Canonically PD-L1 functions as the inhibitory immune checkpoint on cell surface. Recent studies have observed PD-L1 expression in the nucleus of cancer cells. But the biological function of nuclear PD-L1 (nPD-L1) in tumor growth and antitumor immunity is unclear. Here we enforced nPD-L1 expression and established stable cells. nPD-L1 suppressed tumorigenesis and aggressiveness in vitro and in vivo. Compared with PD-L1 deletion, nPD-L1 expression repressed tumor growth and improved survival more markedly in immunocompetent mice. Phosphorylated AMPKα (p-AMPKα) facilitated nuclear PD-L1 compartmentalization and then cooperated with it to directly phosphorylate S146 of histone variant macroH2A1 (mH2A1) to epigenetically activate expression of genes of cellular senescence, JAK/STAT, and Hippo signaling pathways. Lipoic acid (LA) that induced nuclear PD-L1 translocation suppressed tumorigenesis and boosted antitumor immunity. Importantly, LA treatment synergized with PD-1 antibody and overcame immune checkpoint blockade (ICB) resistance, which likely resulted from nPD-L1-increased MHC-I expression and sensitivity of tumor cells to interferon-γ. These findings offer a conceptual advance for PD-L1 function and suggest LA as a promising therapeutic option for overcoming ICB resistance.
{"title":"Nuclear PD-L1 compartmentalization suppresses tumorigenesis and overcomes immunocheckpoint therapy resistance in mice via histone macroH2A1.","authors":"Yong Liu, Zhi Yang, Shuanglian Wang, Rui Miao, Chiung-Wen Mary Chang, Jingyu Zhang, Xin Zhang, Mien-Chie Hung, Junwei Hou","doi":"10.1172/JCI181314","DOIUrl":"10.1172/JCI181314","url":null,"abstract":"<p><p>Canonically PD-L1 functions as the inhibitory immune checkpoint on cell surface. Recent studies have observed PD-L1 expression in the nucleus of cancer cells. But the biological function of nuclear PD-L1 (nPD-L1) in tumor growth and antitumor immunity is unclear. Here we enforced nPD-L1 expression and established stable cells. nPD-L1 suppressed tumorigenesis and aggressiveness in vitro and in vivo. Compared with PD-L1 deletion, nPD-L1 expression repressed tumor growth and improved survival more markedly in immunocompetent mice. Phosphorylated AMPKα (p-AMPKα) facilitated nuclear PD-L1 compartmentalization and then cooperated with it to directly phosphorylate S146 of histone variant macroH2A1 (mH2A1) to epigenetically activate expression of genes of cellular senescence, JAK/STAT, and Hippo signaling pathways. Lipoic acid (LA) that induced nuclear PD-L1 translocation suppressed tumorigenesis and boosted antitumor immunity. Importantly, LA treatment synergized with PD-1 antibody and overcame immune checkpoint blockade (ICB) resistance, which likely resulted from nPD-L1-increased MHC-I expression and sensitivity of tumor cells to interferon-γ. These findings offer a conceptual advance for PD-L1 function and suggest LA as a promising therapeutic option for overcoming ICB resistance.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"134 22","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lung megakaryocytes (Mks) are a unique subset of Mks that are distinct from their bone marrow counterparts. Recent evidence suggests that lung Mks favor an immune phenotype, but have unclear contributions to the total platelet mass. In this issue of the JCI, Livada et al. used an array of complementary in vivo labeling and tracing models in mice to investigate a longstanding question of where lung Mks are derived. By combining these models with stressed conditions, the authors assessed the contribution of lung Mks to total platelet counts in a homeostatic and thrombocytopenic state. Mks were minor contributors to the circulating pool of platelets during homeostasis but increased output during thrombocytopenia. These findings add critical understanding to the development of lung Mks and demonstrate the dynamic potential of these specialized cells to respond to thrombocytopenia.
{"title":"The lung is a megakaryocyte outpost that can defend against thrombocytopenic attack.","authors":"Anthony K Yeung, George J Murphy","doi":"10.1172/JCI186111","DOIUrl":"10.1172/JCI186111","url":null,"abstract":"<p><p>Lung megakaryocytes (Mks) are a unique subset of Mks that are distinct from their bone marrow counterparts. Recent evidence suggests that lung Mks favor an immune phenotype, but have unclear contributions to the total platelet mass. In this issue of the JCI, Livada et al. used an array of complementary in vivo labeling and tracing models in mice to investigate a longstanding question of where lung Mks are derived. By combining these models with stressed conditions, the authors assessed the contribution of lung Mks to total platelet counts in a homeostatic and thrombocytopenic state. Mks were minor contributors to the circulating pool of platelets during homeostasis but increased output during thrombocytopenia. These findings add critical understanding to the development of lung Mks and demonstrate the dynamic potential of these specialized cells to respond to thrombocytopenia.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"134 22","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Genetics of hemostasis: from bedside to bench and back again.","authors":"David Ginsburg","doi":"10.1172/JCI183500","DOIUrl":"10.1172/JCI183500","url":null,"abstract":"","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"134 22","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Super chickens, givers, and collective intelligence: the importance of collaboration, teamwork, and mentorship in science.","authors":"Benjamin D Humphreys","doi":"10.1172/JCI187403","DOIUrl":"10.1172/JCI187403","url":null,"abstract":"","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"134 22","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Parkin, a ring-between-ring-type E3 ubiquitin ligase, first shown to play a critical role in autosomal recessive juvenile Parkinsonism, has recently emerged as a key player in cancer biology. Parkin is now known to serve as a tumor suppressor, and its deregulation frequently promotes tumorigenesis. In this issue of the JCI, Perego et al. expand that role by showing that Parkin expression stimulated an interferon (IFN) response to modulate CD8+ T cell activity. These findings suggest that, in addition to directly inhibiting tumor progression, Parkin enhances antitumor immune responses, highlighting it as a promising therapeutic target for cancer treatment.
{"title":"Parkin paves the path to antitumor immunity: Expanding Parkin's role as a tumor suppressor.","authors":"Hyungsoo Kim, Ze'ev A Ronai","doi":"10.1172/JCI185838","DOIUrl":"10.1172/JCI185838","url":null,"abstract":"<p><p>Parkin, a ring-between-ring-type E3 ubiquitin ligase, first shown to play a critical role in autosomal recessive juvenile Parkinsonism, has recently emerged as a key player in cancer biology. Parkin is now known to serve as a tumor suppressor, and its deregulation frequently promotes tumorigenesis. In this issue of the JCI, Perego et al. expand that role by showing that Parkin expression stimulated an interferon (IFN) response to modulate CD8+ T cell activity. These findings suggest that, in addition to directly inhibiting tumor progression, Parkin enhances antitumor immune responses, highlighting it as a promising therapeutic target for cancer treatment.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"134 22","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Proper embryo implantation is necessary for a successful pregnancy. In this issue of the JCI, Aljubran et al. identified the cell cycle regulatory protein cyclin A2 (CCNA2) as a factor in supporting embryo implantation and embryo development. Endometrial stromal cells showed higher levels of CCNA2 in patients undergoing assisted reproductive technology who had successful pregnancies. CCNA2 expression correlated with stromal cell proliferation and the expression of steroid hormone receptors for estrogen (ESR1, also known as ERα) and progesterone (PGR). Notably, loss of Ccna2 in mouse models resulted in infertility. The uteri of these mice were hypoplastic with reduced estrogen sensitivity, resulting in the disruption of stroma cell decidualization and loss of embryo viability after implantation. These findings demonstrate the importance of stroma cell proliferation in preparing the uterus for embryo implantation. They also identify CCNA2 as a coregulator of steroid hormone receptor signaling and suggest that impaired uterine stroma can underly early pregnancy loss.
{"title":"Cell-cycle machinery is critical in regulating uterine steroid hormone for embryo implantation and development.","authors":"Francesco J DeMayo","doi":"10.1172/JCI186194","DOIUrl":"10.1172/JCI186194","url":null,"abstract":"<p><p>Proper embryo implantation is necessary for a successful pregnancy. In this issue of the JCI, Aljubran et al. identified the cell cycle regulatory protein cyclin A2 (CCNA2) as a factor in supporting embryo implantation and embryo development. Endometrial stromal cells showed higher levels of CCNA2 in patients undergoing assisted reproductive technology who had successful pregnancies. CCNA2 expression correlated with stromal cell proliferation and the expression of steroid hormone receptors for estrogen (ESR1, also known as ERα) and progesterone (PGR). Notably, loss of Ccna2 in mouse models resulted in infertility. The uteri of these mice were hypoplastic with reduced estrogen sensitivity, resulting in the disruption of stroma cell decidualization and loss of embryo viability after implantation. These findings demonstrate the importance of stroma cell proliferation in preparing the uterus for embryo implantation. They also identify CCNA2 as a coregulator of steroid hormone receptor signaling and suggest that impaired uterine stroma can underly early pregnancy loss.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"134 22","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maryam Rezaei, Manqi Liang, Zeynep Yalcin, Jacinta H Martin, Parinaz Kazemi, Eric Bareke, Zhao-Jia Ge, Majid Fardaei, Claudio Benadiva, Reda Hemida, Adnan Hassan, Geoffrey J Maher, Ebtesam Abdalla, William Buckett, Pierre-Adrien Bolze, Iqbaljit Sandhu, Onur Duman, Suraksha Agrawal, JianHua Qian, Jalal Vallian Broojeni, Lavi Bhati, Pierre Miron, Fabienne Allias, Amal Selim, Rosemary A Fisher, Michael J Seckl, Philippe Sauthier, Isabelle Touitou, Seang Lin Tan, Jacek Majewski, Teruko Taketo, Rima Slim
