Shp2-mediated molecular signaling in control of embryonic stem cell self-renewal and differentiation

在干细胞生物学要处理的一个关键问题是控制胚胎的茎(ES ) 的分子的发信号机制细胞 pluripotency。干细胞性质被象脱氧核糖核酸甲基化并且染色质改变那样的特定的抄写因素和 epigenetic 过程支配。几个 cytokines/growth 因素作为批评 ES 房间管理者被识别了。然而，在我们在 ES 房间连接细胞外的信号到 transcriptional 规定的细胞内部的发信号小径的知识有差距。这短评论讨论 Shp2 的生理的角色，细胞质的酷氨酸磷酸酶，在管理 EScell 自强对区别的分子的开关中。Shp2 支持 ES 细胞分化，英皇家空军之阶级最低之兵的主要 throughbi 方向性的调整和 Stat3 小径。在老鼠 ES 房间的 Shp2 的删除导致更有效的自强。这观察提供动力在文化为 ES 房间的维护和扩大开发 Shp2 禁止者。

NO_x reduction in the sintering process

A new process, NOx reduction with recycling flue gas and modifying coke breeze, was proposed. The effects of modified coke breeze and recycled flue gas on NOx reduction were investigated by sinter pot tests. The results show that the NOx reduction rate is over 10wt% in the sintering of modified coke breeze, the effects of the additives on NOx reduction are： CeO2〉CaO〉K2CO3. The NOx reduction rate increases with the amount of recycled flue gas, and is 22.35wt% in the sintering with recycling 30vol% of the flue gas. When 30vol% of the flue gas is recycled into the sintering of CeO2, CaO, and K2CO3 modified coke breeze, the NOx reduction rates are 36.10wt%, 32.56wt%, and 32.17wt%, respectively.

NO_x reduction by coupling combustion with recycling flue gas in iron ore sintering process

A new process called＇NOx reduction by coupling combustion with recycling flue gas（RCCRF）＇was proposed to decrease NOx emission during the iron ore sintering process.The simulation test of NOx reduction was performed over sintered ore and in the process of coke combustion.Experimentally,NOx reduction was also carried out by sintering pot test.For sintered ore,the amount of NOx emission is reduced by 15wt%-25wt% at 400-550oC using 2.0vol% H2 or 2.0vol% CO,or reduced by 10wt%-30wt% at 560-720oC using 0.15vol% NH3.NOx reduction is around 10wt% by coupling combustion of pyrolysis gas and coke,or around 16wt% by recycling flue gas into coke combustion.By RCCRF,the maximum NOx reduction ratio is about 23wt% in coke combustion experiment and over 40wt% in sintering pot test.

Effects of CeO_2 on the XPS valence band spectra of coal under the combustion initialization stage at 400℃

In order to get the catalytic mechanism of CeO2 on graphite and coal at 400℃, the morphologies of coal, graphite, and CeO2 before and after combustion were analyzed through X-ray photoelectron spectroscopy （XPS）. It is found that the particle size of coal is mostly between 11.727 and 64.79 μm, while the particle size of CeO2 is between 1.937 and 11.79 μm. The agglomeration of coal and CeO2 can be seen by scanning electron microscopy （SEM） after reaction. XPS results show that with the addition of CeO2, the intensity of binding energy gets stronger, but there is no energy peak transition. Comparing the character of coal with and without the addition of CeO2, it can be seen that the C C bond fractures first at 400℃, while the C-H energy-band takes electrons at the same time to be far away from the Fermi level, and the O 2s, O 2p, and C sp hybrid orbitals are all excited. Adding CeO2 can enhance the activity of the whole coal. In addition, through XPS analysis, combined with the oxygen transfer theory and the electron transfer theory, the catalytic mechanism of CeO2 for pulverized coal combustion could be obtained.

Dual faces of SH2-containing protein-tyrosine phosphatase Shp2/PTPN11 in tumorigenesis

PTPN11,which encodes tyrosine phosphatase Shp2,is a critical gene mediating cellular responses to hormones and cytokines.Against original prediction as tumor suppressor for tyrosine phosphatases,PTPN11 was first identified as a proto-oncogene because activating mutations of this gene are associated with leukemogenesis.However,most recent experimental data suggest PTPN11/Shp2 acting as a tumor suppressor in hepatocarcinogenesis.This review focuses on the tumor-promoting or suppressing roles of the gene PTPN11/Shp2 in different cell types.

