PONE-D-23-21385Effects of cardiac contractility modulation on autophagy and apoptosis of cardiac myocytes in rabbits with chronic heart failurePLOS ONE

Dear Dr. Hao,

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.

Your manuscript was reviewed by two experts and we received positive feed with major comments.

Please submit your revised manuscript by Jan 27 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,

Partha Mukhopadhyay, Ph.D.

Section Editor

PLOS ONE

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4. 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.

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6. Please include a copy of Table 1-3 which you refer to in your text

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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

Reviewer #2: Partly

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

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: No

Reviewer #2: No

**********

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

Reviewer #2: No

**********

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: This manuscript by Hao et al. reports an interesting study on the application of cardiac contractility modulation (CCM) as an instrument treatment method in case of chronic heart failure. They showed that during heart failure in the rabbit animal model, CCM treatment can be implemented to improve/restore the systolic and diastolic behavior of the heart tissue (myocardium), which might be the result of the inhibition of the cardiomyocytes autophagy. The study itself is well-designed and executed, however, the manuscript is written with little information about the background information on this field and the discussion lacks proper justification/clarification of the presented data. Below are the comments:

1. Authors provide a very short description of the chronic heart failure (CHF) and also mention the current/previous treatment methods (mostly beta-blocker) that have been attempted to treat this disease. However, for the general reader, it would be quite challenging to understand what is CHF and what happens during this phase. Moreover, it would be beneficial for the readers to briefly state the mode of action of the beta-blocker and how/why this method of treatment is less-effective (if it is). Why do the authors think that CCM can be a better strategy to treat CHF?

2. In the line 45-47, authors used a term “molecular modeling”. What does it mean? Molecular modeling of what? How is it happening? (Sorry, if I missed that info somehow!).

3. The methods section is well-written. However, materials section requires more details about the reagents and instruments that were used in these experiments.

4. The line 79 starts with “The slices were stored...”. Slices of what?

5. In figure 3, the authors checked the expression level of Bcl-2, Bax, Caspase-3 and LADH2 in Sham, HF and CCM groups and concluded that the expression of these mRNAs and the respective proteins in cardiomyocytes can reverse the development of cardiomyocytes apoptosis. Can authors also check the protein levels (by western blotting) from those differently-expressed mRNA in Sham, HF and CCM groups and validate the above-mentioned statement?

6. Section 3.6 (line 176-180), authors looked at the cardiomyocytes apoptosis level by TUNEL assay, where they found that overall the apoptosis rate in HF and CCM group was increased compared with that in Sham group. Do authors have any justification of this observation? Also, is there any way to quantify this data (including the statistical significance) to get a better analysis of the apoptosis level?

7. Where is table 1, table 2 and table 3 listed in the manuscript? (Mentioned after the figure legend of figure 2, figure 3 and figure 6).

8. Discussion requires more details and proper explanation of the results that authors presented in the manuscript. What is the molecular mechanism behind the effectiveness of CCM treatment in case of chronic heart failure? How does up regulation/down regulation of those proteins tested here in CCM group of animals justify this treatment mechanistically during chronic heart failure? In the discussion section, authors mentioned that previously they showed the positive effect of CCM in cardiac function, however, did not cite any of their publication. Why?

Overall, this study has merit and the experiments are well controlled and can be a nice addition to the research community of chronic heart failure. That being said, the manuscript requires additional details on the background, significance of this study and proper explanation of their data.

Reviewer #2: There are a few major corrections that need to be met before acceptance of manuscript could be made specifically in materials and methods section, results section. The overall language of the manuscript needs editing too, in order to match the standards of scientific reporting and the journal.

**********

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

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.

Attachments

Attachment

Submitted filename: Review Comments_1.pdf

PONE-D-23-21385R1Effects of cardiac contractility modulation on autophagy and apoptosis of cardiac myocytes in rabbits with chronic heart failurePLOS ONE

Dear Dr. Liu,

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.

Your manuscript was reviewed by same reviewers and we received  positive feedback with few major comments. Please address all of them as appropriate during revision.

Please submit your revised manuscript by Jun 20 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,

Partha Mukhopadhyay, Ph.D.

Section 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.

Additional Editor Comments:

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

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: (No Response)

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: Partly

**********

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: No

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: No

**********

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: This manuscript by Hao et al. reports an interesting study on the application of cardiac contractility modulation (CCM) as an instrument treatment method in case of chronic heart failure. They showed that during heart failure in the rabbit animal model, CCM treatment can be implemented to improve/restore the systolic and diastolic behavior of the heart tissue (myocardium), which might be the result of the inhibition of the cardiomyocytes autophagy. In the revised version, the authors made some textual changes, which comparatively improve the quality of the manuscript. However, very surprisingly, there is no point-by-point response to the questionnaire that was requested by me (at least the revised version I am reading)! So, at this point, it is very difficult for me to make any decision.

