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Alzheimer's disease (AD) heavily impacts human lives and is becoming serious as societies age. Inhibiting and disaggregating β-amyloid aggregates is a possible solution for AD therapy. In this study, a novel type of nanozyme based on Ru 3+ -chelated nanoscale metal organic frameworks (Ru 3+ -NMOFs), displaying strong peroxidase-like activity, was proposed as an inhibitor and disaggregator of β-amyloid aggregates. As a high concentration of hydrogen peroxide is present at the sites of β-amyloid aggregates, Ru 3+ -NMOFs could catalyze the conversion of hydrogen peroxide to hydroxyl radicals. Thus, these hydroxyl radicals would attack the β-amyloid chain, oxidizing it to enhance its hydrophilicity, which results in a decreased hydrophobic interaction and reduced degree of aggregation. Ru 3+ -NMOFs could effectively inhibit as well as disaggregate β-amyloid fibrils both in vitro and in vivo . Additionally, the reduction of the β-amyloid aggregates and the attenuation of reactive oxygen species transfer led to lower levels of inflammatory factors, which could be beneficial in alleviating AD symptoms. In a typical treatment, Ru 3+ -NMOFs could mitigate the paralysis of C. elegans CL2120 and elevate survival rates. This study opens a new avenue for MOF-based nanozymes as potential treatment agents for AD therapy.

The redox-active metal ions, especially Cu 2+ , are highly correlated to Alzheimer's disease (AD) by causing metal ion-mediated oxidative stress and toxic metal-bound β-amyloid (Aβ) aggregates. Numerous pieces of evidence have revealed that the regulation of metal homeostasis could be an effective therapeutic strategy for AD. Herein, in virtue of the interaction of both amino-containing silane and ethylenediaminetetraacetic acid disodium salt for Cu 2+ , the silicon-carbon dots (SiCDs) are deliberately prepared using these two raw materials as the cocarbon source; meanwhile, to realize the local enrichment of SiCDs and further maximize the chelating ability to Cu 2+ , the SiCDs are feasibly loaded to the biocompatible mesoporous silica nanoparticles (mSiO 2 ) with the interaction between residual silane groups on SiCDs and silanol groups of mSiO 2 . Thus-obtained nanocomposites (i.e., mSiO 2 @SiCDs) could serve as an efficient Cu 2+ chelator with satisfactory metal selectivity and further modulate the enzymic activity of free Cu 2+ and the Aβ 42 -Cu 2+ complex to alleviate the pathological oxidative stress with an anti-inflammatory effect. Besides, mSiO 2 @SiCDs show an inspiring inhibitory effect on Cu 2+ -mediated Aβ aggregation and further protect the neural cells against the toxic Aβ 42 -Cu 2+ complex. Moreover, the transgenic Caenorhabditis elegans CL2120 assay demonstrates the protective efficacy of mSiO 2 @SiCDs on Cu 2+ -mediated Aβ toxicity in vivo , indicating its potential for AD treatment.

The pathological aggregation of some proteins is claimed to be highly related to several human diseases, such as β-amyloid 1-42 (Aβ 42 ) to Alzheimer's disease (AD), islet amyloid polypeptide, and insulin to type 2 diabetes mellitus. Therefore, it is in desperate need to develop effective methods for detection of protein aggregates and inhibition of abnormal aggregation. Herein, to construct all-in-one probe with both diagnosis and treatment potentials for protein aggregation diseases, Congo red (CR), a classical staining reagent with red fluorescence signal output for protein aggregates, is deliberately adopted to react with three different reductive carbon sources and ammonium persulfate to generate three CR-derived carbon dots (CDs). The obtained CDs exhibit the capabilities of turn-on red fluorescence imaging of protein aggregates, and/or inhibition of protein aggregation as well as scavenging of free radicals. Among them, CA-CDs, using citric acid as the reductive carbon source, demonstrate the superiority to the other two studied CDs in integrating all of these functions, and particularly exert excellent cytoprotection effect against toxic Aβ 42 species, possessing tremendous potential in diagnosis and treatment of AD for future study. The present study paves a new way to develop all-in-one CDs for the protein disease research., (© 2023 Wiley-VCH GmbH.)

Recent studies have revealed that the interface of gp120 and gp41 and some parts of gp41 are also critical epitopes for elicitation of broadly neutralizing antibodies. Therefore, potential trimeric gp41 or gp140 immunogen candidates are needed. Previously, we developed a trimer motif MTQ and demonstrated that it could help formation of trimeric gp120 and gp140 proteins. In the present study, we immunized Balb/c mice using trimeric gp41-expressing plasmid for prime and monomeric gp41 or trimeric gp140 protein as well as a mutant (Q577A) for boost. The antibody responses in the context of regimens with various immunization intervals and DNA adjuvants including praziquantel (PZQ), cimetidine (CIM), and amiloride (AML) were evaluated. We found that these three adjuvants were not enough to elicit remarkable specific Abs after gp41 DNA immunization, while AML could significantly promote humoral immune responses after protein boosts. Long immunization interval could induce the specific binding Abs earlier and higher and maintain a high level of Abs in the following 27 weeks after final protein boost. Moreover, two times of protein boosts with DNA adjuvant and a longer time interval achieved a higher titer of specific Abs than three times of protein boosts with a shorter time interval. Q577A mutant was benefit for trimeric gp140 boost in the production of binding Abs but harmful to inducing neutralizing Abs, while this mutant in monomeric gp41 presented the opposite trend which may be associated with the immunogen structures. This study highlights the significance of DNA adjuvant Amiloride and long immunization interval in promoting antibody responses and provides new insights into effective HIV immunization regimen design in the future., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)

Two new C21 steroidal glycosides were isolated from Cynanchum otophyllum Schneid. Their structures were elucidated as qinyangshengenin-3-O-β-d-digitoxopyranoside (1) and rostratamine-3-O-β-d-cymaropyranosyl-(1 → 4)-β-d-digitoxopyranoside (2) on the basis of chemical and spectroscopic methods, including 1D and 2D NMR experiments.

Objective: To examine the proliferation of myofibroblast in periodental tension side of beagle dog during experimental tooth movement in orthodontics., Methods: By the fixed orthodontic appliance, the five beagles were treated with 100 g forces that moved medially the maxillary first premolar, and the treatment lasted for four weeks. Using transmission electron microscope and immunohistochemistry, the proliferation of myofibroblast and expression of alpha-smooth muscle actin (alpha-SMA) were evaluated at week 1, 2, 3, 4 or 8 respectively after the orthodontic treatment., Results: During the total of four weeks, the expression of a-SMA increased in week 1 and reached the maximum in week 2; in week 4, the expression of alpha-SMA went back to normal level. Transmission electron microscopy showed that the myofibroblast contained the dense body appearing in cytoplasm., Conclusion: The myofibroblast exists in periodontium and is concerned with the orthodontic tooth movement.