Molecular human reproduction最新文献

{"title":"Aberrant progesterone receptor (PGR) expression is associated with estrogen receptor 1 (ESR1) expression in the endometrium from infertile women with endometriosis.","authors":"Sohyeon Yun, Soo Lim Kim, Eunhee M Jeong, Da-Hye Kang, Keun Cheon Kim, Tae Hoon Kim, Steve L Young, Bruce A Lessey, Jung-Yoon Yoo, Jae-Wook Jeong","doi":"10.1093/molehr/gaag006","DOIUrl":"10.1093/molehr/gaag006","url":null,"abstract":"<p><p>Estrogen receptor 1 (ESR1) and progesterone receptor (PGR) are essential regulators for endometrial receptivity and embryo implantation. Their expression is dysregulated in women with endometriosis-associated infertility. However, the relationship between ESR1 and PGR within the same endometrial cellular compartments has not been clearly defined. In this study, we examined ESR1 and PGR expression and their correlation in mid-secretory phase eutopic endometrium from fertile women without endometriosis (n = 9) and infertile women with endometriosis (n = 11) using immunohistochemistry and multiplex immunofluorescence. ESR1 levels were significantly reduced in endometrial stromal cells from infertile women with endometriosis compared to controls, and this attenuation of ESR1 was tightly associated with reduced PGR expression. In contrast, although epithelial PGR is normally downregulated in receptive mid-secretory phase endometrium, aberrant epithelial PGR overexpression was strongly correlated with epithelial ESR1 levels in infertile women with endometriosis. Multiplex immunofluorescence and AI-assisted single-cell quantitative analysis further confirmed a significant positive correlation between ESR1 and PGR in both stromal and epithelial compartments in the endometriosis group. These findings reveal compartment-specific dysregulation of ESR1 and PGR expression and identify aberrant ESR1-PGR co-expression as a potential molecular feature of a non-receptive eutopic endometrium in endometriosis-associated infertility, underscoring the importance of disrupted steroid hormone signaling in impaired implantation.</p>","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13233088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146125737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"What we could not have known: ovarian cycles, follicle development, and the signature of life.","authors":"Teresa K Woodruff","doi":"10.1093/molehr/gaag010","DOIUrl":"10.1093/molehr/gaag010","url":null,"abstract":"<p><p>Reproductive science is a discipline of generation and for generations. Our work has focused on the signals that drive reproductive cycles at the organismal and the organ level. The principal endocrine signals of male and female reproductive cycles include inhibin and activin, traditional peptide hormones, and at the cellular level, zinc, a workhorse element now elevated to the role of a signal on par with phosphate and calcium. Our studies relied on and built technologies to make our discoveries, including enzymatic sequencing and PCR, alginate beads and microfluidics, and sophisticated elemental imaging and quantitation. Taken together, we described the molecular basis of negative feedback by inhibin in the ovary, engineered ex vivo environments for ovarian follicle development, and discovered the first external signal of a new organism, the zinc spark. Some of this work is being applied to patients who are in danger of losing their fertility in a variety of settings, including during cancer care, a medical field called oncofertility. Advances in reproductive science beckon us to see ourselves in the future, and with the discoveries described here, our view extends further.</p>","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":"32 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13017053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147458777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Butyric acid-based self-assembling nanoparticles: a potential strategy to prevent development of polycystic ovary syndrome.","authors":"Nanoka Sakaguchi, Akari Kusamoto, Miyuki Harada, Babita Shashni, Airi Komura, Ayaka Teshima, Tsurugi Tanaka, Hiroshi Koike, Zixin Xu, Yuma Kawahara, Chihiro Tsuchida, Chisato Kunitomi, Nozomi Takahashi, Yoko Urata, Osamu Wada-Hiraike, Yasushi Hirota, Yukio Nagasaki, Yutaka Osuga","doi":"10.1093/molehr/gaag013","DOIUrl":"10.1093/molehr/gaag013","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age and cannot currently be cured or prevented fundamentally. Prenatal androgen exposure is a key factor in PCOS development, and both PCOS patients and animal models exhibit gut microbiota alterations. We previously demonstrated that prenatally androgenized (PNA) model mice display changes of gut microbiota before the manifestation of PCOS phenotypes, suggesting that an intervention targeting gut microbiota from the early stage of life can prevent development of PCOS. Butyric acid, a short-chain fatty acid produced by bacteria in the intestines, has various physiological effects. We investigated whether butyric acid could prevent PCOS phenotypes in PNA mice when administered from the early stage of life as a nanoparticle-based donor. We have developed butyric acid-based self-assembling nanoparticles (BNP), which release butyric acid in a sustained manner when exposed to digestive enzymes so that butyrate is delivered to the intestines. Control and PNA offspring were administered water containing or lacking BNP from just after weaning until 20 weeks of age. Reproductive and metabolic phenotypes were compared among these offspring (n = 10-14 for each group). Administration of BNP normalized irregular estrus cyclicity and improved the polycystic ovarian morphology, as evidenced by smaller numbers of atretic follicles in PNA offspring. Regarding metabolic phenotypes, administration of BNP improved hypertrophy of adipocytes and insulin resistance. Furthermore, analysis of the gut microbiota suggested that these primary effects were caused by butyrate itself, with an increase in certain butyrate-producing bacteria supporting this mechanism. The present findings indicate that administration of butyric acid to PNA offspring, which are at high risk of developing PCOS, from the early stage of life effectively prevents development of PCOS phenotypes at reproductive ages. Further exploration is necessary to clarify the mechanism by which butyric acid prevents development of PCOS.</p>","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13016983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147317716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Orosomucoid 2 improves reproductive phenotypes in a mouse model of PCOS induced by letrozole under high-fat diet conditions.","authors":"Qiuyu Xu, Shuwen Qiu, Li Wang, Yali Liu, Yan Lu, Ling Wu, Jie Zhang","doi":"10.1093/molehr/gaag005","DOIUrl":"10.1093/molehr/gaag005","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is the most common reproductive endocrine disorder among women of reproductive age. It is characterized by excess androgens, anovulation, and polycystic ovarian morphology, and is often accompanied by obesity, insulin resistance, and glucose metabolism abnormalities. Although PCOS is a complex disease with diverse and uncertain etiologies, metabolic dysfunction and adipose tissue abnormalities are critical components in its pathology. Previous studies have demonstrated that letrozole exposure combined with high-fat diet treatment in female mice produced key endocrine and metabolic features of PCOS, including elevated testosterone levels, anovulation, and adipocyte hypertrophy. Orosomucoid 2 (ORM2), an acute-phase protein predominantly secreted by hepatocytes, plays a regulatory role in metabolic balance and gut microbiota composition. This study aimed to investigate the effects of ORM2 levels on the metabolic and endocrine dysregulations associated with letrozole-induced PCOS in female mice. We established a letrozole-induced PCOS by treating mice with Let+HFD (letrozole and high-fat diet) for 5 weeks. Our findings revealed that compared to control females receiving placebo and high-fat diet treatment, females treated with Let+HFD exhibited significantly reduced hepatic Orm2 expression. Furthermore, Orm2 knockout mice subjected to Let+HFD treatment developed more severe ovarian pathology, higher testosterone levels, hepatocyte hypertrophy, and reduced Ucp1 expression in white adipose tissue compared to wild-type mice. Conversely, supplementation with recombinant ORM2 protein in females under Let+HFD treatment resulted in improved ovarian morphology, reduced hepatocyte cell size, and enhanced Ucp1 expression in white adipose tissue. Overall, this research identifies ORM2 as a promising therapeutic target for PCOS treatment.</p>","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146125818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MHR: the first 30 years.","authors":"Michele Boiani","doi":"10.1093/molehr/gaag008","DOIUrl":"https://doi.org/10.1093/molehr/gaag008","url":null,"abstract":"","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":"32 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147348751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preeclampsia 2.0: limitations and challenges of the two-stage hypothesis, and beyond.","authors":"Berthold Huppertz","doi":"10.1093/molehr/gaag001","DOIUrl":"10.1093/molehr/gaag001","url":null,"abstract":"<p><p>The pregnancy-specific syndrome preeclampsia remains the syndrome of hypotheses. Still, there is not a single hypothesis explaining the etiology of the full spectrum of preeclampsia. This has direct consequences for the clinical management of the syndrome. So far, no single early biomarker has been identified to predict all women who will develop preeclampsia later in pregnancy. Similarly, no preventive treatment for all types of preeclampsia has been integrated into clinical routine. Interestingly, the last decade has not seen much progress in the quest of identifying the pathophysiological processes resulting in the clinical syndrome preeclampsia. This could be due to the following: (i) the preeclampsia definition has been immensely altered and widened to include a large variety of clinical subgroups; and/or (ii) scientists and clinicians still adhere to the already challenged two-stage hypothesis and give only little room for new hypotheses. These two reasons could have thwarted the deciphering of the etiology of preeclampsia. This review will describe the limitations and challenges of the two-stage hypothesis. It will also highlight some of the new ideas and theories that have been put forward. In conclusion, there is an urgent need for new concepts that allow a better explanation of the diversity of preeclampsia regarding symptoms and time of occurrence. This in turn will result in more options to develop specific predictive biomarkers and personalized treatment options.