Diversity of Host Species and Optimized Cultivation Practices for Enhanced Bioactive Compound Production in Cordyceps militaris
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThe authors summarized how different factors, host species, strains, environmental, and cultivation practices affect bioactive compound production in cordyceps. The contents are well written, however are redundant and disorganized. Suggestions for revision are as below:
1. section 2 (host diversity for cordyceps militaris cultivation) and section 3 (difference of host species) until line 237 could be written as one section.
2. Line 177-186 have the same message as 161-167, so suggest to remove these two paragraphs.
3. Table 2 and 3 can be merged.
4. The concept of HPLC for measuring bioactive concentration was explained 3 times (line 170-175, line 204-208, line 223-229).
5. Section 3 can start from line 238, describing environmental factors influencing yield and quality.
6. "Host species" was used to refer to both substrates that C. militaris grows on, and C. militaris species itself. Suggest to change it to avoid confusion.
7. Line 365-389 should be removed since environmental conditions have already been described.
8. Line 422-431 are repetitive and should be removed.
9. In Figure 4, "solid-state-fermentation", "liquid fermentation" and "hybrid systems" should not be listed in sequential order, but rather parallel.
10. Line 513-533 are the exact content as line 490-512.
Author Response
Dear Respective Reviewer,
We are deeply grateful for all your valuable comments to our manuscript. We agreed and revised our manuscript following your comments and suggestions. We send two files: a file is noted with track changes and color letters to indicate where we revised, and another file is the final revised manuscript without track changes. The responses to each your questions are detailed in the table below. Please kindly check.
Author Response File: 
Author Response.docx
Reviewer 2 Report
Comments and Suggestions for AuthorsThe manuscript "Diversity of Host Species and Optimized Cultivation Practices for Enhanced Bioactive Compound Production in Cordyceps militaris" (applsci-3167423), submitted to Applied Sciences, is a review on the production of bioactive compounds by the fungus Cordyceps militaris. Although many reviews have been published in the last five years about this fungus and the bioactive compounds it produces, the work presented here focuses on aspects that have been extensively researched but not compiled until now (at least as far as I have been able to find). The result is a work that integrates everything from the isolation of the fungus to the industrial processes of production of its compounds.
But I am struck by the fact that only one of the references included in the work belongs to the authors who signed the manuscript, and that reference is a review with similar characteristics to this one (content, editorial, etc.):
Trung, N.Q.; Dat, N.T.; Anh, H.N.; Tung, Q.N.; Nguyen, V.T.H.; Van, H.N.B.; Van, N.M.N.; Minh, T.N. Substrate Influence on Enzymatic Activity in Cordyceps militaris for Health Applications. Chemistry 2024, 6, 517-530.
I understand that a review on a particular topic should be written by experts in that topic, so I do not consider the authors to have sufficient scientific authority on the subject of the review (demonstrable in the form of previous publications on the topic) to justify the acceptance of the work they are presenting. It is true that I consider that this point depends on the editorial policy of the journal and the position of the editor, but my decision would be to reject it.
On the other hand, the text is well written, with a very good level of English and an iThenticate score of 6%. But... there are parts of the text that are literally repeated...
Lines 53-67 and lines 422-434.
Lines 490-512 and lines 513-533.
And at other times, there are phrases or concepts repeated several times:
- Lines 31-32 and 53-54, citing different references.
- Lines 119-123, lines 188-189, lines 230-231, and lines 298-299.
Other aspects that could be improved upon are listed below:
- Lines 27-29. Keywords are usually ordered alphabetically.
- Line 31. " Cordyceps" should be written in italics. This also applies to, at least, lines 44, 49, 222, 226, 537, 548, 554, 558, 560, and 561.
- Lines 171-172. “High-Performance Liquid Chromatography (HPLC)”. This abbreviation is defined here in the first place, but is defined twice more: in line 204 and line 224.
- Lines 205-206. “assessing the impact of host species on the quality of C. militaris.” It is not C. militaris, but C. militaris products (or bioactive compounds).
- Figure 3. The authors use 25 °C in the first graph below. Previously in the text and on the unit axis 25°C or the magnitude without space is used. Although both spellings are correct, only one should be used in the text.
- Line 689. “sup-porting”. Please change it to supporting.
Comments on the Quality of English LanguageThe text is well written, with a very good level of English.
Author Response
Dear Respective Reviewer,
We are deeply grateful for all your valuable comments to our manuscript. We agreed and revised our manuscript following your comments and suggestions. We send two files: a file is noted with track changes and color letters to indicate where we revised, and another file is the final revised manuscript without track changes. The responses to each your questions are detailed in the table below. Please kindly check.
Author Response File: Author Response.docx
Reviewer 3 Report
Comments and Suggestions for AuthorsDiversity of Host Species and Optimized Cultivation Practices for Enhanced Bioactive compound Production in Cordyceps militaris.
The author should ensure consistent use of scientific terms throughout the manuscript. For instance, "C. militaris" is used interchangeably with "Cordyceps militaris"; sticking to one form, especially in the same section, would maintain consistency.
line 12: "extensive" is a buzzword and doesn’t carry much meaning. Maybe writing like this may help: Cordyceps militaris, recognized for its diverse and potent medicinal properties, plays a critical role in herbal medicine.
line 18: fungus?
line 32-35: “Among its species………mannitol” the sentence is a bit too long, consider breaking into 2 parts for clarity among readers.
The introduction covers a broad range of topics, from historical perspectives to modern research, without a clear structure. The reader may find it difficult to identify the focus of the paper – a central hypothesis is missing, and the primary objectives of the research. The introduction should speak about what new insights/findings this research brings to the existing body of knowledge.
