Enhanced conversion of sterols to steroid synthons by augmenting the peptidoglycan synthesis gene pbpB in Mycobacterium neoaurum

Some species of mycobacteria have been modified to transform sterols to valuable steroid synthons. The unique cell wall of mycobacteria has been recognized as an important organelle to absorb sterols. Some cell wall inhibitors (e.g., vancomycin and glycine) have been validated to enhance sterol conversion by interfering with transpeptidation in peptidoglycan biosynthesis. Therefore, two transpeptidase genes, pbpA and pbpB, were selected to rationally modify the cell wall to simulate the enhancement effect of vancomycin and glycine on sterol conversion in a 22‐hydroxy‐23,24‐bisnorchol‐4‐ene‐3‐one (4‐HBC) producing strain (WIII). Unexpectedly, the pbpA or pbpB gene augmentation was conducive to the utilization of sterols. The pbpB augmentation strain WIII‐pbpB was further investigated for its better performance. Compared to WIII, the morphology of WIII‐pbpB was markedly changed from oval to spindle, indicating alterations of the cell wall. Biochemical analysis indicated that the altered cell wall properties of WIII‐pbpB might contribute to the positive effect on sterol utilization. The productivity of 4‐HBC was enhanced by 28% in the WIII‐pbpB strain compared to that of WIII. These results demonstrated that the modification of peptidoglycan synthesis can improve the conversion of sterols to steroid synthons in mycobacteria.     

Referencing the trochlear groove based on three-dimensional computed tomography imaging improves the reliability of the measurement of the tibial tuberosity–trochlear groove distance in patients with higher grades of trochlea dysplasia

BackgroundTo determine whether 3D-CT imaging technique is valid and reproducible compared to conventional CT measurement technique (CCT) for the detection of a femoropatellar instability.MethodsPatients who had undergone surgery for femoropatellar instability (patellar instability group) between 2010 and 2016 (n = 37 knees of 35 patients) were retrospectively enrolled. For the matched control group, patients who had acute anterior cruciate ligament injury (< 4 weeks previously; n = 30) were recruited. Preoperative CT data had been obtained in all patients. Inter-rater reliability was calculated for both measurement protocols, and inter-method reliability was calculated between the two imaging modalities. The results are reported using intraclass correlation coefficients (ICCs) and Bland–Altman 95% limits of agreement.ResultsAll patients in the patellar instability group had femoral trochlear dysplasia (Dejour types A: four, B: 19, C: seven, and D: six), but no dysplasia was noted in the control group. In the patellar instability group, the CCT technique showed a poor inter-rater agreement (ICC = 0.74), and the 3D-CT technique still showed excellent inter-rater agreement (ICCs = 0.91). In the sub-analysis of the patellar instability group according to the trochlear dysplasia grade, ICCs were markedly decreased with severe trochlear dysplasia when using CCT technique; however, the 3D-CT technique could provide excellent reliability even with severe trochlear dysplasia.ConclusionThe 3D-CT imaging technique for the measurement of the TT–TG distance can be suggested as a better measurement technique for patellar instability patients with bone abnormality.     

血糖、血脂水平与糖尿病视网膜病变患者视力损害的相关性研究

目的探讨血糖、血脂水平与糖尿病视网膜病变患者视力损害的相关性。方法选取2016年1月至2018年1月我院内分泌科收治的250例DR患者进行研究。根据视力分级标准分为三个组:盲组(n=28),低视力组(n=80),低视力以上组(n=142)。比较各组患者FPG、HbAlC、TC、TG、LDL-C、HDL-C、LDL-C/HDL-C、ApoB、ApoA1、ApoB/ApoA1水平,对FPG、HbA1C、LDL-C/HDL-C及ApoB/ApoA1与DR患者视力损害进行Pearman相关性分析和Logistic回归分析。结果三组患者的TC、TG差异均无统计学意义(P>0.05);与低视力以上组相比,盲组和低视力组FPG、HbAlC、LDL-C、LDL-C/HDL-C、ApoB、ApoB/ApoA1更高,HDL-C、ApoA1更低(P<0.05);盲组FPG、HbAlC、LDL-C、LDL-C/HDL-C、ApoB、ApoB/ApoAl显著高于低视力组,HDL-C、ApoA1显著低于低视力组(P<0. 05)。经Spearman相关性分析,FPG、HbAlC、LDL-C/HDL-C、ApoB/ApoA1比值与DR患者视力损害均呈正相关。经Logistic回归分析,FPG、HbAlC、LDL-C/HDL-C、ApoB/ApoA1均是DR患者视力损害的独立危险因素。结论 FPG、HbAlC、LDL-C/HDL-C、ApoB/ApoA1与DR患者的视力损害有密切关系,通过监测这些指标有利于DR患者视力损害的预测,及时采取治疗措施。     

心可舒片对房颤合并焦虑状态患者的临床疗效及对皮质醇和甲状腺素水平的影响

目的观察心可舒片治疗房颤合并焦虑状态患者的临床疗效及其对皮质醇和甲状腺素水平的影响。方法入选我院2017年1月至2017年10月收治的房颤合并焦虑状态患者34例,随机分为心可舒治疗组18例及对照组16例,治疗组予以心可舒片口服,观察治疗1月后两组患者的临床症状,并测定治疗前后的皮质醇和甲状腺素水平进行组间对比。结果治疗组患者临床症状较对照组进一步改善,且治疗组皮质醇激素水平较治疗前明显下降,与对照组相比差异具有统计学意义(P<0.05),治疗组T4水平较对照组升高(P<0.05),余甲状腺素水平两组患者差异无统计学意义。结论心可舒片可用于治疗房颤合并焦虑状态的患者,改善症状的同时可降低肾上腺皮质激素皮质醇及升高T4水平。     

