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Osteoarthritis (OA) is a common degenerative bone and joint disorder characterized by progressive cartilage degeneration and secondary synovial inflammation. It is a common chronic joint disorder that affects people of all ages (especially the old). Plantamajoside is a phenylpropanoside derived from plantain. It has a variety of biological properties, including antioxidant, anti-malignant cell proliferation, and anti-inflammatory properties. In this study, the latent mechanism of plantamajoside was explored by slowing the in-vivo and in-vitro progression of osteoarthritis. The results revealed that plantamajoside pre-conditioning inhibited IL-1β induced pro-inflammatory factors like COX-2, iNOS, IL-6, and TNF-α. Moreover, plantamajoside also reversed the IL-1 β mediated type II collagen and aggrecan degradation within the extracellular matrix (ECM). The protective effects of plantamajoside have been attributed to the inhibition of both MAPK and NF-κB pathways. Furthermore, our in-vivo research found that plantamajoside could slow the progression of OA in mice. Finally, all findings point to plantamajoside as a potential anti-OA therapeutic candidate.

In this study, Mg single crystals (99.99% purity) were subjected to focused ion beam (FIB) bombardment perpendicular and parallel to the c-axis of the hexagonal close packed (HCP) lattice respectively. The research results indicate that the {1 0 −1 2} twin nucleation induced by FIB micro-stress in magnesium single crystal is dependent on the applied ion current and the crystal orientation. The incident Ga + ions dose increases with ion current, which would enhance the FIB loading micro-stress. And when the FIB incident direction is parallel to the close-packed (0 0 0 1) plane, there would be more ion-atom interactions during FIB bombardment. Both processing mechanisms could lead to larger precipitate-matrix misfit area and further microstructure damage, which might eventually facilitate {1 0 −1 2} twin nucleation.

In this work, a new phenazine-based derivative ( L-1 ) which based on 2,3-diamino-phenazine and 5-(4-chlorphenyl)-2-furaldehyde was designed to act efficiently in a chemodosimeter approach for the rapid and selective detection of silver ion in aqueous solution over a wide pH range. The addition of Ag + to an aqueous solution of L-1 induced a change in the solution color from yellow to shallow orange and fluorescent quenching, indicating that L-1 could act as an excellent ON−OFF-type fluorescent chemosensor for Ag + . With a detection limit of 3.25 × 10 −7 M, the chemosensor shows great potential to monitor Ag + in environmental analysis systems. Furthermore, this sensor can serve as a recyclable component in sensing materials. These properties make L-1 act as an accurate Ag + controlled ON−OFF−ON fluorescence switch and implication (IMP) function logic gate. In addition, the actual usage of sensor L-1 was further demonstrated by test kits and silica gel plates. Notably, the stoichiometry of the complexes between the sensor and Ag + is indicative of a 2:1 ratio which was determined by a Job's plot yielded from fluorescence titrations. And the mode of interaction between Ag + ions and L-1 has been supported by 1 H NMR spectroscopy and mass spectrometry studies.

OmpR, a response regulator of the EnvZ/OmpR two-component system (TCS), controls the reciprocal regulation of two porin proteins, OmpF and OmpC, in bacteria. During signal transduction, OmpR (OmpR-FL) undergoes phosphorylation at its conserved Asp residue in the N-terminal receiver domain (OmpRn) and recognizes the promoter DNA from its C-terminal DNA-binding domain (OmpRc) to elicit an adaptive response. Apart from that, OmpR regulates many genes in Escherichia coli and is important for virulence in several pathogens. However, the molecular mechanism of the regulation and the structural basis of OmpR-DNA binding is still not fully clear. In this study, we presented the crystal structure of OmpRc in complex with the F1 region of the ompF promoter DNA from E. coli. Our structural analysis suggested that OmpRc binds to its cognate DNA as a homodimer, only in a head-to-tail orientation. Also, the OmpRc apo-form showed a unique domain-swapped crystal structure under different crystallization conditions. Biophysical experimental data, such as NMR, fluorescent polarization and thermal stability, showed that inactive OmpR-FL (unphosphorylated) could bind to promoter DNA with a weaker binding affinity as compared with active OmpR-FL (phosphorylated) or OmpRc, and also confirmed that phosphorylation may only enhance DNA binding. Furthermore, the dimerization interfaces in the OmpRc-DNA complex structure identified in this study provide an opportunity to understand the regulatory role of OmpR and explore the potential for this "druggable" target.

