bluuebunny/crossref_metadata_2025 huggingface dataset:
Infectious bursal disease virus affecting interferon regulatory factor 7 signaling through VP3 protein to facilitate viral replication
Authors: Wang Zhiyuan , Chen Yang , Chen Yanyan , Chen Rui , Wang Weiwei , Hu Shichen , Li Yihai , Chen Hongjun , Wei Ping , He Xiumiao
Published: January 2025

Interferon regulatory factor 7 (IRF7)-mediated type I interferon antiviral response is crucial for regulating the host following viral infection in chickens. Infectious bursal disease virus (IBDV) is a double-stranded RNA virus that induces immune suppression and high mortality rates in chickens aged 3-6 weeks. Previous studies have shown that IBDV infection antagonizes the type I interferon production to facilitate viral replication in the cell, and IRF7 signaling might play an important role. However, the underlying mechanisms that enable IBDV to block the IRF7 pathway remain unclear. In this study, we found that IRF7 and IFN-β expression were suppressed in DF-1 cells during infection with very virulent IBDV (vvIBDV), but not with attenuated IBDV, while the virus continued to replicate. Overexpression of IRF7 inhibits IBDV replication while knocking down IRF7 promotes IBDV replication. Overexpression of IRF7 couldn’t compensate the IRF7 protein level in vvIBDV-infected cells, which suggested that IRF7 protein was degraded by IBDV infection. By using inhibitors, the degradation of IRF7 was found to be related to the proteasome pathway. Further study revealed that IRF7 was observed to interact and colocalize with the IBDV VP3 protein. Consistent with IBDV infection results, IBDV VP3 protein was observed to inhibit the IRF7-IFN-β expression, affect the degradation of IRF7 protein via proteasome pathway. All these results suggest that the IBDV exploits IRF7 by affecting its expression and proteasome degradation via the viral VP3 protein to facilitate viral replication in the cells. These findings revealed a novel mechanism that IBDV uses to evade host antiviral defense.
Risk factors for coronary atherosclerotic heart disease in postmenopausal women: a meta-analysis
Authors: Miao Xin , Wu Lixing , Wang Kuiyue , Wang Yuhan , Zhang Linlin
Published: January 2025

Background

Coronary atherosclerotic heart disease (coronary heart disease; CHD) is the leading cause of death in women worldwide, and the number of patients and deaths is increasing each year. Approximately 3.8 million women die from CHD every year globally. After menopause, estrogen levels decrease, and the risk of cardiovascular disease increases substantially; however, research on risk factors for CHD in postmenopausal women has been inconclusive.

Objective

To systematically evaluate the risk factors for CHD in postmenopausal women.

Methods

The PubMed, Embase, Web of Science, CINAHL, CBM, CNKI, and VIP databases were searched up to February 9, 2024, for studies on risk factors for CHD in postmenopausal women. Two researchers independently screened the literature, extracted data, and evaluated the quality of the included literature. STATA17.0 software was used for meta-analysis.

Results

Nine studies involving 29,4103 patients were included. The results of the meta-analysis showed that history of six or more pregnancies (hazard ratio = 1.538, 95% confidence interval: 1.241%–1.906%) was significantly associated with risk of CHD (P < 0.05).

Conclusion

Multiple pregnancies are associated with CHD incidence and related mortality in postmenopausal women. In the future, more and higher quality studies are needed to further verify this conclusion.
Contrastive learning with transformer for adverse endpoint prediction in patients on DAPT post-coronary stent implantation
Authors: Li Fang , Sun Zenan , abdelhameed Ahmed , Duan Tiehang , Rasmy Laila , Hu Xinyue , He Jianping , Dang Yifang , Feng Jingna , Li Jianfu , Wang Yichen , Lyu Tianchen , Braun Naomi , Pham Si , Gharacholou Michael , Fairweather DeLisa , Zhi Degui , Bian Jiang , Tao Cui
Published: January 2025

Background

Effective management of dual antiplatelet therapy (DAPT) following drug-eluting stent (DES) implantation is crucial for preventing adverse events. Traditional prognostic tools, such as rule-based methods or Cox regression, despite their widespread use and ease, tend to yield moderate predictive accuracy within predetermined timeframes. This study introduces a new contrastive learning-based approach to enhance prediction efficacy over multiple time intervals.

Methods

We utilized retrospective, real-world data from the OneFlorida + Clinical Research Consortium. Our study focused on two primary endpoints: ischemic and bleeding events, with prediction windows of 1, 2, 3, 6, and 12 months post-DES implantation. Our approach first utilized an auto-encoder to compress patient features into a more manageable, condensed representation. Following this, we integrated a Transformer architecture with multi-head attention mechanisms to focus on and amplify the most salient features, optimizing the representation for better predictive accuracy. Then, we applied contrastive learning to enable the model to further refine its predictive capabilities by maximizing intra-class similarities and distinguishing inter-class differences. Meanwhile, the model was holistically optimized using multiple loss functions, to ensure the predicted results closely align with the ground-truth values from various perspectives. We benchmarked model performance against three cutting-edge deep learning-based survival models, i.e., DeepSurv, DeepHit, and SurvTrace.

