{"title":"CpG Methylation of Receptor Activator NF-κB (RANK) Gene Promoter Region Delineates Senescence-Related Decrease of RANK Gene Expression.","authors":"Riko Kitazawa, Ryuma Haraguchi, Yuki Murata, Yuki Takaoka, Sohei Kitazawa","doi":"10.1267/ahc.24-00034","DOIUrl":"10.1267/ahc.24-00034","url":null,"abstract":"<p><p>While the rapid decrease in estrogen is well known as the main cause of postmenopausal osteoporosis in women, the precise pathogenesis of senile osteoporosis in the elderly regardless of gender is largely unknown. The age-related epigenetic regulation of receptor activator NF-κB (RANK) gene expression was investigated with the use of a high-passaged mouse osteoclast progenitor cell line, RAW264.7, as an <i>in vitro</i> model of aging. In the RAW264.7 cells after repeated passages, receptor RANK expression was downregulated, resulting in decreased soluble RANK ligand (sRANKL)-induced osteoclastogenesis, expression of tartrate-resistant acid phosphatase-5b (TRAcP) and cathepsin K (CTSK). Methylation-specific PCR and bisulfite mapping revealed hypermethylation of CpG-loci located in the RANK gene promoter in multiple-passaged cells. ICON probe-mediated <i>in situ</i> assessment of methylated-cytosine at the CpG loci revealed an increase in the percentage of methylated RAW264.7 cells in the RANK gene in a passage-dependent manner. Conversely, upon treatment with demethylating agent 5-aza-2-deoxycytidine (5-aza-dC), high-passaged RAW264.7 cells displayed restored expression of the RANK gene, osteoclastogenesis, TRAcP and CTSK. <i>Ex vivo</i> cultures of splenic macrophages from young (10.5 W) and aged (12 M) mice also showed that CpG methylation was predominant in the aged animals, resulting in reduced RANK expression and osteoclastogenesis. Reduced RANK expression by age-related accumulation of DNA methylation, albeit in a limited population of osteoclast precursor cells, might be, at least in part, indicative of low-turnover bone characteristic of senile osteoporosis.</p>","PeriodicalId":6888,"journal":{"name":"Acta Histochemica Et Cytochemica","volume":"57 4","pages":"137-147"},"PeriodicalIF":1.6,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11367149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Purinosomes and Purine Metabolism in Mammalian Neural Development: A Review","authors":"Seiya Yamada, Tomoya Mizukoshi, Ayaka Sato, Shin-ichi Sakakibara","doi":"10.1267/ahc.24-00027","DOIUrl":"https://doi.org/10.1267/ahc.24-00027","url":null,"abstract":"</p><p>Neural stem/progenitor cells (NSPCs) in specific brain regions require precisely regulated metabolite production during critical development periods. Purines—vital components of DNA, RNA, and energy carriers like ATP and GTP—are crucial metabolites in brain development. Purine levels are tightly controlled through two pathways: <i>de novo</i> synthesis and salvage synthesis. Enzymes driving <i>de novo</i> pathway are assembled into a large multienzyme complex termed the “purinosome.” Here, we review purine metabolism and purinosomes as spatiotemporal regulators of neural development. Notably, around postnatal day 0 (P0) during mouse cortical development, purine synthesis transitions from the <i>de novo</i> pathway to the salvage pathway. Inhibiting the <i>de novo</i> pathway affects mTORC1 pathway and leads to specific forebrain malformations. In this review, we also explore the importance of protein-protein interactions of a newly identified NSPC protein—NACHT and WD repeat domain-containing 1 (Nwd1)—in purinosome formation. Reduced Nwd1 expression disrupts purinosome formation, impacting NSPC proliferation and neuronal migration, resulting in periventricular heterotopia. Nwd1 interacts directly with phosphoribosylaminoimidazole–succinocarboxamide synthetase (PAICS), an enzyme involved in <i>de novo</i> purine synthesis. We anticipate this review will be valuable for researchers investigating neural development, purine metabolism, and protein-protein interactions.</p>\u0000<p></p>","PeriodicalId":6888,"journal":{"name":"Acta Histochemica Et Cytochemica","volume":"166 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141505499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yanan Wei, Si Cheng, Takehiro Tsukada, Kotaro Horiguchi, Yoko Fujiwara, Ken Fujiwara
