Node Tissue Research Articles

PATHOMORPHOLOGY OF CHONDROMATOUS HAMARTOMA DEVELOPED IN LUNG TISSUE

The aim of the scientific work. Hamartoma is the most common benign tumor of various organs and is considered a benign tumor arising from non-epithelial mesenchymal tissue, the exact cause of which is still not fully understood. Hamartoma consists of cells developing in any tissue and characteristic of this organ. Endobronchial hamartomas occurring in the lung tissue make up 12-20%. It is characterized by a chondromatous and vascular structure in composition and a nodular appearance during microscopic examination. In this study, it was found that hamartoma of the respiratory tract was morphologically manifested in cases of bleeding by the vascular type. Materials and methods. Autopsies, ileum and oral mucosa materials of various forms of myeloblastic leukemia and sepsis were delivered and organized to the center of pathological anatomy of the republic. Of these, 43 male and 26 female materials were received. The prepared pieces are studied morphologically. Results. When analyzing the results of the morphological study, it was noted that the hamartoma, which grew from the large bronchi, was located in the endobronchial tissue structures of the bronchi. It was found that chondromatous changes in the chondromatous tissue of the hamartoma occur in the nodes and bronchial wall of the chondroma and have an atypical structure. It was noted that the cytoplasm of chondrocytes is strongly vacuolated. Among the pieces of chondromatous tissue, the appearance of tubercles and cystic structures among bundles consisting of soft tissues of the bronchial wall was detected. Summary. It was found that 13.4% of chondromatous hamartomas of the respiratory system are located in the wall of large bronchi, 56.2% in the front segments of the lungs, and the rest in the back segments of the lungs (30.2%). It was found that the hamartoma developed in the wall of the large bronchi consists of multifocal and irregularly located chondromatous tissue nodules, and around them, the soft tissues of the bronchial wall and the mucous membrane have grown in a dysregenerative manner. It was observed that in the hamartoma developed from the bronchi within the lung tissue, chondromatous foci appeared both in the wall of the bronchi and in the alveolar tissue.

Chronic artificial light exposure in daytime and reversed light: Dark cycle inhibit anti-apoptotic cytokines and defect Bcl-2 in peripheral lymphoid tissues during acute systemic inflammatory response to lipopolysaccharide.

The disturbed light: dark (LD) cycle has been associated with critical complications, including obesity, diabetes and cancer. In the present study, we investigated the chronic effects of artificial light at daytime (AL) and light at night (RAL) after intraperitoneal (i.p.) injection of saline and 0.5mg/kg lipopolysaccharide (LPS) in male Wistar rats. Liver and kidney parameters, fasting blood glucose (FBG), melatonin level, immunohistochemical examinations of B-cell lymphoma-2 (Bcl-2) in spleen and mesenteric lymph and serum antiapoptotic cytokines [interleukin (IL-) 2, 7 and 1]. After 16weeks of a daily disturbed LD cycle, RAL increased body weight, upgraded FBG and altered liver and kidney functions with surprisingly increased daytime plasma melatonin. AL+LPS and RAL+LPS rats suffered significantly higher oxidative-nitrosative stress compared to NL+LPS. Oxidative-nitrosative stress was associated with multi-organ inflammation in hepatic, renal, pancreatic, splenic and mesenteric lymph node tissues due to LPS-induced endotoxemia. Anti-apoptotic Bcl-2 activity in peripheral lymphoid organs (spleen and mesenteric lymph node) was lowered due to AL and RAL regimens. At the same pattern, lowering of antiapoptotic serum levels of IL-2, IL-7 and IL-15 indicate alteration of cell cycle and the shifted ability of cells to undergo apoptosis due to abnormal light pollution. Here, the increased lymphocyte apoptosis in lymphoid tissues due to disturbed LD cycle defects the host defense, dysregulates the inflammatory immune response and dysregulates the immune tolerance during acute systemic inflammation due to LPS.

A 3D-printed multi-compartment organ-on-chip platform with a tubing-free pump models communication with the lymph node.