Eukaryotic mRNA biogenesis involves a series of interconnected steps mediated by RNA-binding proteins. The exon junction complex core protein Y14 is required for nonsense-mediated mRNA decay (NMD) and promotes translation. Moreover, Y14 binds the cap structure of mRNAs and inhibits the activity of the decapping enzyme Dcp2. In this report, we show that an evolutionarily conserved tryptophan residue (Trp-73) of Y14 is critical for its binding to the mRNA cap structure. A Trp-73 mutant (W73V) bound weakly to mRNAs and failed to protect them from degradation. However, this mutant could still interact with the NMD and mRNA degradation factors and retained partial NMD activity. In addition, we found that the W73V mutant could not interact with translation initiation factors. Overexpression of W73V suppressed reporter mRNA translation in vitro and in vivo and reduced the level of a set of nascent proteins. These results reveal a residue of Y14 that confers cap-binding activity and is essential for Y14-mediated enhancement of translation. Finally, we demonstrated that Y14 may selectively and differentially modulate protein biosynthesis.

In this study, the hot-rolled AZ31 Mg alloy sheet was subjected to dynamic plastic deformation (DPD) with the compression axis taken at different angles to the sheet normal direction (ND). {10-12} twin variant selected is not always the primary one with the highest Schmid factor (SF). For some twinned grains in which the orientations have a deviation of about 10°–40° from the ideal orientation (i.e. rolling direction) favoring {10-12} twinning under compression loading to the DPD direction, the nucleated twin variants have the highest SFs; with higher deviation of 30°–60°, the first twins to form are low-SF variants in the twinned grains. This non-Schmid effect is probably associated with the local-stress fluctuation near grain boundary due to strain accommodation between grains. And the deviation angle that ranged from 30° to 40° is considered to be a transition of variant selection toward the non-Schmid behavior.

The effect of {10−12} micro-twin lamellar structure on the mechanical properties of magnesium alloy has been examined. It has been found that the detwinning behavior effectively increases the flow stress of Mg alloy, and this strengthening effect becomes more significant with the volume fraction of twin lamellae increasing for the annealed materials. Meanwhile, the refined microstructure caused by the micro-twin lamellae plays an important role in improving the ductility of materials. But a latent Hall–Petch hardening correlated to grain refinement by twin lamellae was not substantiated by experiments, indicating strengthening from twin boundaries is relatively less pronounced below twin lamellae of micrometer scale. Here, the high density of twin boundaries and the high volume fraction of twins are considered as the structural characteristics of the critical {10−12} twin lamellae, which can effectively optimize strength and ductility of magnesium alloy.

The microstructures of the as-rolled magnesium alloy subjected to dynamic plastic deformation along the rolling direction have been investigated. Mostly one { 10 1 ¯ 2 } twin variant or a twin variant pair is activated in a grain, leading to a parallel { 10 1 ¯ 2 } twin lamellar structure. At the stage of twinning-dominated deformation (e { 10 1 ¯ 2 } twin activity. When plastic strain is greater than ∼8%, the twin lamellar structure disappears because the volume fraction of twins almost saturates at a value of ∼90%.

Twin-twin interfaces have long been thought to be responsible for strain hardening during twinning because of their roles on blocking the motion of twinning dislocations and forming boundary dislocations. However, there is still the lack of experimental observation of interface structure due to the great stress concentration on the boundaries. The 7.4° twin-twin interfaces bonding the prismatic planes of both twins in the deformed AZ31 Mg alloy were investigated combining transmission electron microscopy (TEM) observations and theoretical analysis. Mis-layered structure of {0001} planes, i.e. the basal A layer of one twin connecting the basal B layer of another twin, is found in the interface. Modeling analysis indicates that twin-twin interaction mode with the basal mis-layered connection is more energetically favorable than that without it. Meanwhile, misfit dislocations are observed in the interface. This interfacial crystal structure may result in annealed strengthening of detwinning in Mg alloy.

Effect of {10–12} twins on the mechanical properties of magnesium alloy has received considerable research interest. A hot-rolled AZ31 Mg alloy sheet was subjected to dynamic plastic deformation with the aim of introducing {10–12} twin lamellar structure. It has been found that higher strength and better ductility are obtained when tensile loading is perpendicular to the c axis of twin region of the twin lamellar structured sample, indicating that the plasticity improvement caused by twins depends on the special strain path. The fracture morphology of the twin lamellar structured sample shows a dimple fracture mode under tensile loading perpendicular to the c axis, while the cleavage fracture with river pattern has been observed in other fractured samples. Above experimental results indicate that the interaction of dislocations and twin lamellae may play an important role in improving mechanical properties of Mg alloy.

The formation mechanism of the { 11 2 ¯ 1 } deformation twins in polycrystalline cobalt during dynamic plastic deformation has been proposed in this paper. It is found that the dislocation reactions play important roles in the nucleation and growth of { 11 2 ¯ 1 } deformation twins. The basal dislocations dissociate into sessile partials pinned at the intersection of two { 11 2 ¯ 1 } planes and glissile partials glided to nucleate twins on the (0 0 0 2) planes during the deformation. With the help of the applied stress, the dislocation reactions can be repeated, resulting in the formation of { 11 2 ¯ 1 } deformation twins.

Human pancreatitis-associated protein was identified in pathognomonic lesions of Alzheimer disease, a disease characterized by the presence of filamentous protein aggregates. Here, we showed that at physiological pH, human pancreatitis-associated protein forms non-Congo Red-binding, proteinase K-resistant fibrillar aggregates with diameters from 6 up to as large as 68 nm. Interestingly, circular dichroism and Fourier transform infrared spectra showed that, unlike typical amyloid fibrils, which have a cross-beta-sheet structure, these aggregates have a very similar secondary structure to that of the native protein, which is composed of two alpha-helices and eight beta-strands, as determined by NMR techniques. Surface structure analysis showed that the positively charged and negatively charged residues were clustered on opposite sides, and strong electrostatic interactions between molecules were therefore very likely, which was confirmed by cross-linking experiments. In addition, several hydrophobic residues were found to constitute a continuous hydrophobic surface. These results and protein aggregation prediction using the TANGO algorithm led us to synthesize peptide Thr(84) to Ser(116), which, very interestingly, was found to form amyloid-like fibrils with a cross-beta structure. Thus, our data suggested that human pancreatitis-associated protein fibrillization is initiated by protein aggregation primarily because of electrostatic interactions, and the loop from residues 84 to 116 may play an important role in the formation of fibrillar aggregates with a native-like conformation.

A number of beta-microseminoproteins (MSPs) have been identified from different species. MSPs are all non-glycosylated and disulfide bond-rich, but show a relatively low level of conservation. Although all Cys residues are conserved, our previous study showed that the disulfide bond pairings differ in porcine and ostrich MSPs. Despite the variety of biological functions that have been suggested for MSPs, their real function is still poorly understood. Furthermore, no 3D structure has been reported for any MSP, so the determination of the structure and function of MSPs is an interesting and important task. In the present study, we determined the 3D solution structure of porcine MSP on the basis of 1018 restraints. The ensemble of 20 NMR structures was well defined, with average root-mean-square deviations of 0.83(+/-0.16) A for the backbone atoms and 1.37(+/-0.17) A for heavy-atoms in residues 2-90. The 3D structure showed that porcine MSP is clearly composed of two domains, an N-terminal domain consisting of one double-stranded and one four-stranded antiparallel beta-sheet, and a C-terminal domain consisting of two double-stranded antiparallel beta-sheet. The orientation of the two domains was derived mainly on the basis of long-range NOEs and verified using residual dipolar coupling data. No inter-domain hydrophobic interaction or H-bonding was detected. However, a number of charged residues were found in close proximity between the domains, indicating that electrostatic interaction may be the key factor for the orientation of the two domains. This is the first report of a 3D structure for any MSP. In addition, structural comparison based on distance matrix alignment (DALI), class architecture topology and homologous superfamily (CATH) and combinatorial extension (CE) methods revealed that porcine MSP has a novel structure with a new fold providing valuable information for future structural studies on other MSPs and for understanding their biological functions.

The flavivirus envelope protein is the dominant antigen in eliciting neutralizing antibodies and plays an important role in inducing immunologic responses in the infected host. We have determined the solution structure of the major antigenic domain (domain III) of the Japanese encephalitis virus (JEV) envelope protein. The JEV domain III forms a beta-barrel type structure composed of six antiparallel beta-strands resembling the immunoglobulin constant domain. We have also identified epitopes of the JEV domain III to its neutralizing antibody by chemical shift perturbation measurements. Site-directed mutagenesis experiments are performed to confirm the NMR results. Our study provides a structural basis for understanding the mechanism of immunologic protection and for rational design of vaccines effective against flaviviruses.