Dissimilar effects of the hydrophilic carbon dots on the amyloid aggregation of two model proteins and the mechanism discussion.

Many proteins could aggregate into amyloid fibrils under certain conditions. However, the aggregation process and morphology of the fibrils may be significantly different because of the distinct protein structure. In this article, the hydrophilic carbon dots (Lys-CA-CDs) were prepared using lysine (Lys) and citric acid (CA) as reactant under the assistance of a microwave. The dissimilar modulation effect of Lys-CA-CDs on the aggregation process of distinct structure protein was further investigated, where bovine serum albumin (BSA) and hen egg white lysozyme (HEWL) were chosen as model proteins. All results showed that Lys-CA-CDs displayed the contrary influence on the aggregation process of BSA and HEWL. Lys-CA-CDs could induce BSA to aggregate into more wormlike fibrils and inhibit the aggregation of HEWL into hair-like fibrils. The influence on the aggregation process of BSA may be assigned to the increased concentration of BSA around the Lys-CA-CDs caused by their interaction. However, inserting of Lys-CA-CDs into the inner structure of HEWL led to the change of protein secondary structure. The change of secondary structure further made it difficult for HEWL to aggregate into fibrils and Lys-CA-CDs showed the inhibition effect on HEWL aggregation.

[Design, synthesis and evaluation of N-acyl-4-phenylthiazole-2-amines as acetylcholinesterase inhibitors].

N-Acyl-4-phenylthiazole-2-amines were designed and synthesized, moreover their effects on acetylcholinesterase activities were tested. N-Acyl-4-phenylthiazole-2-amines were prepared from substituted 2-bromo-1-acetophenones by three steps reaction, and their AChE inhibitory activities were measured by Ellman method in vitro. The results showed that the target compounds had a certain inhibitory activity on AChE in vitro. Among them, 8c was the best, and IC50 of 8c was 0.51 micromol x L(-1), better than that of rivastigmine and Huperzine-A. The inhibitory activities of N-acyl-4-phenylthiazole-2-amines on acetylcholinesterase are worth while to be further studied.

[Design, synthesis and evaluation of new acetylcholinesterase inhibitors].

A series of novel 2-amino-4-phenylthiazole derivatives were designed and synthesized, furthermore, their inhibition effect on acetylcholinesterase were investigated. 2-Amino-4-phenylthiazoles were prepared from alpha-bromoacetophenones by Hantzsch reaction, acylation reaction and substitution reaction. Moreover, their bioactivities as AChE inhibitors in vitro were measured with Ellman spectrophotometry. The results showed that most of them had a certain inhibition activity on AChE, and the compound 8a was the best of them. The IC50 of 8a to AChE is 3.54 micromol x L(-1), and the value was better than that of rivastigmine. 2-Amino-4-phenylthiazole derivatives showed a certain bioactivity in vitro, which were worth further investigation.

[Design, synthesis and activity of N-acyl-thiochromenothiazol-2-amine as acetylcholinesterase inhibitors].

A series of novel N-acyl-thiochromenothiazol-2-amine derivatives were designed and synthesized, furthermore, their inhibition effect on acetylcholinesterase was investigated. N-Acyl-thiochromenothiazol-2-amines were prepared from thiophenol by Hantzsch reaction, acylation reaction and substitution reaction. Moreover, their bioactivities as AChE inhibitors in vitro were measured with Ellman spectrophotometry. The results showed that most of them had a certain inhibition activity on AChE, and the compound 10a was the best in them. The IC50 of 10a to AChE is 7.92 µmol x L(-1), and the value is better than that of rivastigmine. N-Acyl-thiochromenothiazol-2-amine derivatives showed a certain bioactivity in vitro, which were worth further investigation.

X-ray-activated polymerization expanding the frontiers of deep-tissue hydrogel formation.

Photo-crosslinking polymerization stands as a fundamental pillar in the domains of chemistry, biology, and medicine. Yet, prevailing strategies heavily rely on ultraviolet/visible (UV/Vis) light to elicit in situ crosslinking. The inherent perils associated with UV radiation, namely the potential for DNA damage, coupled with the limited depth of tissue penetration exhibited by UV/Vis light, severely restrict the scope of photo-crosslinking within living organisms. Although near-infrared light has been explored as an external excitation source, enabling partial mitigation of these constraints, its penetration depth remains insufficient, particularly within bone tissues. In this study, we introduce an approach employing X-ray activation for deep-tissue hydrogel formation, surpassing all previous boundaries. Our approach harnesses a low-dose X-ray-activated persistent luminescent phosphor, triggering on demand in situ photo-crosslinking reactions and enabling the formation of hydrogels in male rats. A breakthrough of our method lies in its capability to penetrate deep even within thick bovine bone, demonstrating unmatched potential for bone penetration. By extending the reach of hydrogel formation within such formidable depths, our study represents an advancement in the field. This application of X-ray-activated polymerization enables precise and safe deep-tissue photo-crosslinking hydrogel formation, with profound implications for a multitude of disciplines.

Effect of mono- and diketone group in curcumin analogues on amyloid fibrillation of hen egg white lysozyme.

