Peer Review History

Original SubmissionSeptember 11, 2023
Decision Letter - Arvin Haj-Mirzaian, Editor

PONE-D-23-29456DFMG reduces the angiogenesis to maintain the plaque stability by inhibiting TLR4/VEGF pathway in atherosclerosisPLOS ONE

Dear Dr. Bai,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Dec 29 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Arvin Haj-Mirzaian

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at 

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and 

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. Note from Emily Chenette, Editor in Chief of PLOS ONE, and Iain Hrynaszkiewicz, Director of Open Research Solutions at PLOS: Did you know that depositing data in a repository is associated with up to a 25% citation advantage (https://doi.org/10.1371/journal.pone.0230416)? If you’ve not already done so, consider depositing your raw data in a repository to ensure your work is read, appreciated and cited by the largest possible audience. You’ll also earn an Accessible Data icon on your published paper if you deposit your data in any participating repository (https://plos.org/open-science/open-data/#accessible-data).

3. Thank you for stating the following financial disclosure: 

 " This study is supported by the Natural Science Foundation of China (grant. no. 81370382), and Natural Science Foundation of Hunan Province (grant. no. 14JJ2059 and 2022JJ30415). ZY and LLS are authors who received awards."

  

Please state what role the funders took in the study.  If the funders had no role, please state: ""The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."" 

If this statement is not correct you must amend it as needed. 

Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf.

4. Please include your full ethics statement in the ‘Methods’ section of your manuscript file. In your statement, please include the full name of the IRB or ethics committee who approved or waived your study, as well as whether or not you obtained informed written or verbal consent. If consent was waived for your study, please include this information in your statement as well.

5. PLOS ONE now requires that authors provide the original uncropped and unadjusted images underlying all blot or gel results reported in a submission’s figures or Supporting Information files. This policy and the journal’s other requirements for blot/gel reporting and figure preparation are described in detail at https://journals.plos.org/plosone/s/figures#loc-blot-and-gel-reporting-requirements and https://journals.plos.org/plosone/s/figures#loc-preparing-figures-from-image-files. When you submit your revised manuscript, please ensure that your figures adhere fully to these guidelines and provide the original underlying images for all blot or gel data reported in your submission. See the following link for instructions on providing the original image data: https://journals.plos.org/plosone/s/figures#loc-original-images-for-blots-and-gels. 

  

In your cover letter, please note whether your blot/gel image data are in Supporting Information or posted at a public data repository, provide the repository URL if relevant, and provide specific details as to which raw blot/gel images, if any, are not available. Email us at plosone@plos.org if you have any questions.

6. We notice that your supplementary figures are uploaded with the file type 'Figure'. Please amend the file type to 'Supporting Information'. Please ensure that each Supporting Information file has a legend listed in the manuscript after the references list.

Additional Editor Comments:

==============================

Please add ethical section and prepare all below information:

Ethical Considerations:

All research must adhere to the highest ethical standards. For studies involving animal models, it is imperative that all efforts be made to minimize suffering and reduce the number of animals used, and to justify the species and number of animals used. Authors must clearly state that they have conducted their studies ethically, and they should be prepared to provide evidence of ethical approval by an appropriate committee.

Animal Studies:

For this paper authors must declare that the study was conducted in compliance with the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines. The ARRIVE guidelines provide a checklist of information that should be included in publications reporting animal research, with the aim of improving the reporting standards and ensuring that the data can be thoroughly evaluated.

The ARRIVE guidelines encompass the following key areas:

Study design

Sample size

Animal characteristics

Housing and husbandry

Experimental procedures

Outcome measures

Statistical analysis

Euthanasia Method:

In accordance with the ARRIVE guidelines and ethical treatment of animals, authors must specify the method used for euthanasia of mice. This should include details such as the type of agent used (e.g., barbiturate overdose, carbon dioxide inhalation), the concentration and volume of the agent (where applicable), the method of administration, and any measures taken to ensure that euthanasia is performed as humanely as possible. Justification should be provided for the chosen method, referencing the most recent guidelines for humane killing provided by organizations such as the American Veterinary Medical Association (AVMA) or equivalent bodies.

