Thieno [2, 3-d] pyrimidine inhibits gastric cancer cell proliferation via the down-regulation of bcl-2 and survivin expressions

Purpose: To investigate the effect of thieno [2, 3-d] pyrimidine on gastric cancer (GC) cell proliferation, and elucidate the mechanism of action involved. Methods: Human GC cells (MKN1, MKN28 and SGC 7901) were cultured in RPMI-1640 medium supplemented with 10 % fetal bovine serum (FBS) and 1 % penicillin/ streptomycin solution at 37 °C for 24 h in a humidified atmosphere of 5 % CO2 and 95 % air. After attaining 60 - 70 % confluency, the cells were treated with serum-free medium and graded concentrations of thieno [2, 3-d] pyrimidine (0 – 12 µM) for 24 h. Normal cell culture without thieno [2, 3-d] pyrimidine served as control group. The cells were used in logarithmic growth phase. Cell viability and apoptosis were assessed using 3 (4,5 dimethyl thiazol 2 yl) 2,5 diphenyl 2H tetrazolium bromide (MTT), and flow cytometric assays, respectively. The levels of expression of ZNF139, B cell lymphoma 2 (bcl-2) and survivin in MKN1 cells and orthotopically transplanted mice were determined using Western blotting and real-time quantitative polymerase chain reaction (qRT-PCR). Results: Treatment of MKN1, MKN28 and SGC 7901 cells with thieno [2, 3-d] pyrimidine for 72 h led to significant and dose-dependent reductions in their viabilities, as well as significant and dose-dependent increases in the number of apoptotic cells (p < 0.05). The results of qRT-PCR and Western blotting showed that ZNF139 mRNA and protein expressions in MKN1 cells were significantly down-regulated by thieno [2, 3-d] pyrimidine treatment (p < 0.05). Thieno [2, 3-d] pyrimidine treatment significantly and dose-dependently down-regulated the expressions of bcl 2 and survivin proteins in MKN1 cells and orthotopically transplanted mice (p < 0.05). It also significantly and dose-dependently inhibited the proliferation of GC cells in orthotopic mouse model of GC after 31 days of treatment (p < 0.05). Conclusion: These results suggest that thieno [2, 3-d] pyrimidine suppresses the proliferation of GC cells via down-regulation of the expressions of ZNF139, bcl 2 and sur¬vivin. Thus, it has potentials for development for the management of gastric cancer

Investor emotions and the psychodynamics of asset pricing bubbles: a Chinese perspective

This paper explores the powerful emotions unleashed during asset pricing bubbles. Adopting a psychoanalytic perspective, we develop a five-stage path-dependent model of such financial crises and test this empirically on the Chinese 2005–2008 and 2014–2016 stock market bubbles. Results are consistent with our underlying theory and demonstrate how investors experience a range of highly charged emotions directly related with different market states during such episodes. Our evidence suggests that if we wish properly to understand and explain such destructive events, we also need to recognize the fundamental role investor unconscious fantasies and market psychodynamic processes play in their etiology

Application of metal-organic frameworks, covalent organic frameworks and their derivates for the metal-air batteries

Metal-organic frameworks (MOFs) and covalent organic frameworks (COFs) as the novel porous materials have the merits of diverse, adjustable functionality, high porosity and surface area, which have great application prospects in the gas storage, separation and catalysis. In addition, their derivates make up for the insufficient of electronic conductivity and chemical stability of MOFs and COFs, and provide a new ideal for accurate control of material structure. Up to now, many efficient electrocatalysts have been designed based on MOFs, COFs and their derivates for O2 reduction/evolution reactions (ORR/OER) and CO2 reduction/evolution reactions (CO2RR/CO2ER) in the metal-air batteries. In this review, the latest development of MOFs, COFs and their derivates in the metal-air batteries is summarized, and we discuss the structural characteristics of these materials and their corresponding mechanisms of action. By comprehensively reviewing the advantages, challenges and prospects of MOFs and COFs, we hope that the organic framework materials will shed more profound insights into the development of electrocatalysis and energy storage in the future

Jia-Wei-Kai-Xin-San treatment alleviated mild cognitive impairment through anti-inflammatory and antiapoptotic mechanisms in SAMP8 mice

