PONE-D-23-23562Vitamin K2 (MK-7) attenuates LPS-induced acute lung injury via inhibiting inflammation, apoptosis, and ferroptosisPLOS ONE

Dear Dr. Li,

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PLOS ONE

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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: No

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: 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: No

Reviewer #2: 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

Reviewer #2: 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: Comments to PONE-D-23-23562

As we all know, the COVID-19 pandemic is a research hotspot. Because of this, many researchers are trying to grasp this hotspot. But a lot of the research has nothing to do with COVID-19. The current study can only be said to focus on the relationship between Vitamin K2 and LPS-induced acute lung injury, and the relationship with COVID-19 is minimal. However, the authors introduce too much COVID-19 in the Abstract and Introduction. The authors must be aware of this and make the necessary corrections. There is no need for researchers to rub hot spots.

Lipopolysaccharide (LPS) can indeed cause acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). The symptoms of ALI induced by LPS and those of a new coronavirus infection may share some similarities, but there are important distinctions between the two conditions.

Some of my specific comments can be found below:

1. Lines 76 and 77: This seemingly straightforward sentence is an essential basis for your research, but unfortunately, this reference cannot support this argument. Please carefully check this citation.

2. Line 131: How did the authors choose this exposure dose? Did the mice die at this dose? What is the mortality rate?

3. Lines 269 to 279: Please see my above comments.

4. Lines 351 to 353: This reviewer does not think this sentence could be listed in the Conclusion Section. The authors should never forget that you only injected LPS intraperitoneally into mice and did not artificially infect experimental animals with the new coronavirus.

Reviewer #2: Due to its multiple pharmacological properties, VK2 has become a research hotspot for scientists in recent years, including anti-inflammatory, anti-oxidant, anti-apoptotic, and anti-ferroptosis properties. According to this study, VK2 protects against ALI caused by LPS by suppressing the P38 MAPK signaling pathway and ferroptosis. Overall, the paper is well-written, but a few minor revisions are necessary.

1.     Some abbreviations that appeared in the abstract were not explained, such as "MDA" and "GSH".

2.     In animal experiments, why is it that the positive control group receives the LPS injection first, while the other groups receive the injection afterward? It is necessary to provide a reasonable explanation for this. Would it be better to replace a positive control group?

3.     Is it necessary to replace "treatment" with "pretreatment" in line 239, line 246 and line 345?

4.     As shown in Figures 4 A, B, and C, the results are not significant and require further investigation.

5.     The association between P38 MAPK pathway and Bcl-2 and Caspase-3 needs to be explained in lines 308-310.

6.     The format of the article is not standardized, such as ' Caspase-3 ' in several places without capitalization. It is strongly recommended that you double-check.

7.     The limitations of this experiment were not discussed in the discussion.

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Reviewer #1: Yes: Fan Yang

Reviewer #2: Yes: Li Deng

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Vitamin K2 (MK-7) attenuates LPS-induced acute lung injury via inhibiting inflammation, apoptosis, and ferroptosis

PONE-D-23-23562R1

Dear Dr. Li,

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.

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Kind regards,

Keiko Hosohata, Ph.D.

Academic Editor

PLOS ONE

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

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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

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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: (No Response)

Reviewer #2: Yes

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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 author has fully addressed my previous comments. I think this manuscript is acceptable in its current state.

Reviewer #2: (No Response)

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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: Yes: Fan Yang

Reviewer #2: Yes: Li Deng

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