Verified Rigor RecordRigor Reviewed

Rigor-Reviewed Manuscript

Macrophages depletion alleviates lung injury by modulating AKT3/GXP4 following ventilator associated pneumonia · 10.3389/fimmu.2023.1260584

Name: Verified Rigor Record — Macrophages depletion alleviates lung injury by modulating AKT3/GXP4 following ventilator associated pneumonia · 10.3389/fimmu.2023.1260584
Item: Macrophages depletion alleviates lung injury by modulating AKT3/GXP4 following ventilator associated pneumonia · 10.3389/fimmu.2023.1260584
Rating: 39
Author: Αlpha¹

Paper source

Αlpha¹ Editorial

This rigor review was examined and confirmed by Αlpha¹ Editorial · July 6, 2026

Αlpha¹ Rigor Review

Rigor Reviewed

CRITICAL

Critical rigor failure · Interventional Study

Eight dimensions — click a segment for details

Critical

High-priority

Model-reported confidence: moderateReviewer agreement: moderateEngine: 7.5.0Source: full text

Not verified in this report

No reported statistical tests were found to recompute.

This Αlpha¹ Rigor Review uses AI Rigor Reviewers trained on a curated corpus of high-fidelity and retracted papers, with expert supervision and curation. It can still make mistakes; verify each finding against the source before relying on it.

Critical findings

• Macrophage depletion attenuates ferroptosis of lung epithelial cells by modulating AKT3 following VAP.

The paper has serious methodological and reporting shortcomings, including failure to report basic biological variables (sex, age, strain), lack of randomization and blinding, inadequate statistical reporting, and unsupported causal claims. The paper has been formally retracted, which is a critical validity concern that supersedes individual issues.

Evaluated both computational and in vivo components. The in vivo experiment was the primary focus. Three independent reviewers (same model) provided assessments; their divergences (e.g., on biological variables) were resolved by weighing the evidence. The verification components flagged a retraction, internal contradictions, and unsupported claims, which are incorporated into the assessment.

12 major claims checked against the paper's own evidence: 3 not fully backed by the presented evidence (unsupported or overstated).

10 integrity concerns flagged (1 high).

Rigor

Eight Dimensions1 pass · 6 warn · 1 fail

12 major claims2 unsupported1 overstated4 partial5 supported

The introduction cites literature on macrophages, ferroptosis, and AKT3 in lung cancer, but fails to cite prior work directly linking AKT3 to VAP, which is the study's main focus. The rationale connecting AKT3's role in lung cancer to its hypothesized role in VAP is not clearly argued. Limitations of prior studies on AKT3 or macrophage depletion are not discussed.

Sub-criteria

prior work citedINADEQUATE

premise rationaleINADEQUATE

limitations addressedNOT REPORTED

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 85% conf

Prior work on AKT3 in lung cancer is cited, but the specific premise for VAP is weakly established and limitations of prior research are not addressed.

Evidence

absence[Introduction, paragraph 1]

The introduction cites general roles of macrophages and ferroptosis but not prior work specifically linking AKT3 to VAP.

direct quote[Introduction, final paragraph]

“This study aims to establish a foundation for comprehending the developmental mechanisms of lung macrophages and exploring their potential role in VAP.”

absence[Introduction]

No limitations of prior studies are discussed.

WARNReviewer 2· 80% conf

The paper cites prior work on macrophages, ferroptosis, and AKT3, and provides a logical rationale linking AKT3 to lung injury in VAP. However, it does not adequately address limitations of prior research or describe how the study mitigates them.

Evidence

direct quote[Introduction, paragraphs 1-4]

“Monocytes and macrophages (MΦs) play a critical role as immediate responders to various types of invading pathogens... Ferroptosis is a distinctive form of programmed cell death...”

direct quote[Introduction, last paragraph; Abstract, Methods]

“This study aims to establish a foundation for comprehending the developmental mechanisms of lung macrophages and exploring their potential role in VAP.”

absence[Introduction]

Limitations of prior research are not discussed

WARNReviewer 3· 75% conf

Prior work is cited but the rationale linking AKT3 in lung cancer to macrophage depletion in VAP is weak and the limitations of prior work are not addressed.

Evidence

paraphrase[Introduction, paragraphs 1-4]

“Paragraphs cite general roles of macrophages and ferroptosis, but the specific gap regarding AKT3 in VAP is stated without citing prior work on this gap.”

direct quote[Introduction, final paragraph]

“This study aims to establish a foundation for comprehending the developmental mechanisms of lung macrophages and exploring their potential role in VAP.”

absence[Introduction]

No discussion of limitations of prior research is present.