Multi-organ-on-chip systems (MOOCs) have the potential to mimic communication between organ systems and reveal mechanisms of health and disease. However, many existing MOOCs are challenging for non-experts to implement due to complex tubing, electronics, or pump mechanisms. In addition, few MOOCs have incorporated immune organs such as the lymph node (LN), limiting their applicability to model critical events such as vaccination. Here we developed a 3D-printed, user-friendly device and companion tubing-free impeller pump with the capacity to co-culture two or more tissue samples, including a LN, under a recirculating common media. Native tissue structure and immune function were incorporated by maintaining slices of murine LN tissue ex vivo in 3D-printed mesh supports for at least 24 h. In a two-compartment model of a LN and an upstream injection site in mock tissue, vaccination of the multi-compartment chip was similar to in vivo vaccination in terms of locations of antigen accumulation and acute changes in activation markers and gene expression in the LN. We anticipate that in the future, this flexible platform will enable models of multi-organ immune responses throughout the body.

Differential Expression of miR-192, miR-221, miR-15 Among the Nodule Tissues of Sarcoidosis and Lung Cancer

Background: Patients with sarcoidosis were found to have a higher risk of lung cancer compared to the general population. Being aware of all possible associations between these two diseases and identification of biomarkers such as miRNA profiles can be helpful in differentiating the mechanisms of these two diseases, which can aid in clinical decision-making. Methods: The aim of the study was to investigate the expression of selected miRNAs (miR-192 miR-221, miR-15) in lymph nodes of patients with pulmonary sarcoidosis, non-small cell lung carcinomas (NSCLC) and control group (n = 30 per groups) by qRT-PCR. Results: Relative expression of miR-221 in sarcoidosis and NSCC patients was higher than in the control group. Furthermore, the relative expression of miR-15 in patients with sarcoidosis and NSCLC tissue was lower than in the control group. Interestingly, miR-192 is differentially expressed in sarcoidosis and NSCLC patients compared to the control group. Conclusions: The obtained results suggest that the studied miRNAs may have potential diagnostic and therapeutic implications, but further research is necessary to fully understand their roles in these diseases.

Diagnostic Imaging of Primary Cutaneous Osteoma of the Forehead

Introduction: Osteoma cutis is a rare benign condition characterized by ectopic bone formation in the dermis or subcutaneous tissue. Typically, osteoma cutes result from inflammation, tumors, or scars. However, primary cases occasionally present with no apparent preceding lesion. Case Presentation: we report a case of primary osteoma cutis located on a 20-year-old woman's forehead. Diagnostic imaging revealed a nodule of bone tissue within the dermis and contiguous cartilage tissue, which was later histologically confirmed. The patient underwent surgical resection under local anesthesia and successfully recovered with no neurological symptoms or signs of recurrence 6 months after the surgery. Conclusion: We report this case because, to the best of our knowledge, there have been no reports of primary osteoma cutis with complete preoperative imaging findings.

A specific gene expression program underlies antigen archiving by lymphatic endothelial cells in mammalian lymph nodes.

Lymph node (LN) lymphatic endothelial cells (LEC) actively acquire and archive foreign antigens. Here, we address questions of how LECs achieve durable antigen archiving and whether LECs with high levels of antigen express unique transcriptional programs. We used single cell sequencing in dissociated LN tissue and spatial transcriptomics to quantify antigen levels in LEC subsets and dendritic cell populations at multiple time points after immunization and determined that ceiling and floor LECs archive antigen for the longest duration. We identify, using spatial transcriptomics, antigen positive LEC-dendritic cell interactions. Using a prime-boost strategy we find increased antigen levels within LECs after a second immunization demonstrating that LEC antigen acquisition and archiving capacity can be improved over multiple exposures. Using machine learning we defined a unique transcriptional program within archiving LECs that predicted LEC archiving capacity in mouse and human independent data sets. We validated this modeling, showing we could predict lower levels of LEC antigen archiving in chikungunya virus-infected mice and demonstrated in vivo the accuracy of our prediction. Collectively, our findings establish unique properties of LECs and a defining transcriptional program for antigen archiving that can predict antigen archiving capacity in different disease states and organisms.

TRPS1 is a useful marker in differentiating metastatic breast carcinoma from pancreatic adenocarcinoma in fine-needle aspiration specimens.

