A non-metal route to realize the bio-based polyester of poly(hexylene succinate): preparation conditions,side-reactions and mechanism in sulfonic acid-functionalized Brønsted acidic ionic liquids

A biodegradable linear bio-based polyester of poly(hexylene succinate) was effectively prepared in non-metal sulfonic acid-functionalized Brønsted acidic ionic liquids (SFBAILs) as both the catalyst and the polymerization medium, and the processes of polycondensation and post-polycondensation in SFBAILs were also investigated. In addition, the side reactions which were detrimental to the growth of M_w of poly(hexylene succinate) were evaluated and the synthesis mechanism of poly(hexylene succinate) catalyzed by SFBAILs was discussed with the help of DFT calculations. The result shows that both the imidazole ring and the sulfonic group on cations of SFBAILs play an important role in the catalytic process.

Biobased poly(hexylene succinate) synthesized in sulfonic acid-functionalized Brönsted acidic ionic liquids was monitored by ¹H NMR spectra and DFT calculations.     

A meta-analysis of the associations between the Q141K and Q126X ABCG2 gene variants and gout risk

Background: Gout is an inflammatory disease in which genetic factors play a role. ABCG2 is a urate transporter, and the Q141K and Q126X variants of ABCG2 have been associated with a risk of developing gout, though previous studies of these associations have been inconsistent. Therefore, we conducted a meta-analysis to explore the relationship between these genetic variants and gout. Methods: We examined 8 electronic literature databases. In total, 9 eligible articles on the associations between the Q141K (rs2231142) and Q126X (rs72552713) variants and gout risk, including 11 case-control studies were selected. We used odds ratios (OR) and 95% confidence intervals (CI) to assess the strength of these relationships in dominant, recessive, and co-dominant models. Results: This study included 6652 participants (2499 gout patients and 4153 controls). The Q141K variant was found to significantly increase the risk of gout in Asians (dominant model: OR=2.64, 95% CI=2.04-3.43, P=0.02 for heterogeneity; recessive model: OR=3.19, 95% CI=2.56-3.97, P=0.28 for heterogeneity; co-dominant model: OR=1.37, 95% CI=1.18-1.59, P=0.09 for heterogeneity) and other populations (dominant model: OR=1.85, 95% CI=1.20-2.85, P<0.0001 for heterogeneity; recessive model: OR=3.78, 95% CI=2.28-6.27, P=0.19 for heterogeneity; co-dominant model: OR=1.48, 95% CI=1.26-1.74, P=0.19 for heterogeneity). The Q126X variant also significantly increased the risk of gout in Asians (dominant model: OR=3.87, 95% CI=2.07-7.24, P=0.06 for heterogeneity). Conclusions: These results suggest associations between the rs2231142 and rs72552713 ABCG2 gene polymorphisms and gout risk, which led to unfavorable outcomes. However, studies with larger sample sizes and homogeneous populations should be performed to confirm these results.     

Knockdown of WISP1 inhibit proliferation and induce apoptosis in ALL Jurkat cells

WISP1, a Wnt-induced secreted protein, has been found to have anticancer activity. ALL is a leading cause of death. Here we investigate the WISP1 effects on ALL Jurkat cells. Cell viability was assessed by CCK-8. Cell cycle and apoptosis were detected by flow cytometry. Mitochondrial membrane potential (MMP) was monitored using TMRM. Generation of reactive oxygen species (ROS) was quantified using DCFH-DA. Western blot was used to detect the expression of cell proliferation and apoptosis related genes. The results showed that knockdown of WISP1 significantly inhibited proliferation of Jurkat cells. Parallelly, cell cycle distribution was increased at G1 phase and apoptotic rate was induced after WISP1 knockdown. Furthermore, knockdown of WISP1 induced apoptosis of Jurkat cells was also associated with loss of MMP and generation of ROS. Western blot results showed that the protein expression p-AKT, PCNA, CDK1, P-ERK, CDK2, VEGF, VEGFR2 and Bcl2 were decreased, while the expression of Bax was up-regulated. In conclusion, WISP1 plays an important role in proliferation and apoptosis of Jurkat cells in mitochondria dependent pathway, the specific mechanisms need further study.     