JUST FOR THE RECORD, BELOW WERE SOME OF THE COMMENTS/QUESTIONS THAT I ASKED DURING THE 1ST ROUND OF REVIEW:

1. Authors provided a very short description of the chronic heart failure (CHF) and also mention the current/previous treatment methods (mostly beta-blocker) that have been attempted to treat this disease. However, for the general reader, it would be quite challenging to understand what is CHF and what happens during this phase. Moreover, it would be beneficial for the readers to briefly state the mode of action of the beta-blocker and how/why this method of treatment is less-effective (if it is). Why do the authors think that CCM can be a better strategy to treat CHF?

2. In the line 45-47, authors used a term “molecular modeling”. What does it mean? Molecular modeling of what? How is it happening? (Sorry, if I missed that info somehow!).

3. The methods section is well-written. However, materials section requires more details about the reagents and instruments that were used in these experiments.

4. The line 79 starts with “The slices were stored...”. Slices of what?

5. In figure 3, the authors checked the expression level of Bcl-2, Bax, Caspase-3 and LADH2 in Sham, HF and CCM groups and concluded that the expression of these mRNAs and the respective proteins in cardiomyocytes can reverse the development of cardiomyocytes apoptosis. Can authors also check the protein levels (by western blotting) from those differently expressed mRNA in Sham, HF and CCM groups and validate the above-mentioned statement?

6. Section 3.6 (line 176-180), authors looked at the cardiomyocytes apoptosis level by TUNEL assay, where they found that overall the apoptosis rate in HF and CCM group was increased compared with that in Sham group. Do authors have any justification of this observation? Also, is there any way to quantify this data (including the statistical significance) to get a better analysis of the apoptosis level?

7. Discussion requires more details and proper explanation of the results that authors presented in the manuscript. What is the molecular mechanism behind the effectiveness of CCM treatment in case of chronic heart failure? How does up regulation/down regulation of those proteins tested here in CCM group of animals justify this treatment mechanistically during chronic heart failure? In the discussion section, authors mentioned that previously they showed the positive effect of CCM in cardiac function, however, did not cite any of their publication. Why?

Overall, this study has merit and the experiments are well controlled and can be a nice addition to the research community of chronic heart failure. That being said, the manuscript requires additional details on the background, significance of this study and proper explanation of their data.

Reviewer #2: In the corrected manuscript, there still is some formatting and language issues. So I advise some minor alterations followed with a track changed resubmission.

**********

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.

Attachments

Attachment

Submitted filename: Comments to rebuttal _ 7.pdf

PONE-D-23-21385R2

Effects of cardiac contractility modulation on autophagy and apoptosis of cardiac myocytes in rabbits with chronic heart failure

PLOS ONE

Dear Dr. Liu,

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.

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

Comment from PLOS Office: To comply with PLOS ONE submissions requirements, in your Methods section, please provide additional information regarding the experiments involving animals and ensure you have included details on (1) methods of sacrifice, (2) methods of anesthesia and/or analgesia, and (3) efforts to alleviate suffering, including information regarding humane endpoints. Specifically, please provide more details regarding the methods of sacrifice, as the current statement only reads "the animals in each group were euthanized with an overdose of anesthesia." Please also complete all items on the checklist at the following link: http://journals.plos.org/plosone/s/file?id=bb1d/plos-one-humane-endpoints-checklist.docx. Please upload the completed checklist as file type “Other” when resubmitting your manuscript. This document is for internal journal use only and will not be published if your article is accepted. We very much appreciate your attention to these requests and support of improved reporting standards in PLOS ONE submissions.

Additionally, in reviewing your submission we noticed you did not provide original raw image files supporting blot/gel data in the Figure 1A. We can see that you have provided cropped images of the membranes as supplementary file, however we require the original, uncropped and minimally adjusted images supporting all blot and gel results reported in an article’s figures and supporting information files (https://journals.plos.org/plosone/s/figures#loc-blot-and-gel-reporting-requirements). Can you please comment on this/these issue(s)?

When you reply, please also send the original raw image files (unadjusted, uncropped), clearly labeled and compliant with our guidelines at the above URL.

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

Please submit your revised manuscript by Sep 15 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,

Johanna Pruller, PhD

Associate Editor

PLOS ONE

on behalf of

Partha Mukhopadhyay, Ph.D.

Section 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.

Additional Editor Comments (if provided):

[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: The revised manuscript, titled “Effects of cardiac contractility modulation on autophagy and apoptosis of cardiac myocytes in rabbits with chronic heart failure,” investigated the application of cardiac contractility modulation (CCM) as an instrument treatment method in cases of chronic heart failure. The authors did a satisfying job of editing and revising the content of the manuscript. The authors have responded to all the questions I asked with reasonable and acceptable justification. Finally, the authors made nearly all the corrections and additions (textual, references, etc.) that were needed for the publication. Overall, this manuscript reads really well and would be a nice addition to the research community on chronic heart failure. I would recommend the publication of this manuscript once it satisfies the journal’s guidelines.

Reviewer #2: The authors have addressed the issues that were pointed out. The manuscript now matches the global standards of scientific reporting. This makes the topic to be depicted and understood in an intelligible manner.

********** 

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.

Effects of cardiac contractility modulation on autophagy and apoptosis of cardiac myocytes in rabbits with chronic heart failure

PONE-D-23-21385R3

Dear Dr. Liu,

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.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Partha Mukhopadhyay, Ph.D.

Section Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: