Cover Letter
求职信
Dear Editor and Reviewers,
亲爱的编辑和评审们,
Thank you for your letter and for the reviewers’ insightful comments on our manuscript titled “The Role of BACH1 in Trophoblast Cell Dysfunction and Preeclampsia Development: Focus on Mitochondrial Metabolism and Succinylation Modification” (ID: 101655h). We sincerely appreciate the editor's effort throughout the review process and the valuable feedback from the reviewers, which has been instrumental in revising and improving our paper, as well as guiding our ongoing research. We have carefully revised the manuscript, with all changes highlighted in yellow. Additionally, we have consolidated all original images, including Western blots and compact panels, into a single PDF file labeled "Raw Imaging," which contains the corresponding figure legends. Below, we outline the main corrections made to the manuscript and our responses to the reviewers’ comments:
感谢您来信以及审稿人对我们题为“BACH1 在滋养层细胞功能障碍和妊娠高血压发展中的作用:聚焦线粒体代谢和琥珀酰化修饰”的手稿(ID: 101655h)所提出的深刻意见。我们衷心感谢编辑在审稿过程中的努力以及审稿人提供的宝贵反馈,这对我们修订和改进论文以及指导我们正在进行的研究起到了重要作用。我们已仔细修订了手稿,所有更改均以黄色突出显示。此外,我们已将所有原始图像,包括 Western blot 和紧凑面板,整合到一个标记为“Raw Imaging”的 PDF 文件中,其中包含相应的图例。以下是我们对手稿所做的主要修正以及我们对审稿人意见的回应:
Comments (Reviewer 1):
评论(审稿人 1):
The structure of the article needs to be further condensed and organized. It is best to summarize the first part of informatics and the second part of clinical specimen analysis as preliminary work in the introduction.
文章的结构需要进一步精简和组织。最好在引言中将信息学的第一部分和临床标本分析的第二部分总结为初步工作。
Response: We sincerely apologize for the lack of clarity in the original structure of our manuscript and greatly appreciate your valuable suggestions, which have significantly enhanced its logical flow and readability. In response to your comments, and incorporating feedback from another reviewer suggesting the inclusion of a trophoblast-specific Bach1-overexpressing mouse model, we have reorganized the manuscript structure and made several key adjustments:
我们真诚地为我们手稿原始结构缺乏清晰性而道歉,并非常感谢您宝贵的建议,这些建议显著增强了其逻辑流畅性和可读性。针对您的评论,并结合另一位审稿人建议加入滋养层特异性 Bach1 过表达小鼠模型的反馈,我们已重新组织了手稿结构并进行了几项关键调整:
Incorporating bioinformatics and clinical analysis into the introduction
将生物信息学和临床分析纳入介绍中
Following your recommendation, we have summarized the bioinformatics analysis and clinical specimen results as preliminary findings and integrated them into the introduction section (page 5, lines 101–107). This provides a concise context for subsequent studies and improves the overall flow of the manuscript.
根据您的建议,我们已将生物信息学分析和临床标本结果总结为初步发现,并将其整合到引言部分(第 5 页,第 101-107 行)。这为后续研究提供了简明的背景,并改善了手稿的整体流畅性。
Reorganizing the manuscript structure
重新组织手稿结构
To present a clearer and more logical framework, we have restructured the manuscript into three main levels:
为了呈现一个更清晰和更合逻辑的框架,我们将手稿重组为三个主要层次:
Clinical Exploration: Identification of BACH1 expression patterns and its clinical relevance in PE through bioinformatics and clinical specimen analyses.
临床探索:通过生物信息学和临床标本分析识别 BACH1 表达模式及其在 PE 中的临床相关性。
In Vivo Studies: Establishing the causal relationship between Bach1 and PE, demonstrating that trophoblast-specific Bach1 overexpression during critical stages of placentation is a strong pathogenic factor for PE.
