American Journal of Pathology最新文献

The American Journal of Pathology Launches the Liver Pathobiology Topic Category. 美国病理学杂志推出肝脏病理生物学主题类别。

IF 4.9 2区医学

American Journal of Pathology Pub Date : 2026-10-27 DOI: 10.1016/j.ajpath.2026.10.005

Martha B Furie, William B Coleman, Wen-Xing Ding, Xiao-Ming Yin

引用次数: 0

Effects of Prolonged SARS-CoV-2 Spike Protein Exposure in Long COVID and a Mouse Model of the Disease. 长时间暴露于SARS-CoV2刺突蛋白对长COVID和该疾病小鼠模型的影响

IF 4.9 2区医学

American Journal of Pathology Pub Date : 2026-10-20 DOI: 10.1016/j.ajpath.2026.09.009

Gerard Nuovo, Jeffrey Laurence, Esmerina Tili, Xing Li, Cynthia Magro

{"title":"Effects of Prolonged SARS-CoV-2 Spike Protein Exposure in Long COVID and a Mouse Model of the Disease.","authors":"Gerard Nuovo, Jeffrey Laurence, Esmerina Tili, Xing Li, Cynthia Magro","doi":"10.1016/j.ajpath.2026.09.009","DOIUrl":"10.1016/j.ajpath.2026.09.009","url":null,"abstract":"The question of whether the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein persists in angiotensin converting-enzyme 2-positive (ACE2+) endothelia in the central nervous system (CNS)/other sites and induces a prolonged microvasculature injury syndrome was addressed. People who died of COVID-19, with age-matched controls, and people with long COVID with symptoms persisting from 1 to 5 years, with controls of people who had recovered from COVID-19, were studied. Also compared were wild-type mice injected with the spike protein euthanized at day 5 versus 1.5 months. The ACE2+ microvasculature density in the CNS increased 19-fold in the mice exposed to spike protein for 1.5 months. Human fatal COVID-19 cases exhibited an ACE2+ CNS density of 13.2/3.9 versus 2.1/0.9 for the controls. Long COVID cases showed an ACE2 microvasculature density of 11.9/3.0 versus 3.5/0.9 for the people who recovered from COVID (each, P < 0.001). Viral spike microvasculature density in the CNS was similar in the fatal COVID-19 cases (6.9/2.1) and mice (7.0/4.0) and in the skin of long COVID cases (6.0/1.9) and less in people who recovered from COVID-19 (0.9/0.3) (each, P < 0.001). Microvasculature collagen I deposition was only evident in fatal COVID-19, long COVID, and in the mice exposed to the S1 subunit for 1.5 months. Thus, SARS-CoV-2 spike (S1) protein can persist for months to years with an associated microvasculature pro-inflammatory state and a restrictive fibrosing microangiopathy, and exposure to high-dose S1 markedly increases ACE2 endothelial density.","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149226981","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}

引用次数: 0

Potassium Channel Tetramerization Domain-Containing 10 Modulates Dextran Sodium Sulfate-Induced Ulcerative Colitis via Regulating Intestinal Stem Cell Function. KCTD10通过调节肠道干细胞功能调节dss诱导的溃疡性结肠炎。

IF 4.9 2区医学

American Journal of Pathology Pub Date : 2026-10-20 DOI: 10.1016/j.ajpath.2026.10.004

Daoyuan Wang, Yihui Xiao, Jing Zhang, Cong Ding, Zhuan Li, Kaiqun Ren

{"title":"Potassium Channel Tetramerization Domain-Containing 10 Modulates Dextran Sodium Sulfate-Induced Ulcerative Colitis via Regulating Intestinal Stem Cell Function.","authors":"Daoyuan Wang, Yihui Xiao, Jing Zhang, Cong Ding, Zhuan Li, Kaiqun Ren","doi":"10.1016/j.ajpath.2026.10.004","DOIUrl":"10.1016/j.ajpath.2026.10.004","url":null,"abstract":"The incidence of inflammatory bowel disease (IBD) continues to increase annually, which severely threatens public health. Although estimates indicate that current therapies cause a 30% IBD clinical treatment failure, the precise pathogenesis remains unclear. Here, it was found that a key embryonic development regulator, potassium channel tetramerization domain-containing 10 (KCTD10), is correlated with the severity of IBD. Enhanced KCTD10 expression was observed during enterocolitis. Intestinal epithelial cell-specific knockout of KCTD10 in mice impaired intestinal epithelial barrier function, activated intestinal adaptive immune response, and disrupted intestinal homeostasis. Furthermore, in a dextran sodium sulfate-induced ulcerative colitis model, intestinal epithelial cell deletion of KCTD10 exacerbated colonic inflammation and impaired postinjury repair. Mechanistically, KCTD10 deletion down-regulated intestinal stem cell marker genes and affected their function. Importantly, KCTD10 stabilizes the transcription factor ATOH1 by regulating its ubiquitination, thereby determining the fate of intestinal progenitor cells derived from leucine-rich repeat-containing G-protein-coupled receptor 5+ intestinal stem cells. The data thus revealed a previously undescribed function of KCTD10 in modulating ulcerative colitis by regulating intestinal stem cell function.","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149227019","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}