To identify novel genes responsible for recurrent hydatidiform moles (HMs), we performed exome sequencing on 75 unrelated patients who were negative for mutations in the known genes. We identified biallelic deleterious variants in 6 genes, FOXL2, MAJIN, KASH5, SYCP2, MEIOB, and HFM1, in patients with androgenetic HMs, including a familial case of 3 affected members. Five of these genes are essential for meiosis I, and their deficiencies lead to premature ovarian insufficiency. Advanced maternal age is the strongest risk factor for sporadic androgenetic HM, which affects 1 in every 600 pregnancies. We studied Hfm1-/- female mice and found that these mice lost all their oocytes before puberty but retained some at younger ages. Oocytes from Hfm1-/- mice initiated meiotic maturation and extruded the first polar bodies in culture; however, their meiotic spindles were often positioned parallel, instead of perpendicular, to the ooplasmic membrane at telophase I, and some oocytes extruded the entire spindle with all the chromosomes into the polar bodies at metaphase II, a mechanism we previously reported in Mei1-/- oocytes. The occurrence of a common mechanism in two mouse models argues in favor of its plausibility at the origin of androgenetic HM formation in humans.
{"title":"Defects in meiosis I contribute to the genesis of androgenetic hydatidiform moles.","authors":"Maryam Rezaei, Manqi Liang, Zeynep Yalcin, Jacinta H Martin, Parinaz Kazemi, Eric Bareke, Zhao-Jia Ge, Majid Fardaei, Claudio Benadiva, Reda Hemida, Adnan Hassan, Geoffrey J Maher, Ebtesam Abdalla, William Buckett, Pierre-Adrien Bolze, Iqbaljit Sandhu, Onur Duman, Suraksha Agrawal, JianHua Qian, Jalal Vallian Broojeni, Lavi Bhati, Pierre Miron, Fabienne Allias, Amal Selim, Rosemary A Fisher, Michael J Seckl, Philippe Sauthier, Isabelle Touitou, Seang Lin Tan, Jacek Majewski, Teruko Taketo, Rima Slim","doi":"10.1172/JCI170669","DOIUrl":"10.1172/JCI170669","url":null,"abstract":"<p><p>To identify novel genes responsible for recurrent hydatidiform moles (HMs), we performed exome sequencing on 75 unrelated patients who were negative for mutations in the known genes. We identified biallelic deleterious variants in 6 genes, FOXL2, MAJIN, KASH5, SYCP2, MEIOB, and HFM1, in patients with androgenetic HMs, including a familial case of 3 affected members. Five of these genes are essential for meiosis I, and their deficiencies lead to premature ovarian insufficiency. Advanced maternal age is the strongest risk factor for sporadic androgenetic HM, which affects 1 in every 600 pregnancies. We studied Hfm1-/- female mice and found that these mice lost all their oocytes before puberty but retained some at younger ages. Oocytes from Hfm1-/- mice initiated meiotic maturation and extruded the first polar bodies in culture; however, their meiotic spindles were often positioned parallel, instead of perpendicular, to the ooplasmic membrane at telophase I, and some oocytes extruded the entire spindle with all the chromosomes into the polar bodies at metaphase II, a mechanism we previously reported in Mei1-/- oocytes. The occurrence of a common mechanism in two mouse models argues in favor of its plausibility at the origin of androgenetic HM formation in humans.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"134 22","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shuyan Tang, Ting Guo, Chengcheng Song, Lingbo Wang, Jun Zhang, Aleksandar Rajkovic, Xiaoqi Lin, Shiling Chen, Yujun Liu, Weidong Tian, Bangguo Wu, Shixuan Wang, Wenwen Wang, Yunhui Lai, Ao Wang, Shuhua Xu, Li Jin, Hanni Ke, Shidou Zhao, Yan Li, Yingying Qin, Feng Zhang, Zi-Jiang Chen
Although premature ovarian insufficiency (POI), a common cause of female infertility and subfertility, has a well-established hereditary component, the genetic factors currently implicated in POI account for only a limited proportion of cases. Here, using an exome-wide, gene-based case-control analysis in a discovery cohort comprising 1,027 POI cases and 2,733 ethnically matched women controls from China, we found that heterozygous loss-of-function (LoF) variants of MAX dimerization protein (MGA) were significantly enriched in the discovery cohort, accounting for 2.6% of POI cases, while no MGA LoF variants were found in the matched control females. Further exome screening was conducted in 4 additional POI cohorts (2 from China and 2 from the United States) for replication studies, and we identified heterozygous MGA LoF variants in 1.0%, 1.4%, 1.0%, and 1.0% of POI cases, respectively. Overall, a total of 37 distinct heterozygous MGA LoF variants were discovered in 38 POI cases, accounting for approximately 2.0% of the total 1,910 POI cases analyzed in this study. Accordingly, Mga+/- female mice were subfertile, exhibiting shorter reproductive lifespan and decreased follicle number compared with WT, mimicking the observed phenotype in humans. Our findings highlight the essential role of MGA deficiency for impaired female reproductive ability.
