Linear semantic transformation for semi-supervised medical image segmentation.

Medical image segmentation is a focus research and foundation in developing intelligent medical systems. Recently, deep learning for medical image segmentation has become a standard process and succeeded significantly, promoting the development of reconstruction, and surgical planning of disease diagnosis. However, semantic learning is often inefficient owing to the lack of supervision of feature maps, resulting in that high-quality segmentation models always rely on numerous and accurate data annotations. Learning robust semantic representation in latent spaces remains a challenge. In this paper, we propose a novel semi-supervised learning framework to learn vital attributes in medical images, which constructs generalized representation from diverse semantics to realize medical image segmentation. We first build a self-supervised learning part that achieves context recovery by reconstructing space and intensity of medical images, which conduct semantic representation for feature maps. Subsequently, we combine semantic-rich feature maps and utilize simple linear semantic transformation to convert them into image segmentation. The proposed framework was tested using five medical segmentation datasets. Quantitative assessments indicate the highest scores of our method on IXI (73.78%), ScaF (47.50%), COVID-19-Seg (50.72%), PC-Seg (65.06%), and Brain-MR (72.63%) datasets. Finally, we compared our method with the latest semi-supervised learning methods and obtained 77.15% and 75.22% DSC values, respectively, ranking first on two representative datasets. The experimental results not only proved that the proposed linear semantic transformation was effectively applied to medical image segmentation, but also presented its simplicity and ease-of-use to pursue robust segmentation in semi-supervised learning. Our code is now open at: https://github.com/QingYunA/Linear-Semantic-Transformation-for-Semi-Supervised-Medical-Image-Segmentation.

Deep learning signature based on multiphase enhanced CT for bladder cancer recurrence prediction: a multi-center study.

Background: Accurate stratification of recurrence risk for bladder cancer (BCa) is essential for precise individualized therapy. This study aimed to develop and validate a model for predicting the risk of recurrence in BCa patients postoperatively using 3-phase enhanced CT images. Methods: We retrospectively enrolled 874 BCa patients across four centers between January 2006 and December 2021. Patients from one center were used as training set, while the remaining patients went into the validation set. We trained a deep learning (DL) model based on convolutional neural networks using 3-phase enhanced CT images. The resulting prediction scores were entered into Cox regression analysis to obtain DL scores and construct a DL signature. DL scores and clinical features were then used as deep learning radioclinical signature. The predictive performance of DL signature was assessed according to concordance index and area under curve compared with deep learning radioclinical signature, clinical model and a widely accepted staging grading system. Recurrence-free survival (RFS) and overall survival (OS) were also predicted in order to further assess survival benefits. Findings: DL signature showed strong power for predicting recurrence (concordance index, 0.869; area under curve, 0.889) in validation set, outperforming other models and system. In addition, we divided RFS and OS into high and low risk groups by selecting appropriate cutoff values for DL signature, and calculated cumulative recurrence risk rates for both groups. Interpretation: Our proposed DL signature shows promising potential as clinical aid for predicting postoperative recurrence risk in BCa and for stratifying the risk of RFS and OS, which can be applied to guide personalized precision therapy. Funding: There are no sources of funding for this manuscript.

Cytomegalovirus Pneumonia in Inflammatory Bowel Disease: Literature Review and Clinical Recommendations.

Aim: The objective was to elucidate the correlation between CMVP and immunosuppressive therapy in IBD patients, we hope this review could expand on the significance of CMV as an opportunistic pathogen and the potential impact on morbidity and mortality in IBD patients. Methods: Records and clinical trajectories linked to CMVP in IBD patients were extracted from the PubMed database, irrespective of language barriers. The reference lists incorporated in these studies were manually inspected. Conclusions were generated using straightforward descriptive analysis. Results: In total, 18 IBD patients, including Crohn's disease (CD, 67%) and Ulcerative Colitis (UC, 33%), affected by CMVP were identified from 17 published articles. A minority of these patients (17%) exhibited active disease, whereas the majority (83%) presented with quiescent disease. Fever (100%) and dyspnea (44%) emerged as the most prevalent clinical symptoms. All the patients had undergone immunosuppressive therapy. A significant proportion, up to 89%, had received thiopurine treatment prior to the CMVP diagnosis. Interestingly, none of the patients were subjected to biological therapy. Half of the patients manifested with Hemophagocytic Lymphohistiocytosis (HLH). Almost all patients (94%) were administered antiviral treatment and a substantial 83% experienced full recovery. Immunosuppressive agents were either tapered or discontinued altogether. A subset of patients, 17%, suffered fatal outcomes. Conclusion: Our findings underscore the need for heightened suspicion of CMVP in IBD patients who exhibit symptoms such as fever and dyspnea. During the COVID-19 pandemic, CMVP should be considered a potential differential diagnosis. It was observed that CMVP primarily transpires during CD remission. Azathioprine emerged as the predominant immunosuppressant linked to CMV reactivation. The prompt application of effective antiviral therapy can substantially enhance patient outcomes. CMV vaccine might serve as a viable prevention strategy.