Distinction of metastatic breast carcinoma (BC) to the pancreas from primary pancreatic adenocarcinoma (PAC) is essential but challenging. Breast carcinoma shares similar morphology and exhibits an overlapping immunohistochemistry (IHC) profile with PAC. We investigated the utility of recently reported trichorhinophalangeal syndrome type 1 (TRPS1) IHC in differentiating metastatic BC from PAC in fine-needle aspiration (FNA) specimens. We assessed consecutive patients of PAC (n = 49). Due to limited cases of metastatic BC to the pancreas (n = 3), cases of metastatic BC (n = 23) in various locations, including lymph node, lung, bone, or soft tissue, were included. Immunohistochemistry for TRPS1 was performed by using the cell blocks obtained from FNA. A quantitative score for TRPS1 expression was calculated by multiplying the intensity and the percentage of positive cells. Immunoreactivity scores were assigned as negative, low positive, intermediate positive, or high positive. In 49 PAC cases, 47 (95.9%) exhibited negative while 2 (4.1%) exhibited low positive TRPS1 expression. However, TRPS1 expression was high positive in 23 (88.0%) of 26 metastatic BC cases, including 10 (83.3%) of 12 triple-negative BC (TNBC) and 13 (92.9%) of 14 non-TNBC cases. Our results suggest that TRPS1 IHC represents a highly accurate and reliable method for differentiating metastatic BC from PAC.

Expression and clinical significance of Numb and Notch-1 proteins between tissue of colon cancer and regional lymph node metastases.

To investigate the expression and clinical significance of Notch-1 and Numb protein in colon cancer tissues and regional lymph node metastases. Immunohistochemical method was used to detect the expression of Notch-1 protein and Numb protein in 110 cases of colon cancer tissues, along with tumor adjacent tissues and 56 cases of MLN tissues, and to analyze its role in colon cancer and MLN tissue. Comparing colon cancer tissue or lymph node metastases with tumor adjacent tissue, the positive expression rate of Numb was significantly decreased, while the positive expression of Notch-1 was significantly increased in colon cancer tissue or lymph node metastases (both p<0.05). The expression of Notch-1 and Numb was correlated with the lymph node metastasis, TNM stage, and degree of differentiation (p<0.05). The expression between Numb and Notch-1 showed negative correlation in colon cancer tissues (r=-0.261, p<0.05). There was no relationship between the expression of Numb and Notch-1 protein in colon cancer and metastatic lymph node tissue (p>0.05). Numb expression is decreased and Notch-1 expression is increased in colon cancer tissue and metastatic lymph node tissue, suggesting that the interaction between the two proteins may play a promote role in the development, invasion, and metastasis of colon cancer. There was no relationship between the expression of Numb and Notch-1 protein in colon cancer and metastatic lymph node tissue, suggesting that there is no obvious enhancement of the cancer cells; in the process of lymph node metastasis, the degree of malignant biological behavior remains relatively stable.

D609 Suppresses Antituberculosis Response by Regulating Dendritic Cells Antigen Presentation.

