With the rapid development of cloud computing, more and more enterprises/individuals are starting to outsource local data to the cloud servers. However, under open networks and not fully trusted ...cloud environments, they face enormous security and privacy risks (e.g., data leakage or disclosure, data corruption or loss, and user privacy breach) when outsourcing their data to a public cloud or using their outsourced data. Recently, several studies were conducted to address these risks, and a series of solutions were proposed to enable data and privacy protection in untrusted cloud environments. To fully understand the advances and discover the research trends of this area, this survey summarizes and analyzes the state-of-the-art protection technologies. We first present security threats and requirements of an outsourcing data service to a cloud, and follow that with a high-level overview of the corresponding security technologies. We then dwell on existing protection solutions to achieve secure, dependable, and privacy-assured cloud data services including data search, data computation, data sharing, data storage, and data access. Finally, we propose open challenges and potential research directions in each category of solutions.
Abstract Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with a strong genetic component, characterized by hyperactive T and B cells, autoantibody production, immune complex ...deposition and multi-organ damage. It affects predominantly women of child-bearing age and has population differences in both disease prevalence and severity. Genetic factors are known to play key roles in the disease through the use of association and family studies. Previously, SLE susceptibility genes were mainly revealed through linkage analysis and candidate gene studies. Since 2008, our understanding of the genetic basis of SLE has been rapidly advanced through genome-wide association studies (GWASs). More than 40 robust susceptibility loci have been identified and conformed to be associated with SLE using this technique. Most of these associated genes productions participate in important pathways involved in the pathogenesis of SLE, such as immune complex processing, toll-like receptor signaling, type I interferon production, and so on. A number of susceptibility loci with unknown functions in the pathogenesis of SLE have also been identified, indicating that additional molecular mechanisms contribute to the risk of developing SLE. It is noteworthy that susceptibility loci of SLE are shared by other immune-related diseases. Thus, common molecular pathways may be involved in the pathogenesis of these diseases. In this review, we summarize the key loci, achieving genome-wide significance, which have been shown to predispose to SLE. Analysis of relevant molecular pathways suggests new etiologic clues to SLE development. These genetic loci may help building the foundation for genetic diagnosis and personalized treatment for patients with SLE in the near future. However, substantial additional studies, including functional and gene-targeted studies, are required to confirm the causality of the genetic variants and their biological relevance in SLE development.
Background Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP) is reported to be different in inflammatory patterns of the sinonasal mucosa in white patients. ...Studies in nonwhite populations may further be helpful to understand the pathogenic mechanisms of CRS. Objective To investigate the immunopathologic profiles of CRSwNP and CRSsNP in adult Chinese. Methods Histologic characteristics of surgical samples were analyzed in 50 controls, 94 CRSsNP patients, and 151 CRSwNP patients. Tissue samples from 17 controls, 36 CRSsNP patients, and 45 CRSwNP patients were stained for CD3, CD4, CD8, CD20, CD68, myeloperoxidase, and dendritic cell lysosome-associated membrane protein. Expression profiles of transcription factors of T-cell subsets in relation to cytokines and a marker of natural killer T cell (Vα24) were examined by means of quantitative RT-PCR. Results Over half of CRSwNP patients presented noneosinophilic inflammation. CRSwNP had a higher number of eosinophils, plasma cells, and CD3+ , CD8+ , CD20+ , and CD68+ cells and a lower myeloperoxidase expression rate than CRSsNP. Expression levels of transcription factors and cytokines of TH 1/TH 2/TH 17 were increased, whereas the expression rate of Forkhead box p3 and TGF-β1 was decreased in both CRSsNP and CRSwNP compared with controls. Comparing CRSsNP and CRSwNP, CRSsNP had higher levels of IFN-γ expression, whereas only eosinophilic CRSwNP demonstrated an enhanced expression of GATA-3 and IL-5. Compared with noneosinophilic CRSwNP, an exaggerated TH 2/TH 17 reaction and Vα24 expression were found in eosinophilic CRSwNP. Conclusion Both Chinese CRSsNP and CRSwNP patients demonstrate impaired regulatory T cell function and enhanced TH 1/TH 2/TH 17 responses. CRSsNP is confirmed to be a predominant TH 1 milieu, whereas TH 2 skewed inflammation with predominant TH 17 reactions, and infiltration of natural killer T cells can be demonstrated only in eosinophilic CRSwNP, but not in noneosinophilic CRSwNP.