The study has both computational and in vivo components. The computational analysis is purely descriptive, so most design criteria (randomization, blinding, power, etc.) are not applicable to that part. The in vivo mouse experiment lacks any mention of randomization of animals to groups, blinding of investigators during outcome assessment, an a priori power analysis, and pre-specified inclusion/exclusion criteria. The distinction between biological and technical replicates is not made. No positive or negative controls beyond the normal saline group are described. The outlier handling method is not reported. Independent replication is not reported or planned. The small sample size (N=4 per group for key comparisons) raises concerns about robustness.

Sub-criteria

controlsINADEQUATE

power analysisNOT REPORTED

blinding levelsNOT REPORTED

outlier handlingNOT REPORTED

randomization unitNOT REPORTED

inclusion exclusionNOT REPORTED

randomization methodNOT REPORTED

replicate distinctionNOT REPORTED

independent replicationNOT REPORTED

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 80% conf

The in vivo experiment lacks key design details such as randomization, blinding, power analysis, and pre-specified criteria, while the computational analysis is not assessed for design rigor.

Evidence

absence[Section 2.3]

No randomization method or unit is described for the animal experiment.

direct quote[Section 2.3]

“mice were anesthetized with avertin (15 mg/kg, Sigma) and were intranasally administered either 15 μl of normal saline as the control group, or an equal volume of Pseudomonas aeruginosa (PA) at a concentration.”

direct quote[Figures 5-8]

“N=4”

WARNReviewer 2· 70% conf

The study uses a mouse model of VAP and macrophage depletion with clodronate liposomes. Several design elements are underreported: no randomization method, no blinding, no power analysis, no pre-specified inclusion/exclusion or outlier handling, and no independent replication. Positive/negative controls are lacking beyond a saline control group.

Evidence

direct quote[Methods, sections 2.3, 2.5]

“Wild-type (WT) mice were anesthetized with avertin (15 mg/kg, Sigma) and were intranasally administered either 15 μl of normal saline as the control group... For this study, a total volume of 300 μl of LC or LV was administered intraperitoneally...”

paraphrase[Methods, section 2.3]

“Only a saline control and VAP group are described; no vehicle control for clodronate is mentioned.”

WARNReviewer 3· 70% conf

The in vivo mouse experiment lacks clear randomization, blinding, power analysis, and replication, but inclusion/exclusion and controls are partially reported.

Evidence

absence[Materials and methods, section 2.3]

No method of randomization is reported.

absence[Materials and methods]

Blinding of investigators or assessors is not mentioned.

direct quote[Materials and methods, section 2.5]

“Wild-type (WT) mice were anesthetized with avertin (15 mg/kg, Sigma) and were intranasally administered either 15 μl of normal saline as the control group, or an equal volume of Pseudomonas aeruginosa (PA).”

Sex of the mice is not reported anywhere in the manuscript. No justification for a single-sex study is given. Age, weight, and health status of the mice are entirely absent. The mice are described only as 'Wild-type (WT)', with no specific strain, substrain, or source (vendor/breeder). Housing conditions (light cycle, temperature, enrichment) are not described. As this is an animal study, demographics is not applicable. The absence of nearly all applicable sub-criteria results in a failing score.

Sub-criteria

demographicsN/A

sex reportedNOT REPORTED

sex justifiedN/A

age weight healthNOT REPORTED

housing conditionsNOT REPORTED

species strain sourceNOT REPORTED

Per reviewer (3) — the votes behind the verdict

FAILReviewer 1· 90% conf

The paper fails to report essential biological variables: sex, age, weight, and health status of mice are not provided, and the mouse strain is only described as 'Wild-type (WT)' with no further details on source or substrain.

Evidence

absence[Section 2.3]

No sex, age, weight, or health status of mice is reported.

direct quote[Section 2.3]

“Wild-type (WT) mice were anesthetized with avertin”

WARNReviewer 2· 70% conf

The study uses wild-type mice and reports species and strain, but sex, age, weight, health status, and housing conditions are not reported. The mouse sex is not stated, and no justification is given if single sex is used. Demographics are not applicable.

