Iron deficiency affects oxygen transport and activates HIF1 signaling pathway to regulate phenotypic transformation of VSMC in aortic dissection.

BACKGROUND: Aortic dissection (AD) is a macrovascular disease which is pathologically characterized by aortic media degeneration.This experiment aims to explore how iron deficiency (ID) affects the function of vascular smooth muscle cell (VSMC) and participates in the occurrence and development of AD by regulating gene expression. METHODS: The relationship between iron and AD was proved by Western-blot (WB) and immunostaining experiments in human and animals. Transcriptomic sequencing explored the transcription factors that were altered downstream. WB, flow cytometry and immunofluorescence were used to demonstrate whether ID affected HIF1 expression through oxygen transport. HIF1 signaling pathway and phenotypic transformation indexes were detected in cell experiments. The use of the specific HIF1 inhibitor PX478 further demonstrated that ID worked by regulating HIF1. RESULTS: The survival period of ID mice was significantly shortened and the pathological staining results were the worst. Transcriptomic sequencing indicated that HIF1 was closely related to ID and the experimental results indicated that ID might regulate HIF1 expression by affecting oxygen balance. HIF1 activation regulates the phenotypic transformation of VSMC and participates in the occurrence and development of AD in vivo and in vitro.PX478, the inhibition of HIF1, can improve ID-induced AD exacerbation.

Potential mechanisms of aortic medial degeneration promoted by co-exposure to microplastics and lead.

Microplastics (MPs) have attracted widespread attention because they can lead to combined toxicity by adsorbing heavy metals from the environment. Exposure to lead (Pb), a frequently adsorbed heavy metal by MPs, is common. In the current study, the coexistence of MPs and Pb was assessed in human samples. Then, mice were used as models to examine how co-exposure to MPs and Pb promotes aortic medial degeneration. The results showed that MPs and Pb co-exposure were detected in patients with aortic disease. In mice, MPs and Pb co-exposure promoted the damage of elastic fibers, loss of vascular smooth muscle cells (VSMCs), and release of inflammatory factors. In vitro cell models revealed that co-exposure to MPs and Pb induced excessive reactive oxygen species generation, impaired mitochondrial function, and triggered PANoptosome assembly in VSMCs. These events led to PANoptosis and inflammation through the cAMP/PKA-ROS signaling pathway. However, the use of the PKA activator 8-Br-cAMP or mitochondrial ROS scavenger Mito-TEMPO improved, mitochondrial function in VSMCs, reduced cell death, and inhibited inflammatory factor release. Taken together, the present study provided novel insights into the combined toxicity of MPs and Pb co-exposure on the aorta.

Role of Quercetin in DNA Repair: Possible Target to Combat Drug Resistance in Diabetes.

Diabetes Mellitus (DM) is referred to as hyperglycemia in either fasting or postprandial phases. Oxidative stress, which is defined by an excessive amount of reactive oxygen species (ROS) production, increased exposure to external stress, and an excessive amount of the cellular defense system against them, results in cellular damage. Increased DNA damage is one of the main causes of genomic instability, and genetic changes are an underlying factor in the emergence of cancer. Through covalent connections with DNA and proteins, quercetin has been demonstrated to offer protection against the creation of oxidative DNA damage. It has been found that quercetin shields DNA from possible oxidative stress-related harm by reducing the production of ROS. Therefore, Quercetin helps to lessen DNA damage and improve the ability of DNA repair mechanisms. This review mainly focuses on the role of quercetin in repairing DNA damage and compensating for drug resistance in diabetic patients. Data on the target topic was obtained from major scientific databases, including SpringerLink, Web of Science, Google Scholar, Medline Plus, PubMed, Science Direct, and Elsevier. In preclinical studies, quercetin guards against DNA deterioration by regulating the degree of lipid peroxidation and enhancing the antioxidant defense system. By reactivating antioxidant enzymes, decreasing ROS levels, and decreasing the levels of 8-hydroxydeoxyguanosine, Quercetin protects DNA from oxidative damage. In clinical studies, it was found that quercetin supplementation was related to increased antioxidant capacity and decreased risk of type 2 diabetes mellitus in the experimental group as compared to the placebo group. It is concluded that quercetin has a significant role in DNA repair in order to overcome drug resistance in diabetes.