To elucidate the role of phosphatidylcholine-specific phospholipase C (PC-PLC) in the antituberculosis (anti-TB) immune response mediated by dendritic cells (DCs). In vivo, C57BL/6J mice infected with the Mycobacterium tuberculosis strain H37Rv. Before infection, the mice were pretreated with the PC-PLC inhibitor D609. Bacillary loads in lung and spleen tissues were quantified through colony-forming unit (CFU) assays. Hematoxylin and eosin (H&E) staining was performed to assess inflammatory infiltration and tissue damage. Levels of inflammatory mediators in peripheral venous blood were quantified using enzyme-linked immunosorbent assays (ELISAs). Flow cytometry was employed to determine the proportions of conventional DCs (cDCs) and their subsets, cDC1 and cDC2, within lung, spleen, and lymph node tissues. In vitro, mouse bone marrow-derived dendritic cells (BMDCs) pretreated with D609. The expression levels of chemokines and pro-inflammatory cytokines were assessed via quantitative polymerase chain reaction (qPCR) and ELISA. BMDCs were loaded with H37Rv expressing red fluorescent protein (RFP-H37Rv) or DQ-OVA, and flow cytometry was utilized to analyze the impact of D609 on antigen phagocytosis and processing. Furthermore, flow cytometry was employed to evaluate the effect of D609 pretreatment on the expression levels of costimulatory molecules on BMDCs. The capacity of D609-treated BMDCs to activate and proliferate T cells, as well as to induce interferon-gamma (IFN-γ) secretion, was assessed through a DC-T cell coculture system. In vivo analysis revealed that mice pretreated with D609 exhibited a marked increase in tissue bacterial load, enhanced inflammatory infiltration, and a reduction in pro-inflammatory mediator expression in peripheral venous blood. There was a notable decrease in the number of cDCs in lung and lymph node tissues, with a pronounced reduction in cDC1 in the lungs and cDC2 in the lymph nodes. In vitro studies demonstrated that D609 pretreated BMDCs displayed a significant decline in inflammatory mediator production, antigen phagocytosis, and antigen processing capabilities, potentially due to altered expression of costimulatory molecules. Coculture experiments indicated that D609 pretreated BMDCs showed a substantial reduction in their ability to stimulate T cell activation, proliferation, and IFN-γ secretion. Our findings suggest that PC-PLC plays a critical role in the functionality of DCs, including the production of chemokines and pro-inflammatory cytokines, migration to lymph nodes, and antigen presentation to T cells, which collectively contribute to T cell activation and effective clearance of Mycobacterium tuberculosis. Further investigation into the regulatory mechanisms of PC-PLC in DCs may uncover novel therapeutic targets for the development of advanced anti-TB treatments.

Tectorigenin Reduces Dabie bandavirus-Induced Cytokine Storm by Regulating Toll-Like Receptor 7/Extracellular Signal-Regulated Kinase Pathway.

Severe fever with thrombocytopenia syndrome (SFTS) is a severe emerging infectious disease caused by Dabie bandavirus (DBV). Tectorigenin has been demonstrated to exert anti-inflammatory effect. Here, we aimed to investigate the effects of tectorigenin on DBV-induced cytokine storm. Effects of tectorigenin on cytokines in DBV-infected THP-1 cells and plasma samples of Type I interferon receptor (IFNAR)-/- mice infected with DBV were detected. The changes in body weight and survival time of mice were recorded. The liver, spleen, kidney, and lymph node tissues were collected for hematoxylin-eosin staining. We demonstrated that tectorigenin reduced the expression levels of inflammatory cytokines in both DBV-infected THP-1 cells and plasma samples of IFNAR-/- mice infected with DBV. Tectorigenin attenuated DBV-induced histopathological changes in mice. Mechanistically, tectorigenin attenuated DBV-induced phosphorylation of inhibitor of kappa-B kinase alpha/beta (IKKα/β) of the nuclear factor-κB (NF-κB) signaling pathway, extracellular signal-regulated kinase (ERK) of the mitogen-activated protein kinase (MAPK) signaling pathway and might function by downregulation of Toll-like receptor. The result of this study suggested that tectorigenin exerted anti-inflammatory effects invivo and invitro and could serve as a novel potential therapeutic strategy for SFTS.

Is pT0 a Reliable End Point for Biomarker Discovery for Preoperative Chemotherapy Response in Patients With Bladder Cancer?