Evidence

direct quote[Methods, section 2.3]

“Wild-type (WT) mice were anesthetized with avertin (15 mg/kg, Sigma)...”

absence[Methods, sections 2.3-2.7]

No sex, age, weight, health status, or housing conditions reported

PASSReviewer 3· 80% conf

The species and strain (wild-type mice) are reported, and age/weight/health are not reported, but sex is not reported, which is a gap for an animal study.

Evidence

absence[Materials and methods, section 2.3]

Sex of the mice is not reported.

absence[Materials and methods, section 2.3]

Age and weight of mice are not reported.

absence[Materials and methods]

Housing conditions are not described.

The paper reports approval from the ethics committee of Guangzhou Red Cross Hospital (approval number 2019-145-01). The statement is specific and meets the criteria for an adequate IACUC-equivalent statement. Regulatory compliance is stated as 'conducted in accordance with the local legislation and institutional requirements.' The other sub-criteria (IRB, informed consent) are not applicable as this is an animal study.

Sub-criteria

iacuc statementADEQUATE

informed consentN/A

irb ethics statementN/A

regulatory complianceADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

The animal study received explicit approval from a named ethics committee with a protocol number, satisfying the core reporting requirement.

Evidence

direct quote[Ethics statement]

“The animal study was approved by the ethics committee of Guangzhou Red Cross Hospital (approval number 2019-145-01).”

PASSReviewer 2· 90% conf

Ethical approval for the animal study is reported with the named committee and approval number, and a statement of compliance with local legislation is provided.

Evidence

direct quote[Ethics statement (after Conclusion)]

“The animal study was approved by the ethics committee of Guangzhou Red Cross Hospital (approval number 2019-145-01). The study was conducted in accordance with the local legislation and institutional requirements.”

PASSReviewer 3· 95% conf

Animal ethics approval is reported with a named committee and protocol number; regulatory compliance is stated generically but adequately for an animal study in China.

Evidence

direct quote[Ethics statement]

“The animal study was approved by the ethics committee of Guangzhou Red Cross Hospital (approval number 2019-145-01).”

direct quote[Ethics statement]

“The study was conducted in accordance with the local legislation and institutional requirements.”

Antibodies are listed with catalog numbers (e.g., AF06799), but the vendor is described only as 'AiFang Biological', without a clear institution or city. The software tool 'Xiantao' is named with a URL, but GraphPad Prism 9.0 is named without a version. No cell lines or mycoplasma testing are reported, and the mice are described only as 'Wild-type (WT)' without strain, source, or genotyping for transgenics. The key reagent (clodronate liposomes) is not identified by catalog number or source. These shortcomings warrant a 'warn' status.

Sub-criteria

mycoplasma testingN/A

reagents identifiedNOT REPORTED

organisms identifiedNOT REPORTED

antibodies identifiedINADEQUATE

cell line authenticationN/A

software tools identifiedINADEQUATE

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 85% conf

Key resources are partially identified: antibodies are listed with catalog numbers but the vendor is vaguely named, and the software used is identified. No organisms, cell lines, or reagents are authenticated beyond a basic name.

Evidence

direct quote[Section 2.6]

“The sections were incubated overnight at 4°Cwith the following primary antibodies (all from AiFang Biological) diluted at 1:100: anti-MMP9 (AF06799), anti-MMP19 (AF02793), anti-SFTA1 (AF10524), anti-FTH (AF02247), anti-FTL ( AF301381 ), and anti-GPX4 (AF11931).”

direct quote[Section 2.3]

“Wild-type (WT) mice were anesthetized with avertin”

absence[Section 2.5]

No catalog or source is provided for the clodronate liposomes used for macrophage depletion.

WARNReviewer 2· 70% conf

Antibodies are listed with catalog numbers and supplier, but without RRIDs, lot numbers, or validation data. The clodronate liposomes and other reagents are incompletely identified. Software (GraphPad Prism 9.0, Xiantao tool) is named but without versions or RRIDs.

Evidence

direct quote[Methods, sections 2.5, 2.6]

“anti-MMP9 (AF06799), anti-MMP19 (AF02793), anti-SFTA1 (AF10524), anti-FTH (AF02247), anti-FTL ( AF301381 ), and anti-GPX4 (AF11931)”

direct quote[Methods, sections 2.1, 2.2, 2.7]

“Data processing utilizing Xiantao academic tools... Statistical analysis was performed using GraphPad Prism 9.0.”

