Nanozymes: an emerging field bridging nanotechnology and biology

正Enzymes are biological catalysts that can convert substrates into products in biochemical reactions.In 1926,the first enzyme,urease,was determined to be a protein by James B.Sumner who won the Nobel Prize in 1946.Since then,enzymes have been considered to be proteins,which allows them to achieve their high catalytic activity with high specific activity under mild conditions.However,in general,the enzyme activity of proteins is lost after exposure to extremes of p H and high temperature,and proteins are also susceptible to digestion by proteases in the environment,which dramatically hinders their practical applications in     

Identification of a novel germline BRCA2 variant in a Chinese breast cancer family

Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer‐related deaths in women worldwide. In this study, a large Chinese pedigree with breast cancer including a proband and two female patients was recruited and a familial history of breast cancer was collected by questionnaire. Clinicopathological assessments and neoadjuvant therapy‐related information were obtained for the proband. Blood samples were taken, and gDNA was extracted. The BRCA1/2 and PALB2 genes were screened using next‐generation sequencing by a targeted gene panel. We have successfully identified a novel, germline heterozygous, missense mutation of the gene BRCA2: c.7007G>T, p.R2336L, which is likely to be pathogenic in the proband and her elder sister who both had breast cancer. Furthermore, the risk factors for developing breast cancer in this family are discussed. Thus, genetic counselling and long‐term follow‐up should be provided for this family of breast cancer patients as well as carriers carrying a germline variant of BRCA2: c.7007G>T (p.R2336L).     

Tyrosylprotein Sulfotransferase-1 and Tyrosine Sulfation of Chemokine Receptor 4 Are Induced by Epstein-Barr Virus Encoded Latent Membrane Protein 1 and Associated with the Metastatic Potential of Human Nasopharyngeal Carcinoma

The latent membrane protein 1 (LMP1), which is encoded by the Epstein-Barr virus (EBV), is an important oncogenic protein that is closely related to carcinogenesis and metastasis of nasopharyngeal carcinoma (NPC), a prevalent cancer in China. We previously reported that the expression of the functional chemokine receptor CXCR4 is associated with human NPC metastasis. In this study, we show that LMP1 induces tyrosine sulfation of CXCR4 through tyrosylprotein sulfotransferase-1 (TPST-1), an enzyme that is responsible for catalysis of tyrosine sulfation in vivo, which is likely to contribute to the highly metastatic character of NPC. LMP1 could induce tyrosine sulfation of CXCR4 and its associated cell motility and invasiveness in a NPC cell culture model. In contrast, the expression of TPST-1 small interfering RNA reversed LMP1-induced tyrosine sulfation of CXCR4. LMP1 conveys signals through the epidermal growth factor receptor (EGFR) pathway, and EGFR-targeted siRNA inhibited the induction of TPST-1 by LMP1. We used a ChIP assay to show that EGFR could bind to the TPST-1 promoter in vivo under the control of LMP1. A reporter gene assay indicated that the activity of the TPST-1 promoter could be suppressed by deleting the binding site between EGFR and TPST-1. Finally, in human NPC tissues, the expression of TPST-1 and LMP1 was directly correlated and clinically, the expression of TPST-1 was associated with metastasis. These results suggest the up-regulation of TPST-1 and tyrosine sulfation of CXCR4 by LMP1 might be a potential mechanism contributing to NPC metastasis.     

Determination of material parameters of the two-dimensional Holzapfel–Weizsäcker type model based on uniaxial extension data of arterial walls