体内研究:建立 Bach1 与妊娠高血压(PE)之间的因果关系,证明在胎盘形成的关键阶段,滋养层特异性 Bach1 过表达是妊娠高血压的一个强致病因素。
In Vitro Mechanistic Investigations: Delving into the mechanisms of BACH1-induced PE, including its impact on trophoblast functions, mitochondrial bioenergetics, and integration of metabolomics with succinylation proteomics to uncover the underlying causes of PE development.
体外机制研究:深入探讨 BACH1 诱导的 PE 机制,包括其对滋养层细胞功能、线粒体生物能量学的影响,以及将代谢组学与琥珀酰化蛋白组学相结合,以揭示 PE 发展的潜在原因。
Adding an experimental workflow diagram
添加实验工作流程图
To further enhance the clarity of the manuscript, we have included a detailed experimental workflow diagram (Figure 1) to visually summarize the research design and logical flow of the study.
为了进一步增强手稿的清晰度,我们包含了一个详细的实验工作流程图(图 1),以直观地总结研究设计和研究的逻辑流程。
We hope these revisions improve the manuscript's clarity, logical structure, and overall readability. If you have further suggestions for adjustments, we would be more than happy to revise the manuscript again in accordance with your feedback. Thank you once again for your insightful comments.
我们希望这些修订能提高手稿的清晰度、逻辑结构和整体可读性。如果您有进一步的调整建议,我们将非常乐意根据您的反馈再次修订手稿。再次感谢您富有洞察力的评论。
It is recommended to only retain the cell part of the study. The introduction section should provide a detailed explanation of the purpose, significance, and innovative points of cell research, while the methods section should describe in detail the purpose and significance of each stage of the cell experiment.
建议仅保留研究的细胞部分。引言部分应详细说明细胞研究的目的、意义和创新点,而方法部分应详细描述细胞实验每个阶段的目的和意义。
Response: We greatly appreciate your recommendation to focus on the cell-based research, and we apologize for the lack of clarity in our manuscript structure, which may have led to the impression that the cell experiments were the primary focus of our study.
我们非常感谢您建议我们专注于基于细胞的研究,并对我们手稿结构不够清晰表示歉意,这可能导致了细胞实验是我们研究主要焦点的印象。
The other reviewer suggested supplementing trophoblast-specific BACH1 overexpression animal experiments to address the limitations of our previous systemic overexpression model. These newly added experiments significantly enhance the manuscript by specifically focusing on BACH1 dysregulation in trophoblasts, a critical driver of preeclampsia pathogenesis. Unlike systemic overexpression models, this trophoblast-specific model directly demonstrates that BACH1 dysregulation in trophoblasts is a primary driver of preeclampsia. These results are critical for bridging the gap between clinical observations and cell-based mechanistic studies. This not only strengthens the translational relevance of our findings but also establishes a robust foundation for the subsequent mechanistic investigations in trophoblast models.
另一位审稿人建议补充滋养层特异性 BACH1 过表达动物实验,以解决我们之前系统性过表达模型的局限性。这些新增加的实验通过专门关注滋养层中 BACH1 的失调,显著增强了手稿的质量,而 BACH1 的失调是妊娠高血压病理发生的关键驱动因素。与系统性过表达模型不同,这种滋养层特异性模型直接证明了滋养层中 BACH1 的失调是妊娠高血压的主要驱动因素。这些结果对于弥合临床观察与细胞基础机制研究之间的差距至关重要。这不仅增强了我们发现的转化相关性,还为后续在滋养层模型中的机制研究奠定了坚实的基础。
To address your suggestion, we have carefully reorganized the manuscript to emphasize the central role of cell-based studies while presenting the in vivo experiments as essential supportive evidence. The animal experimental results are now consolidated in Figure 3, whereas the systemic BACH1 overexpression data have been moved to the supplementary materials (Figures S2 and S3). This restructuring highlights the trophoblast-specific mechanisms underlying PE, ensuring the logical flow of the study.