The role of tyrosine phosphatase Shp2 in spermatogonial differentiation and spermatocyte meiosis

The transition from spermatogonia to spermatocytes and the initiation of meiosis are key steps in spermatogenesis and are precisely regulated by a plethora of proteins.However,the underlying molecular mechanism remains largely unknown.Here,we report that Src homology domain tyrosine phosphatase 2(Shp2;encoded by the protein tyrosine phosphatase,nonreceptor type 11[Ptpn11]gene)is abundant in spermatogonia but markedly decreases in meiotic spermatocytes.Conditional knockout of Shp2 in spermatogonia in mice using stimulated by retinoic acid gene 8(Stra8)-cre enhanced spermatogonial differentiation and disturbed the meiotic process.Depletion of Shp2 in spermatogonia caused many meiotic spermatocytes to die;moreover,the surviving spermatocytes reached the leptotene stage early at postnatal day 9(PN9)and the pachytene stage at PN11-13.In preleptotene spermatocytes,Shp2 deletion disrupted the expression of meiotic genes,such as disrupted meiotic cDNA 1(Dmc1),DNA repair recombinase rad51(Rad51),and structural maintenance of chromosome 3(Smc3),and these deficiencies interrupted spermatocyte meiosis.In GC-1 cells cultured in vitro,Shp2 knockdown suppressed the retinoic acid(RA)-induced phosphorylation of extracellular-regulated protein kinase(Erk)and protein kinase B(Akt/PKB)and the expression of target genes such as synaptonemal complex protein 3(Sycp3)and Dmc1.Together,these data suggest that Shp2 plays a crucial role in spermatogenesis by governing the transition from spermatogonia to spermatocytes and by mediating meiotic progression through regulating gene transcription,thus providing a potential treatment target for male infertility.

Deletion of Gab2 in mice protects against hepatic steatosis and steatohepatitis:a novel therapeutic target for fatty liver disease

Fatty liver disease is a serious health problem worldwide and is the most common cause for chronic liver disease and metabolic disorders.The major challenge in the prevention and intervention of this disease is the incomplete understanding of the underlying mechanism and thus lack of potent therapeutic targets due to multifaceted and interdependent disease factors.In this study,we investigated the role of a signaling adaptor protein,GRB2-associated-binding protein 2(Gab2),in fatty liver using an animal disease model.Gab2 expression in hepatocytes responded to various disease factor stimulations,and Gab2 knockout mice exhibited resistance to fat-induced obesity,fat-or alcohol-stimulated hepatic steatosis,as well as methionine and choline deficiency-induced steatohepatitis.Concordantly,the forced expression or knockdown of Gab2 enhanced or diminished oleic acid(OA)-or ethanol-induced lipid production in hepatocytes in vitro,respectively.During lipid accumulation in hepatocytes,both fat and alcohol induced the recruitment of PI3K or Socs3 by Gab2 and the activation of their downstream signaling proteins AKT,ERK,and Stat3.Therefore,Gab2 may be a disease-associated protein that is induced by pathogenic factors to amplify and coordinate multifactor-induced signals to govern disease development in the liver.Our research provides a novel potential target for the prevention and intervention of fatty liver disease.

肿瘤免疫学和免疫治疗:我的旅程从杭州出发（英文）

为庆祝浙江大学生命科学学院九十华诞,谨写此文。作者冯根生是原杭州大学生物学系七七级学生;在杭大求学期间,选修了免疫学和肿瘤生物学,深受启发。冯现在是加州大学圣地亚哥校区医学院病理系和生命科学学院的教授。实验室目前的研究重点是肝癌发病机理和肝癌免疫治疗。这得益于当年在杭大的启蒙教育。

Deciphering the molecular and physiological connections between obesity and breast cancer

Obesity is associated with the higher risk of breast cancer in postmenopausal women.The leptin signaling pathway is recognized to primarily regulate energy balance and associated with breast cancer.Furthermore,the estrogen signaling pathway plays a critical role in breast carcinogenesis.In this review,we discuss how obesity is linked to breast cancer via cross-talk of leptin and estrogen pathways.