引用次数: 0

Peroxin 16 Absence-Associated Hepatocyte Proliferation Is Mediated by Farnesoid X Receptor but Suppressed by Peroxisome Proliferator-Activated Receptor α. PEX16缺失相关的肝细胞增殖由FXR介导，但被PPARα抑制。

IF 4.9 2区医学

American Journal of Pathology Pub Date : 2026-10-13 DOI: 10.1016/j.ajpath.2026.10.002

Xue Chen, Anna Mazur, Krista L Denning, George K Acquaah-Mensah, Thao Thi Nguyen, Wei Xu, Long Wang, Zhongjiao Chen, Maafi R Islam, Wei Li, William Galloway, Jun Fan, James Denvir, Logan Marshall Lawrence, Trudy Atuahene, Subha Arthur, Abdelnaby Khalyfa, Xiaodong Wang, Yongke Lu

{"title":"Peroxin 16 Absence-Associated Hepatocyte Proliferation Is Mediated by Farnesoid X Receptor but Suppressed by Peroxisome Proliferator-Activated Receptor α.","authors":"Xue Chen, Anna Mazur, Krista L Denning, George K Acquaah-Mensah, Thao Thi Nguyen, Wei Xu, Long Wang, Zhongjiao Chen, Maafi R Islam, Wei Li, William Galloway, Jun Fan, James Denvir, Logan Marshall Lawrence, Trudy Atuahene, Subha Arthur, Abdelnaby Khalyfa, Xiaodong Wang, Yongke Lu","doi":"10.1016/j.ajpath.2026.10.002","DOIUrl":"10.1016/j.ajpath.2026.10.002","url":null,"abstract":"Peroxisomal β-oxidation processes substrate that mitochondria cannot handle. For example, C27 bile acid intermediates are subjected to β-oxidation to form C24 bile acids in peroxisomes rather than in mitochondria. Peroxisome proliferation is regulated by peroxisome proliferator-activated receptor α (PPARα), which is mediated by peroxisome membrane protein peroxin 16 (PEX16). Hepatocyte-specific PEX16-deficient (Pex16Alb-Cre) mice exhibit up-regulated PPARα signaling and display hepatocyte proliferation. It is unclear how hepatocytes proliferate in Pex16Alb-Cre mice. In this study, Pex16Alb-Cre mice were treated with the PPARα agonist WY-14,643 and the intestinal bile acid sequestrant cholestyramine. In addition to these pharmacologic interventions, Pex16Alb-Cre mice were subjected to abrogation of PPARα and farnesoid X receptor (FXR) by crossing with PPARα-absent mice and FXR-absent mice, respectively. The results showed that WY-14,643 did not further increase hepatocyte proliferation in Pex16Alb-Cre mice, but PPARα-absent Pex16Alb-Cre mice (Pparα-/-/Pex16Alb-Cre) exhibited increased hepatocyte proliferation. In contrast, FXR-absent Pex16Alb-Cre mice (Fxr-/-/Pex16Alb-Cre) displayed reduced hepatocyte proliferation. Bile acids are FXR agonists. Consistently, serum bile acid levels are elevated in Pex16Alb-Cre mice, and feeding cholestyramine decreased serum bile acid levels and inhibited hepatocyte proliferation in Pex16Alb-Cre mice. These results suggest that hepatocyte proliferation in Pex16Alb-Cre mice is mediated by FXR but inhibited by PPARα.","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178756","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}

引用次数: 0

Neutrophils Drive Pancreatic Inflammation and Tissue Injury but Promote Tissue Repair in Severe Acute Pancreatitis. 中性粒细胞驱动胰腺炎症和组织损伤，但促进严重急性胰腺炎的组织修复。

IF 4.9 2区医学

American Journal of Pathology Pub Date : 2026-10-13 DOI: 10.1016/j.ajpath.2026.09.008

Xiuli Zhang, Xiangyu Chen, Xiaoyu Guo, Rujuan Liu, Sohail Husain, Yun Long, Li Wen

{"title":"Neutrophils Drive Pancreatic Inflammation and Tissue Injury but Promote Tissue Repair in Severe Acute Pancreatitis.","authors":"Xiuli Zhang, Xiangyu Chen, Xiaoyu Guo, Rujuan Liu, Sohail Husain, Yun Long, Li Wen","doi":"10.1016/j.ajpath.2026.09.008","DOIUrl":"10.1016/j.ajpath.2026.09.008","url":null,"abstract":"There are no targeted therapeutic options for severe acute pancreatitis, largely owing to an incomplete understanding of the mechanisms involved in the transition from tissue injury to repair. Neutrophils are central effectors of severe acute pancreatitis, but their temporal contributions to injury and repair remain unresolved. In this study in ROSA26iDTR/MRP8-Cre mice, neutrophil depletion was timed to defined disease stages. Cerulein was administered to induce pancreatitis; neutrophil depletion was achieved using diphtheria toxin administered 0, 1, or 2 days later. The efficiency of neutrophil depletion was measured by flow cytometry. Depletion initiated on day 0 (early injury phase) reduced pancreatic injury by day 2, and histologic recovery from days 4 to 8 was more complete than in controls, a difference best explained by a reduced initial damage burden rather than a direct effect on the repair mechanism. Depletion initiated on day 1 (late injury phase) altered neither injury nor recovery. In contrast, depletion initiated on day 2 (regenerative phase) impaired tissue repair, with persistent acinar-to-ductal metaplasia, prolonged CD45+ infiltration, and an expansion of CD86+ cells (proinflammatory macrophages). Based on these findings, neutrophils may function sequentially as mediators of early pancreatic injury and as required contributors to subsequent resolution, supporting that neutrophil-directed therapy should be timed to suppress pathogenic activity while preserving repair.","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178750","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}

引用次数: 0

Tumor Necrosis Factor Receptor-2 Drives Tumoral Coagulation Factor Synthesis and Enhances Thrombosis in Clear-Cell Renal Cell Carcinoma. 肿瘤坏死因子受体-2驱动肿瘤凝血因子合成并增强透明细胞肾癌血栓形成

IF 4.9 2区医学

American Journal of Pathology Pub Date : 2026-10-13 DOI: 10.1016/j.ajpath.2026.09.006

Rafia S Al-Lamki, Jun Wang, Thomas Willingham, Jordan S Pober, Aviva M Tolkovsky, John R Bradley

{"title":"Tumor Necrosis Factor Receptor-2 Drives Tumoral Coagulation Factor Synthesis and Enhances Thrombosis in Clear-Cell Renal Cell Carcinoma.","authors":"Rafia S Al-Lamki, Jun Wang, Thomas Willingham, Jordan S Pober, Aviva M Tolkovsky, John R Bradley","doi":"10.1016/j.ajpath.2026.09.006","DOIUrl":"10.1016/j.ajpath.2026.09.006","url":null,"abstract":"Clear-cell renal cell carcinoma (ccRCC), the most prevalent form of kidney cancer, is associated with an increased risk of local and systemic thromboembolism and a worse prognosis. The mechanisms that drive the coagulation program in tumors are not known. Combining RNAscope with immunofluorescence, local transcription of the key coagulation factors X and V, as well as prothrombin and fibrinogen chains (α, β, and γ), across tumor cells, vascular endothelial cells, and T cells is significantly enhanced in ccRCC tumors compared with adjacent normal kidney tissue. Elevated intratumoral protein expression of factors X and V is accompanied by local thrombin generation, fibrin deposition, and the presence of intravascular microthrombi, which themselves harbor coagulation transcripts. Mechanistic analysis using ccRCC organ cultures reveals that selective engagement of tumor necrosis factor receptor-2 (TNFR2) by a TNFR2-selective mutein (R2TNF) is sufficient to significantly enhance the transcription and protein expression of the same coagulation program in tumor cells, endothelial cells, and T cells compared with adjacent normal kidney cultures, whereas TNFR2 knockdown attenuates this response. In addition, TNFR2 appears to link inflammatory signaling with activation of the local coagulation system through the phosphatidylinositol 3-kinase/Akt/mitogen activated kinase kinase (MEK)/NF-κB signaling axes. These data provide evidence that locally produced coagulation factors driven by TNFR2 signaling may contribute to intratumoral prothrombotic outcomes in ccRCC, highlighting a novel pathway with potential therapeutic relevance.","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178762","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}