{"title":"Expression of Retinaldehyde Dehydrogenases in the Pituitary Glands of Fetus and Adult Mice","authors":"Yanan Wei, Si Cheng, Takehiro Tsukada, Kotaro Horiguchi, Yoko Fujiwara, Ken Fujiwara","doi":"10.1267/ahc.24-00018","DOIUrl":"https://doi.org/10.1267/ahc.24-00018","url":null,"abstract":"</p><p>Retinoic acid (RA) plays a critical role in cell growth and tissue development. RA is synthesized from retinoids through oxidation processes by the retinaldehyde dehydrogenase (Raldh) family. However, the expression of <i>Raldhs</i> during pituitary development and the identification of <i>Raldh</i>-expressing cells in the adult pituitary have not been fully elucidated. Here, we performed <i>in situ</i> hybridization to localize the three Raldh isoforms (<i>Raldh1-3</i>) in fetal and adult mouse pituitary glands. The results showed that <i>Raldh2</i> expression was observed in Rathke’s pouch from embryonic day 13.5 (E13.5), and this expression was sustained in the anterior lobe of the pituitary primordium from E15.5 to E17.5. In contrast, <i>Raldh1</i> and <i>Raldh3</i> were rarely detectable. Real-time PCR analysis revealed that <i>Raldh2</i> was the predominant isoform expressed in the adult pituitary, although <i>Raldh1</i> was also expressed to a lesser extent. In the adult pituitary, <i>Raldh1</i>-expressing cells were primarily observed in the posterior lobe. <i>Raldh2</i>-expressing cells were found in the marginal cell layer and parenchyma of the anterior lobe and were immunopositive for aldolase C (folliculostellate cells), but not for anterior pituitary hormones. These results suggest that RA is an important regulatory factor in the functions of the pituitary throughout its development in mice.</p>\u0000<p></p>","PeriodicalId":6888,"journal":{"name":"Acta Histochemica Et Cytochemica","volume":"472 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141505502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Integrated Spatial Multi-Omics Study of Postmortem Brains of Alzheimer’s Disease","authors":"Yumiko Toyama, Takashi Nirasawa, Maho Morishima, Yuko Saito, Kazuhiro Irie, Shigeo Murayama, Masaya Ikegawa","doi":"10.1267/ahc.24-00025","DOIUrl":"https://doi.org/10.1267/ahc.24-00025","url":null,"abstract":"</p><p>Pathological hallmark of Alzheimer’s disease (AD) is characterized by the accumulation and aggregation of amyloid β (Aβ) peptides into extracellular plaques of the brain. Clarification of the process of how soluble Aβ starts to assemble into amyloid fibrils is an essential step in elucidating the pathogenesis of AD. In our previous study, Aβ proteoforms including full-length Aβ40 and Aβ42/43 with N- and C-terminal truncated forms were visualized in postmortem brains from AD patients with matrix-assisted laser desorption/ionization-based mass spectrometry imaging (MALDI-MSI). In this study, Aβ proteoforms were consistently visualized by an updated protocol, and uncharacterized peptides such as Aβ1-29 and Aβ10-40 in AD brains were also visualized. To decipher neurotoxic effects of Aβ in patients’ brains, here we integrate liquid chromatography tandem mass spectrometry (LC-MS/MS) based shotgun proteomics with laser microdissection (LMD) excised tissue samples as well as direct tissue imaging with MALDI-MSI. With this approach, we have highlighted dynamic alterations of microtubule associating proteins (MAPs) including MAP1A, MAP1B and MAP2 as well as AD dominant proteins including APP, UCHL1, SNCA, and APOE. Of note, as lipid dysregulation has been implicated with AD pathology, we have challenged to integrate proteomics and lipid imaging for AD and control brain tissue. Spatial multi-omics is also valid to uncover molecular pathology of white matter as well as grey matter and leptomeningeal area, for example, by visualizing heme in patients’ postmortem brains.