N-Acetylglucosamine mitigates lung injury and pulmonary fibrosis induced by bleomycin.

Lung injury and pulmonary fibrosis contribute to morbidity and mortality, and, in particular, are characterized as leading cause on confirmed COVID-19 death. To date, efficient therapeutic approach for such lung diseases is lacking. N-Acetylglucosamine (NAG), an acetylated derivative of glucosamine, has been proposed as a potential protector of lung function in several types of lung diseases. The mechanism by which NAG protects against lung injury, however, remains unclear. Here, we show that NAG treatment improves pulmonary function in bleomycin (BLM)-induced lung injury model measured by flexiVent system. At early phase of lung injury, NAG treatment results in silenced immune response by targeting ARG1+ macrophages activation, and, consequently, blocks KRT8+ transitional stem cell in the alveolar region to stimulate PDGF Rß+ fibroblasts hyperproliferation, thereby attenuating the pulmonary fibrosis. This combinational depression of immune response and extracellular matrix deposition within the lung mitigates lung injury and pulmonary fibrosis induced by BLM. Our findings provide novel insight into the protective role of NAG in lung injury.

Ferroptosis: A potential therapeutic target in autoimmune disease (Review).

Ferroptosis is a distinct type of regulated cell death characterized by iron overload and lipid peroxidation. Ferroptosis is regulated by numerous factors and controlled by several mechanisms. This cell death type has a relationship with the immune system, which may be regulated by damage-associated molecular patterns. Ferroptosis participates in the progression of autoimmune diseases, including autoimmune hepatitis, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, multiple sclerosis, Parkinson's Disease, psoriasis and insulin-dependent diabetes mellitus. The present review summarizes the role of ferroptosis in autoimmune disorders and discusses ferroptosis as a potential therapeutic target for autoimmune disease.

A Hydrazine-Nitrate Flow Battery Catalyzed by a Bimetallic RuCo Precatalyst for Wastewater Purification along with Simultaneous Generation of Ammonia and Electricity.

The traditional technologies for industrial and agricultural effluent treatment are often energy-intensive. Herein, we suggest an electrochemical redox strategy for spontaneous and simultaneous decontamination of wastewater and generation of both fuels and electricity at low cost. Using hydrazine and nitrate effluents as a demonstration, we propose a hydrazine-nitrate flow battery (HNFB) that can efficiently purify the wastewater and meanwhile generate both ammonia fuel and electricity with the assistance of our developed bimetallic RuCo precatalyst. Specifically, the battery delivers a peak power density of 12 mW cm-2 and continuously operates for 20 h with an ammonia yield rate of ca. 0.38 mmol h-1 cm-2 under 100 mA cm-2 . The generated electricity can further drive a hydrazine electrolyzer to produce hydrogen fuel. Our work provides an alternative pathway to purify wastewater and generate high value-added fuels at low cost.

Diagnosis and treatment of gastric hamartomatous inverted polyp (GHIP) by endoscopic submucosal dissection: A case report.

RATIONALE: Gastric hamartomatous inverted polyps (GHIP) is not a common disease, and it has rarely been reported in the literature. Preoperative diagnosis is difficult due to the deep position and surface covered with normal gastric mucosa. However, with the progress of endoscopic technology, endoscopic submucosal dissection (ESD) can play a crucial role in the diagnosis and treatment of GHIP. PATIENT CONCERNS: A 61-year-old Chinese man underwent gastroscopy due to abdominal pain 2 months prior that revealed chronic superficial nonatrophic gastritis with erosion and a submucosal tumor in the gastric body (an ultrasound gastroscopy was recommended). Therefore, he was admitted to our hospital for further diagnosis and treatment. DIAGNOSES: A hemispherical submucosal tumor was found in the middle segment of the stomach, with a size of approximately 30 mm × 35 mm and a smooth surface without central ulceration or mucosal bridge formation. Ultrasound gastroscopy showed that the lesion was a hypoechoic mass with uniform internal echo originating from the muscularis propria. INTERVENTIONS: The tumor was completely removed by using ESD. The postoperative pathological results indicated a monocystic structure in the submucosa that was not connected with the surface mucosa. The surface of the cyst was covered with foveolar cells and mucous-neck cells (part of which had low-grade intraepithelial neoplasia), and GHIP was considered to be diagnosed. OUTCOMES: According to the abovementioned endoscopic and pathological features, the patient was finally diagnosed with GHIP. The patient was successfully discharged after surgery and received regular follow-up observations. LESSONS: GHIP is located in the submucosa layer and has the potential risk of malignant transformation. However, it is not easy to diagnose by using gastroscopy and ultrasound gastroscopy. ESD can obtain complete specimens, which contributes to the diagnosis and treatment of GHIP.