Purpose: Traditional biomarker investigation schemas for chemotherapy response prediction in patients with bladder cancer relying on the pT0 status at radical surgery are confounded by the therapeutic effect of transurethral resection of bladder tumor (TURBT). Studying cN+ patients and assessing pN0 status presents a unique opportunity for overcoming this bias. Materials and Methods: We studied 26 patients with biopsy-proven cTanyN1-3M0 bladder cancer (2005-2016) who underwent induction chemotherapy and radical cystectomy with pelvic lymphadenectomy. Metastasis and overall survival (OS) outcomes were examined using Kaplan-Meier method and compared using log-rank test. Paired pretherapy primary bladder and nodal tissues were available for 10 patients. In these patients, whole-transcriptome RNA-seq analysis was performed on bladder tumor (for pT0 and pN0 prediction) and lymph-nodal metastasis (for pN0 prediction) tissues to identify differentially expressed genes (DEGs) with a false discovery rate &lt; 0.1. Results: pN0 pathologic responders, but not pT0 responders, had significantly improved freedom from metastasis (5-year: pN0 88.9% vs pN+ 27.4%, log-rank P = .018) and OS (5-year: pN0 76.2% vs pN+ 12.2%, log-rank P = .024). Using RNA-seq data, we identified a significant discordance rate of 87.5% between DEG-based predictive signatures for pT0 and pN0 response to cisplatin-based chemotherapy. This datum, combined with the knowledge that ∼40% of patients who achieve pT0 status at radical surgery, achieve it simply through the therapeutic effect of TURBT (SWOG S8710), underscores a substantial bias in the current biomarker discovery initiatives that use pT0 as an end point. Conclusions: Our findings suggest a need for devising novel study designs to aid in the discovery of reliable biomarkers for preoperative chemo/immunotherapy response in bladder cancer. Clinical node-positive patients may be ideally situated but remain understudied.

18F-fluorocholine PET/CT imaging in primary hyperparathyroidism after negative or inconclusive cervical ultrasonography and 99mTc-MIBI scintigraphy.

Primary hyperparathyroidism (pHPT) is a common endocrine disorder characterized by one or more hyperfunctioning parathyroid glands. Definitive surgical treatment demands precise preoperative localisation of hyperfunctioning parathyroid tissue. The purpose of our study is to assess the value of 18F-fluorocholine positron emission tomography (PET/CT) in preoperative localisation of hyperfunctioning parathyroid glands in patients with biochemically confirmed pHPT and negative or inconclusive cervical ultrasonography and 99mTc-MIBI scintigraphy. Our study included 167 patients with biochemically confirmed pHPT and negative or inconclusive cervical ultrasonography and 99mTc-MIBI scintigraphy. In our study 18F-fluorocholine PET/CT detection rate was 92.81% (155/167) with 182 lesions identified. Overall sensitivity, specificity, accuracy, and positive predictive value (PPV) on a per-lesion analysis were 100%, 75%, 95.33%, and 94.74%. Ninety (90/95) lesions were 18F-fluorocholine PET/CT true positive. A total of 86 patients underwent surgical procedures in which 95 histological lesions were removed. Histology revealed 60 adenomas, 25 hyperplasias, 5 lesions described as inconclusive parathyroid tissue, benign lymph node tissue in 4 lesions and 1 false-positive lesion was follicular thyroid adenoma. After surgery, all patients had PTH serum values measured (15min after extirpation or during immediate postoperative recovery). Mean PTH serum values in patients with successful surgery decreased by an average of 62.54% (preoperative PTH 14.74 ± 8.54pmol/L to 6.3 ± 6.8pmol/L). 18F-fluorocholine PET/CT is an accurate, fast, and highly sensitive method for identifying the localization of overactive parathyroid glands in patients with primary hyperparathyroidism.

Genome expression analysis of basic helix-loop-helix transcription factors in Sea buckthorn (Hippophae rhamnoides L.).

The basic helix-loop-helix (bHLH) transcription factor family is one of the largest gene families in plants, extensively involved in plant growth, organ development, and stress responses. However, limited studies of this family are available in sea buckthorn (Hippophae rhamnoides). In this study, we identified 144 bHLH genes in H. rhamnoides (HrbHLH) through a genome-wide search method, then explored their DNA and protein sequences and physicochemical properties. According to the sequence similarities, we classified them into 15 groups with specific motif structures. To explore their expressions, we performed gene expression profiling using RNA-Seq and identified 122 HrbHLH mRNAs were highly expressed, while the remaining 22 HrbHLH genes were expressed at very low levels in all 21 samples. Among these HrbHLH genes, HrbHLH47, HrbHLH74, HrbHLH90, HrbHLH131 showed the highest expression level in the root nodule, root, leaf, stem and fruit tissues. Furthermore, eleven HrbHLH genes displayed increased expressions during the fruit development process of sea buckthorn. Finally, we validated the expression patterns of HrbHLH genes using reverse transcription quantitative real-time PCR (QPCR). This comprehensive analysis provides a useful esource that enables further investigation of the physiological roles and molecular functions of the HrbHLH TFs.

