Though all the marketed drugs of dipeptidyl peptidase IV inhibitors are structurally different, their inherent correlation is worthy of further investigation. Herein we rapidly discovered a novel DPP-IV inhibitor 8g (IC50 = 4.9 nmol.L-1) which exhibits as good activity and selectivity as the market drugs through scaffold hopping and drug splicing strategies based on alogliptin and linagliptin. This study demonstrated that the employment of classic medicinal chemistry strategy to the marketed drugs with specific target is an efficient approach to discover novel bioactive molecules.

Humans ; Liver Cirrhosis ; Renin-Angiotensin System ; Self-Control

Objective To investigate association of vitamin D receptor (VDR) polymorphisms with susceptibility to psoriasis vulgaris and clinical response to calcipotriol in patients with psoriasis vulgaris.Methods A total of 110 patients with psoriasis vulgaris and 183 healthy controls were enrolled into this study,and they were all of Han nationality from Hainan province.Ligase detection reaction (LDR) was conducted to determine the genotypes of VDR gene polymorphisms rs2228570,rs731236,rs1544410 and rs7975232.Single nucleotide polymorphism (SNP)-based association analysis in genotypic and allelic models,and haplotype-based association analysis were then performed.Then,75 patients with psoriasis area and severity index (PASI) scores less than 10 were topically treated with calcipotriol ointment alone.After 6-week treatment,the efficacy of calcipotriol ointment was evaluated,and the correlation between the efficacy and individual genotypes was analyzed.Results The frequency of A allele of rs7975232 in the psoriasis group and control group was 39.09％ and 27.05％ respectively,and the risk of developing psoriasis in rs7975232 A allele carriers was significantly higher than that in non-carriers (OR =1.731,95％ CI:1.213-2.471,P ＜ 0.05).Additionally,the risk of developing psoriasis in individuals with AA genotype (OR =2.404,95％ CI:1.085-5.328,P ＜ 0.05),as well as in individuals with AC genotype (OR =2.143,95％ CI:1.283-3.579,P ＜ 0.05),was significantly higher than that in patients with CC genotype.CTGA haplotype carriers (rs2228570,rs731236,rs1544410,rs7975232,respectively) had significantly higher risk of developing psoriasis compared with non-carriers (OR =1.907,95％ CI:1.132-3.214,P ＜ 0.05).Among 72 patients with mild-to-moderate psoriasis whose PASI scores were less than 10,patients with CC genotype of rs7975232 showed better response to calcipotriol ointment compared with those with AC genotype (OR =3.798,95％ CI:1.061-13.590,P ＜ 0.05) and those with AA genotype (OR =9.667,95％CI:1.556-60.040,P ＜ 0.05).Conclusion VDR polymorphisms are associated with psoriasis susceptibility and clinical response to calcipotriol in patients with psoriasis individuals.

Objective To study gross α and gross β radioactivity in environmental samples in Wuxi, China, and perfect the radioactivity data, and to discover possible radioactive contamination in time. Methods The BH1227 low-background α and β measuring instrument was used to determine gross α and gross β radioactivity in sedimentary dust, aerosol, drinking water, and food samples in Wuxi. Results Among environmental samples collected in Wuxi, 2014—2019, the mean gross α and gross β radioactivity levels were 0.01～5.98 Bq/kg and 9.47～547.86 Bq/kg in food samples, respectively, 1.2～22 mBq/L and 0.1～141 mBq/L in water samples, respectively, 39～44790 mBq/m³ and 743.1～101500 mBq/m³ in sedimentary dust samples, respectively, and 50～1125 μBq/m³ and 38～9510 μBq/m³ in aerosol samples, respectively. Conclusion We should strengthen radioactivity monitoring of environmental samples in Wuxi through increasing the scope and frequency of monitoring, to perfect baseline radioactivity data of Wuxi.