Associations between TNF-α-308A/G Polymorphism and Susceptibility with Dermatomyositis: A Meta-Analysis

Background

Some surveys had inspected the effects of the tumor necrosis factor-α (TNF-α)-308A/G polymorphism on susceptibility to dermatomyositis (DM), and showed mixed results. To briefly review these consequences, a comprehensive meta-analysis was carried out to estimate the relationship between them much more accurately.

Methods

Relevant documents dated to February 2014 were acquired from the PUBMED, MEDLINE, and EMBASE databases. The number of the genotypes and/or alleles for the TNF-α-308A/G in the DM and control subjects was extracted and statistical analysis was conducted using STATA 11.2 software. Summary odds ratios (ORs) with their 95% confidence intervals (95% CIs) were used to calculate the risk of DM with TNF-α-308A/G. Stratified analysis based on ethnicity and control population source was also performed.

Results

555 patients with DM and 1005 controls from eight published investigations were finally involved in this meta-analysis. Combined analysis revealed that the overall ORs for the TNF-α-308A allele were 2.041 (95% CIs 1.528–2.725, P<0.0001) in DM. Stratification by ethnicity indicated the TNF-α-308A allele polymorphism was found to be significantly associated with DM in Europeans (OR = 1.977, 95% CI 1.413–2.765, P<0.0001). The only study conducted on TNF-α-308A/G polymorphism in Asians could not be used in ethnicity-stratified meta-analysis. Meta-analysis of the AA+AG vs. GG (dominant model) and AA vs. GG (additive model) of this polymorphism revealed a significant association with DM in overall populations and Europeans.

Conclusions

Our meta-analysis demonstrated that the TNF-α-308A/G polymorphism in the TNF gene might contribute to DM susceptibility, especially in European population. However, further studies with large sample sizes and among different ethnicity populations should be required to verify the association.     

TaTPP-7A positively feedback regulates grain filling and wheat grain yield through T6P-SnRK1 signalling pathway and sugar–ABA interaction

Grain size and filling are two key determinants of grain thousand-kernel weight (TKW) and crop yield, therefore they have undergone strong selection since cereal was domesticated. Genetic dissection of the two traits will improve yield potential in crops. A quantitative trait locus significantly associated with wheat grain TKW was detected on chromosome 7AS flanked by a simple sequence repeat marker of Wmc17 in Chinese wheat 262 mini-core collection by genome-wide association study. Combined with the bulked segregant RNA-sequencing (BSR-seq) analysis of an F₂ genetic segregation population with extremely different TKW traits, a candidate trehalose-6-phosphate phosphatase gene located at 135.0 Mb (CS V1.0), designated as TaTPP-7A, was identified. This gene was specifically expressed in developing grains and strongly influenced grain filling and size. Overexpression (OE) of TaTPP-7A in wheat enhanced grain TKW and wheat yield greatly. Detailed analysis revealed that OE of TaTPP-7A significantly increased the expression levels of starch synthesis- and senescence-related genes involved in abscisic acid (ABA) and ethylene pathways. Moreover, most of the sucrose metabolism and starch regulation-related genes were potentially regulated by SnRK1. In addition, TaTPP-7A is a crucial domestication- and breeding-targeted gene and it feedback regulates sucrose lysis, flux, and utilization in the grain endosperm mainly through the T6P-SnRK1 pathway and sugar–ABA interaction. Thus, we confirmed the T6P signalling pathway as the central regulatory system for sucrose allocation and source–sink interactions in wheat grains and propose that the trehalose pathway components have great potential to increase yields in cereal crops.     