Soft tissues are anisotropic materials yet a majority of mechanical property tests have been uniaxial, which often failed to recapitulate the tensile response in other directions. This paper aims to study the feasibility of determining material parameters of anisotropic tissues by uniaxial extension with a minimal loss of anisotropic information. We assumed that by preselecting a certain constitutive model, we could give the constitutive parameters based on uniaxial extension data from orthogonal strip samples. In our study, the Holzapfel–Weizsäcker type strain energy density function (H–W model) was used to determine the material parameters of arterial walls from two fresh donation bodies. The key points we applied were the relationships between strain components in uniaxial tensile tests and the methods of stochastic optimisation. Further numerical experiments were taken. The estimate–effect ratio, defined by the number of data with the precision of estimation less than 0.5% over whole size of data, was calculated to demonstrate the feasibility of our method. The material parameters for Chinese aorta and pulmonary artery were given with the maximum root mean square (RMS) errors 0.042, and the minimal estimate–effect ratio in numerical experiments was 90.79%. Our results suggest that the constitutive parameters of arterial walls can be determined from uniaxial extension data, given the passive mechanical behaviour governed by H–W model. This method may apply to other tissues using different constitutive models.     

Polymorphisms of the TLR4 gene and risk of gastric cancer

Objective

Toll-like receptor 4 (TLR4) is an important lipo-polysaccharide (LPS) receptor in gastric epithelial cell signaling transduction and plays critical roles in the development and progression of gastric cancer (GC). We investigated the effects of TLR4 gene polymorphisms and gene–environmental interactions on the risk of GC in Northeastern China.

Methods

We genotyped two single-nucleotide polymorphisms (SNPs) in TLR4 (rs10116253 and rs1927911) in 217 GC patients and 294 cancer-free controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Odds ratio (OR) and 95% confidence intervals (CIs) were estimated by unconditional logistic-regression models.

Results

Individuals carrying CC genotype of rs10116253 and TT genotype of rs1927911 had a significantly decreased risk of GC (adjusted OR = 0.33, 95% CI 0.18–0.60, P < 0.001 and adjusted OR = 0.37, 95% CI 0.21–0.67, P = 0.001 respectively), compared with TT genotype of rs10116253 and CC genotype of rs1927911. In addition, the SNP effects were additive to the effects of some known environmental factors without any interaction between them in the susceptibility to GC.

Conclusion

Our data suggested that TLR4 gene polymorphisms may be associated with a decreased risk of GC in Chinese population. And these SNPs and their combined effects with environmental factors may be associated with the risk of GC.     

Rapidly Raise Blood Sugar Will Aggravate Brain Damage After Severe Hypoglycemia in Rats

Hypoglycemia can cause rapid and severe brain damage. We studied the impact of hypoglycemic brain damage in the insulin-induced hypoglycemic rats. Thirty male rats were divided into normal blood sugar control group (group A), the blank group (group B), and the experimental group which was further divided into four groups according to the level of blood glucose reperfusion i.e., blood glucose ≤3 mmol/L (Group C), ≤6 mmol/L (Group D), ≤9 mmol/L (Group E), and >9 mmol/L (Group F). Each groups had five rats. TUNEL and FJB staining were used to observe the apoptosis and necrosis in the rat hippocampus CA1 and DG regions and transmission electron microscopy for ultra-structures. We observed that neuronal apoptosis and necrosis of group A and B were not obvious. The apoptotic and necrotic neuron cell densities in the hippocampus CA1 and DG regions were moderately detected in group C, D, and E, while we found it maximum in group F. No significant difference was found in apoptotic and necrotic neuron cell density in the hippocampus CA1 and DG regions in group A and B. Apoptotic and necrotic cell density was significantly increased in all experimental groups as compared to the control group. Moreover, the apoptotic and necrotic cell density was significantly higher in group F than other experimental groups (group C, D, and E). However, apoptosis and necrosis in hippocampus CA1 and DG regions was not differed significantly among groups C, D, and E. All results were well supported by transmission electron microscopy. In conclusion, under the condition of the same blood glucose level, the degree of brain damage related to the blood glucose level with hypoglycemia and rapid blood glucose increased after hypoglycemia could cause more significant brain damage.     