High level of thyroid peroxidase antibodies as a detrimental risk of pregnancy outcomes in euthyroid women undergoing ART: A meta-analysis.

Thyroid autoimmunity (TAI) triggered by genetic and epigenetic variation occurs mostly in women of reproductive age. TAI is described mainly by positivity of anti-thyroid peroxidase antibody (TPO-Ab) and/or thyroglobulin antibody (TG-Ab). TPO-Ab, but not TG-Ab, was suggested to be associated with pregnancy outcome in euthyroid women undergoing assisted reproductive technology (ART), but their results are conflicting. This meta-analysis was performed to decide whether the presence of TPO-Ab-in a concentration dependent manner-correlates with the success of ART. A systematic literature search was performed in the PubMed, Web of Science, and EMBASE databases for relevant articles published from January 1999 to April 2022, and these studies focused on the effect of TAI on pregnancy outcomes of women who underwent in vitro fertilization, intracytoplasmic sperm injection and intrauterine insemination and met the inclusion criteria: (i) the studies were prospective or retrospective study; (ii) all patients undergoing ART were tested for thyroid-related antibodies; (iii) the assessed ART outcomes included miscarriage rate (MR) or delivery rate (DR). The exclusion criteria were: (i) female congenital uterine malformation, chromosomal diseases and other infectious diseases; (ii) overt hypothyroidism or pre-existing thyroid disease; (iii) thrombus tendency. We divided the included patients into three groups according to the TPO-Ab threshold they defined: (i) TPO-Ab (-), threshold <34 IU/mL; (ii) TPO-Ab-34, threshold >34 IU/mL; (iii) TPO-Ab-100, threshold >100 IU/mL. We then extracted necessary relevant data, including MR and DR. Egger's test was used to evaluate the risk of publication bias. This meta-analysis included a total of 7 literatures involving 7466 patients with TAI (-) and 965 patients with TAI (+) and revealed that there was no significant difference between group TPO-Ab-34 and group TPO-Ab (-) in MR [risk ratio (RR): 0.61 (0.35, 1.08), p = 0.09] and DR [RR: 0.97 (0.83, 1.13), p = 0.69]. By contrast, compared to TPO-Ab (-) group, TPO-Ab-100 patients showed markedly higher MR [RR: 2.12 (1.52, 2.96), p = 0.0046], and lower DR [RR: 0.66 (0.49, 0.88), p < 0.0001] with high degree of statistical significance. This meta-analysis suggests that, for euthyroid patients, high level of TPO-Ab (>100 IU/mL) could adversely influence the pregnancy outcome of ART.

FDE-net: Frequency-domain enhancement network using dynamic-scale dilated convolution for thyroid nodule segmentation.

Thyroid nodules, a common disease of endocrine system, have a probability of nearly 10% to turn into malignant nodules and thus pose a serious threat to health. Automatic segmentation of thyroid nodules is of great importance for clinicopathological diagnosis. This work proposes FDE-Net, a combined segmental frequency domain enhancement and dynamic scale cavity convolutional network for thyroid nodule segmentation. In FDE-Net, traditional image omics method is introduced to enhance the feature image in the segmented frequency domain. Such an approach reduces the influence of noise and strengthens the detail and contour information of the image. The proposed method introduces a cascade cross-scale attention module, which addresses the insensitivity of the network to the change in target scale by fusing the features of different receptive fields and improves the ability of the network to identify multiscale target regions. It repeatedly uses the high-dimensional feature image to improve segmentation accuracy in accordance with the simple structure of thyroid nodules. In this study, 1355 ultrasound images are used for training and testing. Quantitative evaluation results showed that the Dice coefficient of FDE-Net in thyroid nodule segmentation was 83.54%, which is better than other methods. Therefore, FDE-Net can enable the accurate and rapid segmentation of thyroid nodules.