Fragment viability, regenerative capacity and protoplast isolation of invasive Australian swamp stonecrop (Crassula helmsii)

Australian swamp stonecrop (Crassula helmsii) is an amphibious plant native to Australasia and highly invasive in Europe. Managing the spread and impacts of this invader is challenging due to its ability to regenerate from small vegetative plant fragments. In several infested water systems in the Netherlands, the dispersal of this species is currently being prevented using water filters with a mesh size as small as 1 mm2 in their outflows. However, it remains unclear whether these filters are truly capable of preventing the spread of small regenerative fragments. To identify potential shortcomings in the management of C. helmsii dispersal, we investigated the regeneration of detached vegetative fragments. A laboratory experiment was conducted to study the regenerative capacity of C. helmsii fragments of varying sizes (0.5–2 mm). We examined the growth performance (stem count, cumulative stem length) of fragments originating from nodes, leaves, shoots, roots, and meristem tissue cuts. All fragments originating from nodal tissue were able to successfully regenerate. Isolated meristem tissue of 0.5 mm was able to regenerate but exhibited malformed growth. Shoot tips demonstrated the best growth performance. While we successfully isolated protoplasts from C. helmsii node tissue, our cultures were compromised, and regeneration could not be assessed. Our research indicates regenerative potential from node fragments as small as a cluster of apical meristem cells. These findings suggest shortcomings in current measures for dispersal prevention of C. helmsii, as they do not prevent the dispersal of plant fragments with a length <2 mm. We recommend re-evaluating the effectiveness of various types of dispersal barriers currently applied in vulnerable natural areas to prevent the spread and subsequent regeneration of small vegetative fragments of C. helmsii.

Regulation of cell-mediated immune responses in dairy bulls via long non-coding RNAs from submandibular lymph nodes, peripheral blood, and the spleen

Cell-mediated immune responses (CMIRs) are critical to building a robust immune system and reducing disease susceptibility in cattle. Long non-coding RNAs (lncRNAs) regulate various biological processes. However, to the best of our knowledge, the characterization and functions of lncRNAs and their regulations on the bovine CMIR have not been investigated comprehensively. In this study, experimental bulls were immunized with heat-killed preparation of Candida albicans (HKCA) to induce delayed-type hypersensitivity (DTH). Three bulls were classified as high- CMIR responders and three were low-CMIR responders, based on their classical DTH skin reactions. LncRNAs were identified in the submandibular lymph nodes, peripheral blood, and spleen of high- and low-CMIR animals using strand-specific RNA sequencing. A total of 21,003 putative lncRNAs were identified across tissues, and 420, 468, and 599 lncRNAs were differentially expressed between the two groups in the submandibular lymph node, peripheral blood, and spleen tissues, respectively. Functional analysis of the differentially expressed lncRNA (DElncRNA) target genes showed that a number of immune-related Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were enriched, including immune response, cell adhesion, nucleosome, DNA packaging, antigen processing and presentation, and complement and coagulation cascades. Tissue specificity analysis indicated that lncRNA transcripts have stronger tissue specificity than mRNA. Furthermore, an interaction network was constructed based on DElncRNAs and DEGs, and 11, 14, and 11 promising lncRNAs were identified as potential candidate genes influencing immune response regulation in submandibular lymph nodes, peripheral blood, and spleen tissues, respectively. These results provide a foundation for further research into the biological functions of lncRNAs associated with bovine CMIR and identify candidate lncRNA markers for cell-mediated immune responses.

Single-cell analyses reveal metastasis mechanism and microenvironment remodeling of lymph node in intrahepatic cholangiocarcinoma