Simultaneous Cu(II)-EDTA decomplexation and Cu(II) recovery using integrated contact-electro-catalysis and capacitive deionization from electroplating wastewater.

The complex of heavy metals and organic acids leads to high difficulty in heavy metals separation by traditional technologies. Meanwhile, alkaline precipitation commonly used in industry causes the great consumption of resources and extra pollution. Herein, the effective decomplexation of Cu(Ⅱ)-EDTA and synchronous recycling of Cu2+ were realized by contact-electro-catalysis (CEC) coupled with capacitive deionization (CDI) innovatively. In particular, fluorinated ethylene propylene (FEP) as dielectric powders could generate reactive oxygen species under ultrasonic stimulation, realizing continuous deaminization and decarboxylation of Cu(Ⅱ)-EDTA and accelerating the totally breakage of Cu-O and Cu-N bonds. Additionally, the degradation pathway and intermediates evolution of Cu(Ⅱ)-EDTA were investigated using various characterization methods. It was confirmed that decarboxylation predominantly governed the degradation process of Cu(Ⅱ)-EDTA in CEC. During the course of treatment, the degradation ratio of Cu(Ⅱ)-EDTA reached 86.4 % within 150 min. Impressively, this strategy had satisfactory applicability to other metal combinations and excellent cycle stability. Subsequently, the released Cu ions were captured by CuSe cathode electrode through CDI. This research elucidated the degradation mechanism of persistent organic pollutant during CEC, and provided a novel approach for efficiently treating industrial wastewater containing metal complexes and advancing the exploitation and utilization of new technologies for metal recovery.

Cascade Residual Multiscale Convolution and Mamba-Structured UNet for Advanced Brain Tumor Image Segmentation.

In brain imaging segmentation, precise tumor delineation is crucial for diagnosis and treatment planning. Traditional approaches include convolutional neural networks (CNNs), which struggle with processing sequential data, and transformer models that face limitations in maintaining computational efficiency with large-scale data. This study introduces MambaBTS: a model that synergizes the strengths of CNNs and transformers, is inspired by the Mamba architecture, and integrates cascade residual multi-scale convolutional kernels. The model employs a mixed loss function that blends dice loss with cross-entropy to refine segmentation accuracy effectively. This novel approach reduces computational complexity, enhances the receptive field, and demonstrates superior performance for accurately segmenting brain tumors in MRI images. Experiments on the MICCAI BraTS 2019 dataset show that MambaBTS achieves dice coefficients of 0.8450 for the whole tumor (WT), 0.8606 for the tumor core (TC), and 0.7796 for the enhancing tumor (ET) and outperforms existing models in terms of accuracy, computational efficiency, and parameter efficiency. These results underscore the model's potential to offer a balanced, efficient, and effective segmentation method, overcoming the constraints of existing models and promising significant improvements in clinical diagnostics and planning.

IL-37 ameliorates myocardial fibrosis by regulating mtDNA-enriched vesicle release in diabetic cardiomyopathy mice.