Authors should also ensure that the personnel performing euthanasia are adequately trained and competent in the procedures used.

Ethical Approval:

Authors must state explicitly that the research protocol was approved by an institutional animal care and use committee (IACUC) or equivalent body. The name of the ethics committee that approved the study and the reference number/protocol ID should be provided.

Conflict of Interest:

Authors must declare any potential conflicts of interest relating to their research.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: 1-The title could be changed to "DFMG possibly reduces the angiogenesis …" with this small sample size.

2-Please explain " ImageJ" to the readers who are not familiar with it.

3-In many cases, excessive use of abbreviations can confuse and alienate unfamiliar audiences, and even well-intentioned writers and speakers may overestimate an audience's familiarity with abbreviations. Although abbreviations should not be avoided entirely, using them as a default can be problematic. This manuscript is full of familiar and unfamiliar abbreviations. You should explain each of your abbreviations the first time it appears in the main text, but have not any explanation about some abbreviations, such as miR-140, CCK8, LDH, RPMI-1640, WB, RT-qPCR, lipo2000, IHC, WT group, …. It is one of the rules of providing information for your readers.

4-In contrast, after the first appearance of the abbreviation, the abbreviation should always be used in the rest of the manuscript instead of the complete term. However, you re-explained "DFMG" in the last paragraph of 3.7 or "AS" in the discussion section, line 2.

5-In general, an abbreviation should be used if the term appears at least five times in the main text (The Abstract does not count). If you use the term or phrase only two, three or four times, it should not be abbreviated.

6-What is the meaning of "blank group"?

7-Where is "Table 1"?

8-The methodology needs to be clarified. You explained "methodology" in the "discussion" section; unfamiliar readers (such as clinicians) are confused about in vivo or in vitro study, the number of groups, the sample size in each group, the rational of any particular type of laboratory study, …, before reading discussion. For instance, you should mention the purpose of each study after you did it for your readers because readers may have a different line of attitude from you.

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6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

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[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Revision 1

Response to Reviewers:

Dear Reviewers,

Thank you very much for your time involved in reviewing the manuscript and your very encouraging comments on the merits.

We also appreciate your clear and detailed feedback and hope that the explanation has fully addressed all of your concerns. In the remainder of this letter, we discuss each of your comments individually along with our corresponding responses.

To facilitate this discussion, we first retype your comments in italic font and then present our responses to the comments.

1-The title could be changed to "DFMG possibly reduces the angiogenesis …" with this small sample size.

Response 1: Thank you very much for your suggestion, the title of the article has been modified.

2-Please explain " ImageJ" to the readers who are not familiar with it.

Response 2: We add an explanation for “ImageJ”, The relevant contents are provided below as a screen dump for your quick reference.

3-In many cases, excessive use of abbreviations can confuse and alienate unfamiliar audiences, and even well-intentioned writers and speakers may overestimate an audience's familiarity with abbreviations. Although abbreviations should not be avoided entirely, using them as a default can be problematic. This manuscript is full of familiar and unfamiliar abbreviations. You should explain each of your abbreviations the first time it appears in the main text, but have not any explanation about some abbreviations, such as miR-140, CCK8, LDH, RPMI-1640, WB, RT-qPCR, lipo2000, IHC, WT group, …. It is one of the rules of providing information for your readers.

Response 3: Thank you for the detailed review. We have carefully and thoroughly proofread the manuscript to correct all the abbreviations.

4-In contrast, after the first appearance of the abbreviation, the abbreviation should always be used in the rest of the manuscript instead of the complete term. However, you re-explained "DFMG" in the last paragraph of 3.7 or "AS" in the discussion section, line 2.

Response 4: Thank you for the detailed review. We have carefully and thoroughly proofread the manuscript to correct all the abbreviations.

