Characterization of the putative tryptophan synthase β-subunit from Mycobacterium tuberculosis

The increasing emergence of drug-resistant tuberculosis （TB） poses a serious threat to the control of this disease. It is in urgent need to develop new TB drugs. Tryptophan biosynthetic pathway plays an important role in the growth and replication of Mycobacterium tuberculosis （Mtb）. The β-subunit of tryptophan synthase （TrpB） catalyzes the last step of the tryptophan biosynthetic pathway, and it might be a potential target for TB drug design. In this study, we overexpressed, purified, and characterized the putative TrpB-encoding gene Rv1612 in Mtb H37Rv. Results showed that Mtb His-TrpB optimal enzymatic activity is at pH 7.8 with 0.15 M Na^＋ or 0.18 M Mg^2＋ at 37℃. Structure analysis indicated that Mtb TrpB exhibited a typical β/α barrel structure. The amino acid residues believed to interact with the enzyme cofactor pyridoxal-5＇-phosphate were predicted by homology modeling and structure alignment. The role of these residues in catalytic activity of the Mtb His-TrpB was confirmed by site-directed mutagenesis. These results provided reassuring structural information for drug design based on TrpB.     

生长激素受体及其介导的信号转导

生长激素受体(growth hormone receptor,GHR)是细胞因子／造血因子受体超级家族的一员。它通过二聚体的形式和生长激素(growth hormone,GH)相结合,然后诱发Janus激酶2(Janus kinase 2,JAK2)等细胞因子酪氨酸磷酸化并通过4条不同的途径将信号传入细胞内从而产生一系列的生理效应。现在了解GHR的结构特征、组织分布的基础上,对其介导的信号转导途径作进一步的阐明。     

Dihydroartemisinin-Piperaquine vs. Artemether-Lumefantrine for First-Line Treatment of Uncomplicated Malaria in African Children: A Cost-Effectiveness Analysis

Background

Recent multi-centre trials showed that dihydroartemisinin-piperaquine (DP) was as efficacious and safe as artemether-lumefantrine (AL) for treatment of young children with uncomplicated P. falciparum malaria across diverse transmission settings in Africa. Longitudinal follow-up of patients in these trials supported previous findings that DP had a longer post-treatment prophylactic effect than AL, reducing the risk of reinfection and conferring additional health benefits to patients, particularly in areas with moderate to high malaria transmission.

Methods

We developed a Markov model to assess the cost-effectiveness of DP versus AL for first-line treatment of uncomplicated malaria in young children from the provider perspective, taking into consideration the post-treatment prophylactic effects of the drugs as reported by a recent multi-centre trial in Africa and using the maximum manufacturer drug prices for artemisinin-based combination therapies set by the Global Fund in 2013. We estimated the price per course of treatment threshold above which DP would cease to be a cost-saving alternative to AL as a first-line antimalarial drug.

Results

First-line treatment with DP compared to AL averted 0.03 DALYs (95% CI: 0.006–0.07) and 0.001 deaths (95% CI: 0.00–0.002) and saved $0.96 (95% CI: 0.33–2.46) per child over one year. The results of the threshold analysis showed that DP remained cost-saving over AL for any DP cost below $1.23 per course of treatment.

Conclusions

DP is superior to AL from both the clinical and economic perspectives for treatment of uncomplicated P. falciparum malaria in young children. A paediatric dispersible formulation of DP is under development and should facilitate a targeted deployment of this antimalarial drug. The use of DP as first-line antimalarial drug in paediatric malaria patients in moderate to high transmission areas of Africa merits serious consideration by health policymakers.     

Ordered Hexagonal Nanoplasmonic Au Nanoparticle Arrays: AAO-Assisted Thermal Treatment Synthesis and Application as Surface-Enhanced Raman Scattering Substrates

We have reported on the synthesis of ordered hexagonal Au nanoparticle (NPs) arrays by anodic alumina oxide templates (AAO)-assisted thermal treatment. This simple process has led to the formation of an ordered hexagonal array of Au NPs on the surface of AAO. SERS properties of the ordered hexagonal Au NPs could be obtained by varying the size of Au NPs. Compared with the Au thin film on AAO, the SERS intensity of rhodamine adsorbed on the ordered hexagonal Au NPs was about 1000 times stronger. And the hexagonal Au NPs array films have had stronger Raman-enhanced signal compared to the disorder Au NPs films. Simulations according to the three-dimensional finite-difference time domain (3D-FDTD) have displayed that these electric field enhancements of the ordered hexagonal Au NPs are strongly dependent on the gap distance. Plasmonic ordered hexagonal Au NPs could provide us new platforms to realize novel optoelectronic devices.

     

Interrogation of phosphor-specific interaction on a high-throughput label-free optical biosensor system–Epic® system

The Epic^® system, a high-throughput label-free optical biosensor system, is applied for the biochemical interrogation of phosphor-specific interactions of the 14-3-3 protein and its substrates. It has shown the capability not only for high-throughput characterization of binding rank and affinity but also for the exploration of potential interacting kinases for the substrates. A perspective of biochemical applications for diagnostics and biomarker discovery, as well as cell-based applications for endogenous receptors and viral infection characterization, are also provided.     

五种食用菌氨基酸含量的测定及营养评价

研究测定了五种食用菌中氨基酸的含量,并利用五种非生物学指标对蛋白质的营养价值进行评价。五种食用菌氨基酸种类齐全,必需氨基酸占氨基酸总量的百分比分别达到45.94%、37.62%、42.45%、41.54%、35.98%。茶树菇和姬松茸的限制性氨基酸为半胱氨酸和甲硫氨酸,鸡腿菇、香菇和黑木耳的限制性氨基酸是缬氨酸。不同的评价指标对蛋白质进行营养评价,评价结果会有所差异。     

The protective effects of C16 peptide and angiopoietin-1 compound in lipopolysaccharide-induced acute respiratory distress syndrome

C16 peptide and angiopoietin-1 (Ang-1) have been found to have anti-inflammatory activity in various inflammation-related diseases. However, their combined role in acute respiratory distress syndrome (ARDS) has not been investigated yet. The objective of this study was to investigate the effects of C16 peptide and Ang-1 in combination with lipopolysaccharide (LPS)-induced inflammatory insult in vitro and in vivo. Human pulmonary microvascular endothelial cells and human pulmonary alveolar epithelial cells were used as cell culture systems, and an ARDS rodent model was used for in vivo studies. Our results demonstrated that C16 and Ang-1 in combination significantly suppressed inflammatory cell transmigration by 33% in comparison with the vehicle alone, and decreased the lung tissue wet-to-dry lung weight ratio to a maximum of 1.53, compared to 3.55 in the vehicle group in ARDS rats. Moreover, C  +  A treatment reduced the histology injury score to 60% of the vehicle control, enhanced arterial oxygen saturation (SO₂), decreased arterial carbon dioxide partial pressure (PCO₂), and increased oxygen partial pressure (PO₂) in ARDS rats, while also improving the survival rate from 47% (7/15) to 80% (12/15) and diminishing fibrosis, necrosis, and apoptosis in lung tissue. Furthermore, when C  +  A therapy was administered 4 h following LPS injection, the treatment showed significant alleviating effects on pulmonary inflammatory cell infiltration 24 h postinsult. In conclusion, our in vitro and in vivo studies show that C16 and Ang-1 exert protective effects against LPS-induced inflammatory insult. C16 and Ang-1 hold promise as a novel agent against LPS-induced ARDS. Further studies are needed to determine the potential for C16 and Ang-1 in combination in treating inflammatory lung diseases.