热敏灸联合身痛逐瘀汤治疗腰椎间盘突出症微创术后残留症状的临床研究

[目的]观察热敏灸联合身痛逐瘀汤治疗腰椎间盘突出症微创术后残留腰腿痛的临床疗效。[方法]将2019年3月至2019年12月浙江省中西医结合医院66例符合纳入标准的患者随机分为A组、B组、C组,每组各22例,A组予热敏灸联合身痛逐瘀汤治疗,B组予身痛逐瘀汤治疗,C组予热敏灸治疗。14d治疗结束后,合格病例计66例,采用视觉模拟评分(visual analogue scale,VAS)、日本骨科协会(Japanese Orthopaedic Association,JOA)评分、健康量表评分(36-Item Short Form Survey,SF-36)评估疗效,同时以安全性指标评价治疗安全性。[结果]A组、B组、C组总有效率分别为95-5%、77-3%、81-8%,三组间差异具有统计学意义(P=0-027),A组显著优于B组与C组(P=0-023,P=0-015)。与治疗前比较,三组治疗后的JOA评分均明显升高、VAS评分显著降低(P＜0-05);组间比较,A组JOA评分显著高于B组与C组(P＜0-05),VAS评分明显低于B组和C组(P＜0-05),而B组与C组之间差异无统计学意义(P＞0-05)。除情感功能和社会职能两项,A组SF-36评分均优于B组、C组(P＜0-05),B组与C组间比较各有优劣,但差异无统计学意义(P＞0-05)。本研究过程中无任何明显不良事件的报告。[结论]热敏灸配合身痛逐瘀汤对缓解腰椎间盘突出症微创术后残留症状的疗效显著,明显优于单独使用热敏灸或身痛逐瘀汤,并能有效提高患者术后的生活质量。     

不同密度胸腺囊肿CT表现差异及其病理基础

目的：探讨不同密度胸腺囊肿CT表现差异及其病理基础。方法：回顾分析手术病理证实的45例实性密度胸腺囊肿和23例液性密度胸腺囊肿CT表现及其病理改变。结果：胸腺囊肿密度与囊肿大小有相关性（P＜0.01）。实性密度囊肿形态多较规则,液性密度囊肿以不规则、沿大血管间隙塑形多见,组间分布差异有统计学意义（P＜0.01）。泪滴状及三角状在2组均可见,组间分布差异无统计学意义（P＞0.05）。实性密度囊肿多不膨隆于胸腺轮廓,与液性密度相比差异有统计学意义（P＜0.01）。实性密度胸腺囊肿病理表现为有分泌功能的假复层纤毛柱状上皮或纤毛柱状上皮覆盖,囊壁上皮细胞排列较密实,囊液多浑浊;液性密度胸腺囊肿被覆表面为无分泌功能扁平或柱状上皮为主,排列稀疏甚至缺失,基层薄弱,囊液往往较清亮。囊肿密度与被覆上皮类型有相关性（P＜0.05）。结论：胸腺实性密度囊肿与液性密度囊肿影像学表现有差异,病理基础对理解不同表现胸腺囊肿有帮助。     

Bacterial expression of mutant argininosuccinate lyase reveals imperfect correlation of in-vitro enzyme activity with clinical phenotype in argininosuccinic aciduria

Background

The urea cycle defect argininosuccinate lyase (ASL) deficiency has a large spectrum of presentations from highly severe to asymptomatic. Enzyme activity assays in red blood cells or fibroblasts, although diagnostic of the deficiency, fail to discriminate between severe, mild or asymptomatic cases. Mutation/phenotype correlation studies are needed to characterize the effects of individual mutations on the activity of the enzyme.

Methods

Bacterial in-vitro expression studies allowed the enzyme analysis of purified mutant ASL proteins p.I100T (c.299?T?>?C), p.V178M (c.532?G?>?A), p.E189G (c.566A?>?G), p.Q286R (c.857A?>?G), p.K315E (c.943A?>?G), p.R379C (c.1135?C?>?T) and p.R385C (c.1153?C?>?T) in comparison to the wildtype protein.

Results

In the bacterial in-vitro expression system, ASL wild-type protein was successfully expressed. The known classical p.Q286R, the novel classical p.K315E and the known mutations p.I100T, p.E189G and p.R385C, which all have been linked to a mild phenotype, showed no significant residual activity. There was some enzyme activity detected with the p.V178M (5 % of wild-type) and p.R379C (10 % of wild-type) mutations in which K_m values for argininosuccinic acid differed significantly from the wild-type ASL protein.

Conclusion

The bacterially expressed enzymes proved that the mutations found in patients and studied here indeed are detrimental. However, as in the case of red cell ASL activity assays, some mutations found in genetically homozygous patients with mild presentations resulted in virtual loss of enzyme activity in the bacterial system, suggesting a more protective environment for the mutant enzyme in the liver than in the heterologous expression system and/or in the highly dilute assays utilized here.