Proteomic analysis reveals tanshinone IIA enhances apoptosis of advanced cervix carcinoma CaSki cells through mitochondria intrinsic and endoplasmic reticulum stress pathways

Cervix cancer is the second most common cancer among women worldwide, whereas paclitaxel, the first line chemotherapeutic drug used to treat cervical cancer, shows low chemosensitivity on the advanced cervical cancer cell line. Tanshinone IIA (Tan IIA) exhibited strong growth inhibitory effect on CaSki cells (IC₅₀ = 5.51 μM) through promoting caspase cascades with concomitant upregulating the phosphorylation of p38 and JNK signaling. Comprehensive proteomics revealed the global protein changes and the network analysis implied that Tan IIA treatment would activate ER stress pathways that finally lead to apoptotic cell death. Moreover, ER stress inhibitor could alleviate Tan IIA caused cell growth inhibition and ameliorate C/EBP‐homologous protein as well as apoptosis signal‐regulating kinase 1 mediated cell death. The therapeutic interventions targeting the mitochondrial‐related apoptosis and ER stress responses might be promising strategies to conquer paclitaxel resistance.     

Amino‐functionalized macroporous silica for efficient tryptic digestion in acidic solutions

Amino‐functionalized macroporous silica foam (NH₂‐MOSF) has been developed as a host reactor to realize highly efficient proteolysis in acidic solutions where normal tryptic reactions cannot occur. The digestion protocol consists simply of adding the functionalized NH₂‐MOSF into the protein and trypsin solutions without altering the bulk pH or preloading the enzymes on the materials. With this protocol, digestion of sample fractions from LC can be efficiently realized in the acidic solutions directly. Digestion of a protein fraction extracted from rat liver tissue after LC separation was performed to illustrate this principle, where 103 proteins were successfully identified at pH 3 after 1.5 h of tryptic digestion.     

重度妊娠期肝内胆汁淤积症对母婴结局影响的临床分析

目的：分析重度妊娠期肝内胆汁淤积症（intrahepatic cholestasis of pregnancy,ICP）对母婴结局的影响,以提高对ICP的认识与治疗水平。方法：选择ICP产妇58例,根据ICP分度标准分为轻度组（n=26例）和重度组（n=32例）,比较两组产妇的母婴结局。结果：与轻度组相比,重度组产妇剖宫产率、产后出血与平均产后出血量显著升高或增加,阴道分娩率显著降低,组间比较差异均具有统计学意义（P〈0.05）;重度组新生儿早产、胎儿窘迫、羊水污染和新生儿窒息的发生率均显著上升,新生儿平均出生体重显著降低,组间比较差异均具有统计学意义（P〈0.05）。结论：ICP对产妇及新生儿均有不良影响,对ICP严重程度进行划分,有利于临床处理。对于重度ICP产妇,应尽早采取剖宫产分娩的方式终止妊娠。     

胃食管反流病患者自我管理行为依从性及其影响因素调查

目的：调查分析胃食管反流病患者自我管理行为依从性情况及其影响因素。方法：选取2010年2月-2012年6月来我院就诊治疗的胃食管反流患者150例,利用自我行为管理量表、自我效能量表、焦虑自评量表（SAs）及抑郁自评量表（SDS）进行调查,并采用单因素分析及多因素分析法分析其影响因素。结果：所有150例患者的自我行为管理平均得分为37．12＋4．95分,处于中下游水平,其中治疗依从性较好而疾病知识认知方面较差;而从单因素及多因素分析中得知,胃食管反流病患者自我行为依从性的影响因素主要为自我效能、工作学习压力及文化程度（偏回顾系数=0．301、-2．264、1．403）。结论：胃食管返流病患者的自我管理行为依从性较差,这与其文化程度较低、工作学习压力较大有关,医务人员应指导患者减轻工作学习压力,改善生活方式以提高其自我管理行为依从性。     

云南高黎贡山和怒山外担菌属和隔担菌属真菌

2005至2011年,在云南高黎贡山和怒山进行了野外科学考察,采集了大量真菌标本,经过研究,发现外担菌属18种,隔担菌属11种真菌,研究的标本保藏在中国科学院微生物研究所菌物标本馆.     

