China's industrial green total-factor energy efficiency and its influencing factors: a spatial econometric analysis.

The sustainable development of China's economy is bottlenecked by resource shortage and environmental pollution. As the leading resource consumer and pollutant source, the industrial sector needs to improve its energy efficiency. This paper establishes a super epsilon-based measure (Super-EBM) model with bad outputs like environmental cost and evaluates the industrial green total-factor energy efficiencies (IGTFEEs) of 30 provinces in China during 2000-2017. Unlike previous research, the main contribution of this paper is to choose four environmental pollutants as bad outputs (industrial carbon dioxide, industrial sulfur dioxide, industrial chemical oxygen demand, industrial solid waste). By contrast, the previous studies mostly only take one environmental pollutant as bad output, i.e., the bad outputs are not fully measured. Then, the spatiotemporal dynamics and spatial correlations of the IGTFEEs were analyzed, and the influencing factors of IGTFEE were examined empirically with a spatial econometric model. Finally, this paper adopts generalized method of moments (GMM) to solve the endogenous problem, trying to assure the robustness of estimation results. The results show significant provincial differences in IGTFEE. Most eastern coastal provinces achieved satisfactory IGTFEEs, while most inland provinces had undesirable IGTFEEs. Eastern region achieved the highest IGTFEE, followed by central region; western region had the lowest IGTFEE. The IGTFEE improved over time in some provinces while worsened greatly in some provinces. The IGTFEE in most provinces need to be further improved. Global Moran's I values indicate that the provincial IGTFEEs were clustered in space, rather than randomly distributed. Local indication of spatial association (LISA) map reflects significant local spatial clustering of provincial IGTFEEs. In addition, IGTFEE is significantly promoted by industrial structure, technological innovation, human capital, opening-up, and energy structure yet significantly suppressed by ownership structure and environmental regulation. Considering the endogeneity, GMM results show that the estimation results of the model were robust. Specific policy recommendations include vigorously developing high-tech industries, deepening state-owned enterprises reform, diverting more funds to research and development, cultivating versatile talents, introducing environmentally-friendly foreign capital, accelerating the implementation of clean energy development strategy, and widening the fund channels of pollution control investment.

hnRNPK inhibits GSK3ß Ser9 phosphorylation, thereby stabilizing c-FLIP and contributes to TRAIL resistance in H1299 lung adenocarcinoma cells.

c-FLIP (cellular FLICE-inhibitory protein) is the pivotal regulator of TRAIL resistance in cancer cells, It is a short-lived protein degraded through the ubiquitin/proteasome pathway. The discovery of factors and mechanisms regulating its protein stability is important for the comprehension of TRAIL resistance by tumor cells. In this study, we show that, when H1299 lung adenocarcinoma cells are treated with TRAIL, hnRNPK is translocated from nucleus to cytoplasm where it interacts and co-localizes with GSK3ß. We find that hnRNPK is able to inhibit the Ser9 phosphorylation of GSK3ß by PKC. This has the effect of activating GSK3ß and thereby stabilizing c-FLIP protein which contributes to the resistance to TRAIL in H1299 cells. Our immunohistochemical analysis using tissue microarray provides the clinical evidence of this finding by establishing a negative correlation between the level of hnRNPK expression and the Ser9 phosphorylation of GSK3ß in both lung adenocarcinoma tissues and normal tissues. Moreover, in all cancer tissues examined, hnRNPK was found in the cytoplasm whereas it is exclusively nuclear in the normal tissues. Our study sheds new insights on the molecular mechanisms governing the resistance to TRAIL in tumor cells, and provides new clues for the combinatorial chemotherapeutic interventions with TRAIL.

Cytoplasmic hnRNPK interacts with GSK3ß and is essential for the osteoclast differentiation.

Osteoclast differentiation is a complex and finely regulated physiological process that involves a variety of signaling pathways and factors. Recent studies suggested that the Ser9 phosphorylation of Glycogen synthase kinase-3ß (GSK3ß) is required for the osteoclast differentiation. However, the precise underlying mechanism remains unclear. We have previously identified the heterogeneous nuclear ribonucleoprotein K (hnRNPK) as a putative GSK3ß interactor. In the present study, we demonstrate that, during the RANKL-induced osteoclast differentiation, the PI3K/Akt-mediated Ser9 phosphorylation of GSK3ß provokes the nuclear-cytoplasmic translocation of hnRNPK in an ERK-dependent manner, enhancing the cytoplasmic co-localization and interaction of GSK3ß and hnRNPK. We show that hnRNPK is essential for the osteoclast differentiation, and is involved in several reported functions of GSK3ß, including the activation of NF-κB, the expression of NFATc1, and the acetylation of tubulin, all known to be critical for osteoclast differentiation and functions. We find that hnRNPK is localized in the actin belt, and is important for the mature osteoclast formation. Taken together, we demonstrate here the critical role of hnRNPK in osteoclast differentiation, and depict a model in which the cytoplasmic hnRNPK interacts with GSK3ß and regulates its function.

A homogeneous time-resolved fluorescence-based high-throughput screening for discovery of inhibitors of Nef-sdAb19 interaction.

The human immunodeficiency virus (HIV) protein negative factor (Nef) is important for AIDS pathogenesis. An anti-Nef single-domain antibody (sdAb19) derived from camelids has been previously generated and shown to effectively block the physiological functions of Nef in vitro and in vivo in nef-transgenic mice. However, sdAb19 must be ectopically expressed within the target cell to be able to exert its neutralizing effect on Nef, while the extra-cellular administration method turned out to be ineffective. This might suggest a default of the stability or/and deliverability of sdAb19. The identification of small molecule compounds capable of inhibiting the Nef-sdAb19 interaction and mimicking the neutralizing activity of sdAb19 in vivo would therefore be the means of circumventing the problem encountered with sdAb19. Here we describe the development of a high-throughput screening method combining the homogeneous time-resolved fluorescence (HTRF) and the microscale thermophoresis (MST) techniques for the identification of small-molecule compounds inhibiting the Nef-sdAb19 interaction by binding to Nef protein. Eight small-molecule compounds have been selected for their ability to significantly inhibit the Nef-sdAb19 interaction and to bind to Nef. These molecules could be further assessed for their potential of being the Nef-neutralizing agents in the future.

[Interaction of Flightless I with Nup88 and Importin ß].

High expression of Fightless I (FLII) is associated to multiple tumors. Based on our previous study that FLII might be involved in the nuclear export, we assessed the possible interaction of FLII with the nuclear envelop associating proteins Importin ß and Nup88. We first constructed GST-FLII, GST-LRR recombinant plasmids and transformed them into the Rosetta strain to produce GST-FLII, GST-LRR fusion protein. After purification of these proteins, GST-pull down, as well as co-immunoprecipitation, were used to test the interaction of FLII with Importin ß and Nup88. FLII interacted with Importin ß and Nup88, and FLII LRR domain is responsible for these interactions. Thus, FLII may play a role in nuclear export through interaction with Importin ß and Nup88.