WARNReviewer 3· 75% conf

Antibodies are listed with catalog numbers but without RRIDs or validation data; software is identified but without version numbers for all tools; reagents (e.g., clodronate liposomes) are not fully identified.

Evidence

direct quote[Materials and methods, section 2.6]

“The following primary antibodies (all from AiFang Biological) diluted at 1:100: anti-MMP9 (AF06799), anti-MMP19 (AF02793), anti-SFTA1 (AF10524), anti-FTH (AF02247), anti-FTL (AF301381), and anti-GPX4 (AF11931).”

direct quote[Materials and methods, section 2.3]

“Wild-type (WT) mice were anesthetized with avertin (15 mg/kg, Sigma) and were intranasally administered either 15 μl of normal saline...”

direct quote[Materials and methods, section 2.5]

“For this study, a total volume of 300 μl of LC or LV was administered intraperitoneally...”

Tests are named ('χ2 test', 'Mann-Whitney U test', 'Kruskal-Wallis test'), but only 'χ2 test' is specified without the type (e.g., Pearson, Fisher's). Test assumptions are not verified. Exact p-values are replaced by inequalities ('P < 0.05', '**P < 0.05', '***P < 0.01', '****P < 0.005'), which is imprecise. No effect sizes or confidence intervals are reported alongside p-values. Statistical software is identified (GraphPad Prism 9.0). Data presentation is inadequate: individual data points are not shown, error bars are not defined, and per-group sample size is stated (N=4) but not for all analyses. Mathematical plausibility is not applicable as individual data points are not available for verification.

Sub-criteria

tests namedINADEQUATE

exact p valuesNOT REPORTED

effect sizes ciNOT REPORTED

data presentationINADEQUATE

software identifiedADEQUATE

assumptions verifiedNOT REPORTED

mathematical plausibilityN/A

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 80% conf

Statistical tests are named but incompletely described (e.g., 'χ2 test' without specifying which type), exact p-values are mostly absent, and no effect sizes or confidence intervals are reported. The small sample sizes (N=4) make the reported p-values unreliable, but no arithmetic errors are apparent.

Evidence

direct quote[Section 2.7]

“The χ2 test was used to assess the correlation between AKT3 expression and clinicopathological parameters. The Mann-Whitney U test or Kruskal-Wallis test was applied for other analyses.”

direct quote[Figure legends 6-8]

“significance set at **P < 0.05,***P < 0.01, ****P < 0.005”

absence[Results and Figures]

No effect sizes or confidence intervals are reported.

WARNReviewer 2· 80% conf

Statistical tests (χ², Mann-Whitney U, Kruskal-Wallis) are named, software (GraphPad Prism 9.0) is identified, and exact p-values appear in figures with thresholds (P < 0.05, 0.01, 0.005). However, test assumptions are not verified, effect sizes and confidence intervals are not reported, and data presentation uses bar graphs with error bars, but individual data points are not shown; the figure legends give N=4 per group but do not define what n represents (biological replicates). Mathematical plausibility checks could not be performed as means/SDs are not reported in the text.

Evidence

direct quote[Methods, section 2.7; figure legends 6-8]

“The χ2 test was used to assess the correlation... The Mann-Whitney U test or Kruskal-Wallis test was applied... Two-sided P-values were used, and statistical significance was considered at an alpha level of P< 0.05.”

direct quote[Figure legends 5-8]

“The sample size was N=4 with significance set at **P < 0.05,***P < 0.01, ****P < 0.005.”

WARNReviewer 3· 70% conf

Statistical tests are named, software is identified, and exact p-values are not reported (only thresholds), but data presentation shows per-group n and some error bars, while assumptions are not verified and effect sizes are absent.

Evidence

direct quote[Materials and methods, section 2.7]

“The χ2 test was used to assess the correlation between AKT3 expression and clinicopathological parameters. The Mann-Whitney U test or Kruskal-Wallis test was applied for other analyses.”

direct quote[Results, figure legends]

“The sample size was N=4 with significance set at **P < 0.05,***P < 0.01, ****P < 0.005.”

The data availability statement reads: 'The original contributions presented in the study are included in the article/, further inquiries can be directed to the corresponding authors.' This is a vague mechanism that does not name a repository, platform, or managed-access process, so it is rated as inadequate. The paper used public datasets (TCGA, GEO) but did not deposit any newly generated data (e.g., from the mouse experiments) into a public repository. Raw data from the animal experiments are not available. Code for the analysis using Xiantao is not shared, and the custom analysis steps are not described in sufficient detail for reproducibility. The Xiantao tool is a web-based platform, not customized code.