Through the self-assembly of a 3-EtO salamo H2L with nickel acetate tetrahydrate, Lanthanide nitrate hexahydrate (Ln = Sm and Tb), and terephthalic acid (H2bdc), two new heterobimetallic NiIILnIII ...3d-4f polymers, 2∞Ni(L)Sm(bdc)1.5·CH3OH (1) and 1∞Ni(L)Tb(NO3)(DMF)(bdc) (2) were synthesized, respectively.
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•A Salamo-like N2O4-Donor ligand has been synthesized.•Coordination polymer 1 is a 2D coordination polymer.•Coordination polymer 2 is a 1D chain coordination polymer.
Through the self-assembly of a 3-EtO salamo H2L with nickel acetate tetrahydrate, lanthanide nitrate hexahydrate (Ln = Sm and Tb) and terephthalic acid (H2bdc), two new heterobimetallic NiIILnIII 3d-4f polymers, 2∞Ni(L)Sm(bdc)1.5·CH3OH (1) and 1∞Ni(L)Tb(NO3)(DMF)(bdc) (2) were synthesized, respectively. Coordination polymers 1 and 2 were characterized via elemental analysis, X-ray single-crystal analysis, IR and UV–visible absorption spectroscopy. Coordination polymer 1 is a 2D coordination polymer in which Ni(L)Sm units are linked by exodentate (bdc)2− linker. Coordination polymer 2 is a 1D chain coordination polymer in which the Ni(L)Tb(NO3) moieties are connected by exodentate (bdc)2− linker, and they further form a 3D supramolecular configuration through intermolecular hydrogen bondings. Fluorescence properties of coordination polymers 1 and 2 have been discussed.
Britannin (Bri), isolated from Inula aucheriana, is a sesquiterpene lactone (SL), a class of secondary metabolites. Previous studies have suggested the anti-cancer potential of Bri; however, the ...molecular mechanism remains elusive. The present study investigated the effects of Bri on liver cancer progression. Our findings indicated that Bri significantly suppressed the growth of liver cancer cell lines. Mechanistic researches revealed that Bri induced apoptosis through the extrinsic and intrinsic apoptotic pathways, as evidenced by the increase of Caspase-8, -9 and -3 cleavages. In addition, Bri-triggered autophagy in liver cancer cells, supported by the up-regulation of light chain 3 (LC3) II, p62, autophagy-related 5 (ATG5) and Beclin 1, as well as the occurrence of autophagic vacuoles. Importantly, Bri increased AMPK activation, while decreased the activity of its down-streaming signal, mTOR. Of note, suppression of AMP-activated protein kinase (AMPK) activation using its inhibitor, Compound C, could inhibit both apoptosis and autophagy induced by Bri. Furthermore, Bri was found to induce reactive oxygen species (ROS) generation in hepatic cancer cells. Notably, reducing ROS production by its scavenger, N-acetyl cysteine (NAC), could down-regulate p-AMPK levels, while up-regulate the phosphorylated mechanistic target of rapamycin (p-mTOR) expressions, accompanied with the restored cell viability, as well as the reduced apoptosis and autophagy in Bri-treated liver cancer cells. Finally, Bri inhibited the tumor growth in vivo without side effects. In conclusion, our study illustrated that Bri could induce apoptosis and autophagy by activating AMPK regulated by ROS in liver cancer cells, supplying molecular bases for developing Bri into an effective candidate against liver cancer.
•Britannin inhibits the proliferation of human liver cancer cell lines.•Britannin induces apoptosis and autophagy in human liver cancer cells.•Britannin-induced apoptosis and autophagy are AMPK-dependent regulated by ROS generation.•Britannin reduces tumor growth in xenograft tumor models in vivo.