Results

The final cohort comprised 19,713 adult patients who underwent DES implantation with more than 1 month of records after coronary stenting. Our approach demonstrated superior predictive performance for both ischemic and bleeding events across prediction windows of 1, 2, 3, 6, and 12 months, with time-dependent concordance (Ctd) index values ranging from 0.88 to 0.80 and 0.82 to 0.77, respectively. It consistently outperformed the baseline models, including DeepSurv, DeepHit, and SurvTrace, with statistically significant improvement in the Ctd-index values for most evaluated scenarios.

Conclusion

The robust performance of our contrastive learning-based model underscores its potential to enhance DAPT management significantly. By delivering precise predictive insights at multiple time points, our method meets the current need for adaptive, personalized therapeutic strategies in cardiology, thereby offering substantial value in improving patient outcomes.
Multi-source data recognition and fusion algorithm based on a two-layer genetic algorithm–back propagation model
Authors: Xiong Zhuang , Ma Jun , Chen Bohang , Lan Haiming , Niu Yong
Published: January 2025

Traditional rainfall data collection mainly relies on rain buckets and meteorological data. It rarely considers the impact of sensor faults on measurement accuracy. To solve this problem, a two-layer genetic algorithm–backpropagation (GA-BP) model is proposed. The algorithm focuses on multi-source data identification and fusion. Rainfall data from a sensor array are first used. The GA optimizes the weights and thresholds of the BP neural network. It determines the optimal population and minimizes fitness values. This process builds a GA-BP model for recognizing sensor faults. A second GA-BP network is then created based on fault data. This model achieves data fusion output. The two-layer GA-BP algorithm is compared with a single BP neural network and actual expected values to test its performance. The results show that the two-layer GA-BP algorithm reduces data fusion runtime by 2.37 s compared to the single-layer BP model. For faults such as lost signals, high-value bias, and low-value bias, recognition accuracies improve by 26.09%, 18.18%, and 7.15%, respectively. The mean squared error is 3.49 mm lower than that of the single-layer BP model. The fusion output waveform is also smoother with less fluctuation. These results confirm that the two-layer GA-BP model improves system robustness and generalization.
The formation mechanism of geological disasters on loess fill slopes revealed by the deformation characteristics of remolded loess under different stress paths
Authors: Meng Shuran , Lv Dunyu , Liu Ru , Yu Mancang , Zhang Jianyu
Published: January 2025

In recent years, geological disasters on loess fill slopes have occurred from time to time, which has attracted widespread attention. In order to deeply understand its deformation and failure laws and promote the disaster prevention and mitigation work, this paper takes remolded loess as the research object, systematically explores the effects of three different stress paths (conventional triaxial compression test (CTC), triaxial compression test with constant average principal stress (TC), and triaxial compression test with reduced confining pressure (RTC)) on its mechanical properties, and observes and analyzes its microstructural characteristics by scanning electron microscopy (SEM). The results show that the soil is strain hardening under the CTC path, while it is strain weak hardening under the TC and RTC paths. In the order of CTC, TC, and RTC paths, the shear strength and volume shrinkage of the soil are reduced in turn, and its deformation has both shear reduction and shear expansion plastic deformation. In the order of CTC, TC, and RTC paths, the degree of particle crushing decreases in turn and the pore content increases in turn. It is inferred that in the initial deformation of loess under loading, the soil is compressed and compacted, and its strength is improved to a certain extent. As the loading continues to increase, the deformation rate increases steadily, and the soil deformation develops gradually, which is mainly axial compression deformation, while the lateral bulging deformation is small until it is destroyed. For the deformation behavior in the form of lateral unloading, the soil is maintained in a relatively stable state at the beginning, and the deformation is very small. When the lateral constraint is reduced to a critical state, the structure is completely unstable, and the deformation develops rapidly in a short time until it is destroyed. This study is of great significance for reducing the occurrence of geological disasters on fill slopes in loess areas.
A complete structural analysis of the FⅠ17 strike-slip fault and its hydrocarbon enrichment factors, Tarim basin, NW China
Authors: Chen Shi , Liang Xinxin , Song Xingguo , Zhang Yintao , Xie Zhou , Neng Yuan , Kang Pengfei , Zhou Jianxun
Published: January 2025

The FⅠ17 fault is a prominent strike-slip fault in the central Tarim basin, notable for its hydrocarbon abundance and intricate tectonic attributes, characterized by several deflections in its planar trajectory. Analyzing the FⅠ17 fault offers crucial insights into the role of basement structures on the evolution and formation of intracratonic strike-slip fault systems. This study utilizes the latest seismic data and integrating the foundation of previous research to conduct a detailed investigation into the spatial distribution, deformation intensity, activity phases, and formation mechanisms of the fault. The fault can be divided into three structural layers based on deformation features. The deep layer, situated beneath the TЄ3 interface (the bottom of the Upper Cambrian), shows basement rifts and weak strike-slip activity. The middle layer, spanning from TЄ3 to TO3 (the bottom of the Upper Ordovician), exhibits pronounced deformation with flower-like structures. The upper layer, extending from the TO3 to TP (the bottom of the Permian), is marked by three groups of en-echelon normal faults. Controlled by Precambrian basement heterogeneity, the fault evolved through three stages: weak compressive stress during the Middle -Late Cambrian led to rupture along basement rifts and weak zones that formed the fault’s embryonic shape; strong compressive stress from Middle-Late Ordovician activated and propagated the fault upwards; during the Silurian-Carboniferous, the fault experienced episodic reactivation and result in the emergence of en-echelon normal faults. Hydrocarbon enrichment at the FⅠ17 fault is influenced by source rock distribution, reservoir characteristics, and fault reactivation. Its positioning above the source rock center ensures an ample supply of hydrocarbon. The intense fault activity has created favorable conditions for large-scale fracture-cavity reservoir development, and the reactivation period corresponds with the hydrocarbon accumulation phase, significantly boosts hydrocarbon charging.
The use of propensity score matching to assess the effectiveness of the endometrial receptivity analysis in patients with recurrent implantation failure
Authors: Yu Shuang , Zhang Yongjie , Li Na , Su Zhuolun , Li Wenjing , Lou Hua , Guan Yichun
Published: January 2025