Sub-criteria

code sharingNOT REPORTED

accession numbersADEQUATE

repository depositNOT REPORTED

data availability statementINADEQUATE

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 90% conf

A data availability statement is present but vague ('further inquiries can be directed to the corresponding authors'), and no code is shared. Public data sources (TCGA/GEO) are cited but no repository deposit of newly generated data is made.

Evidence

direct quote[Data availability statement]

“The original contributions presented in the study are included in the article/, further inquiries can be directed to the corresponding authors.”

absence[Data availability statement and Methods]

No newly generated data from the animal experiments were deposited in a public repository.

absence[Methods and Data availability statement]

No custom code was shared, and analysis tools are only mentioned by name.

WARNReviewer 2· 80% conf

A data availability statement is present but vague ('available on request'). No data or code are deposited in a repository, and no accession numbers are provided. Code sharing is not mentioned.

Evidence

direct quote[Data availability statement (after Conclusion)]

“The original contributions presented in the study are included in the article/, further inquiries can be directed to the corresponding authors.”

absence[Entire paper]

No repository deposit, accession numbers, or code sharing mentioned

WARNReviewer 3· 85% conf

A data availability statement is present but vague; no data or code are deposited.

Evidence

direct quote[Data availability statement]

“The original contributions presented in the study are included in the article/, further inquiries can be directed to the corresponding authors.”

absence[Data availability statement]

No code or custom software repository is provided.

Methods are incomplete: the animal model description lacks details on randomization, blinding, and sample size justification, and the statistical analysis is vague. No reporting guideline (e.g., ARRIVE for animal studies) is mentioned. Not all pre-specified outcomes are clearly reported; the initial aims about AKT3's role in lung cancer from TCGA are loosely connected to the VAP experiments. The discussion mentions some limitations (e.g., 'specific mechanism remains unclear') but does not adequately address sources of bias or lack of blinding. The conclusions claim 'macrophage depletion alleviates lung injury by modulating the AKT3/GXP4 signaling pathway,' which implies a causal mechanism that is not fully established by the correlative immunofluorescence data. Funding and conflicts of interest are reported adequately.

Sub-criteria

funding coiADEQUATE

trial registrationN/A

reporting guidelineNOT REPORTED

methods completenessINADEQUATE

all outcomes reportedINADEQUATE

limitations discussedINADEQUATE

conclusions proportionalINADEQUATE

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 85% conf

Methods are partially described but lack critical details for replication. Limitations are insufficiently addressed, and the conclusions are somewhat overstated for the evidence presented. A reporting guideline is not followed, and trial registration is not applicable.

Evidence

absence[Section 2.3, 2.5]

Methods lack critical replication details such as randomization and blinding.

direct quote[Discussion, final paragraph]

“In conclusion, AKT3 plays a significant role in lung cancer development and progression.”

direct quote[Discussion]

“the specific mechanism remains unclear”

FAILReviewer 2· 70% conf

The paper lacks a trial registration number (not applicable), does not reference a reporting guideline, has poor methods completeness, does not report all outcomes transparently, has limitations that are sparsely discussed, and conclusions are somewhat overstated (e.g., claims of mechanism from association data). Funding and COI are reported.

Evidence

direct quote[Methods, Discussion]

“Statistical analysis was performed using GraphPad Prism 9.0... The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.”

direct quote[Abstract, Conclusion]

“Collectively, this study suggests the need for further validation of the immunoregulatory function of AKT3 in lung cancer. Additionally, macrophage depletion mitigates lung injury by modulating the AKT3/GPX4 pathway in the context of VAP.”

WARNReviewer 3· 75% conf

Methods are detailed but have gaps (e.g., no randomization or blinding); no trial registration, reporting guideline, or prospective registration; limitations are discussed but conclusions are partially overstated.

Evidence

absence[Materials and methods]

No reporting guideline (ARRIVE) is mentioned.

direct quote[Conclusion]

“Our study reveals that depletion of macrophages alleviates lung injury by modulating the AKT3/GXP4 signaling pathway in ventilator-associated pneumonia.”

direct quote[Conflict of interest]

“The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.”

24 copyedit issues flagged (9 major): mostly typo, consistency, grammar.

Checked 35 references: 34 verified — 1 retracted.

Reproducibility

2 data/code links checked; 2 live.