KCTD10 Is Involved in the Cardiovascular System and Notch Signaling during Early Embryonic Development

As a member of the polymerase delta-interacting protein 1 (PDIP1) gene family, potassium channel tetramerisation domain-containing 10 (KCTD10) interacts with proliferating cell nuclear antigen (PCNA) and polymerase δ, participates in DNA repair, DNA replication and cell-cycle control. In order to further investigate the physiological functions of KCTD10, we generated the KCTD10 knockout mice. The heterozygous KCTD10^+/− mice were viable and fertile, while the homozygous KCTD10^−/− mice showed delayed growth from E9.0, and died at approximately E10.5, which displayed severe defects in angiogenesis and heart development. Further study showed that VEGF induced the expression of KCTD10 in a time- and dose-dependent manner. Quantitative real-time PCR and western blotting results revealed that several key members in Notch signaling were up-regulated either in KCTD10-deficient embryos or in KCTD10-silenced HUVECs. Meanwhile, the endogenous immunoprecipitation (IP) analysis showed that KCTD10 interacted with Cullin3 and Notch1 simultaneously, by which mediating Notch1 proteolytic degradation. Our studies suggest that KCTD10 plays crucial roles in embryonic angiogenesis and heart development in mammalians by negatively regulating the Notch signaling pathway.     

云南省外来有害生物入侵现状及口岸疫情截获分析

【目的】云南是外来入侵生物的重灾区,了解外来有害生物入侵现状、加强防控尤为紧迫。【方法】从入侵云南外来有害生物类别、入侵途径、造成的损失等方面对云南省外来有害生物的入侵现状进行了阐述,对云南口岸疫情进行统计分析。【结果】按进境检疫物上截获有害生物批次及疫情货物批次统计的国家主要为缅甸、老挝、泰国、越南、荷兰5个国家;按检疫方式分类统计,货检截获批次最多,旅检次之,二者之和占总截获批次的99%;按有害生物类别分类统计,昆虫截获最多,占总截获批次的70.0%至73.9%,杂草、真菌居次,细菌、线虫、病毒、螨类、其他又次之;按货物类别统计,截获有害生物批次最多为粮豆类,占总截获批次的46%。【结论】提出了相应的检疫监管对策与建议,以期为口岸检疫提供参考,降低外来有害生物的入侵风险。     

A novel anti-CEACAM5 monoclonal antibody, CC4, suppresses colorectal tumor growth and enhances NK cells-mediated tumor immunity

Carcinoembryonic antigen (CEA, CEACAM5, and CD66e) has been found to be associated with various types of cancers, particularly colorectal carcinoma, and developed to be a molecular target for cancer diagnosis and therapy. In present study, we generated a novel anti-CEACAM5 monoclonal antibody, namely mAb CC4, by immunizing mice with living colorectal cancer LS174T cells. Immunohistochemical studies found that mAb CC4 specifically and strongly binds to tumor tissues, especially colorectal adenocarcinoma. In xenografted mice, mAb CC4 is specifically accumulated in tumor site and remarkably represses colorectal tumor growth. In vitro functional analysis showed that mAb CC4 significantly suppresses cell proliferation, migration and aggregation of colorectal cancer cells and also raises strong ADCC reaction. More interestingly, mAb CC4 is able to enhance NK cytotoxicity against MHC-I-deficient colorectal cancer cells by blocking intercellular interaction between epithelial CEACAM5 and NK inhibitory receptor CEACAM1. These data suggest that mAb CC4 has the potential to be developed as a novel tumor-targeting carrier and cancer therapeutic.     

Knockdown of CD146 reduces the migration and proliferation of human endothelial cells

Our previous study has demonstrated that CD 146 molecule is a biomarker on vascular endothelium,which is involvedin angiogenesis and tumor growth.However the mechanism behind is not clear.Here we have for the first time devel-oped a novel CD146 blockade system using CD146 siRNA to study its function on endothelial cells.Our data showedthat CD146 siRNA specifically blocked the expression of CD146 on both mRNA and protein levels,leading to thesignificant suppression of HUVEC proliferation,adhesion and migration.These results demonstrate that CD146 playsa key role in vascular endothelial cell activity and angiogenesis,and CD146 siRNA can be used as a new inhibitor foranti-angiogenesis therapy.