</p>\u0000<p></p>","PeriodicalId":6888,"journal":{"name":"Acta Histochemica Et Cytochemica","volume":"166 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141505507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Immunohistochemical Study of Human Mitochondrial Ferritin in the Substantia Nigra Following Subarachnoid Hemorrhage","authors":"Shogo Takahata, Tomoko Kato, Daijiro Yanagisawa, Haruka Tsubaki, Zulzikry Hafiz Abu Bakar, Ken-ichi Mukaisho, Yasushi Itoh, Ikuo Tooyama","doi":"10.1267/ahc.24-00002","DOIUrl":"https://doi.org/10.1267/ahc.24-00002","url":null,"abstract":"</p><p>Mitochondrial ferritin (FtMt) is a novel ferritin that sequesters iron and plays a protective role against oxidative stress. FtMt shares a high homology with H-ferritin but is expressed only in the brain, heart, and testis. In the midbrain, FtMt expression is observed in the substantia nigra. FtMt plays a neuroprotective role in the pathology of neurodegenerative diseases such as Parkinson’s disease, where excessive iron induces oxidative stress, causing cell death. Herein, we investigated FtMt immunoreactivity in the brains of patients with subarachnoid hemorrhage (SAH). Double immunofluorescence labeling of tyrosine hydroxylase (TH) and FtMt showed high colocalization in the substantia nigra pars compacta (SNc) in control and SAH cases. However, in SAH cases, FtMt immunoreactivity was observed in some TH-negative neurons. Double immunofluorescence labeling of glial cell markers and FtMt showed no apparent colocalization. The number and ratio of FtMt-positive but TH-negative neurons significantly differed between the control and SAH groups. Prussian blue staining in SAH cases showed positive iron staining over a wide surface range and the substantia nigra. Thus, FtMt may be related to iron dynamics in the substantia nigra following subarachnoid hemorrhage.</p>\u0000<p></p>","PeriodicalId":6888,"journal":{"name":"Acta Histochemica Et Cytochemica","volume":"14 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140926714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Clinicopathological Significance and Prognostic Role of High Mobility Group Box 1 (HMGB1), Toll-Like Receptor (TLR) 2 and TLR4 in Breast Cancer","authors":"Reina Taguchi, Mio Yamaguchi-Tanaka, Kiyoshi Takagi, Ai Sato, Yasuhiro Miki, Minoru Miyashita, Takashi Suzuki","doi":"10.1267/ahc.24-00006","DOIUrl":"https://doi.org/10.1267/ahc.24-00006","url":null,"abstract":"</p><p>High-mobility group box 1 (HMGB1) functions as damage-associated molecular pattern (DAMPs), released into extracellular space during cellular stress. Extracellular HMGB1 act as signal molecules through Toll-like receptor (TLR) 2 or TLR4, exerting diverse functions in both normal cells and malignant cells including breast cancer. However, their comprehensive examination in breast cancer tissues is lacking. Thus, we immunolocalized them in 112 breast cancer tissues, correlating their immunoreactivity with clinicopathological parameters and clinical outcomes to clarify their significance in breast cancer. We demonstrated that nuclear HMGB1 immunoreactivity was correlated with tumor progression and longer disease-free survival. In contrast, TLR2 immunoreactivity was correlated with increased cell proliferation and shorter disease-free survival, dependent on cytoplasmic HMGB1 immunoreactivity. Additionally, TLR4 immunoreactivity correlated with chemoresistance, regardless of cytoplasmic HMGB1 immunoreactivity. It was therefore considered that TLR2 collaboratively contributed to breast cancer progression with HMGB1-DAMPs to become a worse prognostic factor. Meanwhile, TLR4 served as a worse prognostic factor associated with chemoresistance, irrespective of HMGB1.