</p>","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12820888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145912229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stage-dependent sphingosine-1-phosphate pathway modulation as a therapeutic strategy in a murine model of adenomyosis.","authors":"Marlyne Squatrito, Silvia Blacher, Julie Vervier, Laëtitia Bernet, Alessandra Camboni, Marie-Madeleine Dolmans, Carine Munaut","doi":"10.1093/molehr/gaag009","DOIUrl":"10.1093/molehr/gaag009","url":null,"abstract":"<p><p>Adenomyosis is characterized by chronic inflammation, myometrial remodeling, and subfertility, yet therapeutic options that preserve reproductive potential remain limited. Sphingosine-1-phosphate (S1P) signaling regulates immune-cell trafficking, vascular remodeling, and tissue invasion, but its contribution to adenomyosis remains poorly defined. This study investigated the temporal regulation of this pathway in a tamoxifen-induced murine model of adenomyosis and evaluated whether its pharmacological inhibition alters uterine immune profiles and lesion severity. A total of 122 female CD1 mice were used (79 adenomyosis, 43 control). Preventive treatment (with FTY720) started at weaning, while therapeutic interventions (with FTY720 and SKI-5C) were initiated at 6 weeks. Outcomes included body/uterine weight, lesion prevalence, grading and depth, immune-cell phenotyping by flow cytometry, and uterine expression of inflammatory, angiogenic, and invasion-associated genes. Early disease (at 4 weeks) was marked by increased expression of S1PR1/2 and downregulation of SGPL, while established disease (at 12 weeks) showed that S1PR1 remained elevated with additional upregulation of SPHK1 and S1PR4. Preventive FTY720 reduced lesion depth and grade, whereas therapeutic SKI-5C decreased lesion prevalence and invasion. Uterine weight remained reduced across adenomyosis groups and was not restored by treatment. Immune profiling revealed no major differences in total T-cell abundance between the control and adenomyosis groups. However, SKI-5C treatment was associated with the most pronounced modulation of uterine immune cells, particularly affecting T- and NK-cell-related subsets. Gene expression analyses demonstrated increased interleukin-6 in early disease and modulation of urokinase-type plasminogen activator associated with the treatments. Study limitations included constraints related to immune-cell recovery from uterine tissue, the relatively short duration of treatment, and translational differences between murine and human adenomyosis. Overall, these findings indicate that S1P signaling contributes to immune microenvironment remodeling and lesion progression in adenomyosis. These results support S1P pathway modulation as a promising therapeutic strategy meriting evaluation in human studies.</p>","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146207299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SARS-CoV-2 infects human primary cytotrophoblasts mainly through a non-canonical entry route.","authors":"Hélène Pinatel, Marie-Eve Brien, Mathilde Broquière, Marie-Pier Scott-Boyer, Arnaud Droit, Sylvie Girard, Géraldine Delbès, Laurent Chatel-Chaix, Cathy Vaillancourt","doi":"10.1093/molehr/gaag015","DOIUrl":"10.1093/molehr/gaag015","url":null,"abstract":"<p><p>Since the beginning of the COVID-19 pandemic, vulnerable populations such as pregnant persons have been at higher risk of severe symptoms and poor outcomes. Although reports of SARS-CoV-2 vertical transmission remain rare, several studies showed that maternal infection during pregnancy can induce histomorphological and inflammatory alterations in the placenta. However, the permissiveness of human trophoblasts to various variants of the virus remains poorly characterized. In this study, human primary villous cytotrophoblasts isolated from term placentas, along with trophoblastic cell lines BeWo, JEG-3, and HIPEC-65 were infected with the ancestral SARS-CoV-2 strain, which disseminated worldwide in early 2020. Permissiveness was assessed with quantitative RT-PCR, immunostaining of viral protein Nucleocapsid, and plaque assays. To investigate viral entry routes, cells were treated with Camostat mesylate (an inhibitor of the co-entry factor TMPRSS2) or chloroquine phosphate (an endosomal entry inhibitor) and viral fitness was assessed by plaque assays. Primary villous cytotrophoblasts and JEG-3 cells were also tested for infection with three pre-omicron SARS-CoV-2 variants of concern. Our results show that primary villous cytotrophoblasts are permissive to all tested SARS-CoV-2 strains in vitro. Infection with the ancestral SARS-CoV-2 strain relies mainly on a non-canonical endosomal entry pathway. Notably, JEG-3 cells represent an appropriate and convenient model for studying trophoblast infection by SARS-CoV-2, as they exhibit high permissiveness to the ancestral strain, and the SARS-CoV-2 entry pathway is similar to that in villous cytotrophoblasts. Overall, this study reveals that the cytotrophoblastic permissiveness to SARS-CoV-2 depends on the viral genetic nature and provides new insights into its entry route in human trophoblasts.