5-In general, an abbreviation should be used if the term appears at least five times in the main text (The Abstract does not count). If you use the term or phrase only two, three or four times, it should not be abbreviated.

Response 5: Thank you very much for your advice, which has been modified in the article.

6-What is the meaning of "blank group"?

Response 6: This is a translation error, which is modified in the article as “Vehicle group” and “Wild Type”, respectively.

7-Where is "Table 1"?

Response 7: We uploaded Table 1 in the article

8-The methodology needs to be clarified. You explained "methodology" in the "discussion" section; unfamiliar readers (such as clinicians) are confused about in vivo or in vitro study, the number of groups, the sample size in each group, the rational of any particular type of laboratory study, …, before reading discussion. For instance, you should mention the purpose of each study after you did it for your readers because readers may have a different line of attitude from you.

Response 8: Thanks for your great suggestion on improving the accessibility of our manuscript. We add the title of the research purpose in each method section.

We would like to take this opportunity to thank you for all your time involved and this great opportunity for us to improve the manuscript. We hope you will find this revised version satisfactory.

Sincerely,

The Authors: Pingjuan Bai

Response to Editor:

Dear Arvin Haj-Mirzaian,

Thank you for your prompt and constructive feedback on my manuscript entitled " DFMG may potentially decrease angiogenesis to preserve plaque stability by inhibiting the TLR4/VEGF pathway in atherosclerosis," which I submitted to PLOS ONE. I appreciate the time and effort you and the reviewers have invested in evaluating my work.

I have carefully considered each of your comments and made the necessary revisions to address the concerns raised. Below, I outline the changes made in response to your suggestions:

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

Response 1: I have made revisions according to the formatting requirements of the PLOS ONE journal.

2. Note from Emily Chenette, Editor in Chief of PLOS ONE, and Iain Hrynaszkiewicz, Director of Open Research Solutions at PLOS: Did you know that depositing data in a repository is associated with up to a 25% citation advantage (https://doi.org/10.1371/journal.pone.0230416)? If you’ve not already done so, consider depositing your raw data in a repository to ensure your work is read, appreciated and cited by the largest possible audience. You’ll also earn an Accessible Data icon on your published paper if you deposit your data in any participating repository (https://plos.org/open-science/open-data/#accessible-data).

Response 2: Thank you for your valuable advice. However, I have not yet uploaded the raw experimental data to the repository at the moment.

3. Thank you for stating the following financial disclosure:

" This study is supported by the Natural Science Foundation of China (grant. no. 81370382), and Natural Science Foundation of Hunan Province (grant. no. 14JJ2059 and 2022JJ30415). ZY and LLS are authors who received awards."

Please state what role the funders took in the study. If the funders had no role, please state: ""The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.""

If this statement is not correct you must amend it as needed.

Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf.

Response 3: This study is supported by the Natural Science Foundation of China (Grant No. 81370382) and the Natural Science Foundation of Hunan Province (Grant No. 14JJ2059 and 2022JJ30415). Xiaohua Fu and Yong Zhang, recipients of awards. Their contribution to this article involved reviewing and editing.

4. Please include your full ethics statement in the ‘Methods’ section of your manuscript file. In your statement, please include the full name of the IRB or ethics committee who approved or waived your study, as well as whether or not you obtained informed written or verbal consent. If consent was waived for your study, please include this information in your statement as well.

Response 4: We have incorporated an ethical statement and supplied the complete name and code of the Ethics Committee for the "mice" section in the Methods.

5. PLOS ONE now requires that authors provide the original uncropped and unadjusted images underlying all blot or gel results reported in a submission’s figures or Supporting Information files. This policy and the journal’s other requirements for blot/gel reporting and figure preparation are described in detail at https://journals.plos.org/plosone/s/figures#loc-blot-and-gel-reporting-requirements and https://journals.plos.org/plosone/s/figures#loc-preparing-figures-from-image-files. When you submit your revised manuscript, please ensure that your figures adhere fully to these guidelines and provide the original underlying images for all blot or gel data reported in your submission. See the following link for instructions on providing the original image data: https://journals.plos.org/plosone/s/figures#loc-original-images-for-blots-and-gels.