Background and AimsLymph node metastasis (LNM) is a major determinant of recurrence and prognosis in intrahepatic cholangiocarcinoma (iCCA). LNM disrupts T-cell-mediated cytotoxicity, promotes tumor-specific immune tolerance, and facilitates distant metastasis. Despite its importance, extensive research on LMN in iCCA is lacking. This study aimed to systematically explore the heterogeneity of the LNM-associated microenvironment in iCCA by integrating single-cell and multiomics analyses, identifying metastasis-associated cell subgroups, and validating these findings through multiple cohorts. MethodsWe analyzed single-cell transcriptomics data from primary tumors, cancer-adjacent liver tissues, and tumor-draining lymph nodes of four iCCA patients who underwent radical surgery. Additionally, we collected 81 tumor and matched lymph node tissue sections from iCCA patients. We performed single-cell RNA sequencing and multiplex immunohistochemistry (mIHC), followed by differential gene expression analysis, functional enrichment analysis, single-cell copy number variation assessment, and pseudotime analysis. ResultsOur analysis revealed the complex heterogeneity of the iCCA LNM-associated microenvironment. We found a significant increase in stromal and mature immune cells in the metastatic lymph nodes. T cells constitute the predominant component, with diverse functional subtypes. We identified CD36+ macrophages and SAA1+ tumor cells as key players in the metastatic process. The SAA1-CD36 receptor‒ligand pair may be crucial in forming the LNM-associated microenvironment. ConclusionWe identified several metastasis-associated cell subgroups. These findings provide new insights into the mechanisms underlying LNM in iCCA and lay the groundwork for the development of novel therapeutic strategies. Our study highlights the importance of single-cell technologies in understanding tumor microenvironment complexity and offers valuable resources for future research. Impact and implicationsThe lack of single-cell transcriptome analysis of iCCA lymph node metastases has prevented us from understanding the underlying mechanisms of disease progression. To fill this knowledge gap, we elucidated the unique ecosystem of iCCA lymph node metastases, which is an important advance in clarifying the impact of the immune environment on the development of this disease. The results of this study identified several LNM-related therapeutic targets, which will not only be helpful to basic researchers but also provide potential diagnostic and treatment ideas for physicians, thereby helping patients and their caregivers develop more personalized treatment plans. This finding is highly important for improving the prognosis of patients with advanced iCCA in the future.

Establishment of a rhesus macaque model for coxsackievirus A6 infection: Pilot study to evaluate infection initiated through the respiratory or digestive track

Coxsackievirus A6 (CVA6) is a primary pathogen associated with hand, foot, and mouth disease (HFMD) and is typified by fever, rashes or herpetic lesions at distinct locations. Although HFMD patients exhibit mild symptoms, a subset of patients may develop severe complications, such as viral encephalitis, myocarditis, pneumonia, and neurological disorders. However, in addition to rodent models, such as the CVA6-infected mouse model, no definitive nonhuman primate animal model or related research or analysis tool is available, which makes the development of suitable nonhuman primate animal models particularly crucial. In this study, 3- to 4-month-old rhesus monkeys were infected via the respiratory or digestive tract, and the pathogenic, pathological, and immunological alterations following CVA6 infection were investigated. The results revealed that the infected rhesus monkeys exhibited symptoms similar to those of patients, including signs of HFMD, blood cell changes, viremia, viral excretion, and inflammatory reactions during the acute phase (1–11 days). Pathological observations revealed inflammatory reactions in the intestinal and lymph node tissues. Notably, the acute symptoms gradually waned in the recovery phase (12–120 days), and a high level of neutralizing antibodies was sustained. Intriguingly, no significant disparity was observed between the infections initiated via the respiratory or digestive tract in terms of clinical symptoms, hemogram results or virus shedding. Overall, this study yielded a comprehensive dataset regarding the physiological, pathological, and immunological outcomes of CVA6 infection in a primate host, enhancing our comprehension of the mechanism of CVA6 infection and providing essential data for related vaccine and drug development.

Integrative multi-omics analysis reveals the role of tumor-associated endothelial cells and their signature in prognosis of intrahepatic cholangiocarcinoma