</p>","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13019026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147307801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Variable partition of non-homogeneous ooplasm sets the stage for divergent potency of 2-cell stage blastomeres.","authors":"Thomas Nolte, Reza Halabian, Steffen Israel, Yutaka Suzuki, Hannes C A Drexler, Wojciech Makalowski, Georg Fuellen, Michele Boiani","doi":"10.1093/molehr/gaag004","DOIUrl":"10.1093/molehr/gaag004","url":null,"abstract":"<p><p>Following fertilization in mice and humans, the first two blastomeres are not equivalent, but one produces more epiblast than the other (imbalance); therefore, they do not feature equal totipotency. Research into the causes has overlooked that the epiblast imbalance is preceded by a fertilization imbalance, since in nature, the spermatozoon fertilizes the oocyte preferentially in the animal hemisphere near the animal-vegetal midline (equator). We conceived a hypothesis that the two imbalances are linked to each other, and broke it down into testable predictions. If the two imbalances were interdependent, then changing the site of sperm entry into the oocyte should change the extent of the epiblast imbalance. Thus, we evened out the fertilization imbalance, using ICSI to fertilize mouse oocytes also in the vegetal hemisphere and the equator. Resultant embryos were split at the 2-cell stage, and the twin blastocysts originating from the sister blastomeres were analyzed. Against the similarity in mRNA levels of epiblast genes, twin blastocysts differed in epiblast function, as measured by NANOG protein expression and derivation of embryonic stem cells, and the epiblast imbalance was greater after oocyte fertilization at the equator. There is no simple way to explain the positional effect other than through differences in the molecular composition of the ooplasm, which, moreover, should also be apportioned variably at the first zygotic division. We tested these predictions by measuring the orientation of the first zygotic division regarding the ICSI site, and the composition of bisected oocytes' hemispheres using half-cell proteomics. Since we found that the hemispheres have different compositions depending on the bisection axis, and the angle of the first division is variable, we propose that the variable partition of non-homogeneous ooplasm sets the stage for the epiblast imbalance. These results revive the role of the oocyte's molecular architecture on embryogenesis in a mammalian species hitherto considered mostly regulative in development.</p>","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13098151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mechanisms of ovarian fibrosis.","authors":"Beyza Gaye Edepli, Aylin Yaba","doi":"10.1093/molehr/gaaf058","DOIUrl":"10.1093/molehr/gaaf058","url":null,"abstract":"<p><p>Ovarian fibrosis is increasingly recognized as a pivotal factor contributing to ovarian ageing, dysfunction, and female infertility. It results from chronic or repetitive ovarian injury, such as that caused by repeated ovulation, which induces inflammation and excessive extracellular matrix (ECM) deposition, predominantly by activated fibroblasts and myofibroblasts. The key molecular pathways driving ovarian fibrosis include transforming growth factor-beta (TGF-β)/Smad signalling, Wnt/β-catenin, and PI3K/Akt pathways, which orchestrate fibroblast activation, ECM remodelling, and tissue stiffening. Elevated collagen types I and III, fibronectin, and hyaluronan characterize the fibrotic ovarian stroma, disrupting normal folliculogenesis and steroidogenesis. Ovarian fibrosis is also implicated in reproductive pathologies such as polycystic ovary syndrome, premature ovarian insufficiency and endometriosis, and may contribute to an increased risk of ovarian cancer, although definitive causal links require further elucidation. Current therapeutic strategies remain largely experimental, focusing on antifibrotic agents such as pirfenidone, TGF-β inhibitors, and modulation of oxidative stress, alongside emerging interventions such as stem cell therapies, which are offer potential avenues for intervention in the ovary. This review synthesizes current insights into the cellular and molecular mechanisms driving ovarian fibrosis, its association with reproductive disorders, and emerging therapeutic strategies. It underscores key knowledge gaps and emphasizes the need for future research focused on fibroblast activation, inflammatory signalling, and immune-ECM interactions to facilitate the development of targeted, long-term interventions aimed at preventing or reversing ovarian fibrosis and preserving female fertility.</p>","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12776365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145636011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}