Receptor‐like kinase OsSIK1 improves drought and salt stress tolerance in rice (Oryza sativa) plants

Receptor‐like kinases (RLKs) play essential roles in plant growth, development and responses to environmental stresses. A putative RLK gene, OsSIK1, with extracellular leucine‐rich repeats was cloned and characterized in rice (Oryza sativa). OsSIK1 exhibits kinase activity in the presence of Mn²⁺, and the OsSIK1 kinase domain has the ability to autophosphorylate and phosphorylate myelin basic protein (MBP). OsSIK1 promoter‐GUS analysis revealed that OsSIK1 is expressed mainly in the stem and spikelet in rice. The expression of OsSIK1 is mainly induced by salt, drought and H₂O₂ treatments. Transgenic rice plants with overexpression of OsSIK1 show higher tolerance to salt and drought stresses than control plants. On the contrary, the knock‐out mutants sik1‐1 and sik1‐2, as well as RNA interference (RNAi) plants, are sensitive to drought and salt stresses. The activities of peroxidase, superoxide dismutase and catalase are enhanced significantly in OsSIK1‐overexpressing plants. Also, the accumulation of H₂O₂ in leaves of OsSIK1‐overexpressing plants is much less than that of the mutants, RNAi plants and control plants, as measured by 3,3′‐diamino benzidine (DAB) staining. We also show that OsSIK1 affects stomatal density in the abaxial and adaxial leaf epidermis of rice. These results indicate that OsSIK1 plays important roles in salt and drought stress tolerance in rice, through the activation of the antioxidative system.     

Preparation and Characterization of a Silk Fibroin/Polyurethane Fiber Blend Membrane Containing Actinomycin X2 with Excellent Mechanical Properties and Enhanced Antibacterial Activities

Development of suitable antimicrobial biomaterials for hygienic wound dressing and healing is an important requirement for medical application. Durable mechanical properties increase the application range of biomaterial in different environmental and biological conditions. Due to the inherent brittleness of silk fibroin (SF), polyurethane fiber (PUF) was used to modify SF containing actinomycin X2 (Ac.X2) to prepare silk fibroin@actinomycin X₂/polyurethane fiber (ASF/PUF) blend membranes. The ASF/PUF blend membrane was developed by solution casting method. Incorporation of PUF improved the flexibility of material and introduction of Ac.X2 has increased antibacterial activity of materials. Excellent mechanical properties (tensile strength up to 25.7 MPa and elongation at break up to 946.5 %) of 50 % SF+50 % PUF blend membrane were proved by tensile testing machine. FT-IR spectra, TGA, contact angle and DMA were tested to prove the blend membrane's physico-chemical characteristics. ASF/PUF blend membrane displayed satisfactory antibacterial activity against S. aureus, and the cytotoxicity tests showed that the blend membrane has better biosafety compared to directly applied Ac.X2 in soluble form. These results suggest that the modification of SF through PUF for development of flexible antibacterial membranes has great potential application value in the field of silk-like material fabrication.     

Critical Structure Sparing in Stereotactic Ablative Radiotherapy for Central Lung Lesions: Helical Tomotherapy vs. Volumetric Modulated Arc Therapy

Background

Helical tomotherapy (HT) and volumetric modulated arc therapy (VMAT) are both advanced techniques of delivering intensity-modulated radiotherapy (IMRT). Here, we conduct a study to compare HT and partial-arc VMAT in their ability to spare organs at risk (OARs) when stereotactic ablative radiotherapy (SABR) is delivered to treat centrally located early stage non-small-cell lung cancer or lung metastases.

Methods

12 patients with centrally located lung lesions were randomly chosen. HT, 2 & 8 arc (Smart Arc, Pinnacle v9.0) plans were generated to deliver 70 Gy in 10 fractions to the planning target volume (PTV). Target and OAR dose parameters were compared. Each technique’s ability to meet dose constraints was further investigated.

Results

HT and VMAT plans generated essentially equivalent PTV coverage and dose conformality indices, while a trend for improved dose homogeneity by increasing from 2 to 8 arcs was observed with VMAT. Increasing the number of arcs with VMAT also led to some improvement in OAR sparing. After normalizing to OAR dose constraints, HT was found to be superior to 2 or 8-arc VMAT for optimal OAR sparing (meeting all the dose constraints) (p = 0.0004). All dose constraints were met in HT plans. Increasing from 2 to 8 arcs could not help achieve optimal OAR sparing for 4 patients. 2/4 of them had 3 immediately adjacent structures.

Conclusion

HT appears to be superior to VMAT in OAR sparing mainly in cases which require conformal dose avoidance of multiple immediately adjacent OARs. For such cases, increasing the number of arcs in VMAT cannot significantly improve OAR sparing.     