Background

One potential cause of implantation failure is abnormal endometrial receptivity, and how to objectively evaluate endometrial receptivity has been a matter of great concern. Endometrial receptivity analysis (ERA), a next-generation sequencing-based test that assesses endometrial gene expression, may be valuable in predicting endometrial receptivity, but whether ERA improves pregnancy outcomes in patients with recurrent implantation failure (RIF) is currently controversial. The purpose of this study was to investigate the effect of ERA on pregnancy outcomes in patients with RIF.

Methods

We performed a retrospective cohort study analysis for a population of patients with RIF undergoing frozen embryo transfer (FET) cycles in the reproductive center of the Third Affiliated Hospital of Zhengzhou University from January 2019 to December 2022(n=1598). FET cycles with personalized embryo transfer (PET) under ERA guidance were included in the ERA group (n=43); after using propensity score matching (PSM), a total of 120 FET cycles were included as a control group. Pregnancy outcomes were compared between the two groups. Further, the relationship between the number of previous implant failures and the rate of implant window displacement was discussed. The factors affecting the window of implantation (WOI) displacement were also assessed.

Results

There was no statistically significant difference in embryo implantation rate, clinical pregnancy rate, spontaneous abortion rate, and live birth rate between the ERA group and the matched control patients (P > 0.05). There was no significant difference in the rate of WOI displacement between patients in the moderate or severe groups (P > 0.05) and no significant difference in pregnancy outcome ( P>0.05). Finally, analysis of the clinical data of patients in the receptive and non-receptive groups did not uncover any factors influencing WOI displacement.

Conclusion

The results of the study showed no significant difference in pregnancy outcomes in patients who received ERA compared to those who did not.
Novel perspectives on the pharmacological treatment of thyroid-associated ophthalmopathy
Authors: Li Zilin
Published: January 2025

Thyroid-associated ophthalmopathy (TAO), an autoimmune disease closely related to thyroid dysfunction, remains a challenging ophthalmic condition among adults. Its clinical manifestations are complex and diverse, and disease progression can lead to exophthalmos, diplopia, exposure keratitis, corneal ulceration, and compressive optic neuropathy, resulting in irreversible vision damage or even blindness. Traditional treatment methods for TAO, including glucocorticoids, immunosuppressants, and radiation therapy, often have limitations and side effects, making this disease problematic in ophthalmology. As a result, the development of novel targeted drugs has become a research hotspot for addressing the pathogenesis of TAO. A range of novel targeted drugs, such as teprotumumab and tocilizumab, have been successfully developed and demonstrated remarkable efficacy in relieving inflammation and managing this disease. In addition, some drug candidates and molecular targets identified in the TAO in vitro model have shown promising prospects. This article briefly reviews the potential new strategies for future clinical treatment and the progress of new drug therapies for TAO.
A trend of osteocalcin in diabetes mellitus research: bibliometric and visualization analysis
Authors: Liu Zixu , Mao Yuchen , Yang Kangping , Wang Shukai , Zou Fang
Published: January 2025

Background

Osteocalcin has attracted attention for its potential role in diabetes management. However, there has been no bibliometric assessment of scientific progress in this field.

Methods

We analysed 1680 articles retrieved from the Web of Science Core Collection (WoSCC) between 1 January 1986 and 10 May 2024 using various online tools.

Result

These papers accumulated 42,714 citations,with an average of 25.43 citations per paper. Publication output increased sharply from 1991 onwards. The United States and China are at the forefront of this research area.

Discussion

The keywords were grouped into four clusters: ‘Differential and functional osteocalcin genes’, ‘Differential expression of osteocalcin genes in relation to diabetes mellitus’, ‘Role of osteocalcin in the assessment of osteoporosis and diabetes mellitus’, and ‘Indirect involvement of osteocalcin in metabolic processes’. Analysis using the VoS viewer suggests a shift in research focus towards the correlation between osteocalcin levels and diabetic complications, the clinical efficacy of therapeutic agents or vitamins in the treatment of osteoporosis in diabetic patients, and the mechanisms by which osteocalcin modulates insulin action. The proposed focus areas are “osteocalcin genes”, “insulin regulation and osteoporosis “, “different populations”, “diabetes-related complications” and “type 2 diabetes mellitus”,“effect of osteocalcin expression on insulin sensitivity as well as secretion”,“osteocalcin expression in different populations of diabetic patients and treatment-related studies”.
Identification of a pancreatic stellate cell gene signature and lncRNA interactions associated with type 2 diabetes progression
Authors: Qiu Jinjun , Zhu Peng , Shi Xing , Xia Jinquan , Dong Shaowei , Chen Liqun
Published: January 2025

Background

Type 2 diabetes (T2D) has become a significant global health threat, yet its precise causes and mechanisms remain unclear. This study aims to identify gene expression patterns specific to T2D pancreatic islet cells and to explore the potential role of pancreatic stellate cells (PSCs) in T2D progression through regulatory networks involving lncRNA-mRNA interactions.

