底物中的硅原子对酶反应的影响

在酶工程学的研究史上,人们一方面不断地研制开发新的酶种;一方面利用固定化、酶分子改造和修饰等技术来提高酶的活性和稳定性;另一方面,则不断地开拓酶的新用途。酶催化非天然化合物的生物合成和转化（正是这一方面研究的新进展）。由于有机硅化合物在有机合成,尤其...     

Trastuzumab in the adjuvant treatment of HER2-positive early breast cancer patients: a meta-analysis of published randomized controlled trials

Background

Adjuvant trastuzumab therapy has yielded conflicting results for overall survival, concerns about central nervous system (CNS) metastasis, and questions about optimal schedule. Therefore, we carried out a meta-analysis to assess the benefits of concurrent or sequential trastuzumab with adjuvant chemotherapy for early breast cancer patients with HER2-positive tumors.

Methods

Computerized and manual searches were performed to identify randomized clinical trials comparing adjuvant chemotherapy with or without trastuzumab in HER2-positive early breast cancer patients. Odds ratios were used to estimate the association between the addition of trastuzumab to adjuvant chemotherapy and various survival outcomes. The fixed-effects or random-effects model was used to combine data.

Findings

With six eligible studies identified, this analysis demonstrated that patients with HER2-positive breast cancer derived benefit in disease-free survival, overall survival, locoregional recurrence and distant recurrence (all P<0.001) from the addition of trastuzumab to adjuvant chemotherapy, whereas trastuzumab did worse in CNS recurrence as compared to the control group (P = 0.018). Furthermore, concomitant use of trastuzumab significantly lowered the hazard of death (P<0.001) but bore a higher incidence of CNS recurrence (P = 0.010), while statistical significance failed to be discerned for either overall survival (P = 0.069) or CNS metastasis (P = 0.374) between the sequential and observation arms.

Conclusion

This analysis verifies the efficacy of trastuzumab in the adjuvant setting. Additionally, our findings indirectly corroborate the superiority of concurrent trastuzumab to sequential use and also illuminate that prolonged survival is the possible reason for the higher incidence of CNS with trastuzumab versus observation.     

Life prediction for a vacuum fluorescent display based on two improved models using the three‐parameter Weibull right approximation method

To obtain precise life information for vacuum fluorescent displays (VFDs), luminance degradation data for VFDs were collected from a group of normal life tests. Instead of exponential function, the three‐parameter Weibull right approximation method (TPWRAM) was applied to describe the luminance degradation path of optoelectronic products, and two improved models were established. One of these models calculated the average life by fitting average luminance degradation data, and the other model obtained VFD life by combining the approximation method with luminance degradation test data from each individual sample. The results indicated that the test design under normal working stress was appropriate, and the selection of censored test data was simple. The two models improved by TPWRAM both revealed the luminance decaying law for VFD, and the pseudo failure time was accurately extrapolated. It was further confirmed by comparing relative error that using the second model gave a more accurate prediction of VFD life. The improved models in this study can provide technical references for researchers and manufacturers in aspects of life prediction methodology for its development.     

Similar Metabolic Changes Induced by HIPVs Exposure as Herbivore in Ammopiptanthus mongolicus

Herbivore-induced plant volatiles (HIPVs) are important compounds to prim neighboring undamaged plants; however, the mechanism for this priming process remains unclear. To reveal metabolic changes in plants exposed to HIPVs, metabolism of leaves and roots of Ammopiptanthus mongolicus seedlings exposed to HIPVs released from conspecific plants infested with larvae of Orgyia ericae were analyzed together with control and infested seedlings using nuclear magnetic resonance (NMR)-based metabolic technology and multi variate data analysis. Results presented showed that HIPVs exposure led to similar but specific metabolic changes compared with those induced by infestation in both leaves and roots. Furthermore, both HIPVs exposure and herbivore attack resulted in metabolic changes involving a series of primary and secondary metabolites in both leaves and roots. Taken together, these results suggested that priming of yet-damaged plants may be achieved by reconfiguring metabolic pathways in leaves and roots to make similar concentrations for all metabolites as those in seedlings infested. Therefore, we propose that improved readiness of defense induction of primed plants toward subsequent herbivore attack may be based on the similar metabolic profiling induced by HIPVs exposure as those caused by herbivore.     