Curcumin has attracted more attention because of its inhibition efficacy on protein amyloid fibrillation. However, the inhibition mechanism was still ambiguous and the clinical application of curcumin was greatly limited because of its poor stability at physiological conditions for the presence of ß-diketone moiety. In this paper, a new mono-ketone-containing curcumin analogue (MDHC) was designed and synthesized to realize the possible inhibition mechanism and unveil the important role of ß-diketone moiety of curcumin in the inhibition process of amyloid fibrillation using hen egg white lysozyme (HEWL) as model protein. Although all experiment results (ThT, CR, ANS and TEM) showed that the inhibitory capacity of curcumin was better than MDHC, MDHC still could show obvious inhibition effect. Molecular docking showed that both curcumin and MDHC could bind with HEWL by hydrogen bond of phenloic hydroxyl and the binding energy of MDHC was higher than that of curcumin. All the findings inferred that ß-diketone group was one of great important groups in the inhibition process of HEWL amyloid fibrillation, which provided more room to construct novel inhibition reagents.

Recent Studies on Hydrogels Based on H2O2-Responsive Moieties: Mechanism, Preparation and Application.

H2O2 is essential for cellular processes and plays a vital role in the regulation of cell signaling pathways, which can be viewed as a warning signal for many kinds of disease including cancer, cardiovascular disease, reproductive abnormalities, diabetes, and renal failure. A H2O2-responsive hydrogel (H2O2-Gel) is a promising candidate for biomedical applications because of its good biocompatibility, similarity to soft biological tissues, ease of preparation, and its ability to respond to H2O2. In this study, the H2O2-responsive moieties used to fabricate H2O2-Gels were reviewed, including thioethers, disulfide bonds, selenides, diselenium bonds, diketones, boronic, and others. Next, the preparation method of H2O2-Gel was divided into two major categories according to their reaction mechanisms: either self-crosslinking or mechanisms entailing the addition of difunctional crosslinkers. Last, the applications of H2O2-Gels were emphasized, which have been viewed as desirable candidates in the fields of drug delivery, the detection of H2O2, glucose-responsive systems, ROS scavengers, tissue engineering, and cell-encapsulation.

Facile One-Pot Synthesis of Hyperbranched Glycopolymers in Aqueous Solution via a Hydroxy/Cu(III) Redox Process.

In this study, a self-condensing vinyl copolymerization/redox (SCVP/Redox) system was constructed to prepare hyperbranched poly(methyl-6-O-methacryloyl-α-D-glucoside) by using Cu(III) as the initiator in aqueous solution, in which the -OH group in C-2, C-3 and C-4 position on pyranose rings could be initiated by Cu(III). The branched and linear units were clearly distinguished by nuclear magnetic resonance (1H NMR) to estimate the degree of branching (DB). When the ratio of Cu(III) to monomer fixed at 0.5:1, the DB value reached 0.32, which was higher than the product initiated by Ce(IV). Moreover, the inhibition activity of the products on amyloid fibrillation was investigated by using the hen egg-white lysozyme (HEWL) as a model based on the difference of the initiation sites. The results showed that the -OH groups in C-4 position might play an important role in this process.

Hyperbranched Glycopolymers of 2-(α-d-Mannopyranose) Ethyl Methacrylate and N,N'-Methylenebisacrylamide: Synthesis, Characterization and Multivalent Recognitions with Concanavalin A.

A series of novel hyperbranched poly[2-(α-d-mannopyranosyloxy) ethyl methacrylate-co-N,N'-methylenebisacrylamide] (HPManEMA-co-MBA) are synthesized via a reversible addition fragmentation polymerization (RAFT). The dosage ratios of linear and branch units are tuned to obtain different degree of branching (DB) in hyperbranched glycopolymers. The DB values are calculated according to the content of nitrogen, which are facilely determined by elemental analysis. The lectin-binding properties of HPManEMA-co-MBA to concanavalin A (ConA) are examined using a turbidimetric assay. The influence of defined DB value and molecular weight of HPManEMA-co-MBA on the clustering rate is studied. Notably, HPManEMA-co-MBAs display a low cytotoxicity in the MTT assay, thus are potential candidates for biomedical applications.

Facile construction of a hyperbranched poly(acrylamide) bearing tetraphenylethene units: a novel fluorescence probe with a highly selective and sensitive response to Zn2.

Thermo-responsive hyperbranched copoly(bis(N,N-ethyl acrylamide)/(N,N-methylene bisacrylamide)) (HPEAM-MBA) was synthesized by using reversible addition-fragmentation chain-transfer polymerization (RAFT). Interestingly, the zinc ion (Zn2+) was found to have a crucial influence on the lowest critical solution temperature (LCST) of the thermo-responsive polymer. The tetraphenylethylene (TPE) unit was then introduced onto the backbone of the as-prepared thermo-responsive polymer, which endows a Zn2+-responsive "turn-off" effect on the fluorescence properties. The TPE-bearing polymer shows a highly specific response over other metal ions and the "turn-off" response can even be tracked as the concentration of Zn2+ reduces to 2 × 10-5 M. The decrement of fluorescence intensity was linearly dependent on the concentration of Zn2+ in the range of 4-18 µmol L-1. The flexible, versatile and feasible approach, as well as the excellent detection performance, may generate a new type of Zn2+ probe without the tedious synthesis of the moiety bearing Zn2+ recognition units.