Methods

In this study, we screened for upregulated genes in T2D pancreatic islet samples using bulk sequencing (bulkseq) datasets and mapped these gene expression profiles onto three T2D single-cell RNA sequencing (scRNAseq) datasets. The identified T2D-specific gene features were further validated in an additional T2D scRNAseq dataset, a T1D scRNAseq dataset, and a T2D bulkseq dataset. To investigate regulatory networks, we analyzed the potential lncRNA-mRNA interactions within T2D peripheral blood mononuclear cell (PBMC) bulkseq data.

Results

Our analysis identified a specific gene panel—COL1A2, VCAN, and SULF1—that was consistently upregulated in T2D pancreatic islet samples. Expression of this gene panel was strongly associated with the activation of pancreatic stellate cells (PSCs), suggesting a unique T2D-specific signature characterized by COL1A2hi/VCANhi/SULF1hi PSCs. This signature was exclusive to T2D and was not observed in Type 1 diabetes (T1D) samples, indicating a distinct role for activated PSCs in T2D progression. Furthermore, we identified six long non-coding RNAs (lncRNAs) that potentially interact with the COL1A2hi/VCANhi/SULF1hi PSCs. These lncRNAs were mapped to a lncRNA-mRNA network, suggesting they may modulate immune responses and potentially reshape the immune microenvironment in T2D.

Discussion

Our findings highlight the potential immune-regulatory role of PSCs in T2D and suggest that PSC-related lncRNA-mRNA networks could serve as novel therapeutic targets for T2D treatment. This research provides insights into PSCs as a modulator in T2D progression, paving the way for innovative treatment strategies.
An EfficientNetv2-based method for coal conveyor belt foreign object detection
Authors: Hu Tao , Zhuang Deyu , Qiu Jinbo
Published: January 2025

The detection and recognition of foreign objects on coal conveyor belts play a crucial role in coal production. This article proposes a foreign object detection method for coal conveyor belts based on EfficientNetv2. Since MBConv and Fused-MBConv structures in EfficientNetv2 employ information compression and fusion strategies, which may lead to the loss of important information and affect the integrity of feature extraction, a hard shuffle attention (Hard-SA) mechanism is utilized to enhance the focus on important features and improve the representation ability of coal conveyor belts image features. To address the potential gradient disappearance issue during the backpropagation process of the network, an elastic exponential linear unit (EELU) activation function is introduced. Additionally, since the cross-entropy loss function may not be flexible enough to handle complex data distributions and may fail to fit the non-linear relationships between data well, a Polyloss function is adopted. Polyloss can better adapt to the complex data distribution and task requirements of coal mine images. The experimental results show that the proposed method achieves an accuracy of 93.02%, which is 2.39% higher than that of EfficientNetv2. It also outperforms some other state-of-the-art (SOTA) models and can effectively complete the detection of foreign objects on coal conveyor belts.
Species distribution modelling and landscape connectivity as tools to inform management and conservation for the critically endangered Himalayan brown bear (Ursus arctos isabellinus) in the Deosai National Park, Pakistan
Authors: Fida Tosif , Mohammadi Alireza , Almasieh Kamran , Bosso Luciano , Ud Din Shams , Shamas Urwah , Nawaz Muhammad Ali , Kabir Muhammad
Published: January 2025

The main cause of the global threat to large carnivore populations living in high-altitude areas is human pressure. The Himalayan brown bear (Ursus arctos isabellinus, hereafter bear) is listed as a critically endangered species, and it dominates the higher altitudes of the North and Western Himalayan landscapes. Here, we used species distribution modelling and landscape connectivity to find bears’ suitable habitats and corridors in the Deosai National Park (DNP) and surrounding areas. Species distribution models detected a bear’s suitable habitat of 1,125 km2, of which ca. 73% was covered by DNP. The most crucial predictors in determining the bears’ distribution were elevation—particularly if it was between 3,500 and 4,500 meters above sea level—as well as the bears’ distance from rivers, cattle, and the DNP borders. We discovered robust connectivity among presence points in the core of the study area, particularly within the DNP boundaries, by using the electrical circuit theory models. Landscape connectivity values were indeed low in some areas outside and close to the DNP confines. Based on our findings, it is imperative to protect habitats and corridors that allow the bears to migrate between the suitable patches, particularly beyond the park’s boundaries, to improve bear conservation.
Uncovering somatic mosaic variants of PIK3CA-related overgrowth disorders – three cases with different clinical presentations
Authors: Tooming M. , Mertsina P. , Kahre T. , Teek R. , Vainumäe I. , Lilles S. , Wojcik M. H. , Ilves P. , Õunap K.
Published: January 2025

Introduction

PIK3CA related disorders (PRD, OMIM: *171834) are genetic disorders resulting from pathogenic somatic mosaic variants in the PIK3CA gene, which encodes a protein crucial for regulating cell growth and division. PRD typically manifest during the post-zygotic phase, leading to a broad spectrum of overgrowth and vascular malformations affecting various body regions.