Y染色体AZF微缺失在男性不育患者中的临床研究

目的研究男性不育患者的Y染色体AZF微缺失情况,分析Y染色体AZF微缺失与性激素水平及男性不育之间的关系。方法选取医院2017年1月至2018年7月收治的120例男性不育患者(其中包含98例非梗阻无精子症患者和22例严重少精症患者),和40例同期体检精液参数正常的体检人员作为研究对象,分别设为A组、B组和对照组,对比分析3组受试者的Y染色体AZF微缺失情况以及性激素指标水平。结果120例男性不育患者中共检出16例Y染色体AZF微缺失,A组的缺失率为14.29%,B组为9.09%,对照组未发现缺失,A组的缺失率显著高于对照组(P<0.05)。16例Y染色体AZF微缺失的患者中,共包含12个位点缺失,其中单纯AZFb型、AZFb+c型、AZFc+d型和AZFb+c+d型分别3例、2例、10例和1例;3组的睾酮水平无明显差别(P>0.05),A组的黄体生成素和促卵泡生成素水平显著高于对照组(P<0.05);AZFb+c+d型基因缺失患者的FSH指标水平显著高于无AZF基因缺失和AZFb型、AZFb+c型、AZFc+d型缺失患者(P<0.05)。结论Y染色体AZF基因微缺失可能是影响非梗阻性无精子症的重要因素之一,男性不育症患者的Y染色体AZF微缺失与患者的FSH水平具有密切关系,在临床诊治中,Y染色体AZF基因检测能够为男性不育症诊断提供更加科学的依据。     

Preparation of Light‐Responsive Aliphatic Polycarbonate via Versatile Polycondensation for Controlled Degradation

Starting from (2,2,5‐trimethyl‐1,3‐dioxan‐5‐yl)methanamine with light‐responsive 4,5‐dimethoxy‐2‐nitrobenzyl protecting groups, a variety of light‐responsive copolycarbonates (LrPCs) are synthesized by a general two‐step polycondensation using lithium acetylacetonate (LiAcac) as catalyst. UV/Vis, ¹H nuclear magnetic resonance (NMR), and size exclusion chromatography (SEC) confirm the rapid decomposition of these polymers in response to irradiation with UV light. Stable and monodisperse nanoparticles with hydrodynamic diameters of 100 nm, formulated from 25% LrPC and 75% poly(lactic‐co‐glycolic acid) (PLGA), undergo rapid disruption upon triggering with UV light, while standard PLGA nanoparticles remain stable. Moreover, differing from the ring‐opening polymerization (ROP) of trimethylene carbonate‐based monomers, direct polycondensation of 1,3‐propanediol‐based monomers with pendent functional groups and other diols will enable the introduction of various properties into the polycarbonate backbone, and expand the family of biodegradable synthetic polymers for potential biomedical applications.     

The influence of ICAM1 rs5498 on diabetes mellitus risk: evidence from a meta-analysis

Inflammation Research - Both type 1 diabetes (T1D) and type 2 diabetes (T2D) are classified as forms of diabetes mellitus (DM) and commonly considered inflammatory process. Intercellular adhesion...     

TNF-α/calreticulin dual signaling induced NLRP3 inflammasome activation associated with HuR nucleocytoplasmic shuttling in rheumatoid arthritis

Inflammation Research - The present study was undertaken to validate whether TNF-α and calreticulin (CRT) serve as dual signaling to activate nucleotide-binding oligomerization domain-,...     

Novel missense mutation in VPS33B is associated with isolated low gamma‐glutamyltransferase cholestasis: Attenuated,incomplete phenotype of arthrogryposis,renal dysfunction,and cholestasis syndrome

The typical phenotype of arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome involves three cardinal symptoms as the name describes, harboring biallelic mutations on VPS33B or VIPAS39. Except for ARC syndrome, low gamma‐glutamyltransferase (GGT) cholestasis often implies hereditary hepatopathy of different severity; however, some remain undiagnosed. Several monogenic defects typically with multiorgan manifestations may only present liver dysfunction at times, such as DGUOK defect and AGL defect. Previously, four VPS33B mutated cases were reported without arthrogryposis, or with less severe symptoms and longer lifespan, indicating the possibility of incomplete ARC phenotype of isolated hepatopathy. So we retrospectively reviewed all patients with confirmed VPS33B/VIPARS39 defect in our center and identified three presenting isolated low‐GGT cholestasis with intractable pruritus. Distinguished from others with typical ARC phenotype, these patients did not suffer the other two typical characteristics, survived much longer, and shared a novel missense VPS33B variation c.1726T>C, p.Cys576Arg, causing declined protein expression and abolished interaction with VIPAS39 in‐vitro. Serum bile acid profiles of our VPS33B/VIPAS39 mutated patients revealed similar changes to primary defect of bile salt export pump, among which those with isolated cholestasis phenotype had a higher level of total secondary bile acids than that with typical ARC phenotype, indicating the partial residual function of VPS33B.