A rare discal cyst with concurrent double-level isthmic lumbar spondylolisthesis: a case report and literature review.

We presented a 47-year old male diagnosed as a discal cyst with concurrent isthmic lumbar spondylolisthesis, which was not reported in the literature previously. A cystectomy with two-segmental transforaminal lumbar interbody fusion and instruments was performed. The association between concurrent discal cyst and isthmic spondylolisthesis may be illuminated by excessive strain and focal degeneration of the disc. Preoperative discography is probably unnecessary when surgical resection and histopathology are indicated for the patient.

Atypical aggressive vertebral hemangioma of the sacrum with postoperative recurrence: A case report.

BACKGROUND: Aggressive vertebral hemangioma (VH) is an uncommon lesion in the adult population. The vast majority of aggressive VHs have typical radiographic features. However, preoperative diagnosis of atypical aggressive VH may be difficult. Aggressive VHs are likely to recur even with en bloc resection. CASE SUMMARY: A 52-year-old woman presented with a 3-mo history of numbness and pain in her right lower extremity. Physical examination showed sacral tenderness and limited mobility, and the muscle strength was grade 4 in the right digital flexor. Computed tomography revealed osteolytic bone destruction from S1 to S2. Magnetic resonance imaging (MRI) showed that the mass was compressing the dural sac; it was heterogeneously hypointense on T1-weighted MRI and hyperintense on T2-weighted MRI, and gadolinium contrast enhancement showed that the tumor was heterogeneously enhanced and invading the vertebral endplate of S1. The patient developed progressive back pain and numbness in the bilateral extremities 6 mo postoperatively, and MRI examination showed recurrence of the mass. The mass was larger in size than before the operation, and it was extending into the spinal canal. CONCLUSION: The radiographic findings of atypical aggressive VH include osteolytic vertebral bone destruction, extension of the mass into the spinal canal, and heterogeneous signal intensity on T1-, T2-, and enhanced T1-weighted MRI. These characteristics make preoperative diagnosis difficult, and biopsy is necessary to verify the lesion. Surgical decompression and gross total resection are recommended for treatment of aggressive VH. However, recurrence is inevitable in some cases.

miR-33a-5p Targets RAP2A to Mediate the Sensitivity of Gastric Cancer Cells to 5-FU.

Objective: The objective of this study is to explore the effects of microRNA-33a-5p (miR-33a-5p)-ras-related protein Rap-2a (RAP2A) on biological functions of gastric cancer (GC) and to find the potential functional mechanism. Methods: We measured the miR-33a-5p expression in 30 GC tissues and cellular level and 30 adjacent normal tissues as control. Besides, the expression of miR-33a-5p was checked at cell level as well. To screen the possible targets of miR-33a-5p, prediction software was used and gene RAP2A attracted our attention. Through a series of experiments including real-time polymerase chain reaction (qRT-PCR), luciferase assay, and western blotting (WB), we verified RAP2A as a potential target of miR-33a-5p. The impacts of miR-33a-5p and RAP2A on biological functions of GC cell lines (BGC-823 and MGC-803) were analyzed by subsequent experiments. Cell invasion was tested by invasion assays. Cell proliferation was measured by cell counting kit-8 (CCK-8) assay. Cell clone was measured by clone formation assays. Finally, the expression of RAP2A protein was analyzed by WB assay. Results: We found miR-33a-5p was expressed lowly in GC tissues and cells. Overexpression of miR-33a-5p in BGC-823 and MGC-803 cells greatly inhibited the cell invasion and colony number. Furthermore, compared to sh-control (shControl), RAP2A knockdown (sh-RAP2A/shRAP2A) raised the sensitivity of GC cells to 5-FU significantly, characterized as reducing cell apoptosis. Conclusions: The expression of miR-33a-5p was lower in GC cell lines and tissues obviously, indicating that miR-33a-5p served as the antitumor gene in GC. The expression of RAP2A regulated negatively the sensitivity of GC cells to 5-FU. According to our in vitro experiments, miR-33a-5p/RAP2A was likely to become a new therapeutic target for GC.

Coronary functional assessment in non-obstructive coronary artery disease: Present situation and future direction.

