PONE-D-25-33250TRIM37-Mediated PEX5 Stabilization via Monoubiquitination Alleviates Oxidative Stress and Demyelination in Multiple SclerosisPLOS ONE

Dear Dr. Fu,

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Based on the reviewers' suggestions, the paper needs major revision. The reviewers' comments can be found below.

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Academic Editor

PLOS ONE

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This research was supported by the 2024 Science and Technology Plan of the Health Commission of Heilongjiang Province (Grant No.: 20240303070234). We would like to extend our sincerest gratitude to the Health Commission of Heilongjiang Province and its relevant administrative departments. The successful execution and outcome of this project would not have been possible without your strategic support and scientific management for medical research.

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The research work presented in this article was supported by the 2024 Science and Technology Plan of the Health Commission of Heilongjiang Province. The project number is 20240303070234, with Jiang Lai serving as both the project leader and the recipient of the grant. The grant was awarded by the Health Commission of Heilongjiang Province.

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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: Yes

Reviewer #3: Partly

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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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: Minor considerations must be addressed,

1) Title and key words must include that results are from experimental models

2) Line 41 a reference is needed after age range

3) Line 86 Caps are missing

4) Line 332 use subscript number for peroxide

Reviewer #2: Excellent reasearch article.Written according to all the rules.The study meets all ethical and integrity standards required for publication in a peer-reviewed scientific journal.The authors clearly state that all animal experiments were conducted in accordance with the ARRIVE guidelines and were approved by the Animal Ethics Committee of Beidahuang Group General Hospital (Approval No.: KY2024092003).The use of appropriate anesthesia (sodium pentobarbital) and euthanasia methods (CO₂ exposure followed by cervical dislocation) reflects compliance with internationally accepted guidelines for humane animal care and use in biomedical research.The study was funded by the Health Commission of Heilongjiang Province, and the authors explicitly declare that the funding body had no role in the study design, data analysis, publication decision, or manuscript preparation.The authors declare no competing interests, which supports the transparency and credibility of the research.All relevant data are made available within the manuscript and supplementary files, in accordance with open access data policies and good scientific practice.The methodology is sound, experiments were replicated, appropriate controls were used, and statistical analyses were correctly applied. The discussion also acknowledges limitations, which strengthens the overall reliability of the findings.

Reviewer #3: The authors present an interesting study on the regulatory role of TRIM37 in peroxidation and its impact on oxidative stress and demyelination in Multiple Sclerosis. However, substantial modifications are needed for publication:

-The context is heavily focused on the pathophysiology of MS, but no background has been provided regarding TRIM37 and peroxidation in relation to Multiple Sclerosis. Therefore, it is unclear what has previously been described and why this particular protein was chosen over others.

-The study objectives have not been outlined.

-The methodology is confusing and appears to be disorganized.

-Although the results are statistically significant, the conclusions and the implications for MS—both physiopathologically and therapeutically—are exaggerated and inconsistent with the findings. It would be advisable to moderate these conclusions.

-The limitations section does not include other relevant factors, such as those inferred from the bioinformatic analysis or the lack of assessment of additional oxidative stress parameters.

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Reviewer #1: Yes:  Alfredo Sanabria-Castro

Reviewer #2: No

Reviewer #3: No

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Attachments

Attachment

Submitted filename: Review PLOS ONE.docx

TRIM37-mediated stabilization of PEX5 via monoubiquitination attenuates oxidative stress and demyelination in multiple sclerosis insights from EAE and LPC-induced experimental models

PONE-D-25-33250R1

Dear Dr. Fu,

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,

Tanja Grubić Kezele, Ph.D., M.D.

Academic Editor

PLOS ONE

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