Mechanical Effects of Elastic Crystals Driven by Natural Sunlight and Force.

Flexible crystals that can capture solar energy and convert it into mechanical energy are promising for a wide range of applications such as information storage and actuators, but obtaining them remains a challenge. Herein, an elastic crystal of a barbiturate derivative was found to be an excellent candidate, demonstrating plastic bending behavior under natural sunlight irradiation. 1 H NMR and high-resolution mass spectrum data of microcrystals before and after light irradiation demonstrated that light-induced [2+2] cycloaddition was the driving force for the photomechanical effects. Interestingly, the crystals retained elastic bending even after light irradiation. This is the first report of flexible crystals that can be driven by natural sunlight and that have both photomechanical properties and elasticity. Furthermore, regulation of the passive light output direction of the crystals and transport of objects by applying mechanical forces and light was demonstrated.

Molecular recognition and binding of CcrA from Bacteroides fragilis with cefotaxime and ceftazidime by fluorescence spectra and molecular docking.

In search of new super-bacterial inhibitor agents, the recognition and binding mechanism of the B1 subclass MßL CcrA from Bacteroides fragilis with cefotaxime (CTX) and ceftazidime (CAZ) were studied using spectroscopy analysis and molecular docking. The results showed that the fluorescence quenching of CcrA induced by CTX and CAZ were all due to the complex formation, which belonged to static quenching and was forced by hydrogen bonds and Van der Waals forces, despite the greater binding ability of CTX with CcrA than CAZ. Upon recognizing CTX or CAZ, the CcrA opened its binding pocket by the microenvironmental and conformational of three loops changing to promote an induced-fit of the freshly introduced antibiotics. In addition, the whole antibiotic molecule ultimately entered the active pocket of CcrA with its original carbonate replaced by the carboxyl oxygen of the hexatomic ring adjacent to the ß-lactam ring in CTX or CAZ, forming a new tetrahedral coordination structure at the Zn2 site. Moreover, the difference in steric hindrance and electrostatic effects of the side chain affected the binding ability of the two antibiotics to the CcrA. This work showed the refined procedures of the antibiotics binding to CcrA and might provide useful information hint for the new strategy of developing the novel and innovative super-bacterial antibiotics.

Guanosine Borate Hydrogel and Self-Assembled Nanostructures Capable of Enantioselective Aldol Reaction in Water.

A guanosine-based hydrogel formed by the self-assembly of guanosine and 4-((l-prolinamide)methyl)phenylboronic acid was constructed. The G quartets were selectively stabilized by K+ ions to form a self-supporting transparent hydrogel. These guanosine-derived assemblies were used to catalyze the aldol reaction in water without any additives, affording desirable conversion and enantioselectivity of the product. The controlled assays of small-molecule components indicated that the stable assemblies were the definite species that achieved high enantioselective catalysis. The current catalytic system can be readily recovered by simple extraction and still acquired good performance of the reaction after four cycles.

Metallo-beta-lactamase CphA evolving into more efficient hydrolases through gene mutation is a novel pathway for the resistance of super bacteria.

The evolution of metallo-beta-lactamase CphA in discontinuous gradient concentration of imipenem was investigated in this work. The results suggested that single-base mutations K218R, K249T, K249M, Q253H, and a frameshift mutation M1 were observed. Compared with wild type, the minimum inhibitory concentration (MICs) of K249T, K249M, and M1 increased by at least 128 times and that of K218R increased by 64 times. And the catalytic efficiency increased by 312% and 653%, respectively. It is speculated from the details of the structural changes revealed by molecular dynamics simulations that the carbon skeleton migration caused by the outward motion of the loop 3 in the mutant may have significantly increased the cavity volume of the binding pocket, which is more conducive to the entry and expulsion of imipenem and its hydrolytic product. And the conformational change of the TDRAGGN (71-77) is located at the bottom of the binding pocket from order α-helix to disorder random coil enabled the binding pocket to be more conducive to accommodate and hold the imipenem respectively. All these indicated that during the repeated drug resistance, the wild-type achieved gene mutations and conformational change and evolved to the mutant enzymes with a more delicate structure and stronger hydrolysis ability. KEY POINTS: • The mutation and evolution of CphA under the selective pressure of imipenem. • The CphA evolved to the mutants with stronger hydrolysis capacity. • A novel pathway for the resistance of super bacteria.