Structure and chromosomal localization of the human glycogenin-2 gene GYG2

Glycogenin-2 is one of two self-glucosylating proteins involved in the initiation phase of the synthesis of the storage polysaccharide glycogen. Cloning of the human glycogenin-2 gene, GYG2, has revealed the presence of 11 exons and a gene of more than 46 kb in size. The structure of the gene explains much of the observed diversity in glycogenin-2 cDNA sequences as being due to alternate exon usage. In some cases, there is variation in the splice junctions used. Over regions of protein sequence similarity, the GYG2 gene structure is similar to that of the other glycogenin gene, GYG. A genomic GYG2 clone was used to localize the gene to Xp22.3 by fluorescence in-situ hybridization. Localization close to the telomere of the short arm of the X chromosome is consistent with mapping information obtained from glycogenin-2 STS sequences. Glycogenin-2 maps between the microsatellite anchor markers AFM319te9 (DXS7100) and AFM205tf2 (DXS1060), and its 3' end is 34.5 kb from the 3' end of the arylsulphatase gene ARSD. GYG2 is outside the pseudoautosomal region PAR1 but still in a region of X-Y shared genes. As is true for several other genes in this location, an inactive remnant of GYG2, consisting of exons 1-3, may be present on the Y chromosome.     

TBK1 Facilitates GLUT1-Dependent Glucose Consumption by suppressing mTORC1 Signaling in Colorectal Cancer Progression

Intestinal inflammation is a vital precipitating factor of colorectal cancer (CRC), but the underlying mechanisms are still elusive. TANK-binding kinase 1 (TBK1) is a core enzyme downstream of several inflammatory signals. Recent studies brought the impacts of TBK1 in malignant disease to the forefront, we found aberrant TBK1 expression in CRC is correlated with CRC progression. TBK1 inhibition impaired CRC cell proliferation, migration, drug resistance and tumor growth. Bioinformatic analysis and experiments in vitro showed overexpressed TBK1 inhibited mTORC1 signaling activation in CRC along with elevated GLUT1 expression without inducing GLUT1 translation. TBK1 mediated mTORC1 inhibition induces intracellular autophagy, which in turn decreasing GLUT1 degradation. As a rescue, blocking of autophagosome and retromer respectively via autophagy-related gene 7 (ATG7) or TBC1 Domain Family Member 5 (TBC1D5) silence diminished the regulation of TBK1 to GLUT1. GLUT1 staining presented that TBK1 facilitated GLUT1 membrane translocation which subsequently enhanced glucose consumption. Inhibitor of TBK1 also decreased GLUT1 expression which potentiated drug-sensitivity of CRC cell. Collectively, TBK1 facilitates glucose consumption for supporting CRC progression via initiating mTORC1 inhibition induced autophagy which decreases GLUT1 degradation and increases GLUT1 membrane location. The adaptive signaling cascade between TBK1 and GLUT1 proposes a new strategy for CRC therapy.     

一个基于能量的突触可塑性模型

研究表明能量可能是支配神经元活动的统一原则,编码能力与能量成本的比率最大化被认为是突触连接在选择性压力下改变的关键原则之一,这意味着突触范围内能量的变化与突触可塑性有关。为此,建立一个基于能量的突触可塑性模型。当突触后膜瞬时功率高于功率阈值时突触权重增加,反之突触权重下降。该模型可再现脉冲频率依赖可塑性以及脉冲时间依赖可塑性这两种主要的突触可塑性实验结果,并且和其他公认的突触可塑性模型相比具有优越性。结果表明,能量是影响突触可塑性的关键因素,对进一步理解突触连接的选择性和神经网络动力学特征提供了一个新思路。