrophoretic mobility (EM) and molecular weight (MW) of the encoded major γ-gliadin, restriction fragment length polymorphism patterns (RFLPs) (three different markers), Gli-B1-γ-gliadin-pseudogene known SNP markers (Single nucleotide polymorphisms) and sequencing the pseudogene GAG56B. It was discovered that encoded γ-gliadins, with contrasting EM, had similar MWs. However, seven allelic variants (designated from I to VII) differed among them in the other six tests: I (alleles Gli-B1i, k, m, o), II (Gli-B1n, q, s), III (Gli-B1b), IV (Gli-B1e, f, g), V (Gli-B1h), VI (Gli-B1d) and VII (Gli-B1a). Allele Gli-B1c (variant VIII) was identical to the alleles from group IV in four of the tests. Some tests might show a fine difference between alleles belonging to the same variant. Our results attest in favor of the independent origin of at least seven variants at the Gli-B1 locus that might originate from deeply diverged genotypes of the donor(s) of the B genome in hexaploid wheat and therefore might be called “heteroallelic”. The donor’s particularities at the Gli-B1 locus might be conserved since that time and decisively contribute to the current high genetic diversity of common wheat.     

The Alkylquinolone Repertoire of Pseudomonas aeruginosa is Linked to Structural Flexibility of the FabH‐like 2‐Heptyl‐3‐hydroxy‐4(1H)‐quinolone (PQS) Biosynthesis Enzyme PqsBC

Pseudomonas aeruginosa is a bacterial pathogen that causes life‐threatening infections in immunocompromised patients. It produces a large armory of saturated and mono‐unsaturated 2‐alkyl‐4(1H)‐quinolones (AQs) and AQ N‐oxides (AQNOs) that serve as signaling molecules to control the production of virulence factors and that are involved in membrane vesicle formation and iron chelation; furthermore, they also have, for example, antibiotic properties. It has been shown that the β‐ketoacyl‐acyl‐carrier protein synthase III (FabH)‐like heterodimeric enzyme PqsBC catalyzes the last step in the biosynthesis of the most abundant AQ congener, 2‐heptyl‐4(1H)‐quinolone (HHQ), by condensing octanoyl‐coenzyme A (CoA) with 2‐aminobenzoylacetate (2‐ABA), but the basis for the large number of other AQs/AQNOs produced by P. aeruginosa is not known. Here, we demonstrate that PqsBC uses different medium‐chain acyl‐CoAs to produce various saturated AQs/AQNOs and that it also biosynthesizes mono‐unsaturated congeners. Further, we determined the structures of PqsBC in four different crystal forms at 1.5 to 2.7 Å resolution. Together with a previous report, the data reveal that PqsBC adopts open, intermediate, and closed conformations that alter the shape of the acyl‐binding cavity and explain the promiscuity of PqsBC. The different conformations also allow us to propose a model for structural transitions that accompany the catalytic cycle of PqsBC that might have broader implications for other FabH‐enzymes, for which such structural transitions have been postulated but have never been observed.     

Hydrolytic degree and antioxidant activity of purified casein characterised by different haplotypes (αs1-, β- and k-casein) after enzymatic hydrolysis with pepsin and enzymatic extract from Pleurotus eryngii

The aim of this study was to estimate the hydrolytic degree and antioxidant activity of purified casein characterised by different haplotypes (α_s1-, β- and k-casein) after in vitro digestion with two different enzymatic systems: pepsin from porcine gastric mucosa (EP) and a crude enzymatic extract from the edible mushroom Pleurotus eryngii. The used enzymes showed a different mode of casein catalysis with a consequent production of peptides of different antioxidant activity. The CN haplotype significantly influenced peptides production; in fact, the amino acid substitutions caused by genetic polymorphisms at the α_s1-, β- and k-CN loci influenced the sites of enzymatic cleavage and therefore the produced peptides. The above is evidenced by the different antioxidant activity found in the hydrolysates depending on the used enzymatic system, the CN haplotype, and the CN haplotype × enzymatic treatment interaction. The findings of this study are a perspective for the production of specific foods that exert a biological effect in addition to the nutritional one.     

The impact of recrystallisation on the freeze-thaw cycles of red seabream (Pagrus major) fillets

Recrystallisation often occurs in the freeze-thaw cycles and results in poor food quality. This study was undertaken to analyse the effects of recrystallisation on the changes of protein conformation and moisture migration within red seabream fillets after the freeze-thaw cycles. The UV second-derivative spectroscopy, intrinsic fluorescence measurement and Raman spectroscopy were employed to evaluate the protein conformational changes. The Low-field NMR spectra analysis was used to evaluate moisture migration. The results indicated that the freeze-thaw cycles altered the secondary and tertiary structure of proteins. It was noticed that interactions between water and protein molecules were decreased gradually and eventually induced the thermal instability of the myosin molecules. The immobilised water content declined and the free water content increased. There were significant destructions in fillet muscle microstructure. These observations unambiguously reflect how the recrystallisations affect the protein conformation and moisture migration patterns of red seabream fillets during freeze-thaw cycles.     

CYP2D6基因多态性对托烷司琼预防化疗所致恶心呕吐效果的影响

肿瘤对人类健康造成很大威胁。化疗作为一种全身性的治疗方法，在肿瘤治疗中的地位不可动摇。化疗所致恶心呕吐（chemotherapy induced nausea and vomiting, CINV）是化疗过程中常见的不良反应，严重影响了患者的情绪、生活质量和肿瘤的控制。CINV的防治对肿瘤患者来说非常重要。托烷司琼是较常用的5-羟色胺Ⅲ亚型（5-hydroxytryptamine type 3, 5-HT3）受体拮抗剂，在防治CINV方面具有很好的临床效果，但仍有部分患者使用托烷司琼后效果不佳。越来越多的研究表明这些个体差异可能与基因多态性密切相关。本文就细胞色素P450 2D6（cytochrome P450 2D6, CYP2D6）基因多态性对托烷司琼预防CINV效果的影响作一综述，以期为基因多态性指导下的临床个体化用药提供思路。     

pazopanib血药浓度个体差异与细胞色素P450 3A4基因多态性的关系初探

目的：分析健康受试者口服pazopanib片后体内药代动力学（PK）规律，初步探讨pazopanib片PK个体差异的遗传学机制。方法：14例健康男性受试者分别在给药当天单次口服pazopanib片（200 mg）后，采集基线至96 h血液样本，用LC-MS/MS法测定服药后各时间点血药浓度，用WinNonlin 6.3软件计算药代动力学相关参数，采用SNapShot法测定细胞色素P450 3A4（CYP3A4）基因多态性。结果：Cmax变化范围（7 361.65-26 081.00） ng/mL，平均值±标准差（15 410.72±6 366.21） ng/mL ；tmax变化范围（1.50-4.00） h、平均值±标准差（2.50±0.83） h；AUC0-t变化范围（228 013.55-775 231.63）ng·mL-1·h，平均值±标准差（516 279.90±175 688.41）ng·mL-1·h。个体间Cmax、AUC相差达3倍以上，tmax可相差2倍以上；14例受试者CYP3A4（RS35599367）位点皆为野生型。结论：pazopanib片在中国健康男性志愿者中个体差异较大，未观察到CYP3A4（rs35599367）位点单核苷酸多态性，pazopanib个体间PK差异可能与其他药物代谢相关基因多态性有关。