Methods

Conventional diagnostic methods struggle to detect and confirm pathogenic PIK3CA gene variants due to the mosaic nature of these disorders and the limited accessibility of affected tissues. In this study, we conducted comprehensive genomic profiling on a cohort of individuals with PRD to address these diagnostic challenges.

Results

Our analysis revealed significant diagnostic challenges posed by somatic mosaicism in PRD. The comprehensive genomic profiling allowed for the meticulous evaluation of potentially pathogenic gene variants in affected individuals and their corresponding tissues.

Discussion

Our findings advocate for the adoption of comprehensive genomic profiling in clinical practice to improve the detection and management of PRD. This approach can enhance patient care by providing a more accurate diagnosis and better understanding of the genetic underpinnings of PRD.
Identification and validation of BATF as a prognostic biomarker and regulator of immune cell infiltration in acute myeloid leukemia
Authors: Zhao Zhe , Wang Dongmei , Sheng Xue , Li Shuying , Liu Tingting , Chang Mengyuan , Feng Lei , Zhang Di , Ji Chunyan , Lu Fei , Ye Jingjing
Published: January 2025

Background

Basic leucine zipper ATF-like transcription factor (BATF) is a nuclear basic leucine zipper protein affiliated with the AP-1/ATF superfamily. Previous research has confirmed that BATF expression plays a significant role in the tumour microenvironment. However, the associations between BATF expression and prognoses in acute myeloid leukaemia (AML) patients and their immunological effects remain unclear.

Methods

Genomic and clinical AML data were got from the TCGA (TCGA-LAML) and GEO (GSE37642) databases for the subsequent analysis. The expression levels of BATF in AML patients were assessed using GEPIA, and the results were verified by qRT-PCR and Western blotting. In the meantime, the prognostic value of BATF was evaluated using univariate and multivariate analyses, receiver operating characteristic (ROC) curve (AUC) analysis, and Kaplan-Meier (KM) survival analysis. EdU, colony formation, and CCK-8 assays were employed to evaluate the proliferation of cells. Moreover, we detected the association of BATF expression with drug sensitivity through database analysis and in vivo experiments. To further investigate the mechanism of action of BATF in AML, RNA sequencing (RNA-seq) analysis was performed, followed by pathway enrichment analysis using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Meanwhile, we detected the connection between BATF expression and the proportions of immune cells via flow cytometry in C1498 mouse model of AML. Finally, we investigated the association between BATF expression and cell-cell communication within the AML cell population using single-cell sequencing.

Results

In this study, we thoroughly investigated the role of BATF in AML. First, we observed a significant elevation in the expression of BATF in patients and cells in AML. Further analysis revealed an association between high BATF expression and poor prognosis in AML. Additionally, BATF expression was found to promote the proliferative capacity of AML cells. Moreover, the results showed that the expression level of BATF dramatically affected the effect of chemotherapy in AML patients. We also discovered that BATF expression could activate multiple immune-related pathways, altering the proportions of CD8+T cells and NK cells, suggesting that BATF may be a regulator of immune cell infiltration. Finally, there were differences in receptor ligand pairs between AML cells with high and low expression of BATF and immune cells.

Conclusion

Bioinformatics analysis and experimental verification revealed that BATF expression could alter the proportions of CD8+T cells and NK cells in AML and affect drug sensitivity, making it a potential treatment target for AML.
Unravelling the impact of SARS-CoV-2 on hemostatic and complement systems: a systems immunology perspective
Authors: Murad Didar , Paracha Rehan Zafar , Nisar Maryum
Published: January 2025

The hemostatic system prevents and stops bleeding, maintaining circulatory integrity after injury. It directly interacts with the complement system, which is key to innate immunity. In coronavirus disease 2019 (COVID-19), dysregulation of the hemostatic and complement systems has been associated with several complications. To understand the essential balance between activation and regulation of these systems, a quantitative systems immunology model can be established. The dynamics of the components are examined under three distinct conditions: the disease state representing symptomatic COVID-19 state, an intervened disease state marked by reduced levels of regulators, and drug interventions including heparin, tranexamic acid, avdoralimab, garadacimab, and tocilizumab. Simulation results highlight key components affected, including thrombin, tissue plasminogen activator, plasmin, fibrin degradation products, interleukin 6 (IL-6), the IL-6 and IL-6R complex, and the terminal complement complex (C5b-9). We explored that the decreased levels of complement factor H and C1-inhibitor significantly elevate these components, whereas tissue factor pathway inhibitor and alpha-2-macroglobulin have more modest effects. Furthermore, our analysis reveals that drug interventions have a restorative impact on these factors. Notably, targeting thrombin and plasmin in the early stages of thrombosis and fibrinolysis can improve the overall system. Additionally, the regulation of C5b-9 could aid in lysing the virus and/or infected cells. In conclusion, this study explains the regulatory mechanisms of the hemostatic and complement systems and illustrates how the biopathway machinery sustains the balance between activation and inhibition. The knowledge that we have acquired could contribute to designing therapies that target the hemostatic and complement systems.
Increases in the susceptibility of human endometrial CD4+ T cells to HIV-1 infection post-menopause are not dependent on greater viral receptor expression frequency
Authors: vom Steeg Landon G. , Shen Zheng , Collins Jane , Patel Mickey V. , Barr Fiona D. , Hopkins Daniel C. , Ochsenbauer Christina , Wira Charles R.
Published: January 2025