为了回应您的建议,我们仔细重新组织了手稿,以强调基于细胞的研究的核心作用,同时将体内实验呈现为重要的支持证据。动物实验结果现在集中在图 3 中,而系统性 BACH1 过表达的数据已移至补充材料(图 S2 和 S3)。这种重组突出了与 PE 相关的滋养层特异性机制,确保了研究的逻辑流畅性。
Furthermore, in the Introduction, we have incorporated descriptions addressing the purpose, significance, and innovative aspects of our cell research (page 5-6, lines 108-120). The revised paragraph is as follows:
此外,在引言中,我们加入了关于我们细胞研究的目的、意义和创新方面的描述(第 5-6 页,第 108-120 行)。修订后的段落如下:
“Insufficient remodeling of uterine spiral arteries due to EVT dysfunction is a critical issue in PE development, emphasizing the need to understand the molecular mechanisms driving this dysfunction. This study systematically investigates the pivotal role of BACH1 in EVT dysfunction, emphasizing its molecular involvement in PE. Importantly, this research represents the comprehensive examination of BACH1’ s regulation of EVT biological functions, particularly its effects on mitochondrial metabolism and protein succinylation modification. Using primary EVTs and HTR8/SVneo cells, we elucidate the pivotal role of BACH1 in EVT dysfunction and PE progression. Moreover, this study explores the effect of trophoblast-specific overexpression of BACH1 on placentation and PE phenotypes in two distinct mouse models: an adenovirus system and a placental-targeted delivery system. Our findings provide new insights into PE pathology and identify BACH1 as a promising target for PE prediction and treatment, with significant clinical potential.”
“由于 EVT 功能障碍,子宫螺旋动脉重塑不足是 PE 发展的一个关键问题,强调了理解驱动这种功能障碍的分子机制的必要性。本研究系统地调查了 BACH1 在 EVT 功能障碍中的关键作用,强调了其在 PE 中的分子参与。重要的是,这项研究代表了对 BACH1 调节 EVT 生物功能的全面检查,特别是其对线粒体代谢和蛋白质琥珀酰化修饰的影响。通过使用原代 EVT 和 HTR8/SVneo 细胞,我们阐明了 BACH1 在 EVT 功能障碍和 PE 进展中的关键作用。此外,本研究探讨了 BACH1 在两个不同小鼠模型中对滋养层特异性过表达对胎盘形成和 PE 表型的影响:一种腺病毒系统和一种胎盘靶向递送系统。我们的发现为 PE 病理提供了新的见解,并将 BACH1 确定为 PE 预测和治疗的有前景的靶点,具有重要的临床潜力。”
Additionally, the Methods section has been updated to include relevant descriptions of the objectives and significance of the cell experiments. We appreciate your guidance in helping us strengthen our manuscript.
此外,方法部分已更新,以包括细胞实验的相关目标和重要性的描述。我们感谢您的指导,帮助我们加强我们的手稿。
We hope this revised structure successfully balances the suggestions from both reviewers and enhances the manuscript’ s overall coherence and impact. However, if you feel further adjustments are needed, particularly regarding the focus on cell-based research, we are more than willing to make additional revisions in accordance with your feedback. Thank you again for your thoughtful and valuable recommendations.
我们希望这个修订后的结构能够成功平衡两位审稿人的建议,并增强手稿的整体连贯性和影响力。然而,如果您认为需要进一步调整,特别是在关注细胞研究方面,我们非常愿意根据您的反馈进行额外的修订。再次感谢您深思熟虑和宝贵的建议。
The statistical analysis of clinical specimens should indicate whether the selection of cases in each group follow the principle of randomization.
临床标本的统计分析应表明每组病例的选择是否遵循随机化原则。
Response: We thank the reviewer for this valuable feedback regarding the statistical analysis of clinical specimens. In response, we have added a description confirming that case selection in each group follows a randomization principle. This update can be found on page 7, lines 144-148. Your suggestion has been instrumental in strengthening the rigor of our analysis. The revised paragraph is as follows:
我们感谢审稿人对临床标本统计分析的宝贵反馈。作为回应,我们添加了一段描述,确认每组的病例选择遵循随机化原则。此更新可以在第 7 页,第 144-148 行找到。您的建议对增强我们分析的严谨性起到了重要作用。修订后的段落如下:
“In the collected clinical samples, specimens were selected from each group using simple random sampling to ensure unbiased representation for subsequent experiments. Specifically, each specimen was assigned a unique identifier, and a random number generator was employed to select a predetermined number of specimens from each group.”