Combination of 1,4-naphthoquinone with benzothiazoles had selective algicidal effects against harmful algae

A series of naphthoquinone-benzothiazole conjugates were synthesized as algicides, and their efficacies against harmful algal blooming species, such as Chattonella marina, Heterosigma akashiwo and Cochlodinium polykrikoides, were examined. The introduction of substituted benzothiazole at the C2 position of 1,4-naphthoquinone (compounds 1–9) resulted in higher algicidal activity against C. polykrikoides than the C6 conjugates (compounds 10–20). On the other hand, of the C6 conjugates, compounds 11 and 12 exhibited better algicidal activity against H. akashiwo, C. marina, and C. polykrikoides than the C2 conjugates. Further structure-activity analysis indicated that a replacement of the methoxy groups with hydroxyl groups (compounds 21–26) decreased the algicidal activity significantly. Among the various synthetic naphthoquinonebezothiazole conjugates tested, compound 12 was found to affect the most significant decrease in the level of C. polykrikoides growth, with an IC₅₀ of 0.19 μM. Compound 11 was found to be the most potent inhibitor against H. akashiwo and C. polykrikoides, with IC₅₀ values of 0.32 and 0.12 μM, respectively. Overall, these results highlight a possible method for controlling and inhibiting red tide forming algae using NQ derivatives.     

根据中肠病变程度估计松毛虫CPV产量和采收时机

将感染质型多角体病毒的松毛虫中肠分为四种类型 ,研究各型所占比例与病毒产量间的关系 ,结果显示单位虫重的病毒产量随Ⅰ、Ⅱ类比例的增大而增高 ,Ⅰ、Ⅱ类比例为 2 1% - 80 %时 ,每公斤虫的病毒产量为 5.59× 10 10 PIB - 55.2 1× 10 10 PIB ,适宜的采收时机为Ⅰ、Ⅱ类比例为 60 % -80 %时 ,此时采收 ,每公斤虫可产出质型多角体病毒 37.2 1× 10 10 PIB～ 55.2 1× 10 10 PIB     

Over-expression of Roquin aggravates T cell mediated hepatitis in transgenic mice using T cell specific promoter

Chronic hepatitis is a major cause of liver cancer, so earlier treatment of hepatitis might be reducing liver cancer incidence. Hepatitis can be induced in mice by treatment with Concanavalin A (Con A); the resulting liver injury causes significant CD4⁺ T cell activation and infiltration. In these T cells, Roquin, a ring-type E3 ubiquitin ligase, is activated. To investigate the role of Roquin, we examined Con A-induced liver injury and T cell infiltration in transgenic (Tg) mice overexpressing Roquin specifically in T cells. In Roquin Tg mice, Con A treatment caused greater increases in both the levels of liver injury enzymes and liver tissue apoptosis, as revealed by TUNEL and H&E staining, than wild type (WT) mice. Further, Roquin Tg mice respond to Con A treatment with greater increases in the T cell population, particularly Th17 cells, though Treg cell counts are lower. Roquin overexpression also enhances increases in pro-inflammatory cytokines, including IFN-γ, TNF-α and IL-6, upon liver injury. Furthermore, Roquin regulates the immune response and apoptosis in Con A induced hepatitis via STATs, Bax and Bcl2. These findings suggest that over-expression of Roquin exacerbates T-cell mediated hepatitis.     

A Novel Class of Herbicides (Specific Inhibitors of Imidazoleglycerol Phosphate Dehydratase)

A new mode of herbicidal action was established by finding specific inhibitors of imidazoleglycerol phosphate dehydratase, an enzyme of histidine (His) biosynthesis. Three triazole phosphonates inhibited the reaction of the enzyme with Ki values of 40 [plus or minus] 6.5, 10 [plus or minus] 1.6, and 8.5 [plus or minus] 1.4 nM, respectively, and were highly cytotoxic to cultured plant cells. This effect was completely reversed by the addition of His, proving that the cytotoxicity was primarily caused by the inhibition of His biosynthesis. These inhibitors showed wide-spectrum, postemergent herbicidal activity at application rates ranging from 0.05 to 2 kg/ha.