BACKGROUND: Diabetic cardiomyopathy (DCM), a serious complication of diabetes, leads to structural and functional abnormalities of the heart and ultimately evolves to heart failure. IL-37 exerts a substantial influence on the regulation of inflammation and metabolism. Whether IL-37 is involved in DCM is unknown. METHODS: The plasma samples were collected from healthy controls, diabetic patients and DCM patients, and the level of IL-37 and its relationship with heart function were observed. The changes in cardiac function, myocardial fibrosis and mitochondrial injury in DCM mice with or without IL-37 intervention were investigated in vivo. By an in vitro co-culture approach involving HG challenge of cardiomyocytes and fibroblasts, the interaction carried out by cardiomyocytes on fibroblast profibrotic activation was studied. Finally, the possible interactive mediator between cardiomyocytes and fibroblasts was explored, and the intervention role of IL-37 and its relevant molecular mechanisms. RESULTS: We showed that the level of plasma IL-37 in DCM patients was upregulated compared to that in healthy controls and diabetic patients. Both recombinant IL-37 administration or inducing IL-37 expression alleviated cardiac dysfunction and myocardial fibrosis in DCM mice. Mechanically, hyperglycemia impaired mitochondria through SIRT1/AMPK/PGC1α signaling, resulting in significant cardiomyocyte apoptosis and the release of extracellular vesicles containing mtDNA. Fibroblasts then engulfed these mtDNA-enriched vesicles, thereby activating TLR9 signaling and the cGAS-STING pathway to initiate pro-fibrotic process and adverse remodeling. However, the presence of IL-37 ameliorated mitochondrial injury by preserving the activity of SIRT1-AMPK-PGC1α axis, resulting in a reduction in release of mtDNA-enriched vesicle and ultimately attenuating the progression of DCM. CONCLUSIONS: Collectively, our study demonstrates a protective role of IL-37 in DCM, offering a promising therapeutic agent for this disease.

Targeted blocking of EGFR and GLUT1 by compound H reveals a new strategy for treatment of triple-negative breast cancer and nasopharyngeal carcinoma.

BACKGROUND: Cytoplasmic epidermal growth factor receptor (EGFR) is overexpressed in both nasopharyngeal carcinoma (NPC) and triple-negative breast cancer (TNBC), while clinical outcome and prognosis vary greatly among patients treated with gefitinib, and all patients eventually develop resistance to this agent. Therefore, we propose a new concept for synthesizing multitarget compounds and reveal new therapeutic strategies for NPC and TNBC expressing EGFR. METHODS: Compound H was synthesized in our previous study. Molecular docking, and cell thermal shift assays (CETSAs) and drug affinity responsive target stability(DARTS) were used to confirm the binding of compound H to EGFR and GLUT1. Methylthiazolyldiphenyl-tetrazolium bromide(MTT), annexin V-PE assays, mitochondrial membrane potential (MMP) assays, and animal models were used to evaluate the inhibitory effect of compound H on TNBC cell lines. Energy metabolism tests, Western blotting, and immunofluorescence staining were performed to evaluate the synergistic effects on EGFR- and glucose transporter type 1(GLUT1)-mediated energy metabolism. RESULTS: Compound H can simultaneously act on the EGFR tyrosine kinase ATP-binding site and inhibit GLUT1-mediated energy metabolism, resulting in reductions in ATP, MMP, intra-cellular lactic acid, and EGFR nuclear transfer. The anti-tumor activity of compound H is significantly superior to the combination of GLUT1 inhibitor BAY876 and EGFR inhibitor gefitinib. Compound H has remarkable anti-proliferative effects on TNBC MDA-MB231 cells, and importantly, no obvious toxicity effects of compound H were found in vivo. CONCLUSIONS: Synergistic effects of inhibition of EGFR- and GLUT1-mediated energy metabolism by compound H may present a new strategy for the treatment of TNBC and NPC.

Ursolic acid alleviates lupus nephritis by suppressing SUMO1-mediated stabilization of NLRP3.