Elastic Organic Crystals Based on Barbituric Derivative: Multi-faceted Bending and Flexible Optical Waveguide.

Elastic organic single crystals with light-emitting and multi-faceted bending properties are extremely rare. They have potential application in optical materials and have attracted the extensive attention of researchers. In this paper, we reported a structurally simple barbituric derivative DBDT, which was easily crystallized and gained long needle-like crystals (centimeter-scale) in DCM/CH3 OH (v/v=2/8). Upon applying or removing the mechanical force, both the (100) and (040) faces of the needle-like crystal showed reversible bending behaviour, showing the nature of multi-faceted bending. The average hardness (H) and elastic modulus (E) were 0.28±0.01 GPa and 4.56±0.03 GPa for the (040) plane, respectively. Through the analysis of the single crystal data, it could be seen that the van der waals (C-H⋅⋅⋅π and C-H⋅⋅⋅C), H-bond (C-H⋅⋅⋅O) and π⋅⋅⋅π interactions between molecules were responsible for the generation of the crystal elasticity. Interestingly, elastic crystals exhibited optical waveguide characteristics in straight or bent state. The optical loss coefficients measured at 627 nm were 0.7 dBmm-1 (straight state) and 0.9 dBmm-1 (bent state), while the optical loss coefficient (α) were 1.5 dBmm-1 (straight state) and 1.8 dBmm-1 (bent state) at 567 nm. Notably, the elastic organic molecular crystal based on barbituric derivative could be used as the candidate for flexible optical devices.

Byakangelicin protects against carbon tetrachloride-induced liver injury and fibrosis in mice.

Liver fibrosis is a disease caused by long-term damage that is related to a number of factors. The current research on the treatment of liver fibrosis mainly focuses on the activation of hepatic stellate cell, in addition to protecting liver cells. byakangelicin has certain anti-inflammatory ability, but its effect on liver fibrosis is unclear. This study aims to explore whether byakangelicin plays a role in the development of liver fibrosis and to explore its mechanism. We determined that byakangelicin has a certain ability to resist fibrosis and reduce liver cell damage in a model of carbon tetrachloride-induced liver fibrosis in mice. Thereafter, we performed further verification in vitro. The signalling pathways of two important pro-fibrotic cytokines, transforming growth factor-ß and platelet-derived growth factor, were studied. Results showed that byakangelicin can inhibit related pathways. According to the hepatoprotective effect of byakangelicin observed in animal experiments, we studied the effect of byakangelicin on 4-HNE-induced hepatocyte (HepG2) apoptosis and explored its related pathways. The results showed that byakangelicin could attenuate 4-HNE-induced hepatocyte apoptosis via inhibiting ASK-1/JNK signalling. In conclusion, byakangelicin could improve carbon tetrachloride-induced liver fibrosis and liver injury by inhibiting hepatic stellate cell proliferation and activation and suppressing hepatocyte apoptosis.

Guanosine-Based Self-Assembly as an Enantioselective Catalyst Scaffold.

A self-assembled G-quadruplex formed by guanosine and borate as the chiral scaffold was used to catalyze the asymmetric Friedel-Crafts reaction in water. Catalysis, depending on the self-assembly of guanosine and borate into a fibrillar structure in the presence of Cu2+ ions, can be modulated by the assembly concentration, temperature, and amount of Cu2+ ions. Detailed spectral experiments proved that the guanosine-based assembly in solution was responsible for the enantioselective catalysis, rather than small-molecule species. Some of the similar G-quartet assemblies were unable to promote the asymmetric reaction, implying unique properties of the current system, including excellent lifetime stability and supramolecular chiral structures. This work provided the first example of the self-assembled G-quadruplex achieving enantioselective catalysis and some perspective to better understand the design of nucleoside-based self-assemblies for an enantioselective reaction. In view of guanosine as a building block, these findings may be applied to discuss the prebiotic chiral catalyst preceded ribozymes.

A tetraphenylethene-based Schiff base AIEgen with a large Stokes shift as probe for highly sensitive and selective detection of aqueous Cu2+ ions and its application in cell imaging.