Epidemiological evidence suggests that post-menopausal women are more susceptible to HIV infection following sexual intercourse than are younger cohorts for reasons that remain unclear. Here, we evaluated how menopause-associated changes in CD4+ T cell numbers and subsets as well as HIV coreceptor expression, particularly CCR5, in the endometrium (EM), endocervix (CX), and ectocervix (ECX) may alter HIV infection susceptibility. Using a tissue-specific mixed cell infection model, we demonstrate that while no changes in CD14+ macrophage infection susceptibility were observed, CD4+ T cell HIV-1 infection frequency increases following menopause in the EM, but not CX nor ECX. Unexpectedly, the CD4+ T cell expression of two known correlates of HIV infection susceptibly, CCR5 and integrin-α4β7, increased following menopause across all three tissues despite only being associated with increased infection frequency in EM derived CD4+ T cells. After controlling for changes in the expression of either receptor, both CCR5 and α4β7 expressing CD4+ T cells isolated from the EM of post-menopausal women remained more susceptible to HIV-1 infection than those isolated from pre-menopausal women. Shifts in T helper subset composition, including increases in Th1 frequency and decreases in Th17 and Treg frequency were also observed in the EM only following menopause, but did not correlate with increased infection frequency. Treatment of EM derived CD4+ T cells with 17β-estradiol (E2) prior to viral infection, reduced infection frequency independent of changes in either CCR5 or α4β7 expression frequency. Our results demonstrate that the susceptibility of EM derived CD4+ T cells to HIV-1 infection increases post menopause but is unlikely to be driven by increased expression frequency of either CCR5 or integrin-α4β7. These findings contribute to our understanding of how advanced age alters HIV infection risk which will become increasingly important as the human population continues to age.
New insights into the ferroptosis and immune infiltration in endometriosis: a bioinformatics-based analysis
Authors: Liu Lusha , Han Feifei , Du Naiyi , Liu Yakun , Duan Aihong , Kang Shan , Li Bin
Published: January 2025

Background

Ferroptosis, a recently discovered iron-dependent cell death, is linked to various diseases but its role in endometriosis is still not fully understood.

Methods

In this study, we integrated microarray data of endometriosis from the GEO database and ferroptosis-related genes (FRGs) from the FerrDb database to further investigate the regulation of ferroptosis in endometriosis and its impact on the immune microenvironment. WGCNA identified ferroptosis-related modules, annotated by GO & KEGG. MNC algorithm pinpointed hub FRGs. Cytoscape construct a ceRNA network, and ROC curves evaluated diagnostic efficacy of hub FRGs. Consensus cluster analysis identified ferroptosis subclusters, and CIBERSORT assessed immune infiltration of these subclusters. Finally, RT-qPCR validated hub FRG expression in clinical tissues.

Results

We identified two ferroptosis modules of endometriosis, and by enrichment analysis, they are closely linked with autophagy, mTOR, oxidative stress, and FOXO pathways. Furthermore, we identified 10 hub FRGs, and the ROC curve showed better predictive ability for diagnosing. RT-qPCR confirmed that the tissue expression of 10 hub FRGs was mostly consistent with the database results. Subsequently, we developed a ceRNA network based on 4 FRGs (BECN1, OSBPL9, TGFBR1, GSK3B). Next, we identified two ferroptosis subclusters of endometriosis and discovered that they are closely linked with endometriosis stage. Importantly, immune enrichment analysis illustrated that the expression levels of immune cells and immune checkpoint genes were significantly different in the two ferroptosis subclusters. Specifically, the ferroptosis subcluster with stage III-IV of endometriosis is more inclined to the immunosuppressive microenvironment.

Conclusions

Our study showed that ferroptosis may jointly promote endometriosis progression by remodeling the immune microenvironment, offering new insights into pathogenesis and therapeutics.
Early transcriptomic changes at the skin interface during Powassan virus transmission by Ixodes scapularis ticks
Authors: Paine Dakota N. , Hermance Meghan , Thangamani Saravanan
Published: January 2025

Introduction

Powassan virus (POWV), a vector-borne pathogen transmitted by Ixodes ticks in North America, is the causative agent of Powassan encephalitis. As obligate hematophagous organisms, ticks transmit pathogens like POWV at the tick bite site, specifically during the initial stages of feeding. Tick feeding and salivary factors modulate the host’s immunological responses, facilitating blood feeding and pathogen transmission. However, the mechanisms of immunomodulation during POWV transmission remain inadequately understood. In this study, we investigated the global cutaneous transcriptomic changes associated with tick bites during POWV transmission.

Methods

We collected skin biopsies from the tick attachment sites at 1, 3, and 6 h after feeding by POWV-infected and uninfected ticks, followed by RNA sequencing of these samples. Differentially expressed genes were analyzed for pathway enrichment using gene ontology and pathway enrichment analyses.

Results

Our findings reveal that tick feeding alone significantly impacts the skin transcriptome within the first 1 to 3 h of tick attachment. Although early POWV transmission induces minimal changes in the local environment, a pronounced shift toward a proinflammatory state is observed 6 h after tick attachment, characterized by neutrophil recruitment and interleukin signaling.