The manuscript states that "C. militaris, an entomopathogenic fungus, is highly valued in traditional Chinese medicine for its broad therapeutic properties” but have cited only 1 paper to support the claim. This claim is broad and should require specific references or detailed evidence like what was found in those papers.
line 34 and 54: “Therapeutic properties” has been mentioned multiple times in introduction without been properly backed by proper citations. It would be more scientifically sound to provide specific examples of studies and what they found that support these claims.
line 36: broad range of physiological activities is vague and should be more precisely defined like what kind of specific activities are talked about.
line 58-59: “which contributes to its antioxidant, anti-inflammatory, anti-cancer, and immune-modulating effects” - The introduction appears to overstate the efficacy of Cordyceps militaris in areas such as anti-cancer and immune-modulating effects with just 1 citation. While promising results may exist, the manuscript should be cautious in making definitive claims and should instead emphasize the potential of these effects based on existing supporting evidence. Like what was found and how it affects cancer etc.
The text mentions that different host species influence the production of bioactive compounds, but it does not sufficiently explain the underlying mechanisms. For example, why do Lepidoptera hosts result in higher levels of cordycepin? A separate topic of discussion between the host and fungus would strengthen the manuscript.
line 171-175: The paper mentions high-performance liquid chromatography (HPLC) for measuring cordycepin yields but should also discuss the limitations or challenges of using this method and what other key methods can be used to detect compounds.
It would be beneficial to discuss why certain hosts yield more cordycepin? and what are the broader implications for commercial production. Simply listing data without deeper interpretation limits the value of the information.
There are inconsistencies in terminology, such as the use of different terms for the same concept (e.g., "yield" vs. "production").
line 182-186: While the section briefly mentions ongoing research and genetic strategies to improve cordycepin production, it should provide specific future research directions like explaining some of the strategies would be beneficial.
line 326: While genetic engineering and CRISPR/Cas system is mentioned briefly, the author should delve into specific examples of how genetic modifications have been used to optimize C. militaris cultivation. Discussing specific CRISPR/Cas applications or successful examples of strain improvement would add depth to this section.
line 348-351: the sentence “Molecular adaptations…. environmental conditions” is too long. Consider breaking the sentence for clarity among readers.
line 397: The text mentions contamination risks in traditional methods but does not elaborate on how these risks can be mitigated or what specific challenges are faced during the isolation process. A detailed discussion on how to manage or reduce contamination would make this section more practical for researchers and cultivators.
line 581-586: The paper does not discuss the limitations of using different host species for cultivation. While it mentions ecological and ethical concerns, it lacks a thorough discussion on how these limitations might affect the scalability/consistency of bioactive compound production.
The author should expand the discussion on the environmental and economic implications of using different host species, particularly in relation to sustainability and cost-effectiveness.
Focus more on providing in-depth analysis, regarding modern techniques, the variability of bioactive compounds, and the challenges of integrating C. militaris into mainstream medicine,
or,
Do a restructuring to separate the review of traditional and modern cultivation methods more clearly, which would improve the flow and coherence of the discussion.
Make sure tables and figures obey journal specifications and format.
Author Response
Dear Respective Reviewer,
We are deeply grateful for all your valuable comments to our manuscript. We agreed and revised our manuscript following your comments and suggestions. We send two files: a file is noted with track changes and color letters to indicate where we revised, and another file is the final revised manuscript without track changes. The responses to each your questions are detailed in the table below. Please kindly check.
Author Response File: Author Response.docx
Round 2
Reviewer 2 Report
Comments and Suggestions for AuthorsThe manuscript "Diversity of Host Species and Optimized Cultivation Practices for Enhanced Bioactive Compound Production in Cordyceps militaris" applsci-3167423-peer-review-v2), submitted to Applied Sciences, represents a new version of a paper I previously reviewed. The revised manuscript is more comprehensive and incorporates all the suggested corrections. The primary reason for its initial rejection, namely the failure to provide sufficient justification for the development of a review on the subject, has been explained, contextualized and corrected. I am therefore no longer in a position to maintain my previous decision.
Following the implementation of the aforementioned corrections, new errors have emerged, which must be addressed:
- Lines 722-723. The references cited in the text as 6 and 7 are incomplete or incorrect. In the first instance, the references in question should be completed. In the second case, it will be necessary to renumber all references subsequent to reference 7.
- Line 767. The genus name of the fungus should be changed to Ophiocordyceps. This also applies to lines 772 and 806.
- Line 772. The format of the references should be revised. The abbreviation "J. invertebrate pathology" is not abbreviated as the rest of the references.
Author Response
We are deeply grateful for all your valuable comments to our manuscript. We agreed and revised our manuscript following your comments and suggestions. We send two files: a file is noted with track changes and color letters to indicate where we revised, and another file is the final revised manuscript without track changes. The responses to each your questions are detailed in the table below. Please kindly check.
Author Response File: Author Response.docx
Reviewer 3 Report
Comments and Suggestions for AuthorsLine 41: immune modulating should be immunomodulating
"anti-cancer" is sometimes hyphenated and other times not. Choose one form and stick to it consistently.
Author Response
We are deeply grateful for all your valuable comments to our manuscript. We agreed and revised our manuscript following your comments and suggestions. We send two files: a file is noted with track changes and color letters to indicate where we revised, and another file is the final revised manuscript without track changes. The responses to each your questions are detailed in the table below. Please kindly check.
Author Response File: Author Response.docx