</p>\u0000<p></p>","PeriodicalId":6888,"journal":{"name":"Acta Histochemica Et Cytochemica","volume":"32 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140617689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Membrane-Targeted palGFP Predominantly Localizes to the Plasma Membrane but not to Neurosecretory Vesicle Membranes in Rat Oxytocin Neurons","authors":"Hirotaka Sakamoto, Ayumu Inutsuka","doi":"10.1267/ahc.24-00001","DOIUrl":"https://doi.org/10.1267/ahc.24-00001","url":null,"abstract":"</p><p>Recent advances in viral vector technology, specifically using adeno-associated virus (AAV) vectors, have significantly expanded possibilities in neuronal tracing. We have utilized the Cre/loxP system in combination with AAV techniques in rats to explore the subcellular localization of palmitoylation signal-tagged GFP (palGFP) in oxytocin-producing neurosecretory neurons. A distinctive branching pattern of single axons was observed at the level of the terminals in the posterior pituitary. Despite challenges in detecting palGFP signals by fluorescent microscopy, immunoelectron microscopy demonstrated predominant localization on the plasma membrane, with a minor presence on the neurosecretory vesicle membrane. These findings suggest that membrane-anchored palGFP may undergo exocytosis, translocating from the plasma membrane to the neurosecretory vesicle membrane. In this study, we observed characteristic axon terminal structures in the posterior pituitary of oxytocin neurons. This study indicates the importance of understanding the plasma membrane-specific sorting system in neuronal membrane migration and encourages future studies on the underlying mechanisms.</p>\u0000<p></p>","PeriodicalId":6888,"journal":{"name":"Acta Histochemica Et Cytochemica","volume":"27 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140602254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Pathophysiological Implications of Protein Lactylation in Pancreatic Epithelial Tumors","authors":"Tomoki Takata, Akihiro Nakamura, Hiroaki Yasuda, Hayato Miyake, Yoshio Sogame, Yuki Sawai, Michiyo Hayakawa, Kentaro Mochizuki, Ryuta Nakao, Takehiro Ogata, Hisashi Ikoma, Eiichi Konishi, Yoshinori Harada, Eigo Otsuji, Yoshito Itoh, Hideo Tanaka","doi":"10.1267/ahc.24-00010","DOIUrl":"https://doi.org/10.1267/ahc.24-00010","url":null,"abstract":"</p><p>Protein lactylation is a post-translational modification associated with glycolysis. Although recent evidence indicates that protein lactylation is involved in epigenetic gene regulation, its pathophysiological significance remains unclear, particularly in neoplasms. Herein, we investigated the potential involvement of protein lactylation in the molecular mechanisms underlying benign and malignant pancreatic epithelial tumors, as well as its role in the response of pancreatic cancer (PC) cells to gemcitabine. Increased lactylation was observed in the nuclei of intraductal papillary mucinous adenoma, non-invasive intraductal papillary mucinous carcinoma, and invasive carcinoma, in parallel to the upregulation of hypoxia-inducible factor-1α. This observation indicated that a hypoxia-associated increase in nuclear protein lactylation could be a biochemical hallmark in pancreatic epithelial tumors. The standard PC chemotherapy drug gemcitabine suppressed histone lactylation <i>in vitro</i>, suggesting that histone lactylation might be relevant to its mechanism of action. Taken together, our findings suggest that protein lactylation may be involved in the development of pancreatic epithelial tumors and could represent a potential therapeutic target for PC.