“在收集的临床样本中,使用简单随机抽样从每个组中选择标本,以确保后续实验的无偏代表性。具体而言,每个标本被分配一个唯一标识符,并使用随机数生成器从每个组中选择预定数量的标本。”
4.Add a flowchart to the methodology section to reflect the internal logic of the article design.
4. 在方法论部分添加一个流程图,以反映文章设计的内部逻辑。
Response: We appreciate the reviewer’s excellent suggestion to include a flowchart in the methodology section. In response, we have added a flowchart at the beginning of the Methods section to clearly illustrate the study’s design and internal logic (Figure 1). Your input has greatly improved the clarity of our manuscript. The flowchart is as follows:
我们感谢审稿人提出的优秀建议,在方法部分中加入流程图。作为回应,我们在方法部分的开头添加了一个流程图,以清晰地说明研究的设计和内部逻辑(图 1)。您的意见大大提高了我们手稿的清晰度。流程图如下:
Comments (Reviewer 2):
评论(审稿人 2):
Comment to author: In this manuscript, the authors reported the role of BACH1 in preeclampsia via affecting mitochondrial metabolism and succinylation modification. Several issues need to be addressed before publication can be recommended.
对作者的评论:在这篇手稿中,作者报告了 BACH1 在子痫前期中的作用,涉及线粒体代谢和琥珀酰化修饰。在推荐发表之前,需要解决几个问题。
Major
主要
1.In vivo, the authors used an intravenous injection of adenovirus carrying Bach1 (Ad-Bach1) into pregnant mice on GD 8.5 to establish a mouse model with Bach1 overexpression, and it would be better to validate some key experiments in EVTs-specific Bach1 knock-in mice.
1. 在体内,作者在妊娠第 8.5 天对怀孕小鼠进行携带 Bach1 的腺病毒(Ad-Bach1)静脉注射,以建立 Bach1 过表达的小鼠模型,并且在特定于 EVTs 的 Bach1 敲入小鼠中验证一些关键实验会更好。
Response: Thank you for your constructive suggestion to use EVTs-specific Bach1 knock-in mice. This approach effectively addresses the limitations of our systemic overexpression model and highlights the crucial role of trophoblast cells in preeclampsia, providing a solid foundation for subsequent mechanistic investigations. After conducting an in-depth review of the current literature, we found that the methods for placenta-specific gene editing include placental-targeted nanoparticles[1, 2], the use of placental-specific Cre recombinase (Tpbpa/Ada Cre) mice in combination with the floxed system[3], CRISPR/Cas9 gene editing with placental-specific promoters[4], and adenoviral transduction of mouse blastocysts followed by embryo transfer[5].
感谢您提出使用 EVTs 特异性 Bach1 敲入小鼠的建设性建议。这种方法有效地解决了我们系统性过表达模型的局限性,并突出了滋养层细胞在子痫前期中的关键作用,为后续的机制研究提供了坚实的基础。在对当前文献进行深入审查后,我们发现胎盘特异性基因编辑的方法包括胎盘靶向纳米颗粒[1, 2]、结合 floxed 系统使用胎盘特异性 Cre 重组酶(Tpbpa/Ada Cre)小鼠[3]、使用胎盘特异性启动子的 CRISPR/Cas9 基因编辑[4],以及小鼠胚泡的腺病毒转导后进行胚胎移植[5]。
Given these constraints, we have chosen to use a placental-targeted nanoparticle delivery system (plCSA-BP)[6], which our team has successfully employed in previous studies[7]. This innovative system utilizes synthetic placental chondroitin sulfate A-binding peptide (plCSA-BP) conjugated to nanoparticles. This approach specifically targets trophoblast cells, thereby avoiding interactions with other cell types or chondroitin sulfate-expressing cells in different tissues. Additionally, plCSA-BP has no adverse effects on maternal and fetal tissue, does not cross the placental barrier to enter the fetus, and does not accumulate in the fetus, with no significant fetal toxicity observed.