BACKGROUND: Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease that affects multiple organs and cause a wide range of severe clinical manifestations, including lupus nephritis (LN), which is a major risk factor for morbidity and mortality in individual with SLE. Ursolic acid (UA) is a natural compound with favorable anti-inflammatory properties and has been employed to treat multiple disease, including inflammatory diseases, diabetes, and Parkinson's disease. However, its therapeutic potential on LN and the underlying mechanisms remains unclear. PURPOSE: This aim of this study was to investigate the impact of UA on LN and its underlying mechanism. METHODS: MRL/lpr lupus-prone mouse model was used and UA was administered orally for 8 weeks. Dexamethasone was used as a positive control. After 8 weeks of administration, the spleen-to-body-weight ratio, renal function, urine albumin excretion, cytokines levels, and the deposition of immune complex were measured. The primary mouse glomerular mesangial cells (GMCs) and SV40-MES-13 were stimulated by lipopolysaccharide (LPS), either alone or in combination with nigericin, to establish an in vitro model. The activation of NLRP3 inflammasome were investigated both in vivo and in vitro using qRT-PCR, immunoblotting, and immunofluorescence. RESULTS: Our results revealed that UA prominently alleviated LN in MRL/lpr lupus-prone mice, leading to a significant reduction in proteinuria production, infiltration of immune cells infiltration, and histopathological damage in the renal tissue. In addition, UA exerted inhibitory effects on the secretion of IL-1ß, IL-18, and caspase-1, pyroptosis, and ASC speck formation in primary mouse GMCs and SV40-MES-13 cells. Furthermore, UA facilitated the degradation of NLRP3 by suppressing SUMO1-mediated SUMOylation of NLRP3. CONCLUSION: UA possess a therapeutical effect on LN in MRL/lpr mice by enhancing the degradation of NLRP3 through inhibition of SUMO1-mediated SUMOylation of NLRP3. Our findings provide a basis for proposing UA as a potential candidate for the treatment of LN.

A Current Understanding of FXR in NAFLD: The multifaceted regulatory role of FXR and novel lead discovery for drug development.

The global prevalence of nonalcoholic fatty liver disease (NAFLD) has reached 30 %, with an annual increase. The incidence of NAFLD-induced cirrhosis is rapidly rising and has become the leading indicator for liver transplantation in the US. However, there are currently no US Food and Drug Administration-approved drugs for NAFLD. Increasing evidence underscores the close association between NAFLD and bile acid metabolism disorder, highlighting the feasibility of targeting the bile acid signaling pathway for NAFLD treatment. The farnesoid X receptor (FXR) is an endogenous receptor for bile acids that exhibits favorable effects in ameliorating the metabolic imbalance of bile acids, lipid disorders, and disruption of intestinal homeostasis, all of which are key characteristics of NAFLD, making FXR a promising therapeutic target for NAFLD. The present review provides a comprehensive overview of the diverse mechanisms through which FXR improves NAFLD, with particular emphasis on its involvement in regulating bile acid homeostasis and the recent advancements in drug development targeting FXR for NAFLD treatment.

[Clinical and Mechanism Research Progress in Amelioration of Mild Cognitive Impairment via Meditation].

Mild cognitive impairment(MCI)has a high risk of progressing to dementia,with no recommended therapies.Recent studies have shown that meditation has huge potential to improve the cognitive function,with low cost and high safety,being suitable to be applied in the treatment of neurological and psychotic disorders.This paper reviews the application and prospects of meditation in treating MCI from the concept,clinical efficacy,and mechanism of meditation,aiming to provide reference for future clinical studies.

Gentisic acid prevents colorectal cancer metastasis via blocking GPR81-mediated DEPDC5 degradation.