Background. Alleviating mild cognitive impairment (MCI) is crucial to delay the progression of Alzheimer’s disease (AD). Jia-Wei-Kai-Xin-San (JWKXS) is applied for treating AD with MCI. However, the mechanism of JWKXS in the treatment of MCI is unclear. Thus, this study aimed to investigate the effect and mechanism of JWKXS in SAMP8 mice models of MCI. Methods. MCI models were established to examine learning and memory ability and explore the pathomechanisms in brain of SAMP8 mice at 4, 6, and 8 months. The mice were treated for 8 weeks and the effects of JWKXS on MCI were characterized through Morris water maze and HE/Nissl’s/immunohistochemical staining. Its mechanism was predicted by the combination of UPLC-Q-TOF/MS and system pharmacology analysis, further verified with SAMP8 mice, BV2 microglial cells, and PC12 cells. Results. It was found that 4-month-old SAMP8 mice exhibited MCI. Two months of JWKXS treatment improved the learning and memory ability, alleviated the hippocampal tissue and neuron damage. Through network pharmacology, four key signaling pathways were found to be involved in treatment of MCI by JWKXS, including TLR4/NF-κB pathway, NLRP3 inflammasome activation, and intrinsic and extrinsic apoptosis. In vitro and in vivo experiments demonstrated that JWKXS attenuated neuroinflammation by inhibiting microglia activation, suppressing TLR4/NF-κB and NLRP3 inflammasome pathways, and blocking the extrinsic and intrinsic apoptotic pathways leading to neuronal apoptosis suppression in the hippocampus. Conclusion. JWKXS treatment improved the learning and memory ability and conferred neuroprotective effects against MCI by inducing anti-inflammation and antiapoptosis. Limitations. The small sample size and short duration of the intervention limit in-depth investigation of the mechanisms. Future Prospects. This provides a direction for further clarification of the anti-AD mechanism, and provides certain data support for the formulation to move toward clinical practice

Land Management and Rural Development in Northwest China

In order to break away from the overreliance on a single industry and the simple supply of agricultural products, rural multifunctional research has gradually received public attention. To a certain extent, multifunctional classification governance paths can enhance rural competitiveness and land use efficiency and alleviate the problems of local poverty and unbalanced development in rural regions. Based on the theory of rural multifunctionality, this paper reveals the spatial characteristics and coordination of rural multifunctionality at the township scale, analyzes the barrier functions of different regions, and clarifies the direction of rural development using the rural assessment method, the trade-off synergy model, and the dysfunctional diagnostic model, taking Yongchang County in the western corridor of China as an example. On this basis, we further discuss the path selection of rural governance in northwest China. The results show that: (1) The spatial distribution of rural functions has pronounced heterogeneity, with better life security functions and ecological background functions, and similar spatial patterns; economic development functions are on the low side, showing the divergent characteristics of enhancement from the township center to the surrounding area. The functions of agricultural production are low, and the spatial distribution is similar to that for the living guarantee function. (2) The living guarantee function has a strong trade-off effect on the ecological background function, and the living guarantee and ecological background functions have a synergistic effect on the agricultural development function. (3) We classified types of villages according to the intensity index of village function trade-offs and clarified the functional development characteristics of each administrative village. The incompatibility of village functions caused by different demands is the root hinderance to the development of villages

An Analysis of the Patents concerning Hevea brasiliensis

This paper mainly analyzes the application data of patents concerning Hevea brasiliensis in the world and China from the perspectives of time, research field, and the geographical distribution of applicants. It also interprets the patents for invention in China from time, research field, and types of applicants. Based on the study, it shows that although the patent applications fluctuate, the general trend is rising. And the patents are mostly concentrated in plant protection, and agricultural biotechnology. The Chinese applicants of patents for invention largely work in the research institutes, and most of these patents focus on the field of plant protection, agricultural biotechnology, and agro-processing. However, the foreign applicants mainly work in companies, and most of these patents only focus on plant protection. These findings will provide a reference for formulating development policies about natural rubber industry in China

Functional disruption of human leukocyte antigen II in human embryonic stem cell

BACKGROUND: Theoretically human embryonic stem cells (hESCs) have the capacity to self-renew and differentiate into all human cell types. Therefore, the greatest promise of hESCs-based therapy is to replace the damaged tissues of patients suffering from traumatic or degenerative diseases by the exact same type of cells derived from hESCs. Allo-graft immune rejection is one of the obstacles for hESCs-based clinical applications. Human leukocyte antigen (HLA) II leads to CD4+ T cells-mediated allograft rejection. Hence, we focus on optimizing hESCs for clinic application through gene modification RESULTS: Transcription activator-like effector nucleases (TALENs) were used to target MHC class II transactivator (CIITA) in hESCs efficiently. CIITA-/-hESCs did not show any difference in the differentiation potential and self-renewal capacity. Dendritic cells (DCs) derived from CIITA-/-hESCs expressed CD83 and CD86 but without the constitutive HLA II. Fibroblasts derived from CIITA-/-hESCs were powerless in IFN-γ inducible expression of HLA II CONCLUSION: We generated HLA II defected hESCs via deleting CIITA, a master regulator of constitutive and IFN-γ inducible expression of HLA II genes. CIITA-/-hESCs can differentiate into tissue cells with non-HLA II expression. It's promising that CIITA-/-hESCs-derived cells could be used in cell therapy (e.g., T cells and DCs) and escape the attack of receptors' CD4+ T cells, which are the main effector cells of cellular immunity in allograf