pH and heat-induced structural changes of bovine apo-α-lactalbumin

The effects of pH and thermal treatments on conformation and association state of Ca²⁺-depleted bovine α-lactalbumin (apo-α-LA) have been studied by fluorescence spectroscopy, and molecular modelling. The experimental results demonstrate a third-state model for heat-induced unfolding of apo-α-LA, at pH 2.0, and an all-or-none transition of apo-α-LA, at pH 4.5 and 7.0, respectively. The heat-induced changes in the secondary and tertiary structure of α-LA were outlined after running molecular dynamics simulations at 25 °C and 80 °C, at neutral pH, therefore supporting the experimental observations. Our data provides insight into the mechanism of pH- and heat-dependent structural changes and oligomerization of α-LA, and will be helpful in understanding the ability of this protein to interact with certain compounds of biological interest.     

Molecular modeling on HIF-2α–ARNT dimer destabilization caused by R171A and/or V192D mutations in HIF-2α

Oxygen homeostasis in normal and tumor cells is mediated by hypoxia-inducible factors (HIFs), which are active as heterodimer complexes, such as HIF-2α–aryl hydrocarbon receptor nuclear translocator (ARNT) and HIF-1α–ARNT. A series of mutations on the interfaces between HIF-2α and ARNT and on the domain–domain interface within HIF-2α has been reported to exert varying effects on HIF-2α–ARNT dimerization. In the present study, molecular dynamic simulations were conducted to evaluate HIF-2α mutations, namely R171A, V192D, and R171A/V192D, which are not involved in the interaction with ARNT but impede HIF-2α–ARNT dimerization. Our results indicate that these mutations induct local conformation leading to a shortened (by V192D) or widened (by R171A and R171A/V192D) Y91–E346 separation distance, where E346 and Y91 are located on the HIF-2α and interact with ARNT according to electrostatic and geometrical shape complementarity, respectively.     

Theoretical study of the zero-gap organic conductor α-(BEDT-TTF)2I3

Abstract

The quasi-two-dimensional molecular conductor α-(BEDT-TTF)₂I₃ exhibits anomalous transport phenomena where the temperature dependence of resistivity is weak but the ratio of the Hall coefficient at 10 K to that at room temperature is of the order of 10⁴. These puzzling phenomena were solved by predicting massless Dirac fermions, whose motions are described using the tilted Weyl equation with anisotropic velocity. α-(BEDT-TTF)₂I₃ is a unique material among several materials with Dirac fermions, i.e. graphene, bismuth, and quantum wells such as HgTe, from the view-points of both the structure and electronic states described as follows. α-(BEDT-TTF)₂I₃ has the layered structure with highly two-dimensional massless Dirac fermions. The anisotropic velocity and incommensurate momenta of the contact points, ±k₀, originate from the inequivalency of the BEDT-TTF sites in the unit cell, where ±k₀ moves in the first Brillouin zone with increasing pressure. The massless Dirac fermions exist in the presence of the charge disproportionation and are robust against the increase in pressure. The electron densities on those inequivalent BEDT-TTF sites exhibit anomalous momentum distributions, reflecting the angular dependences of the wave functions around the contact points. Those unique electronic properties affect the spatial oscillations of the electron densities in the vicinity of an impurity. A marked behavior of the Hall coefficient, where the sign of the Hall coefficient reverses sharply but continuously at low temperatures around 5 K, is investigated by treating the interband effects of the magnetic field exactly. It is shown that such behavior is possible by assuming the existence of the extremely small amount of electron doping. The enhancement of the orbital diamagnetism is also expected. The results of the present research shed light on a new aspect of Dirac fermion physics, i.e. the emergence of unique electronic properties owing to the structure of the material.     

α-氰基二苯乙烯类液晶研究进展

分类综述了α-氰基二苯乙烯类液晶的研究进展,包括氰基二苯乙烯棒状液晶、氰基二苯乙烯弓形液晶及氰基二苯乙烯多链形液晶,盘状液晶等。介绍了他们自组装成的多种液晶相及光电性质,以及对光、电、磁、压力等多种环境因素快速的响应性质。氰基二苯乙烯类液晶作为一种新型的荧光液晶材料,具有压敏效应、聚集发光效应及离子识别效应等,已成为当前人们重点研发的功能材料。     

FUZZY REASONING USING POSITIONAL INFORMATION

Abstract

The paper argues in favour of reasoning methods that process positional information, i.e. information about the position of the input with respect to the class prototype, and thus achieve a better specification of the corresponding output class. It is shown that such an approach leads to reducing or cancelling unwanted nonlinearities (of input-output characteristic) imposed by reasoning methods, nonlinearities that alter the dependence expressed in the knowledge base. Two methods which use positional information are presented: (a) the mapping of o-cut borders (MACB) (Stoica, 1993, Proc. Fifth IFSA World Congress, pp. 1266-1269), inspired from a particular interpretation of the representation theorem and (b) the Left/Right Centre of Gravity (L/R COG) (Ghanayem, 1995, Proc. IEA/AIE, pp. 41 -45). The methods are tested in implementing a power system stabiliser (PSS) Simulation results show better performance of methods that use positional information, as compared with classic Mamdani (Mamdani, 1975, International Journal of Man-Machine Studies, 7, 1-13) reasoning. Reflections on a “best” reasoning method conclude the paper.     