BACKGROUND: Metastasis driven by epithelial-mesenchymal transition (EMT) remains a significant contributor to the poor prognosis of colorectal cancer (CRC), and requires more effective interventions. GPR81 signaling has been linked to tumor metastasis, while lacks an efficient specific inhibitor. PURPOSE: Our study aimed to investigate the effect and mechanism of Gentisic acid on colorectal cancer (CRC) metastasis. STUDY DESIGN: A lung metastasis mouse model induced by tail vein injection and a subcutaneous graft tumor model were used. Gentisic acid (GA) was administered by an intraperitoneal injection. HCT116 was treated with lactate to establish an in vitro model. METHODS: MC38 cells with mCherry fluorescent protein were injected into tail vein to investigate lung metastasis ability in vivo. GA was administered by intraperitoneal injection for 3 weeks. The therapeutic effect was evaluated by survival rates, histochemical analysis, RT-qPCR and live imaging. The mechanism was explored using small interfering RNA (siRNA), Western blotting, RT-qPCR and immunofluorescence. RESULTS: GA had a therapeutic effect on CRC metastasis and improved survival rates and pathological changes in dose-dependent manner. GA emerged as an GPR81 inhibitor, effectively suppressed EMT and mTOR signaling in CRC induced by lactate both in vivo and in vitro. Mechanistically, GA halted lactate-induce degradation of DEPDC5 through impeding the activation of Chaperone-mediated autophagy (CMA). CONCLUSION: CMA-mediated DEPDC5 degradation is crucial for lactate/GPR81-induced CRC metastasis, and GA may be a promising candidate for metastasis by inhibiting GPR81 signaling.

Impact of transcranial electrical stimulation on serum neurotrophic factors and language function in patients with speech disorders.

BACKGROUND: Speech disorders have a substantial impact on communication abilities and quality of life. Traditional treatments such as speech and psychological therapies frequently demonstrate limited effectiveness and patient compliance. Transcranial electrical stimulation (TES) has emerged as a promising non-invasive treatment to improve neurological functions. However, its effectiveness in enhancing language functions and serum neurofactor levels in individuals with speech disorders requires further investigation. AIM: To investigate the impact of TES in conjunction with standard therapies on serum neurotrophic factor levels and language function in patients with speech disorders. METHODS: In a controlled study spanning from March 2019 to November 2021, 81 patients with speech disorders were divided into a control group (n = 40) receiving standard speech stimulation and psychological intervention, and an observation group (n = 41) receiving additional TES. The study assessed serum levels of ciliary neurotrophic factor (CNTF), glial cell-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF), as well as evaluations of motor function, language function, and development quotient scores. RESULTS: After 3 wk of intervention, the observation group exhibited significantly higher serum levels of CNTF, GDNF, BDNF, and NGF compared to the control group. Moreover, improvements were noted in motor function, cognitive function, language skills, physical abilities, and overall development quotient scores. It is worth mentioning that the observation group also displayed superior performance in language-specific tasks such as writing, reading comprehension, retelling, and fluency. CONCLUSION: This retrospective study concluded that TES combined with traditional speech and psychotherapy can effectively increase the levels of neurokines in the blood and enhance language function in patients with speech disorders. These results provide a promising avenue for integrating TES into standard treatment methods for speech disorders.

Carbapenem-resistant Gram-negative bacteria (CR-GNB) in ICUs: resistance genes, therapeutics, and prevention - a comprehensive review.

Intensive care units (ICUs) are specialized environments dedicated to the management of critically ill patients, who are particularly susceptible to drug-resistant bacteria. Among these, carbapenem-resistant Gram-negative bacteria (CR-GNB) pose a significant threat endangering the lives of ICU patients. Carbapenemase production is a key resistance mechanism in CR-GNB, with the transfer of resistance genes contributing to the extensive emergence of antimicrobial resistance (AMR). CR-GNB infections are widespread in ICUs, highlighting an urgent need for prevention and control measures to reduce mortality rates associated with CR-GNB transmission or infection. This review provides an overview of key aspects surrounding CR-GNB within ICUs. We examine the mechanisms of bacterial drug resistance, the resistance genes that frequently occur with CR-GNB infections in ICU, and the therapeutic options against carbapenemase genotypes. Additionally, we highlight crucial preventive measures to impede the transmission and spread of CR-GNB within ICUs, along with reviewing the advances made in the field of clinical predictive modeling research, which hold excellent potential for practical application.

