Ablative Radiotherapy Reprograms the Tumor Microenvironment of a Pancreatic Tumor in Favoring the Immune Checkpoint Blockade Therapy

The low overall survival rate of patients with pancreatic cancer has driven research to seek a new therapeutic protocol. Radiotherapy (RT) is frequently an option in the neoadjuvant or palliative settings for pancreatic cancer treatment. This study explored the effect of RT protocols on the tumor microenvironment (TME) and their consequent impact on anti-programmed cell death ligand-1 (PD-L1) therapy. Using a murine orthotopic pancreatic tumor model, UN-KC-6141, RT-disturbed TME was examined by immunohistochemical staining. The results showed that ablative RT is more effective than fractionated RT at recruiting T cells. On the other hand, fractionated RT induces more myeloid-derived suppressor cell infiltration than ablative RT. The RT-disturbed TME presents a higher perfusion rate per vessel. The increase in vessel perfusion is associated with a higher amount of anti-PD-L1 antibody being delivered to the tumor. Animal survival is increased by anti-PD-L1 therapy after ablative RT, with 67% of treated animals surviving more than 30 days after tumor inoculation compared to a median survival time of 16.5 days for the control group. Splenocytes isolated from surviving animals were specifically cytotoxic for UN-KC-6141 cells. We conclude that the ablative RT-induced TME is more suited than conventional RT-induced TME to combination therapy with immune checkpoint blockade.     

Tempering–preservation treatment inactivated lipase in wheat bran and retained phenolic compounds

Wheat bran is rich in functional ingredients, but the high level of lipase limits its applications. Tempering–preservation treatment (at 70–90 °C with moisture of 20%–40% for 1–4 h) was exploited for stabilising wheat bran and its effect on polyphenols was investigated. The results showed that more lipase was inactivated at higher tempering moisture, temperature and longer time. The optimum condition for inactivation of wheat bran lipase was 30% moisture and 90 °C for 4 h. The inactivation rate reached 93.8% with a residual enzyme activity of 0.264 U g⁻¹. Under the optimum condition, the sum of free phenolic acids rose from 25.4 to 55.8 µg g⁻¹. As for bound phenolic acids, there was a slight increase of hydroxybenzoic acid derivatives but a slight decrease of hydroxycinnamic acid derivatives. The total contents of phenolic acids before and after stabilisation were not significantly different. This study showed the possibility of using tempering–preservation as an efficient method for inactivation of wheat bran lipase while maintaining its phenolic compounds, which could be used in the production of whole wheat flour.     

A Dual Inhibitor of DYRK1A and GSK3β for β-Cell Proliferation: Aminopyrazine Derivative GNF4877

Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation.     

低温脂肪酶产生菌的筛选、鉴定及其部分酶学性质

从南极乔治王岛冻土来源的76株低温细菌中筛选到13株低温脂肪酶产生菌，对其中的BTsl0022菌株进行鉴定。通过生理生化特征、16s rDNA基因序列的同源性和系统发育分析发现，菌株RTsl0022属于假单胞菌属(Pseudomonas)，但与已定名的假单胞菌有一定的差异，与未定名的Pseudomonas sp．PsB的亲缘关系最接近，故将其暂定名为Pseudomonas sp．BTsl0022。对该菌脂肪酶的酶学性质初步研究表明，酶的最适作用温度为24℃，对热敏感，60℃处理30min仅残留25％酶活性，酶的适宜作用pH范围在7．0～9．0，最适pH为8．0。     

Monoacylglycerols derived from butter oil by Penicillium roquefortii in suspension cultures

Structural isomers of monoacylglycerols (monoglycerides, MAGs) were identified and compared after degradation of butter oil by two strains of Penicillium roquefortii and a commercial lipase from P roquefortii (EC 3.1.1.3) at pH 7.0 and 10 °C. The conditions were selected as they were comparable with those used in the manufacture of blue mould‐ripened cheese. The commercial lipase was selected to compare with the fungal strains in terms of acyl migration. Results showed that the main isomers formed by lipolysis with the commercial lipase were sn‐2 MAGs (64 mol%), whilst spores and emerging mycelia of P roquefortii produced mainly sn‐1(3) MAGs (83–90 mol%). The work reported here may lead to further assessment of different MAG structural isomers as natural preservatives in foods and dairy products. © 2002 Society of Chemical Industry     

甘三酯立体专一分析的研究：（Ⅱ）甘三酯立体专一分析方法初探

在第一部分综合讨论的基础上对甘三酯立体专一分析方法作了初步探讨。以液体油(菜油)及固体脂(猪脂)为基质,系统地研究了这一分析方法,取得了经验并补充了一些具体验证方法。分析液体油的结果与文献数据相一致,分析猪脂的结果欠佳,还存在一些问题需待进一步研究。     

Impact of the addition of an enzyme pool on an activated sludge system treating dairy wastewater under fat shock loads

BACKGROUND: The application of lipase‐rich enzyme pools (such as the crude solid enzymatic preparation (SEP) obtained from Penicillium restrictum solid‐state fermentation of agro‐industrial wastes) to activated sludge systems may be an effective strategy for preventing various operational problems. The continuous addition of SEP to the treatment system can become cost‐prohibitive when in situ production and/or storage are factored in. The application of SEP to high‐fat wastewater treatment would only be justified as an emergency measure, such as a sudden increase in the fat content of the bioreactor influent. Therefore, the primary objective of this work was to investigate the efficiency of a crude SEP during fat shock loads, simulated through the periodic addition of dairy industry waste containing high fat concentrations to the feed stock of an activated sludge system, operated in continuous mode. RESULTS: The test bioreactor exhibited a higher average chemical oxygen demand (COD) removal efficiency than the control bioreactor (83% for control and 90% for test) and the fat accumulation in the biological flocs of the test bioreactor was 3.2 times lower than that in the control bioreactor. Turbidity was also lower in the effluent of the test bioreactor (123 and 66 FTU in control and test, respectively) and it had a shorter recovery time between shock loads, especially when the interval between loads was shorter than one month (biweekly and weekly shock loads). CONCLUSION: The addition of SEP during fat overloads in the reactor feed maintained efficient COD removal in the test bioreactor for 270 days without any operational problems. Copyright © 2008 Society of Chemical Industry     

Lipase‐catalyzed dynamic kinetic resolution of (R,S)‐fenoprofen thioester in isooctane

A lipase‐catalyzed enantioselective hydrolysis process under in situ racemization of the remaining (R)‐thioetser substrate with trioctylamine as the catalyst was developed for the production of (S)‐fenoprofen from (R,S)‐fenoprofen 2,2,2‐trifluoroethyl thioester in isooctane. Detailed investigations of trioctylamine concentration on the enzyme activation and the kinetic behavior of the thioester in racemization and enzymatic reactions were conducted, in which good agreement between the experimental data and theoretical results was observed. © 2002 Society of Chemical Industry