This study aims to investigate the interplay between tumor-associated endothelial cells (TECs) and immune cells within the tumor microenvironment (TME) and its impact on tumor prognosis. We conducted single-cell RNA sequencing (scRNA-seq) of tumor, normal, and lymph node tissues obtained from intrahepatic cholangiocarcinoma (ICC) patients to reveal the role of TECs in tumor angiogenesis and their significant heterogeneity. Meanwhile, we identified genes highly expressed in TECs and constructed TEC signatures (TEC.Sig). Next, we calculated TEC scores of samples based on TEC.Sig. Patients with higher TEC scores exhibited a higher frequency of KRAS mutations, which was associated with increased infiltration of neutrophils and immature dendritic cells (iDCs), and decreased numbers of natural killer (NK), CD4 + T, and CD8 + T effector memory (Tem) cells, indicating an inflammation-dominated immunosuppressive phenotype. In contrast, BAP1 mutations and CXCL12 overexpression showed a contrasting trend. Spatial transcriptomics analysis and histological experiments further confirmed that TECs interacted with various tumor-killing immune cells through the CXCL12/CXCR4 axis. Multiple tumor immunotherapy datasets confirmed that the TEC.Sig could predict patient responses to immunotherapy. The TEC score is a promising and reliable biomarker for predicting genetic mutations and prognosis in ICC patients. Enhancing the regulation of the CXCL12/CXCR4 signaling pathway may represent a potential novel therapeutic target for ICC treatment.

Inorganic nitrogen inhibits symbiotic nitrogen fixation through blocking NRAMP2-mediated iron delivery in soybean nodules

Symbiotic nitrogen fixation (SNF) in legume-rhizobia serves as a sustainable source of nitrogen (N) in agriculture. However, the addition of inorganic N fertilizers significantly inhibits SNF, and the underlying mechanisms remain not-well understood. Here, we report that inorganic N disrupts iron (Fe) homeostasis in soybean nodules, leading to a decrease in SNF efficiency. This disruption is attributed to the inhibition of the Fe transporter genes Natural Resistance-Associated Macrophage Protein 2a and 2b (GmNRAMP2a&2b) by inorganic N. GmNRAMP2a&2b are predominantly localized at the tonoplast of uninfected nodule tissues, affecting Fe transfer to infected cells and consequently, modulating SNF efficiency. In addition, we identified a pair of N-signal regulators, nitrogen-regulated GARP-type transcription factors 1a and 1b (GmNIGT1a&1b), that negatively regulate the expression of GmNRAMP2a&2b, which establishes a link between N signaling and Fe homeostasis in nodules. Our findings reveal a plausible mechanism by which soybean adjusts SNF efficiency through Fe allocation in response to fluctuating inorganic N conditions, offering valuable insights for optimizing N and Fe management in legume-based agricultural systems.

Eosinophilic gastroenteritis, a rare case report and literature review

Abstract Introduction/Objective Eosinophilic gastroenteritis (EGE) is a rare inflammatory condition affecting the gastrointestinal tract, initially described by Kaijser et al. in 1937. It manifests as eosinophil-rich infiltration throughout the GI tract, often accompanied by peripheral eosinophilia. EGE is categorized under eosinophilic gastrointestinal disorders (EGIDs), alongside eosinophilic esophagitis (EOE) and eosinophilic colitis (EC). Symptoms vary based on the affected GI segment. This report aims to present a case of extensive EGE in a young male patient and review of similar cases to enhance clinical and histopathologic understanding. Methods/Case Report A 29-year-old male presented with abdominal pain, nausea, vomiting, and recent weight loss. He had a history of similar abdominal symptoms for a few years. Previous extensive investigations were inconclusive. Current imaging revealed soft tissue nodules, mild splenomegaly, and biliary dilation. Laboratory tests showed no significant abnormalities. Endoscopy revealed a gastric antral ulcer with marked eosinophilic infiltration on microscopy. Results (if a Case Study enter NA) NA Conclusion Eosinophilic gastroenteritis is an uncommon disease that presents with variable non-specific symptoms which require a high level of suspicion for diagnosis. EGE diagnosis requires excluding other causes of eosinophil accumulation. There is no clear distinction between the upper normal and abnormally increased eosinophils in GIT biopsies. Peripheral eosinophilia is common, along with other abnormal laboratory findings. Diagnosis relies on histopathology due to nonspecific symptoms. Clinicians and pathologists face challenges in diagnosing EGE, emphasizing the importance of considering it in the differential diagnoses. Efforts to establish diagnostic criteria for EGE are limited, despite its long-known existence. The condition’s vague symptoms necessitate a high level of clinical suspicion, with diagnosis primarily based on histopathologic features.