Modulation of β-amyloid aggregation by graphene quantum dots

Misfolding and abnormal aggregation of β-amyloid peptide is associated with the onset and progress of Alzheimer's disease (AD). Therefore, modulating β-amyloid aggregation is critical for the treatment of AD. Herein, we studied the regulatory effects and mechanism of graphene quantum dots (GQDs) on 1–42 β-amyloid (Aβ1–42) aggregation. GQDs displayed significant regulatory effects on the aggregation of Aβ1–42 peptide as detected by thioflavin T (ThT) assay. Then, the changes of confirmations and structures induced by GQDs on the Aβ1–42 aggregation were monitored by circular dichroism (CD), dynamic light scattering (DLS) and transmission electron microscope (TEM). The in vitro cytotoxicity experiments further demonstrated the feasibility of GQDs on the regulation of Aβ1–42 aggregation. Meanwhile, the structural changes of a Aβ1–42/GQDs mixture in different pH revealed that electrostatic interaction was the major driving force in the co-assembly process of Aβ1–42 and GQDs. The proposed mechanism of the regulatory effects of GQDs on the Aβ1–42 aggregation was also deduced reasonably. This work not only demonstrated the potential feasibility of GQDs as therapeutic drug for AD but also clarified the regulatory mechanism of GQDs on the Aβ1–42 aggregation.


24-Apr-2019
Dear Mr Liu: Title: Modulation of β-Amyloid Aggregation by Graphene Quantum Dots Manuscript ID: RSOS-190271 Thank you for submitting the above manuscript to Royal Society Open Science. On behalf of the Editors and the Royal Society of Chemistry, I am pleased to inform you that your manuscript will be accepted for publication in Royal Society Open Science subject to minor revision in accordance with the referee suggestions. Please find the reviewers' comments at the end of this email.
The reviewers and handling editors have recommended publication, but also suggest some minor revisions to your manuscript. Therefore, I invite you to respond to the comments and revise your manuscript.
Please also include the following statements alongside the other end statements. As we cannot publish your manuscript without these end statements included, if you feel that a given heading is not relevant to your paper, please nevertheless include the heading and explicitly state that it is not relevant to your work. We have included a screenshot example of the end statements for reference.
• Ethics statement Please clarify whether you received ethical approval from a local ethics committee to carry out your study. If so please include details of this, including the name of the committee that gave consent in a Research Ethics section after your main text. Please also clarify whether you received informed consent for the participants to participate in the study and state this in your Research Ethics section. *OR* Please clarify whether you obtained the necessary licences and approvals from your institutional animal ethics committee before conducting your research. Please provide details of these licences and approvals in an Animal Ethics section after your main text. *OR* Please clarify whether you obtained the appropriate permissions and licences to conduct the fieldwork detailed in your study. Please provide details of these in your methods section.
Because the schedule for publication is very tight, it is a condition of publication that you submit the revised version of your manuscript before 03-May-2019. Please note that the revision deadline will expire at 00.00am on this date. If you do not think you will be able to meet this date please let me know immediately.
To revise your manuscript, log into https://mc.manuscriptcentral.com/rsos and enter your Author Centre, where you will find your manuscript title listed under "Manuscripts with Decisions". Under "Actions," click on "Create a Revision." You will be unable to make your revisions on the originally submitted version of the manuscript. Instead, revise your manuscript and upload a new version through your Author Centre.
When submitting your revised manuscript, you will be able to respond to the comments made by the referees and upload a file "Response to Referees" in "Section 6 -File Upload". You can use this to document any changes you make to the original manuscript. In order to expedite the processing of the revised manuscript, please be as specific as possible in your response to the referees.
When uploading your revised files please make sure that you have: 1) A text file of the manuscript (tex, txt, rtf, docx or doc), references, tables (including captions) and figure captions. Do not upload a PDF as your "Main Document". 2) A separate electronic file of each figure (EPS or print-quality PDF preferred (either format should be produced directly from original creation package), or original software format) 3) Included a 100 word media summary of your paper when requested at submission. Please ensure you have entered correct contact details (email, institution and telephone) in your user account 4) Included the raw data to support the claims made in your paper. You can either include your data as electronic supplementary material or upload to a repository and include the relevant doi within your manuscript 5) All supplementary materials accompanying an accepted article will be treated as in their final form. Note that the Royal Society will neither edit nor typeset supplementary material and it will be hosted as provided. Please ensure that the supplementary material includes the paper details where possible (authors, article title, journal name).
Supplementary files will be published alongside the paper on the journal website and posted on the online figshare repository (https://figshare.com). The heading and legend provided for each supplementary file during the submission process will be used to create the figshare page, so please ensure these are accurate and informative so that your files can be found in searches. Files on figshare will be made available approximately one week before the accompanying article so that the supplementary material can be attributed a unique DOI. ********************************************** RSC Associate Editor: Comments to the Author: (There are no comments.) RSC Subject Editor: Comments to the Author: (There are no comments.) ********************************************** Reviewer comments to Author: Reviewer: 1 Comments to the Author(s) The manuscript by Liu et al. is a nice piece of research and should be accepted. I recommend certain minor revisions with the language used and it would be nice if help of native english speaker could be sought. In general, the modulator effect of GQDs on Aβ1-42 aggregation is very well explained and well-characterized by the techniques like TEM, XPS, FTIR and CD. Finally, MTT assay is also done which proves GQD are bio-compatible and can serve as good therapeutic tool against Alzheimer's.