鉴于这些限制,我们选择使用一种靶向胎盘的纳米颗粒递送系统(plCSA-BP)[6],我们的团队在之前的研究中成功应用了该系统[7]。这一创新系统利用合成的胎盘软骨素硫酸盐 A 结合肽(plCSA-BP)与纳米颗粒结合。这种方法专门靶向滋养层细胞,从而避免与其他细胞类型或在不同组织中表达软骨素硫酸盐的细胞的相互作用。此外,plCSA-BP 对母体和胎儿组织没有不良影响,不会穿过胎盘屏障进入胎儿,也不会在胎儿中积累,未观察到显著的胎儿毒性。
We intravenously administered nanoparticles containing either a control plasmid (plCSA-vector) or a Bach1 overexpression plasmid (plCSA-Bach1) to pregnant mice on GD 8.5, 10.5, and 12.5. In vivo imaging demonstrated fluorescence signals in the uterine region within 30 minutes of injection, with no fluorescence detected in other tissues. Subsequent analysis confirmed that the fluorescence signals were exclusively localized to the placenta, with no signals in the fetus. On GD 18.5, immunofluorescence staining of placental tissue revealed co-localization of Bach1 with the trophoblast marker CK7, and a significant increase in Bach1 fluorescence in the plCSA-Bach1 group. This trophoblast-specific overexpression of Bach1 led to the induction of a PE-like phenotype, including a marked increase in blood pressure from GD 14.5 and decreased fetal and placental weights (Figure 3).
我们在妊娠第 8.5、10.5 和 12.5 天通过静脉注射了含有对照质粒(plCSA-vector)或 Bach1 过表达质粒(plCSA-Bach1)的纳米颗粒。体内成像显示,在注射后 30 分钟内,子宫区域出现荧光信号,而在其他组织中未检测到荧光。后续分析确认荧光信号仅局限于胎盘,胎儿中没有信号。在妊娠第 18.5 天,胎盘组织的免疫荧光染色显示 Bach1 与滋养层细胞标记物 CK7 的共定位,并且在 plCSA-Bach1 组中 Bach1 荧光显著增加。这种滋养层细胞特异性的 Bach1 过表达导致了类似 PE 的表型诱导,包括从妊娠第 14.5 天开始血压显著升高以及胎儿和胎盘重量减少(图 3)。
Compared to the adenovirus system, which may affect other tissues, the trophoblast-specific nanoparticle approach provides more convincing evidence. These results highlight that Bach1 overexpression in trophoblast cells contributes to PE development. This targeted nanoparticle system offers a reliable alternative for studying Bach1 in trophoblast dysfunction, closely mimicking its distribution in human placental tissue. We sincerely thank you again for your insightful feedback, which has significantly enhanced the quality of our manuscript.
与可能影响其他组织的腺病毒系统相比,滋养层特异性纳米颗粒方法提供了更有说服力的证据。这些结果强调了 Bach1 在滋养层细胞中过表达与 PE 发展之间的关系。该靶向纳米颗粒系统为研究滋养层功能障碍中的 Bach1 提供了可靠的替代方案,紧密模拟了其在人体胎盘组织中的分布。我们再次衷心感谢您富有洞察力的反馈,这显著提升了我们手稿的质量。
2.The authors showed that BACH1 worked by modulating succinylation modifications. Further experiments were needed to verify the function of BACH1 in PE after the treatment with succinylation inhibitors.
2. 作者们表明 BACH1 通过调节琥珀酰化修饰发挥作用。需要进一步实验来验证 BACH1 在琥珀酰化抑制剂处理后在 PE 中的功能。
Response: We greatly appreciate your insightful suggestion to further validate the function of BACH1 in preeclampsia through treatment with succinylation inhibitors. This suggestion significantly enhances the rigor of our study, providing a clear pathway to confirm that BACH1 modulates trophoblast cell biological functions through its influence on succinylation modifications. In response to the suggestion, we have conducted additional experiments to investigate the role of succinylation in mediating BACH1-induced trophoblast dysfunction.