Discussion

These transcriptomic data elucidate the dynamic changes at the tick bite site, transitioning from changes that assist blood meal acquisition to a proinflammatory phase that may facilitate viral dissemination.
Targeted intra-tumoral hyperthermia using uniquely biocompatible gold nanorods induces strong immunogenic cell death in two immunogenically ‘cold’ tumor models
Authors: Kennedy Barry E. , Noftall Erin B. , Dean Cheryl , Roth Alexander , Clark Kate N. , Rowles Darren , Singh Kulbir , Pagliaro Len , Giacomantonio Carman A.
Published: January 2025

Introduction

Hyperthermia is an established adjunct in multimodal cancer treatments, with mechanisms including cell death, immune modulation, and vascular changes. Traditional hyperthermia applications are resource-intensive and often associated with patient morbidity, limiting their clinical accessibility. Gold nanorods (GNRs) offer a precise, minimally invasive alternative by leveraging near-infrared (NIR) light to deliver targeted hyperthermia therapy (THT). THT induces controlled tumor heating, promoting immunogenic cell death (ICD) and modulating the tumor microenvironment (TME) to enhance immune engagement. This study explores the synergistic potential of GNR-mediated THT with immunotherapies in immunogenically ‘cold’ tumors to achieve durable anti-tumor immunity.

Methods

GNRs from Sona Nanotech Inc.™ were intratumorally injected and activated using NIR light to induce mild hyperthermia (42–48°C) for 5 minutes. Tumor responses were analyzed for cell death pathways and immune modulation. The immunogenic effects of THT were assessed alone and in combination with intratumoral interleukin-2 (i.t. IL-2) or systemic PD-1 immune checkpoint blockade. Immune cell infiltration, gene expression changes, and tumor growth kinetics were evaluated.

Results

THT reduced tumor burden through cell death mechanisms, including upregulated ICD marked by calreticulin exposure within 48 hours. By 48 hours, CD45+ immune cell levels were increased, including increased levels of immunosuppressive M2 macrophages. While THT led to innate immune cell stimulations highlighted by gene expression upregulation in the STING cGAS pathway and enhanced M1 and dendritic cell levels, tumor regrowth was observed within six days post-treatment. To enhance THT's immunogenic effects, the therapy was combined with intratumoral interleukin-2 (i.t. IL-2) or systemic PD-1 immune checkpoint blockade. Sequential administration of i.t. IL-2 post-THT induced robust CD8+ T-cell infiltration and led to sustained tumor regression in both treated and distant tumors, accompanied by the emergence of memory T cells. However, IL-2-induced immunosuppressive T-reg populations were also sustained to tumor endpoint suggesting that therapy could be further enhanced. Additionally, PD-1 expression, which was upregulated in CD8+ T cells by THT, was targeted with systemic PD-1 inhibition, further augmenting immune engagement within the TME.

Discussion

These combinatory treatments demonstrated synergistic effects, promoting durable anti-tumor responses and immune memory. Collectively, GNR-mediated THT effectively reduces tumor burden and remodels the TME, potentiating systemic immunity and enhancing the impact of complementary immunotherapies.
Multiomics characterization of breast angiosarcoma from an Asian cohort reveals enrichment for angiogenesis signaling pathway and tumor-infiltrating macrophages
Authors: Ko Tun Kiat , Guo Zexi , Kannan Bavani , Lim Boon Yee , Lee Jing Yi , Li Zhimei , Lee Elizabeth Chun Yong , Teh Bin Tean , Chan Jason Yongsheng
Published: January 2025

Introduction

Recent epidemiological data suggests a rising incidence of breast angiosarcoma (AS-B) in the Western population, with over two-thirds related to irradiation or chronic lymphedema. However, unlike head and neck angiosarcoma (AS-HN), AS-B disease characteristics in Asia remain unclear.

Methods

We examined clinical patterns of angiosarcoma patients (n = 176) seen in an Asiantertiary cancer center from 1999 to 2021, and specifically investigated the molecular and immune features of AS-B in comparison to AS-HN. Data from whole genome sequencing (WGS), NanoString gene expression profiling and 10x Genomics Visium spatial transcriptomics were analyzed.

Results

Majority of cases were AS-HN (n = 104; 59.1%), while AS-B (n = 16, all females) accounted for 9.1% of the cases. The median age at diagnosis was 43 years (range, 26 to 74). Based on WGS, 4 of the 7 AS-B had non-synonymous somatic variants in 47 genes (range, 2 to 28 per case). These genes were functionally annotated and were enriched in cancer-related pathways such as regulation of cell differentiation, VEGFR and receptor tyrosine kinases signaling pathways. By NanoString gene expression profiling, ASB, compared to AS-HN, were enriched for angiogenesis, notch signaling and metastasis-associated matrix remodeling pathways. Additionally, AS-B were enriched for macrophages and CD8+ T cells expression signatures. Similarly, Visium spatial transcriptomics showed that AS-B were enriched for macrophages and T-cells.