Αlpha¹ Rigor Action ItemsFinal pass before journal submission

This paper has been formally retracted, which indicates a serious validity concern that should be weighed by readers. The methodological rigor is insufficient to support the conclusions; an informed reader should consider the lack of essential design details, the absence of data and code, and the retraction status before relying on the findings.

1.
CRITICALother
Address the formal retraction of this paper (Retraction: Macrophages depletion alleviates lung injury by modulating AKT3/GXP4 following ventilator associated pneumonia). Readers should be aware that the paper has been retracted.
The paper has been formally retracted, which is a critical issue that supersedes all other concerns.
2.
CRITICALrigor
Remove or provide direct evidence for the unsupported claim 'Macrophage depletion attenuates ferroptosis of lung epithelial cells by modulating AKT3 following VAP', as no AKT3 modulation was measured in the animal model.
The claim is unsupported; the study does not present any direct evidence of AKT3 modulation by macrophage depletion.
3.
CRITICALrigor
Remove or provide direct evidence for the unsupported claim 'Macrophage depletion alleviates lung injury by modulating the AKT3/GPX4 pathway in VAP', as no causal pathway manipulation was performed.
The claim of a causal mechanism is not supported by the correlative data; the paper lacks AKT3 knockout or inhibition experiments.
4.
CRITICALreporting
Report the specific mouse strain, sex, age, weight, and vendor/source in the Methods (Section 2.3) to satisfy biological variables requirements.
These details are essential for reproducibility and interpretation; their absence is a major reporting gap.
5.
CRITICALdata code
Deposit raw data from the animal experiments (e.g., fluorescence intensity values) in a public repository (e.g., Figshare, Zenodo) and update the data availability statement with a DOI.
The current data availability statement is vague and does not provide a concrete access mechanism, which is a fundamental requirement for data-driven research.
6.
HIGHrigor
Describe the randomization method and unit for allocating mice to groups in Section 2.3 to improve study design.
Randomization is a key element of experimental design to minimize bias; its absence weakens the validity of the results.
7.
HIGHrigor
State the blinding status of investigators and assessors, or justify why blinding was not performed, in Section 2.3 or 2.7.
Blinding reduces bias in outcome assessment; its absence should be acknowledged.
8.
HIGHstatistics
Report exact p-values (e.g., p = 0.023) instead of threshold inequalities throughout the Results and figure legends.
Exact p-values allow readers to assess the strength of evidence; threshold-only reporting is imprecise.
9.
HIGHstatistics
Include effect sizes (e.g., mean differences) and confidence intervals for the main comparisons (e.g., MMP9 expression between groups).
Effect sizes and confidence intervals provide information about the magnitude and precision of effects, which p-values alone do not.
10.
HIGHother
Remove the retracted citation (AKT3-mediated IWS1 phosphorylation promotes the proliferation of EGFR-mutant lung adenocarcinomas through cell cycle-regulated U2AF2 RNA splicing, doi:10.1038/s41467-021-24795-1) or replace it with a non-retracted source.
Citing retracted literature can propagate incorrect findings; the reference should be replaced.
11.
HIGHreporting
Add a dedicated 'Limitations' section in the Discussion that addresses the lack of randomization, small sample size, and correlational nature of the AKT3 findings.
Acknowledging limitations is part of transparent reporting and helps readers interpret the findings appropriately.
12.
MEDIUMcopyedit
Fix the title spelling from 'AKT3/GXP4' to 'AKT3/GPX4' throughout the manuscript, including the title, abstract, and text.
The correct abbreviation for glutathione peroxidase 4 is GPX4; GXP4 is a typo that should be corrected for consistency.
13.
MEDIUMcopyedit
Correct the Methods section 2.5, which describes an ischemia/reperfusion (I/R) model instead of the VAP model; replace with the correct VAP protocol.
The current text appears to be a copy-paste error from another study, which confuses the experimental model.
14.
MEDIUMcopyedit
Define the abbreviation 'DM' (likely 'depletion of macrophages') upon first use in the Results section and use consistently throughout.
Undefined abbreviations reduce clarity and should be defined at first occurrence.
15.
MEDIUMreporting
Provide RRIDs and lot numbers for all antibodies in Section 2.6, and specify the source and catalog number for clodronate liposomes in Section 2.5.
These details are necessary for reproducibility and to ensure that other researchers can obtain the same reagents.

Full text (34,897 chars)Analyzed: Jul 6, 2026

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