卵巢早衰(POI)是导致女性不孕和不育的常见原因之一,虽然它具有公认的遗传因素,但目前与 POI 有关的遗传因素只占病例的有限比例。在此,我们对由1027例POI病例和2733名来自中国的种族匹配女性对照组成的发现队列进行了基于基因的全外显子组病例对照分析,发现MAX二聚化蛋白(MGA)的杂合子功能缺失(LoF)变异在发现队列中明显富集,占POI病例的2.6%,而在匹配对照女性中未发现MGA LoF变异。我们在另外 4 个 POI 队列(2 个来自中国,2 个来自美国)中进行了进一步的外显子组筛查,以进行复制研究,结果发现分别有 1.0%、1.4%、1.0% 和 1.0% 的 POI 病例存在杂合 MGA LoF 变异。总之,在 38 个 POI 病例中总共发现了 37 个不同的杂合 MGA LoF 变异,约占本研究分析的 1,910 个 POI 病例的 2.0%。因此,与 WT 小鼠相比,Mga+/- 雌性小鼠生育力低下,生殖寿命缩短,卵泡数量减少,与人类观察到的表型相似。我们的研究结果突显了MGA缺乏对雌性生殖能力受损的重要作用。
{"title":"MGA loss-of-function variants cause premature ovarian insufficiency.","authors":"Shuyan Tang, Ting Guo, Chengcheng Song, Lingbo Wang, Jun Zhang, Aleksandar Rajkovic, Xiaoqi Lin, Shiling Chen, Yujun Liu, Weidong Tian, Bangguo Wu, Shixuan Wang, Wenwen Wang, Yunhui Lai, Ao Wang, Shuhua Xu, Li Jin, Hanni Ke, Shidou Zhao, Yan Li, Yingying Qin, Feng Zhang, Zi-Jiang Chen","doi":"10.1172/JCI183758","DOIUrl":"10.1172/JCI183758","url":null,"abstract":"<p><p>Although premature ovarian insufficiency (POI), a common cause of female infertility and subfertility, has a well-established hereditary component, the genetic factors currently implicated in POI account for only a limited proportion of cases. Here, using an exome-wide, gene-based case-control analysis in a discovery cohort comprising 1,027 POI cases and 2,733 ethnically matched women controls from China, we found that heterozygous loss-of-function (LoF) variants of MAX dimerization protein (MGA) were significantly enriched in the discovery cohort, accounting for 2.6% of POI cases, while no MGA LoF variants were found in the matched control females. Further exome screening was conducted in 4 additional POI cohorts (2 from China and 2 from the United States) for replication studies, and we identified heterozygous MGA LoF variants in 1.0%, 1.4%, 1.0%, and 1.0% of POI cases, respectively. Overall, a total of 37 distinct heterozygous MGA LoF variants were discovered in 38 POI cases, accounting for approximately 2.0% of the total 1,910 POI cases analyzed in this study. Accordingly, Mga+/- female mice were subfertile, exhibiting shorter reproductive lifespan and decreased follicle number compared with WT, mimicking the observed phenotype in humans. Our findings highlight the essential role of MGA deficiency for impaired female reproductive ability.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"134 22","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joseph R Trinko, Ethan Foscue, Edward M Kong, Aakash Basu, Anouk M Corstens, Summer L Thompson, Alfred P Kaye, Jane R Taylor, Ralph J DiLeone
{"title":"Xylazine induces dopamine release and augments the effects of fentanyl.","authors":"Joseph R Trinko, Ethan Foscue, Edward M Kong, Aakash Basu, Anouk M Corstens, Summer L Thompson, Alfred P Kaye, Jane R Taylor, Ralph J DiLeone","doi":"10.1172/JCI183354","DOIUrl":"10.1172/JCI183354","url":null,"abstract":"","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"134 22","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"It takes a village.","authors":"Alex D Waldman","doi":"10.1172/JCI188177","DOIUrl":"10.1172/JCI188177","url":null,"abstract":"","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"134 22","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}