Discussion

In conclusion, in our AS-B cases, we observed a convergence of both mutational and expression signatures on angiogenic-related pathways. Thus, anti-angiogenic therapy could be an option to treat AS-B.
Expert insights on Hodgkin’s lymphoma development in an activated PI3K delta syndrome patient undergoing leniolisib treatment
Authors: Conti Francesca , Moratti Mattia , Sabattini Elena , Zinzani Pier Luigi
Published: January 2025

Activated PI3K delta syndrome (APDS) is a primary immunodeficiency that is caused by mutations in the PI3K signalling pathway resulting in either gain-of-function or loss-of-function phenotypes of APDS 1 and 2. Malignancy is one of the most serious complications associated with APDS patients, with the most commonly occurring of these being lymphoma, and is the most common cause of death in APDS patients. Management of APDS is complex and variable due to the heterogeneous nature of the disease and ranges from antimicrobial and immunosuppressant agents to haematopoetic stem cell transplantation. More recently, an increasing level of interest has been shown in the use of more targeted agents such as PI3Kδ-specific inhibitors. Here, we provide expert perspective on the suspected causality of a case of lymphoma observed in a 20-year-old female patient who was included in a clinical trial of leniolisib, a PI3K inhibitor.
Single-cell RNA-seq reveals immune cell heterogeneity and increased Th17 cells in human fibrotic skin diseases
Authors: Deng Cheng-Cheng , Xu Xue-Yan , Zhang Yan , Liu Long-Can , Wang Xuan , Chen Jun-Yi , Yao Liu-Yi , Zhu Ding-Heng , Yang Bin
Published: January 2025

Background

Fibrotic skin disease represents a major global healthcare burden, characterized by fibroblast hyperproliferation and excessive accumulation of extracellular matrix components. The immune cells are postulated to exert a pivotal role in the development of fibrotic skin disease. Single-cell RNA sequencing has been used to explore the composition and functionality of immune cells present in fibrotic skin diseases. However, these studies detected the gene expression of all cells in fibrotic skin diseases and did not enrich immune cells. Thus, the precise immune cell atlas in fibrotic skin diseases remains unknown. In this study, we plan to investigate the intricate cellular landscape of immune cells in keloid, a paradigm of fibrotic skin diseases.

Methods

CD45+ immune cells were enriched by fluorescence-activated cell sorting. Single-cell RNA sequencing was used to analyze the cellular landscape of immune cells in keloid and normal scar tissues. Ki-67 staining, a scratch experiment, real-time PCR, and Western blotting were used to explore the effect of the Th17 cell supernatant on keloid fibroblasts.

Results

Our findings revealed the intricate cellular landscape of immune cells in fibrotic skin diseases. We found that the percentage of Th17 cells was significantly increased in keloids compared to normal scars. All the subclusters of macrophages and dendritic cells (DCs) showed similar proportions between keloid samples and normal scar samples. However, upregulated genes in keloid M1 macrophages, M2 macrophages, and cDC2 are associated with the MHC class II protein complex assembly and antigen assembly, indicating that macrophages and cDC2 are active in keloids. Functional studies suggested that the supernatant of Th17 cells could promote proliferation, collagen expression, and migration of keloid fibroblasts through interleukin 17A. Importantly, increased Th17 cells are also found in other fibrotic skin diseases, such as hypertrophic scars and scleroderma, suggesting this represents a broad mechanism for skin fibrosis.

Conclusion

In summary, we built a single-cell atlas of fibrotic skin diseases in this study. In addition, we explored the function of Th17 cell-fibroblast interaction in skin fibrosis. These findings will help to understand fibrotic skin disease pathogenesis in depth and identify potential targets for fibrotic skin disease treatment.
Comparison of safety and effectiveness of medical adhesive and metal spring coil in preoperative localization of peripheral pulmonary nodules
Authors: Wang Yifei , Yue Zhenhua , Shi Xiaoqian , Xia Guozhan , Qin Linlin , Sun Qi , Huang Yiling , Chen Rong , Zhao Xuewei , Wang Mingdong
Published: January 2025

Background

Accurate preoperative positioning is the key to the success of thoracoscopic surgery for small pulmonary nodules. There are many methods for locating pulmonary nodules in clinical practice, but there are currently few research reports on the value of medical adhesive localization.

Objective

To compare the clinical value of two positioning methods, medical adhesive and metal spring coil, in the preoperative application of VATS through retrospective analysis.

Methods

A total of 288 patients who underwent thoracoscopic surgery in our hospital from January 2021 to June 2024 due to the discovery of solitary pulmonary nodules during chest CT examination were included in this study. Preoperative patients were randomly divided into two groups, with 205 patients undergoing preoperative medical adhesive positioning (Group A) and 83 patients undergoing metal spring coil positioning (Group B). After the positioning was completed, record the positioning time of each group of patients and the immediate pain score 15 min after the positioning was completed, the complications located in each group of patients, and whether there was positioning failure or not.

Results

The localization success rate of the medicine adhesive positioning group [99.5% (204/205)] was higher than that of the metal spring coil positioning group [91.6% (76/83)] (P = 0.001). The positioning time of the medical adhesive positioning group was 12.00 (10.00, 14.00) min, which was shorter than the 13.00 (11.00, 16.00) min of the micro coil group (P = 0.001). The immediate pain score (2.32 ± 0.79) of the medical adhesive positioning group 15 min after positioning was significantly lower than that of the metal spring coil positioning group (3.97 ± 0.54) (P < 0.001). The incidence of complications such as pneumothorax [15.7% (13/83) vs 5.4% (11/205), P = 0.004], pulmonary hemorrhage/hemoptysis [20.5% (17/83) vs 4.9 (10/205), P < 0.001] was significantly higher in the metal coil positioning group than in the medical adhesive positioning group.

Conclusion

Preoperative medical adhesive positioning for pulmonary nodules is safe, reliable, and effective. Compared with metal spring coil positioning, it has shorter positioning time, milder pain after positioning, lower incidence of positioning related complications, and more flexible arrangement of surgical timing after positioning. It has high clinical application value.