Reviewer: 2
Comments to the Author(s) In this manuscript, authors studied the regulatory effects and mechanism of graphene quantum dots (GQDs) on 1-42 β-amyloid (Aβ1-42) aggregation. Based on their study, the mechanism of the regulatory effects of GQDs on the Aβ1-42 aggregation was proposed. This manuscript is well suitable for publication in Royal Society Open Science after minor revision.
1. It's better to describe more clearly (with more detail) about the experimental procedures, especially concerning the fiber formation and inhibition process (including pH adjustment). 2. Fig. 3  You can expect to receive a proof of your article in the near future. Please contact the editorial office (openscience_proofs@royalsociety.org and openscience@royalsociety.org) to let us know if you are likely to be away from e-mail contact. Due to rapid publication and an extremely tight schedule, if comments are not received, your paper may experience a delay in publication.
Royal Society Open Science operates under a continuous publication model (http://bit.ly/cpFAQ). Your article will be published straight into the next open issue and this will be the final version of the paper. As such, it can be cited immediately by other researchers. As the issue version of your paper will be the only version to be published I would advise you to check your proofs thoroughly as changes cannot be made once the paper is published.
In order to raise the profile of your paper once it is published, we can send through a PDF of your paper to selected colleagues. If you wish to take advantage of this, please reply to this email with the name and email addresses of up to 10 people who you feel would wish to read your article.
On behalf of the Editors of Royal Society Open Science and the Royal Society of Chemistry, we look forward to your continued contributions to the Journal.

Best wishes, Andrew Dunn
On behalf of the Subject Editor Professor Anthony Stace and the Associate Editor . Appendix A

Response to the Reviewer #1's comments
We would like to express our sincere thanks to your positive comments, which are quite helpful to improve the quality of our article. We have revised our paper according to your comments. The main revisions are listed as follows:

Point 1:
I recommend certain minor revisions with the language used and it would be nice if help of native English speaker could be sought.

Author's Response:
Thanks a lot for your kind advice. We have modified the article carefully in terms of language. The changes have been highlighted in yellow.

Response to the Reviewer #2's comments
We would like to express our sincere thanks to your positive comments. Those comments are all valuable for improving our paper. We have revised the manuscript point-by-point according to your comments. The main revisions are listed as follows:

Point 1:
It's better to describe more clearly (with more detail) about the experimental procedures, especially concerning the fiber formation and inhibition process (including pH adjustment).

Author's Response:
Thanks a lot for your kindly advices. We have described the experimental procedure more clearly according to your suggestion. Last, the morphology of the mixture was observed by TEM after being incubated for 72 h.

Author's Response:
Thanks a lot for your suggestion. We are sorry for the careless mistakes in the manuscript. We have checked the whole article and all the similar mistakes have been corrected.