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All issues indicated by the reviewers were adequately addressed and the revised manuscript is acceptable now.
[# PeerJ Staff Note - this decision was reviewed and approved by Sonia Oliveira, a PeerJ Section Editor covering this Section #]
The article is thorough and clear after revision.
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The author has basically made appropriate and reasonable responses to my previous review comments.The quality of the entire review has improved compared to before,and I have no further comments now.
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This manuscript provides a review of the current research progress of tsRNAs in renal disease, covering their definitions, biological functions, and involvement in AKI, CKD, and LN. However, several revisions would enhance its clarity and relevance.
Lines 17-18: The sentence is a fragment lacking a main verb. Revise it to form a complete thought sentence. Proofread other sections to enhance sentence readability.
Line 59: The discussion of tRF2Cancer and the lipoma tissue example feels disconnected from the review’s focus on kidney disease. It would be better to add more transitions to connect it to renal contexts.
The review omits tsRNAs in polycystic kidney disease (PKD) and renal cell carcinoma.
While tsRNAs are presented as potential biomarkers, their specificity across kidney diseases is not addressed. Include a discussion on this, and comparing tsRNAs to established biomarkers like creatinine, albuminuria, or miRNAs to highlight their difference.
The review lacks a detailed discussion on challenges of current research on tsRNAs and proposed solutions for future research.
Explore how tsRNA data could be combined with genomics and proteomics to deepen insights into kidney diseases.
Table 1 Discrepancy: Table 1 lists "FGF11" as the target of tDR-012842, conflicting with "FGF10" on Page 9, Line 163. Correct this inconsistency for accuracy.
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This review summarizes recent advances in tsRNA research in kidney diseases; however, it lacks novelty compared to existing reviews and suffers from insufficient depth, incomplete coverage, and inadequate critical analysis. Substantial improvements are needed to enhance its scholarly value, as detailed below:
1.The description of tsRNA mechanisms (e.g., inflammation/apoptosis regulation mentioned in the Abstract) is superficial. Expand coverage to include validated pathways like RNA interference, transcriptional regulation, ribosome biogenesis, and retrotransposon suppression.
2.Incomplete AKI literature: Critical tsRNA-AKI studies are missing.
3. Since the clinical application potential is stated, the comparative advantages of tsRNAs over existing biomarkers (e.g., specificity, stability) remain unexplored. It is suggested to strengthen translational analysis with data-driven discussion.
4.Inadequate references: it is suggested to expand literature to include:
tsRNA-epigenetic crosstalk (e.g., DNA methylation/histone modification); Clinical applications (e.g., nanodelivery systems for diagnostics/therapeutics)
5. Structural disorganization (Section 3): The abrupt introduction of databases (e.g., tRF2Cancer) disrupts flow. Relocate technical platforms (PANDORA-seq, databases) to the Conclusion as "Methodological Challenges/Future Directions."
6. Overreliance on expression profiling/bioinformatic predictions. Please address functional validation gaps (e.g., Co-IP, RNA pull-down) or explicitly discuss this limitation in the Conclusion.
7.The disease scope seems narrow, it is suggested to expand coverage to major renal pathologies like Renal cell carcinoma; Kidney transplantation; FSGS or at least alternatively, justify omissions by highlighting research gaps.
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