In your cover letter, please note whether your blot/gel image data are in Supporting Information or posted at a public data repository, provide the repository URL if relevant, and provide specific details as to which raw blot/gel images, if any, are not available. Email us at plosone@plos.org if you have any questions.

Response 5: The blot/gel images in this article have been uploaded in the required PDF format as requested.

6. We notice that your supplementary figures are uploaded with the file type 'Figure'. Please amend the file type to 'Supporting Information'. Please ensure that each Supporting Information file has a legend listed in the manuscript after the references list

Response 6: We have made revisions and re-uploaded.

The following are comments in response to other editors:

All procedures involving animals were conducted in strict accordance with ARRIVE guidelines for the care and use of laboratory animals and were approved by the Ethics Committee of Hunan Normal University (Approval No. 2013289). Researchers engaged in animal experimentation possess the Laboratory Animal Professional Post qualification, verified by the certificate code 20180054.

The -7-week-old SPF-grade ApoE gene knockout mice and the 6-7-week-old SPF-grade TLR4 gene knockout mice were graciously donated by the Collaborative Innovation Center for Model Animal at Wuhan University (Animal Qualification Testing Report Number: BJYRL-WBKH-20160224A1). The ApoE and TLR4 double gene knockout mice were bred by our research team through the mating of the aforementioned gene knockout mice. Non-transgenic mice with the same genetic background, aged 5-6 weeks (SPF-grade C57 BL/6 mice), were procured from Hunan Slake Company. All experimental mice were housed in the SPF-grade animal facility at the School of Medicine, Hunan Normal University, maintaining a 12-hour light/12-hour dark cycle. More detailed experimental methods and schematic diagrams can be found in the Methods section of the manuscript and in the S1 figures.

Conflict of 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.

I believe these revisions have strengthened the manuscript, improving its overall clarity and coherence. I trust that these changes align with the expectations of PLOS ONE and enhance the quality of the manuscript.

Please find the revised manuscript attached. I hope these modifications meet the standards of the journal. If you require any further clarification or additional information, please do not hesitate to contact me.

Thank you once again for your valuable guidance throughout this process. I look forward to hearing from you soon.

Sincerely,

The Authors: Pingjuan Bai

Attachments
Attachment
Submitted filename: Response to Editor.docx
Decision Letter - Arvin Haj-Mirzaian, Editor

PONE-D-23-29456R1DFMG may potentially decrease angiogenesis to preserve plaque stability by inhibiting the TLR4/VEGF pathway in atherosclerosisPLOS ONE

Dear Dr. Bai,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Mar 28 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.
If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Arvin Haj-Mirzaian

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: 1- "… counted by ImageJ (ImageJ is a java-based … of Health (NIH)." can be revised as "… counted by ImageJ [ImageJ is a Java-based … of Health (NIH)]."

2- You mentioned, "We uploaded Table 1 in the article," but the location of "Table 1" is not specified.

3- Kindly provide an explanation regarding the number of groups and the corresponding sample size in each group.

Reviewer #2: Dear Editor,

On the manuscript entitled: DFMG may potentially decrease angiogenesis to preserve plaque stability by inhibiting the TLR4/VEGF pathway in atherosclerosis.

Comments:

This is an interesting study. Authors addressed comments raised by reviewers however some issues should be clarified before acceptance.

1- There are various typo errors in the text.

2- Mice add to the title

3- “Detection of blood lipids in mice” change to “Detection of blood lipids”

4- Real-time fluorescence quantitative PCR change to “quantitative Real-time PCR”

5- Method for anesthesia should be clarified. What did you mean from “The next day, the mice were anesthetized by abdominal cavity”?

6- Discussion should be began with your core finding.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Revision 2

respond to reviewer

Dear Reviewer,

Thank you very much for your valuable comments and suggestions on our manuscript. We have carefully considered and revised the manuscript according to your guidance.