</p>\u0000<p></p>","PeriodicalId":6888,"journal":{"name":"Acta Histochemica Et Cytochemica","volume":"45 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140582419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"C-C Chemokine 21-Expressing T-cell Zone Fibroblastic Reticular Cells, Abundant in Lymph Nodes, Are Absent in Cancer Lymphoid Stroma","authors":"Haruo Ohtani, Kazuhiko Matsuo, Kosuke Kitahata, Eiichi Sato, Takashi Nakayama","doi":"10.1267/ahc.23-00066","DOIUrl":"https://doi.org/10.1267/ahc.23-00066","url":null,"abstract":"</p><p>Cancer tissue generally possesses an immunosuppressive microenvironment. However, some cancers are associated with lymphoid stroma (i.e., a widely developed tertiary lymphoid structure). The T-cell zone (paracortex) of secondary lymphoid organs, particularly lymph nodes, is characterized by an abundance of T-cell zone fibroblastic reticular cells (TCZ-FRCs) that express C-C motif chemokine ligand 21 (CCL21) and smooth muscle actin (SMA). We analyzed the presence of TCZ-FRCs in 30 cases of carcinomas with lymphoid stroma of the breast, stomach, colon, tongue, and skin. Immunohistochemistry corroborated the abundance of CCL21<sup>+</sup> SMA<sup>+</sup> TCZ-FRCs in the normal lymph nodes. In sharp contrast, all 30 carcinomas with lymphoid stroma displayed no CCL21<sup>+</sup> SMA<sup>+</sup> TCZ-FRCs despite the affluence of T cells. Real-time reverse transcription polymerase chain reaction confirmed a marked decrease in the messenger ribonucleic acid expression of CCL21 and its receptor C-C motif chemokine receptor 7 in cancer lymphoid stroma compared to that in lymph nodes. Next, we analyzed the T cell phenotypes. The cancer lymphoid stroma demonstrated an abundance of CD3<sup>+</sup> CD62L<sup>−</sup> memory-type T cells, in contrast to the presence of CD3<sup>+</sup> CD62L<sup>+</sup> naïve- and central memory T cells in the T cell zone of lymphoid tissues. Our data demonstrated the following: 1) Cancer lymphoid stroma lacked TCZ-FRCs with abundance of more activated T cells than in lymph nodes and 2) these were common phenomena in cancer lymphoid stroma irrespective of the histological types and organs involved.</p>\u0000<p></p>","PeriodicalId":6888,"journal":{"name":"Acta Histochemica Et Cytochemica","volume":"14 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140582592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Effects of Corticosteroid Administration and Treadmill Exercise on Marrow Adipose Tissue and Trabecular Bone after Anterior Cruciate Ligament Reconstruction in Rats","authors":"Akinori Kaneguchi, Kaoru Yamaoka, Junya Ozawa","doi":"10.1267/ahc.23-00068","DOIUrl":"https://doi.org/10.1267/ahc.23-00068","url":null,"abstract":"</p><p>We aimed to investigate the effects of short-term corticosteroid administration after anterior cruciate ligament (ACL) reconstruction on marrow adipose tissue (MAT) and trabecular bone mass, as well as to examine whether treadmill exercise can mitigate MAT increase and trabecular bone deterioration caused by corticosteroid. ACL-reconstructed rats were divided into groups: no intervention, daily treadmill exercise (60 min/day), administration of the steroidal drug dexamethasone (250 μg/kg on days 0–5, 7, and 9 post-operatively), or dexamethasone administration combined with treadmill exercise. Untreated rats were served as controls. At day 10 or 30 post-operatively, histological assessments were performed in the proximal tibial epiphysis. MAT accumulation and trabecular bone loss were observed after ACL reconstruction. Dexamethasone promoted MAT accumulation at day 10 post-operatively but did not affect the trabecular bone loss. The MAT accumulation caused by dexamethasone reversed within 21 days after discontinuation. Treadmill exercise did not influence the changes in the MAT and trabecular bone areas. Short-term corticosteroid administration after ACL reconstruction promoted MAT accumulation while not affecting trabecular bone area. The MAT accumulation resulting from corticosteroid administration was reversible after discontinuation. Treadmill exercise could not mitigate the accumulation of MAT caused by corticosteroid administration and did not affect trabecular bone area.</p>\u0000<p></p>","PeriodicalId":6888,"journal":{"name":"Acta Histochemica Et Cytochemica","volume":"8 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139922105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}