我们非常感谢您提出的深刻建议,通过使用琥珀酰化抑制剂进一步验证 BACH1 在妊娠高血压中的功能。这个建议显著增强了我们研究的严谨性,为确认 BACH1 通过其对琥珀酰化修饰的影响调节滋养层细胞生物功能提供了明确的途径。针对这一建议,我们进行了额外的实验,以研究琥珀酰化在介导 BACH1 诱导的滋养层细胞功能障碍中的作用。
Through a comprehensive review of the literature, we identified that glycine can inhibit protein succinylation by reducing the supply of succinyl-CoA [8, 9]. To determine whether glycine could reverse BACH1 overexpression-induced trophoblast dysfunction by inhibiting succinylation, we performed rescue experiments by adding glycine to both the vector and OE-BACH1 groups of HTR8/SVneo cells.
通过对文献的全面审查,我们发现甘氨酸可以通过减少琥珀酰辅酶 A 的供应来抑制蛋白质琥珀酰化[8, 9]。为了确定甘氨酸是否可以通过抑制琥珀酰化逆转 BACH1 过表达引起的滋养层细胞功能障碍,我们对 HTR8/SVneo 细胞的载体组和 OE-BACH1 组进行了添加甘氨酸的救援实验。
Our results demonstrated that glycine treatment effectively reversed the impairments in cell proliferation, tube formation, and invasion caused by BACH1 overexpression (Figure 8). These findings further validate that BACH1 influences trophoblast biological functions by regulating the succinylation of downstream proteins.
我们的结果表明,甘氨酸处理有效逆转了 BACH1 过表达引起的细胞增殖、管道形成和侵袭的损伤(图 8)。这些发现进一步验证了 BACH1 通过调节下游蛋白的琥珀酰化影响滋养层细胞的生物功能。
We deeply appreciate the reviewer’s suggestion, as it has strengthened the mechanistic understanding of our study and provided additional evidence for the role of BACH1-mediated succinylation in the pathogenesis of PE.
我们非常感谢审稿人的建议,因为这增强了我们研究的机制理解,并为 BACH1 介导的琥珀酰化在 PE 发病机制中的作用提供了额外证据。
Minor
小型
Quantitative analysis of the images of immunofluorescence should be provided.
应提供免疫荧光图像的定量分析。
Response: Thank you for the valuable suggestion. We have added fluorescence intensity quantifications for all immunofluorescence images in the manuscript, including Figure 2N and Figure 3C, to enhance the accuracy and clarity of the data presentation.
感谢您的宝贵建议。我们已在手稿中为所有免疫荧光图像添加了荧光强度定量,包括图 2N 和图 3C,以提高数据呈现的准确性和清晰度。
In Figures 2H and 2I, scale bars should be added.
在图 2H 和 2I 中,应添加比例尺。
Response: Thank you for the suggestion. Scale bars have been added to Figures 2H and 2I as requested.
感谢您的建议。根据要求,已在图 2H 和 2I 中添加比例尺。
The authors should recheck the manuscript for grammar errors.
作者应重新检查手稿中的语法错误。
Response: Thank you for pointing this out. We have thoroughly reviewed the manuscript and corrected all grammatical errors to ensure clarity and accuracy. The manuscript has also been re-checked and revised by a native speaker to further ensure language quality.
感谢您指出这一点。我们已经彻底审查了手稿,并纠正了所有语法错误,以确保清晰和准确。手稿还经过了母语者的重新检查和修订,以进一步确保语言质量。
References
参考文献
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List of Changes:
变更列表:
Introduction:
介绍:
Condensed the bioinformatics and clinical sample findings as preliminary results (page 5, lines 101-107).
将生物信息学和临床样本的发现浓缩为初步结果(第 5 页,第 101-107 行)。
Added descriptions regarding the purpose, significance, and innovative aspects of the cellular research (pages 5-6, lines 108-120).
添加了关于细胞研究的目的、意义和创新方面的描述(第 5-6 页,第 108-120 行)。
Methods:
方法:
Included an experimental flowchart (Figure 1).