引用次数: 0

The Link between Activation of Lens Resident Immune Cells and Recruitment of Immune Cells to the Lens Capsule Surface in Response to Induction of Experimental Autoimmune Uveitis. EAU诱导下晶状体囊表面免疫细胞募集与晶状体驻留免疫细胞活化的关系

IF 4.9 2区医学

American Journal of Pathology Pub Date : 2026-10-13 DOI: 10.1016/j.ajpath.2026.09.007

JodiRae DeDreu, Caitlin M Logan, Mary J Mattapallil, Rachel R Caspi, Mary Ann Stepp, A Sue Menko

{"title":"The Link between Activation of Lens Resident Immune Cells and Recruitment of Immune Cells to the Lens Capsule Surface in Response to Induction of Experimental Autoimmune Uveitis.","authors":"JodiRae DeDreu, Caitlin M Logan, Mary J Mattapallil, Rachel R Caspi, Mary Ann Stepp, A Sue Menko","doi":"10.1016/j.ajpath.2026.09.007","DOIUrl":"10.1016/j.ajpath.2026.09.007","url":null,"abstract":"In experimental autoimmune uveitis (EAU) mice, immune cells with an immunoregulatory phenotype are recruited to the surface of the avascular lens, traveling across ciliary zonule fibrils from the vasculature-rich ciliary body. It was also discovered that the lens epithelium harbors a population of tissue-resident immune cells, a cell type associated with inducing immune responses in response to danger signals in their environment, including recruitment of immune cells that function in immune surveillance and resolution of inflammation. In this study, the phenotype and localization of lens-resident immune cells (LR-ICs) are examined, their presence in adult mouse lenses is quantified, and whether there is a relationship between recruitment of lens capsule-associated immune cells (LCA-ICs) and the activation of LR-ICs in EAU is investigated. This study focused on the time period between induction of uveitis and the height of inflammation in the eyes of EAU mice. High-resolution confocal microscopy was performed on mouse eyes immunolabeled for molecules that detect activated resident immune cells or LCA-ICs. Quantification revealed that few LCA-ICs are recruited to the lens surface before the height of EAU inflammation, with the correlation between recruitment of immune cells to the lens capsule surface and the activation of LR-ICs occurring at the height of inflammation. These findings suggest LR-IC activation may contribute to regulation of inflammatory responses in the eye.","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178728","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}

引用次数: 0

Direct Stimulation of Ephrin-B1 Induces Calcium-Independent Podocyte Injury through Cdc42-Calcineurin Activation. 直接刺激Ephrin-B1可通过活化cdc42钙调磷酸酶诱导钙依赖性足细胞损伤。

IF 4.9 2区医学

American Journal of Pathology Pub Date : 2026-10-13 DOI: 10.1016/j.ajpath.2026.10.001

Yoshiyasu Fukusumi, Ying Zhang, Hidenori Yasuda, Mutsumi Kayaba, Hiroshi Kawachi

{"title":"Direct Stimulation of Ephrin-B1 Induces Calcium-Independent Podocyte Injury through Cdc42-Calcineurin Activation.","authors":"Yoshiyasu Fukusumi, Ying Zhang, Hidenori Yasuda, Mutsumi Kayaba, Hiroshi Kawachi","doi":"10.1016/j.ajpath.2026.10.001","DOIUrl":"10.1016/j.ajpath.2026.10.001","url":null,"abstract":"Although a subset of nephrotic syndrome has been reported to be caused by autoantibodies against nephrin, its etiology remains poorly understood. A previous study demonstrated that anti-nephrin antibodies phosphorylate not only nephrin but also ephrin-B1 at the slit diaphragm of podocytes. However, the pathogenic role of ephrin-B1 in nephrotic syndrome remains unclear. The present study, using cultured human podocytes, demonstrated that direct stimulation of ephrin-B1 with soluble EphB2 or an anti-ephrin-B1 antibody induced phosphorylation of both ephrin-B1 and nephrin. Neither EphB2 nor the anti-ephrin-B1 antibody induced calcium influx, whereas the anti-nephrin antibody did. Phosphorylated ephrin-B1 dissociated from Par6, and the released Par6 subsequently interacted with Cdc42. This interaction promoted Cdc42 activation, leading to altered regulation of Snail and STAT3. These alterations resulted in decreased expression of nephrin and ephrin-B1 and induced claudin-1 expression. A Cdc42 inhibitor prevented both the down-regulation of nephrin and ephrin-B1 and the induction of claudin-1 expression. In contrast, a calcineurin inhibitor and an angiotensin II type 1 receptor blocker prevented the down-regulation of nephrin and ephrin-B1 but failed to prevent claudin-1 induction. This study proposed a novel potential etiology of nephrotic syndrome caused by direct stimulation of ephrin-B1. Targeting Cdc42 may represent a more effective therapeutic strategy for restoring podocyte homeostasis.","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178614","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}