Non-obstructive coronary artery disease (CAD), which is defined as coronary stenosis <50%, has been increasingly recognized as an emerging entity in clinical practice. Vasomotion abnormality and coronary microvascular dysfunction are two major mechanisms contributing to the occur of angina with non-obstructive CAD. Although routine coronary functional assessment is limited due to several disadvantages, functional evaluation can help to understand the pathophysiological mechanism and/or to exclude specific etiologies. In this review, we summarized the potential mechanisms involved in ischemia with non-obstructive coronary arteries (INOCA) and myocardial infarction with non-obstructive coronary arteries (MINOCA), the two major form of non-obstructive CAD. Additionally, we reviewed currently available functional assessment indices and their use in non-obstructive CAD. Furthermore, we speculated that novel technique combined anatomic and physiologic parameters might provide more individualized therapeutic choice for patients with non-obstructive CAD.

Ferroptosis in COVID-19-related liver injury: A potential mechanism and therapeutic target.

The outbreak and worldwide spread of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a threat to global public health. SARS-CoV-2 infection not only impacts the respiratory system but also causes hepatic injury. Ferroptosis, a distinct iron-dependent form of non-apoptotic cell death, has been investigated in various pathological conditions, such as cancer, ischemia/reperfusion injury, and liver diseases. However, whether ferroptosis takes part in the pathophysiological process of COVID-19-related liver injury has not been evaluated yet. This review highlights the pathological changes in COVID-19-related liver injury and presents ferroptosis as a potential mechanism in the pathological process. Ferroptosis, as a therapeutic target for COVID-19-related liver injury, is also discussed. Discoveries in these areas will improve our understanding of strategies to prevent and treat hepatic injuries caused by COVID-19.

HuR Promotes the Progression of Gastric Cancer through Mediating CDC5L Expression.

Methods: We performed qRT-PCR, cell cycle assay, cell migration, and mouse transplantation model analysis in our experiments. It has been clarified that HuR and microRNAs (miRNAs) have important interplays in the regulation of tumor progression. Results: This study found microRNA-133b (miR-133b), as a HuR-sponged miRNA in GC cells. Downregulation of HuR can promote the expression of miR-133b and further affect the downstream cyclin CDC5L. The expressions of miR-133b were slightly lower in GC tissues than adjacent normal tissues. Conclusion: Our studies suggest that HuR and miR-133b are involved in the development and pathological process of GC cells.

Early detection of a cesarean scar pregnancy with placenta increta by contrast-enhanced ultrasound in the first trimester: A case report and literature review.

Cesarean scar pregnancy (CSP) is a rare form of ectopic pregnancy, which is a long-term complication of cesarean section. Prompt and accurate diagnosis of CSP is important to decrease maternal mobility and mortality. However, it is difficult to make an early detection for CSP complicated with morbidly adherent placenta. Contrast-enhanced ultrasound with the advantage in blood flow imaging is low-cost, time-saving, safe and more accessible in clinical practice. Here, we report a case with early detection of CSP with placenta increta by contrast-enhanced ultrasound and its successful uterine-sparing surgical management.

Comparative Analysis of Serum Proteins Between Hepatitis B Virus Genotypes B and C Infection by DIA-Based Quantitative Proteomics.

PURPOSE: In clinical practice, the clinicopathological profiles and outcomes of patients infected with hepatitis B virus (HBV) are different between genotypes B and C. However, little is known about the potential mechanism and differences in specific biological pathways associated with the different genotype. This study aimed to compare the serum protein profile between patients infected with HBV genotype B and those infected with HBV genotype C. PATIENTS AND METHODS: A total of 54 serum samples from patients with chronic HBV genotype B infection and those with chronic HBV genotype C infection, and healthy controls were used for the proteomic analysis (n = 18 samples in per group). Serum proteomic profiles were analyzed using data-independent acquisition (DIA)-based liquid chromatography-mass spectrometry to identify differentially expressed proteins (up- or downregulation of at least 1.5-fold) between serum samples from HBV patients infected with HBV genotype B and those infected with genotype C. RESULTS: We identified 1010 proteins, 53 of which were differentially expressed between the serum samples of the healthy controls and those of HBV genotype B infected patients, and 59 that were differentially expressed between the samples of the healthy controls and those of HBV genotype C infected patients. Furthermore, our results indicated that two proteins identified as being differentially expressed (VWF and C8B) have potential as biomarkers for distinguishing genotype B infected HBV patients from those infected with genotype C. CONCLUSION: The results of our DIA-based quantitative proteomic analysis revealed that HBV genotypes B and C are associated with different molecular profiles and may provide fundamental information for further detailed investigations of the molecular mechanism underlying these differences.