Large Scale Fabrication of Gold Nano-Structured Substrates Via High Temperature Annealing and Their Direct Use for the LSPR Detection of Atrazine

The present work is reporting on the fabrication of localized surface plasmonic resonant (LSPR) gold nano-structures on glass substrate by using different high annealing temperatures (500 °C, 550 °C, 600 °C) of initially created semi-continue gold films (2 nm and 5 nm) by the electron beam evaporation technique. Interestingly, well-defined gold nano-structures were also obtained from continuous 8 nm evaporated gold film - known as the value above gold percolated thickness - once exposed to high temperatures. The surface morphology and plasmonic spectroscopy of “annealed” nano-structures were controlled by key experimental parameters such as evaporated film thickness and annealing temperature. By using scanning electron microscopy (SEM) characterization of annealed surface it was noticed that the size and inter-particle distance between nano-structures were highly dependent on the evaporated thin film thickness, while the nanoparticle shape evolution was mainly affected by the employed annealing temperature. Due to the well-controlled morphology of gold nano-particles, prominent and stable LSPR spectra were observed with good plasmon resonance tunability from 546 nm to 780 nm that recommend the developed protocol as a robust alternative to fabricate large scale LSPR surface. An example of a LSPR-immunosensor is reported. Thus, the monoclonal anti-atrazine antibodies immobilizion on the “annealed” gold nano-structures, as well as the specific antigen (atrazine) recognition were monitored as variations of the resonance wavelength shifts and optical density changes in the extinction measurements.     

Biological Relevance of the Interaction Between Resveratrol and Insulin

In view of synergistic effect of resveratrol and insulin in the prevention and treatment of many chronic diseases, the interaction between them was studied and its biological implication was further discussed. Insulin could interact with resveratrol to form 1:1 complex with the binding constant of 1.03?×?10³ M^?1 at 298 K. The binding was spontaneous and insulin/resveratrol complex formation was an exothermal reaction. Hydrogen bond and van der Waals force played key roles in the binding process. Kinetic study indicates that resveratrol binding to insulin conformed to the first-order exponential decay function. The interaction decreased the polarity around tyrosine residue and α-helical content, destroyed the disulfide bridges, depolymerized insulin dimers to monomer, and altered the orientation of aromatic side chains in the insulin. Additionally, insulin increased resveratrol stability. These results well confirm synergistic effect of resveratrol and insulin in vitro. It would give a deeper insight into resveratrol as a kind of food functional factor.     

Adiponectin Mediates the Metabolic Effects of FGF21 on Glucose Homeostasis and Insulin Sensitivity in Mice

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Prediction of Drug-Target Interactions for Drug Repositioning Only Based on Genomic Expression Similarity

Small drug molecules usually bind to multiple protein targets or even unintended off-targets. Such drug promiscuity has often led to unwanted or unexplained drug reactions, resulting in side effects or drug repositioning opportunities. So it is always an important issue in pharmacology to identify potential drug-target interactions (DTI). However, DTI discovery by experiment remains a challenging task, due to high expense of time and resources. Many computational methods are therefore developed to predict DTI with high throughput biological and clinical data. Here, we initiatively demonstrate that the on-target and off-target effects could be characterized by drug-induced in vitro genomic expression changes, e.g. the data in Connectivity Map (CMap). Thus, unknown ligands of a certain target can be found from the compounds showing high gene-expression similarity to the known ligands. Then to clarify the detailed practice of CMap based DTI prediction, we objectively evaluate how well each target is characterized by CMap. The results suggest that (1) some targets are better characterized than others, so the prediction models specific to these well characterized targets would be more accurate and reliable; (2) in some cases, a family of ligands for the same target tend to interact with common off-targets, which may help increase the efficiency of DTI discovery and explain the mechanisms of complicated drug actions. In the present study, CMap expression similarity is proposed as a novel indicator of drug-target interactions. The detailed strategies of improving data quality by decreasing the batch effect and building prediction models are also effectively established. We believe the success in CMap can be further translated into other public and commercial data of genomic expression, thus increasing research productivity towards valid drug repositioning and minimal side effects.     

Detecting Genetic Association of Common Human Facial Morphological Variation Using High Density 3D Image Registration

Human facial morphology is a combination of many complex traits. Little is known about the genetic basis of common facial morphological variation. Existing association studies have largely used simple landmark-distances as surrogates for the complex morphological phenotypes of the face. However, this can result in decreased statistical power and unclear inference of shape changes. In this study, we applied a new image registration approach that automatically identified the salient landmarks and aligned the sample faces using high density pixel points. Based on this high density registration, three different phenotype data schemes were used to test the association between the common facial morphological variation and 10 candidate SNPs, and their performances were compared. The first scheme used traditional landmark-distances; the second relied on the geometric analysis of 15 landmarks and the third used geometric analysis of a dense registration of ∼30,000 3D points. We found that the two geometric approaches were highly consistent in their detection of morphological changes. The geometric method using dense registration further demonstrated superiority in the fine inference of shape changes and 3D face modeling. Several candidate SNPs showed potential associations with different facial features. In particular, one SNP, a known risk factor of non-syndromic cleft lips/palates, rs642961 in the IRF6 gene, was validated to strongly predict normal lip shape variation in female Han Chinese. This study further demonstrated that dense face registration may substantially improve the detection and characterization of genetic association in common facial variation.