Synthesis and characterization of α/β-Bi2O3 with enhanced photocatalytic activity for 17α-ethynylestradiol

The α/β-Bi₂O₃ photocatalyst was successfully synthesized by a novel solvothermal-calcination method. The physical and chemical properties of as-prepared samples were characterized based on XRD, XPS, SEM, TEM, EDS, BET, UV–vis DRS and PL techniques. The synthesized α/β-Bi₂O₃ photocatalyst exhibited enhanced photocatalytic activity for 17α-ethinylestradiol (EE2), and 96.9% of EE2 was degraded after only 24 min of visible-light irradiation using α/β-Bi₂O₃ as photocatalyst. The reaction rate constant over α/β-Bi₂O₃ photocatalyst was 1.42, 2.23, 9.22 and 54.1 times higher than pure β-Bi₂O₃, α-Bi₂O₃+β-Bi₂O₃, α-Bi₂O₃ and P25 respectively. Effect of catalyst dosage and pH value was investigated. The possible photocatalytic mechanism has been discussed on the basis of the theoretical calculation and the experimental results. α/β-Bi₂O₃ was a fairly stable and efficient photocatalyst under the studied experimental conditions, proving that the α/β-Bi₂O₃ photocatalyst was a promising photocatalyst for the practical application.     

Cell-Based Optimization of Covalent Reversible Ketoamide Inhibitors Bridging the Unprimed to the Primed Site of the Proteasome β5 Subunit

The ubiquitin-proteasome system (UPS) is an established therapeutic target for approved drugs to treat selected hematologic malignancies. While drug discovery targeting the UPS focuses on irreversibly binding epoxyketones and slowly-reversibly binding boronates, optimization of novel covalent-reversibly binding warheads remains largely unattended. We previously reported α-ketoamides to be a promising reversible lead motif, yet the cytotoxic activity required further optimization. This work focuses on the lead optimization of phenoxy-substituted α-ketoamides combining the structure-activity relationships from the primed and the non-primed site of the proteasome β5 subunit. Our optimization strategy is accompanied by molecular modeling, suggesting occupation of P1′ by a 3-phenoxy group to increase β5 inhibition and cytotoxic activity in leukemia cell lines. Key compounds were further profiled for time-dependent inhibition of cellular substrate conversion. Furthermore, the α-ketoamide lead structure 27 does not affect escape response behavior in Danio rerio embryos, in contrast to bortezomib, which suggests increased target specificity.     

Uncoupling tumor necrosis factor-α and interleukin-10 at tumor immune microenvironment of breast cancer through miR-17-5p/MALAT-1/H19 circuit

Triple Negative Breast Cancer (TNBC) immunotherapy has recently shown promising approach. However, some TNBC patients presented with resistance. One of the reasons was attributed to the excessive release of cytokines at the tumor microenvironment (TME) such as Tumor necrosis factor alpha (TNF-α) and Interleukin-10 (IL-10). Fine regulation of these cytokines’ levels via non-coding RNAs (ncRNAs) might alleviate the immune quiescent nature of TME at TNBC tumors. However, the extrapolation of ncRNAs as therapeutic tools is highly challenging. Therefore, disentanglement the nature for the isolation of natural compounds that could modulate the ncRNAs and their respective targets is an applicable translational therapeutic approach. Hence, this study aimed to targeting the chief immune suppressive cytokines at the TME (TNF-α and IL-10) via ncRNAs and to examine the effects of Rosemary aerial parts extract on the expression levels of these ncRNAs in TNBC. Results revealed miR-17-5p as a dual regulator of TNF-α and IL-10. Moreover, an intricate interaction has been shown between miR-17-5p and the oncogenic lncRNAs: MALAT1 and H19. Knocking down of MALAT1 and/or H19 caused an induction in miR-17-5p and reduction in TNF-α and IL-10 expression levels. miR-17-5p was found to be down-regulated, while TNF-α, IL-10, MALAT1 and H19 were up-regulated in BC patients. Forced expression of miR-17-5p in MDA-MB-231 cells reduced TNF-α, IL-10, MALAT1 and H19 expression levels, as well as several BC hallmarks. In a translational approach, ursolic acid (UA) isolated from rosemary induced the expression of miR-17-5p, MALAT1 and decreased H19 expression levels. In conclusion, this study suggests miR-17-5p as a tumor suppressor and an immune-activator miRNA in BC through tuning up the immunological targets TNF-α, IL-10 at the TME and the oncological mediators MALAT1 and H19 lncRNAs.