Roflupram protects against rotenone-induced neurotoxicity and facilitates α-synuclein degradation in Parkinson's disease models.

We have previously shown that roflupram (ROF) protects against MPP+-induced neuronal damage in models of Parkinson's disease (PD). Since impaired degradation of α-synuclein (α-syn) is one of the key factors that lead to PD, here we investigated whether and how ROF affects the degradation of α-syn in rotenone (ROT)-induced PD models in vivo and in vitro. We showed that pretreatment with ROF (10 µM) significantly attenuated cell apoptosis and reduced the level of α-syn in ROT-treated SH-SY5Y cells. Furthermore, ROF significantly enhanced the lysosomal function, as evidenced by the increased levels of mature cathepsin D (CTSD) and lysosomal-associated membrane protein 1 (LAMP1) through increasing NAD+/NADH and the expression of sirtuin 1 (SIRT1). Pretreatment with an SIRT1 inhibitor selisistat (SELI, 10 µM) attenuated the neuroprotection of ROF, ROF-reduced expression of α-syn, and ROF-increased expression levels of LAMP1 and mature CTSD. Moreover, inhibition of CTSD by pepstatin A (20 µM) attenuated ROF-reduced expression of α-syn. In vivo study was conducted in mice exposed to ROT (10 mg·kg-1·d-1, i.g.) for 6 weeks; then, ROT-treated mice received ROF (0.5, 1, or 2 mg·kg-1·d-1; i.g.) for four weeks. ROF significantly ameliorated motor deficits, which was accompanied by increased expression levels of tyrosine hydroxylase, SIRT1, mature CTSD, and LAMP1, and a reduced level of α-syn in the substantia nigra pars compacta. Taken together, these results demonstrate that ROF exerts a neuroprotective action and reduces the α-syn level in PD models. The mechanisms underlying ROF neuroprotective effects appear to be associated with NAD+/SIRT1-dependent activation of lysosomal function.

The Link Between Ferroptosis and Cardiovascular Diseases: A Novel Target for Treatment.

Ferroptosis is an iron-dependent cell death, which is characterized by iron overload and lipid peroxidation. Ferroptosis is distinct from apoptosis, necroptosis, autophagy, and other types of cell death in morphology and function. Ferroptosis is regulated by a variety of factors and controlled by several mechanisms, including mitochondrial activity and metabolism of iron, lipid, and amino acids. Accumulating evidence shows that ferroptosis is closely related to a majority of cardiovascular diseases (CVDs), including cardiomyopathy, myocardial infarction, ischemia/reperfusion injury, heart failure, and atherosclerosis. This review summarizes the current status of ferroptosis and discusses ferroptosis as a potential therapeutic target for CVDs.

The Transcription Factor SUB1 Is a Master Regulator of the Macrophage TLR Response in Atherosclerosis.

Toll-like receptor 2 and 4 (TLR2, TLR4) signaling is implicated in atherosclerotic plaque formation. The two-stage master regulator Virtual Inference of Protein-activity by Enriched Regulon (VIPER) analysis of macrophage TLR2 and TLR4 signature genes integrated with coexpression network genes derived from 371 patient-derived carotid specimens identifies activated RNA polymerase II transcriptional coactivator p15 (SUB1/Sub1, PC4) as a master regulon in the atherogenic TLR response. It is found that TLR2 and TLR4 signaling is proinflammatory and proatherosclerotic in chow-fed apolipoprotein E-deficient (ApoE-/- ) mice. Through transgenic myeloid-specific Sub1 knockout in ApoE-/- mice, it is discovered that these proatherosclerotic effects of TLR2 and TLR4 signaling are mediated by Sub1. Sub1 knockout in macrophages enhances anti-inflammatory M2 macrophage polarization and cholesterol efflux. Irradiated low density lipoprotein receptor-deficient (Ldlr-/- ) mice transplanted with Sub1-/- murine bone marrow display reduced atherosclerosis. Promoter analysis reveals Sub1-dependent activation of interferon regulatory factor 1 (Irf1) transcription in a casein kinase 2 (Ck2)-dependent manner, and Sub1-knockout macrophages display decreased Irf1 expression. Artificial Irf1 overexpression in Sub1-knockout macrophages enhances proinflammatory M1 skewing and lowers cholesterol clearance. In conclusion, the TLR master regulon Sub1, and its downstream effect on the transcription factor Irf1, promotes a proinflammatory M1 macrophage phenotype and enhances atherosclerotic burden in vivo.