In this work, an AIE-active tetraphenylethene-based Schiff base fluorescent probe 3 with a large Stokes shift (247 nm) was designed and synthesized. It was found that the aggregated probe 3 exhibited very high selectivity and anti-interference ability for Cu2+ in PBS buffer (70% fw) through a fluorescence "turn-off" strategy. Job's plot and NMR analysis indicated the two phenolic hydroxyl groups of the benzene ring and the N atom (-CH=N-) on probe 3 interacted with Cu2+ ions in a 1:1 stoichiometric ratio. A comprehensive analysis of the Stern-Volmer and binding constant indicated a rather strong interaction between probe 3 and Cu2+ ions. Probe 3 illustrated excellent sensitivity toward Cu2+ under ppb level (4.5 nM) and achieved more than 95% recovery in river, lake and tap water toward estimation of Cu2+ ions in the analytical applications. Moreover, probe 3 was able to realize bioimaging of HepG2 cells and be quenched by intracellular Cu2+ ions, making it promising as a sensitive Cu2+ sensor for organisms.

Screening and identification of bioactive components resistant to metallo-beta-lactamase from Schisandra chinensis (Turcz.) Baill. by metalloenzyme-immobilized affinity chromatography.

The screening and identification of bioactive components, which are effectively resistant to metallo-beta-lactamase (MßL), were studied in the alcohol extract of Schisandra chinensis (Turcz.) Baill. by metalloenzyme-immobilized affinity chromatography. Taking bizinc metalloenzyme beta-lactamase II from Bacillus cereus (Bc II) and monozinc metalloenzyme CphA from aeromonas hydrophila (CphA) as examples, we studied the feasibility of this scheme based on the construction of metalloenzyme-immobilized chromatographic model. It was found that the Bc II- and CphA-immobilized chromatographic column could be used not only to explore the interaction between the MßL and their specific ligands, but also to screen the bioactive components from traditional Chinese medicine. The Bc II-and CphA-immobilized columns were used to screen the bioactive components from the alcohol extract of Schisandra chinensis (Turcz.) Baill. Time-of-flight tandem mass spectrometry analysis and molecular docking revealed that isobutyl 3-O-sulfo-ß-D-galactopyranoside is the effective bioactive components that could bind with metalloenzyme Bc II. It is believed that our current work may provide a methodological reference for screening MßL inhibitors from traditional Chinese medicine.

A guanosine-based 2-formylphenylborate ester hydrogel with high selectivity to K+ ions.

Guanosine-based supramolecular hydrogels are particularly of interest for biomaterial and biomedical purposes, as they are generally biocompatible and stimuli-responsive. We found a strong and long-life transparent hydrogel made by mixing guanosine (G) with 1 equiv. of 2-formylbenzeneboronic acid (2FPB) and KOH. Alkali cations can assist the stacking of individual G-quartet to give extended nanowires, but only K+ ion induces the formation of a stable and self-supporting network hydrogel for a couple of months. Data from variable temperature NMR indicated that guanosine 2-formylbenzeneborate ester and G are the key components of the self-assembly. Further, G-2FPB-K+ hydrogel solution can induce berberine (BBR) fluorescence, showing high selectivity to K+ ion and anti-ion interference capability. A good linear relationship between fluorescent intensity and K+ concentration allowed us to directly detect K+ levels in human blood serum.

Human laminin α3 chain G1 domain is a receptor for plasminogen Kringle 5 on human endothelial cells by biological specificity technologies and molecular dynamic.

Human plasminogen Kringle 5 is known to pose a more potent anti-angiogenesis effect by inducing endothelial cell apoptosis. Our previous studies have identified the peptide IGNSNTL as a binding sequence of Kringle 5 using Ph.D.-7 phage display peptide library and enzyme-linked immunosorbent assay. Here, eleven proteins were screened and summarized by BLAST, laminin α3 chain G1 domain (LG1) was considered as the most potential receptor based on E value and domain function. The specific interaction of them was directly revealed through ligand blot and a strong concentration-dependent manner occurred between them (Ka 4.30 × 105 L mol-1) in frontal chromatography observation. Moreover, R10A/P83R substitution Kringle 5 decreased the affinity capacity to LG1. Furthermore, a remarkable conformational change from random coil3 to α helix and α1 helix to random coil were observed to the structural compactness and stability for LG1. Surface loops and coils also showed fluctuations up to some extent, giving the binding surface greater flexibility and correspondingly allowing for induced-fit binding, which was -23.87 kcal mol-1 of the free energy with electrostatic force as a main driver. Taken together, not only effective theoretical prediction and experiment validated that LG1 is receptor of Kringle 5, but also give an new perspective of the binding mechanism of Kringle 5 and its specific receptor and could facilitate the development of novel agent targeted toward pathologic angiogenesis.