引用次数: 0

Foundation Model-Based Computational Pathology Predicts Breast Cancer Biomarker Status from Intraoperative Frozen Sections. 基于基础模型的计算病理学预测术中冷冻切片的乳腺癌生物标志物状态。

IF 4.9 2区医学

American Journal of Pathology Pub Date : 2026-10-05 DOI: 10.1016/j.ajpath.2026.09.005

Shun Liu, Jun Li, Yixiang Lian, Jie Lan, Tingyu Zhang, Huiru He, Meng Du, Haijun Luo, Zhiyi Chen

{"title":"Foundation Model-Based Computational Pathology Predicts Breast Cancer Biomarker Status from Intraoperative Frozen Sections.","authors":"Shun Liu, Jun Li, Yixiang Lian, Jie Lan, Tingyu Zhang, Huiru He, Meng Du, Haijun Luo, Zhiyi Chen","doi":"10.1016/j.ajpath.2026.09.005","DOIUrl":"10.1016/j.ajpath.2026.09.005","url":null,"abstract":"Prediction of breast cancer biomarkers from routine formalin-fixed, paraffin-embedded (FFPE) hematoxylin and eosin (H&E) images has been explored previously, but whether biomarker-associated morphologic signals can be reliably captured from artifact-prone intraoperative frozen-section (FS) specimens remains insufficiently studied. This retrospective proof-of-concept study developed a foundation model-based multiple-instance learning framework to predict estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 status directly from H&E-stained intraoperative FS whole slide images of 248 patients with breast cancer, using postoperative immunohistochemistry and fluorescence in situ hybridization as ground truth. Exploratory feature evaluation identified UNI2-h as a suitable encoder for downstream modeling. In fivefold cross-validation, areas under the receiver operating characteristic curve were 0.847 for ER, 0.906 for PR, 0.893 for HER2, and 0.799 for Ki-67, with moderate agreement for ER, PR, and HER2 and fair agreement for Ki-67. An exploratory within-cohort cross-preparation analysis showed limited FFPE-to-FS transferability, whereas the FS-trained model retained relatively favorable performance on FFPE images. Attention heat maps highlighted tumor regions with biologically plausible biomarker-associated morphologic patterns. These findings provide proof of concept that intraoperative FS H&E images retain learnable biomarker-associated morphologic signals despite preparation-related alterations.","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103108","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}

引用次数: 0

Multi-Omic Analysis of Peripheral Circulating Neutrophils and the Effects of Transmigration. 外周循环中性粒细胞的多组学分析及其转运的影响。

IF 4.9 2区医学

American Journal of Pathology Pub Date : 2026-10-03 DOI: 10.1016/j.ajpath.2026.08.010

Laura C Morales, Anjelica L Gonzalez

{"title":"Multi-Omic Analysis of Peripheral Circulating Neutrophils and the Effects of Transmigration.","authors":"Laura C Morales, Anjelica L Gonzalez","doi":"10.1016/j.ajpath.2026.08.010","DOIUrl":"10.1016/j.ajpath.2026.08.010","url":null,"abstract":"Neutrophils, the most prevalent leukocytes in circulation, are integral to initiating and resolving inflammatory responses. Although traditionally viewed as a homogeneous population, emerging studies have revealed significant phenotypic heterogeneity and functional versatility within the neutrophil population. However, developing a consensus on neutrophil markers for precise and comprehensive identification of neutrophil phenotypes at baseline is essential to deepen understanding of their biology. In this study, a combination of single-cell RNA sequencing and advanced multiplex flow cytometry analyses was used to examine the transcriptional and proteomic landscapes of human neutrophils in healthy peripheral blood while using functional assays to assess their migratory capabilities and phenotypic alterations after transmigration. Through transcriptional and proteomic analyses, the findings identify three distinct neutrophil profiles, each characterized by specific effector functions and migratory patterns. These subsets demonstrated distinction in the expression of markers related to neutrophil maturation, aging, immune modulation, and inflammatory responses, suggesting a complex spectrum of neutrophil states in circulation and after vascular transmigration. The findings advance the field's understanding of neutrophil heterogeneity and offer a more nuanced view of their roles in homeostasis and the immune response.","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103053","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}

引用次数: 0