The separation of racemic molecules is of substantial significance not only for basic science but also for technical applications, such as fine chemicals and drug development. Here we report two ...isostructural chiral metal-organic frameworks decorated with chiral dihydroxy or -methoxy auxiliares from enantiopure tetracarboxylate-bridging ligands of 1,1'-biphenol and a manganese carboxylate chain. The framework bearing dihydroxy groups functions as a solid-state host capable of adsorbing and separating mixtures of a range of chiral aromatic and aliphatic amines, with high enantioselectivity. The host material can be readily recycled and reused without any apparent loss of performance. The utility of the present adsorption separation is demonstrated in the large-scale resolution of racemic 1-phenylethylamine. Control experiments and molecular simulations suggest that the chiral recognition and separation are attributed to the different orientations and specific binding energies of the enantiomers in the microenvironment of the framework.
Hydrotropy is a phenomenon where the presence of a large quantity of one solute enhances the solubility of another solute. The mechanism of this phenomenon remains elusive and a topic of debate. This ...study employed molecular dynamics simulation to investigate solute interactions of a model system consisting of a hydrotropic agent, caffeine (CAF), a poorly water-soluble solute, riboflavin (RBF), and water. The study demonstrates that CAF and RBF undergo molecular parallel stacking in the aqueous solution, a result correlating closely to the self-stacking of CAF under the same conditions. The correlations are found both structurally and dynamically, suggesting that the self-stacking of CAF is the primary effect, and incorporation of RBF is the secondary effect. The solute stacking gives rise to the partitioning of solutes and water, which helps restoring the normal water structure and drives down the system energy. The interactions between the solutes are found insignificant to the solute clustering. The dynamic data confirm that the solute stacks are dynamically active. These results suggest that hydrotropic effect of CAF may be attributed to solute parallel stacking.
Evolved through the past 60years, molecular simulations have become one of the most important analytical tools in many theoretical and applied scientific disciplines. This paper provides a brief ...introduction to molecular simulations as a means of addressing important scientific questions of interest to pharmaceutical scientists. The focus is on fundamental questions such as: (1) Why do simulations work? (2) How to simulate? (3) How to make the results of simulations “real?” (4) Where can simulations be applied? To demonstrate the fundamental rationale of molecular simulations, three perspectives, thermodynamics, statistical mechanics, and general statistics, are compared. The concept of stochasticity is introduced, followed by a brief account of the two major methods used in simulations, molecular dynamics and Monte Carlo simulations. A brief discussion is then given on force fields to indicate their central importance. To facilitate the discussion about possible applications to pharmaceutical systems, the characteristics of molecular simulations are first compared with those of laboratory experiments. Case studies are then introduced to demonstrate the strengths of simulations. Some frequently encountered questions also are presented and discussed.
Ideally, the throughput of a Multipath TCP (MPTCP) connection should be as high as that of multiple disjoint single-path TCP flows. In reality, the throughput of MPTCP is far lower than expected. In ...this paper, we conduct an extensive simulation-based study on this phenomenon, and the results indicate that a subflow experiencing high delay and loss severely affects the performance of other subflows, thus becoming the bottleneck of the MPTCP connection and significantly degrading the aggregate goodput. To tackle this problem, we propose Fountain code-based Multipath TCP (FMTCP), which effectively mitigates the negative impact of the heterogeneity of different paths. FMTCP takes advantage of the random nature of the fountain code to flexibly transmit encoded symbols from the same or different data blocks over different subflows. Moreover, we design a data allocation algorithm based on the expected packet arriving time and decoding demand to coordinate the transmissions of different subflows. Quantitative analyses are provided to show the benefit of FMTCP. We also evaluate the performance of FMTCP through ns-2 simulations and demonstrate that FMTCP outperforms IETF-MPTCP, a typical MPTCP approach, when the paths have diverse loss and delay in terms of higher total goodput, lower delay, and jitter. In addition, FMTCP achieves high stability under abrupt changes of path quality.
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