Regarding your points about the lack of specific location for figure files, inadequate explanation of group numbers, and inaccuracies in terminology and expressions, we have made revisions to the manuscript and provided explanations in the response letter. Additionally, we have corrected typos and grammatical errors in the text.

To facilitate this discussion, we first retype your comments in italic font and then present our responses to the comments.

Reviewer #1:

1- "… counted by ImageJ (ImageJ is a java-based … of Health (NIH)." can be revised as "… counted by ImageJ [ImageJ is a Java-based … of Health (NIH)]."

Response:Thank you for such careful review, we have made modifications to the paper.

2- You mentioned, "We uploaded Table 1 in the article," but the location of "Table 1" is not specified.

Response:We apologize for the inconvenience. Table 1 was inadvertently uploaded to the submission system, and we have now included Table 1 in the paper.

3- Kindly provide an explanation regarding the number of groups and the corresponding sample size in each group.

Response:The groupings for the in vitro experiments have been incorporated into the methods section of the article, whereas detailed explanations of the groupings for the in vivo animal experiments are provided in Figure S1.

Reviewer #2

1- There are various typo errors in the text.

Response: Thank you for your meticulous review of the article, and we have rectified these errors accordingly.

2- Mice add to the title

Response: We changed the paper title to “DFMG decreases angiogenesis to uphold plaque stability by inhibiting the TLR4/VEGF pathway in mice.”

3- “Detection of blood lipids in mice” change to “Detection of blood lipids”

Response: Thank you for your suggestion, it has been changed to “Detection of blood lipids”.

4- Real-time fluorescence quantitative PCR change to “quantitative Real-time PCR”

Response: Thank you for your suggestion, it has been changed to “quantitative Real-time PCR”.

5- Method for anesthesia should be clarified. What did you mean from “The next day, the mice were anesthetized by abdominal cavity”?

Response: Thank you very much for your suggestion. The description has been revised in the article accordingly.

6- Discussion should be began with your core finding.

Response: Thank you for your valuable suggestions. We have incorporated a section in the discussion of the article highlighting the core findings of our study.

We appreciate your thorough review and helpful feedback. We believe that the revised manuscript is more refined, and we look forward to your further assessment.

Thank you once again for your time and expertise.

Best regards,

Sincerely,

The Authors: Pingjuan Bai

Respond to editor:

Dear Arvin Haj-Mirzaian,

We would like to express our sincere gratitude to you and the reviewers for the constructive feedback and valuable suggestions provided for our manuscript entitled " DFMG decreases angiogenesis to uphold plaque stability by inhibiting the TLR4/VEGF pathway in mice"[ PONE-D-23-29456R1]. We have carefully considered all the comments and suggestions provided by the reviewers and have made the necessary revisions to improve the quality and clarity of the manuscript.

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Response:

After a thorough examination of the references section of our paper, we confirm that no citations of retracted papers were found. Furthermore, the format of the references adheres to the requirements of your esteemed journal.

We believe that these revisions have strengthened the manuscript and addressed the concerns raised by the reviewers. We hope that these changes meet the expectations of the journal and contribute to the improvement of the manuscript.

Thank you once again for the opportunity to revise and resubmit our manuscript. We look forward to hearing from you regarding the further processing of our submission.

Sincerely,

Pingjuan Bai

Attachments
Attachment
Submitted filename: Response to Editor.docx
Decision Letter - Arvin Haj-Mirzaian, Editor

DFMG decreases angiogenesis to uphold plaque stability by inhibiting the TLR4/VEGF pathway in mice

PONE-D-23-29456R2

Dear Dr. Bai,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Dr. Arvin Haj-Mirzaian

Academic Editor

PLOS ONE

Formally Accepted
Acceptance Letter - Arvin Haj-Mirzaian, Editor

PONE-D-23-29456R2

PLOS ONE

Dear Dr. Bai,

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Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Arvin Haj-Mirzaian

Academic Editor

PLOS ONE

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