包含了一个实验流程图(图 1)。
Added descriptions addressing the significance and objectives of the cellular experiments.
添加了描述,阐明了细胞实验的重要性和目标。
Added a statement confirming that case selection in each group follows the principle of randomization (page 7, lines 144-148).
添加了一项声明,确认每组中的案例选择遵循随机化原则(第 7 页,第 144-148 行)。
Provided a detailed description of the synthesis method for trophoblast-targeted nanoparticles (page 11-12, lines 237-248).
提供了针对滋养层细胞靶向纳米颗粒的合成方法的详细描述(第 11-12 页,第 237-248 行)。
Included the method for constructing the trophoblast-specific BACH1 overexpression mouse model (page 12, lines 249-268).
包括了构建滋养层特异性 BACH1 过表达小鼠模型的方法(第 12 页,第 249-268 行)。
Results:
结果:
Moved the experimental flowchart to Figure 1.
将实验流程图移至图 1。
Figure 2 now includes fluorescence intensity quantification (Figure 2N).
图 2 现在包括荧光强度定量(图 2N)。
Added experimental results from the trophoblast-specific Bach1 overexpression mouse model (Figure 3).
添加了来自滋养层特异性 Bach1 过表达小鼠模型的实验结果(图 3)。
Moved data from the adenovirus system mouse model to supplementary materials (Figures S2, S3).
将腺病毒系统小鼠模型的数据移至补充材料(图 S2,S3)。
Added glycine rescue experiments for HTR8/SVneo cells in both the vector and OE-BACH1 groups (Figure 8B-8E).
在载体组和 OE-BACH1 组中增加了对 HTR8/SVneo 细胞的甘氨酸拯救实验(图 8B-8E)。
The Graphic Abstract is now included as Figure 9.
图形摘要现在作为图 9 包含在内。
Acknowledgments:
致谢:
Added acknowledgments to Professor Baozhen Zhang and Professor Gao (Page 38, Lines 820-824).
在第 38 页,第 820-824 行添加了对张宝珍教授和高教授的致谢。
General Corrections:
一般修正:
Conducted a thorough review of the manuscript to correct grammatical errors and make necessary revisions.
对手稿进行了全面审查,以纠正语法错误并进行必要的修订。
We sincerely thank the editor and the reviewers for your diligent efforts and constructive feedback throughout the review process. Your valuable insights have greatly enhanced our manuscript, and we truly appreciate the time and thoughtfulness you have dedicated to our work.
我们衷心感谢编辑和评审在整个审稿过程中所付出的辛勤努力和建设性反馈。您宝贵的见解极大地提升了我们的手稿,我们非常感激您为我们的工作所投入的时间和深思。
After careful consideration, we kindly request a revision of the author order, designating Lujia Sun as a co-first author (second position). Lujia Sun made substantial contributions during the revision process, including research design, conducting experiments, data analysis, and manuscript revision. Given these significant contributions, we believe that listing Lujia Sun as a co-first author more accurately reflects their involvement in the study. All authors have reached a consensus regarding this proposed change, and no conflicts of interest exist. Should this request not align with the editor’s requirements, we fully respect your decision.
经过仔细考虑,我们恳请对作者顺序进行修订,将 Lujia Sun 指定为共同第一作者(第二位)。Lujia Sun 在修订过程中做出了重要贡献,包括研究设计、进行实验、数据分析和手稿修订。鉴于这些重要贡献,我们认为将 Lujia Sun 列为共同第一作者更能准确反映他们在研究中的参与。所有作者已就这一提议达成共识,并且不存在利益冲突。如果该请求与编辑的要求不符,我们完全尊重您的决定。
We hope for your understanding and support in this matter. Should any further modifications be necessary, we are more than willing to make additional changes to further improve the manuscript.
我们希望您能理解和支持此事。如果需要进一步的修改,我们非常愿意进行额外的更改,以进一步改善手稿。
We look forward to your positive response and are grateful for your continued consideration.
我们期待您的积极回复,并感谢您持续的关注。
Sincerely yours,
诚挚的您,
Hongbo Qi
齐洪波
2025/01/27