The volume-regulated anion channel (VRAC) is a key player in the volume regulation of vertebrate cells. This ubiquitously expressed channel opens upon osmotic cell swelling and potentially other cues and releases chloride and organic osmolytes, which contributes to regulatory volume decrease (RVD). A plethora of studies have proposed a wide range of physiological roles for VRAC beyond volume regulation including cell proliferation, differentiation and migration, apoptosis, intercellular communication by direct release of signaling molecules and by supporting the exocytosis of insulin. VRAC was additionally implicated in pathological states such as cancer therapy resistance and excitotoxicity under ischemic conditions. Following extensive investigations, 5 years ago leucine-rich repeat-containing family 8 (LRRC8) heteromers containing LRRC8A were identified as the pore-forming components of VRAC. Since then, molecular biological approaches have allowed further insight into the biophysical properties and structure of VRAC. Heterologous expression, siRNA-mediated downregulation and genome editing in cells, as well as the use of animal models have enabled the assessment of the proposed physiological roles, together with the identification of new functions including spermatogenesis and the uptake of antibiotics and platinum-based cancer drugs. This review discusses the recent molecular biological insights into the physiology of VRAC in relation to its previously proposed roles.

The economies of China-Japan-Korea (CJK) are complementary, with their proximity resulting in the three countries having a high degree of interdependence with respect to trade. Currently, trade among these countries relies mainly on port-centered shipping. The development of the shipping network is integral for in-depth integration of CJK trade. This paper analyzes the overall characteristics, centrality, spatial structure, and vulnerability of the CJK shipping network using the methods of complex network analysis, blocking flow theory, and interruption and deletion of hub ports. The main findings are as follows: 1) The CJK shipping network has a small average path length and clustering coefficient, and its degree distribution follows a power-law distribution, which make the network present obvious characteristics of a Barabási-Albert scale-free. 2) The characteristics of the multi-center point of the CJK shipping network can alleviate traffic pressure. At the same time, the network shows a clear hierarchy in the port transportation system, with cargo transport relying mainly on the 'hub port-hub port' connection. 3) The CJK shipping network is relatively stable. Compared with ports in Japan and Korea, the main hub ports in China have a greater impact on the stability of the shipping network, in particular those ports of the central coastal region, including Shanghai, Ningbo, and Lianyungang.

In this study, backpropagation neural network (BPNN) and generalized regression neural network (GRNN) approaches are used to predict the frost-heaving ratio (FR) of the saline soil specimen collected from Nong'an, Western Jilin, China. Four variables, namely, water content (WC), compactness, temperature, and content of soluble salts (CSS), are considered in predicting FR. A total of 360 pieces of data, collected from the experimental results, in which 30 pieces of data were selected randomly as the testing set data and the rest of the data were treated as the training set data, are applied to develop the prediction models. The predicted data from the models are compared with the experimental data. Then, the results of the two approaches are compared to obtain a relatively reliable model. Results indicate that the prediction model for the FR of saline soil in Nong'an can be successfully established using the GRNN method. Four new GRNN models are constructed for sensitivity analysis to assess the influence degree of the influencing factors, and the results indicate that water content is the most influential variable in the FR of the saline soil specimen, whereas content of soluble salts is the least influential variable.

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Cells possess the capability to adjust their volume for various physiological processes, presumably including cell proliferation and migration. The volume-regulated anion channel (VRAC), formed by LRRC8 heteromers, is critically involved in regulatory volume decrease of vertebrate cells. The VRAC has also been proposed to play a role in cell cycle progression and cellular motility. Indeed, recent reports corroborated this notion, with potentially important implications for the VRAC in cancer progression. In the present study, we examined the role of VRAC during cell proliferation and migration in several cell types, including C2C12 myoblasts, human colon cancer HCT116 cells, and U251 and U87 glioblastoma cells. Surprisingly, neither pharmacological inhibition of VRAC with 4-[(2-Butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-inden-5-yl)oxy]butanoic acid (DCPIB), carbenoxolone or 5-nitro-2-(3-phenylpropyl-amino)benzoic acid (NPPB), nor siRNA-mediated knockdown or gene knockout of the essential VRAC subunit LRRC8A affected cell growth and motility in any of the investigated cell lines. Additionally, we found no effect of the VRAC inhibition using siRNA treatment or DCPIB on PI3K/Akt signaling in glioblastoma cells. In summary, our work suggests that VRAC is dispensable for cell proliferation or migration.

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