Vanillic acid restores homeostasis of intestinal epithelium in colitis through inhibiting CA9/STIM1-mediated ferroptosis.

The damage of integrated epithelial epithelium is a key pathogenic factor and closely associated with the recurrence of ulcerative colitis (UC). Here, we reported that vanillic acid (VA) exerted potent therapeutic effects on DSS-induced colitis by restoring intestinal epithelium homeostasis via the inhibition of ferroptosis. By the CETSA assay and DARTS assay, we identified carbonic anhydrase IX (CAIX, CA9) as the direct target of VA. The binding of VA to CA9 causes insulin-induced gene-2 (INSIG2) to interact with stromal interaction molecule 1 (STIM1), rather than SREBP cleavage-activating protein (SCAP), leading to the translocation of SCAP-SREBP1 from the endoplasmic reticulum (ER) to the Golgi apparatus for cleavage into mature SREBP1. The activation of SREBP1 induced by VA then significantly facilitated the transcription of stearoyl-CoA desaturase 1 (SCD1) to exert an inhibitory effect on ferroptosis. By inhibiting the excessive death of intestinal epithelial cells caused by ferroptosis, VA effectively preserved the integrity of intestinal barrier and prevented the progression of unresolved inflammation. In conclusion, our study demonstrated that VA could alleviate colitis by restoring intestinal epithelium homeostasis through CA9/STIM1-mediated inhibition of ferroptosis, providing a promising therapeutic candidate for UC.

Sex differences in the association of the uric acid to high-density lipoprotein cholesterol ratio with coronary artery disease risk among Chinese nondialysis patients with CKD stages 3-5.

BACKGROUND AND AIMS: Evidence has indicated that serum uric acid (UA) and high-density lipoprotein cholesterol (HDL-C) are positively and negatively associated with coronary artery disease (CAD). The UA to HDL-C ratio (UHR) has recently drawn attention as a new predictor for metabolic syndrome, inflammation and atherosclerosis. However, the association between the UHR and CAD in nondialysis chronic kidney disease (CKD) patients is still unclear. METHODS AND RESULTS: We retrospectively analysed 733 733 nondialysis patients with CKD stage 3-5 who received their first coronary artery angiography (CAG), including 510 participants with CAD. All laboratory indicators were collected within one week before CAG. The median UHR of CAD and non-CAD patients was 15.52% and 12.29%, respectively. In multivariate analysis, female patients with a high UHR were 4.7 times more at risk of CAD than those with a lower UHR. Meanwhile, the positive association of the UHR with the severity of coronary artery stenosis (CAS) persisted significantly in female CAD subjects but not in males. In addition, receiver operating characteristic (ROC) curves were constructed for CAD and severe CAS. The area under the curve (AUC) for the UHR was higher than that for UA and HDL-C alone in female patients [UHR (AUC): 0.715 for CAD and 0.716 for severe CAS]. CONCLUSIONS: An elevated UHR was independently related to an increased CAD risk and the severity of CAS in nondialysis female patients with CKD stage 3-5, and was more predictive of the onset of CAD and the severity of CAS than UA or HDL-C alone.

UHPLC-MS/MS Assay for Quantification of Legubicin, a Novel Doxorubicin-Based Legumain-Activated Prodrug, and Its Application to Pharmacokinetic and Tissue Distribution Studies.

Legubicin, a novel prodrug based on doxorubicin, has both albumin-binding and legumain-activating properties. The aim of this study was to develop and validate a UHPLC-MS/MS method for investigating the in vivo pharmacokinetics and tissue distribution profiles of legubicin in rats and tumor-bearing mice following intravenous administration, and to compare this prodrug with the positive control drug doxorubicin. The study employed a UHLC-MS/MS method to determine the levels of albumin-bound of legubicin and two metabolites (free Leu-DOX and DOX) in plasma, tumor, and tissue samples. This method was validated for good selectivity, high sensitivity, excellent extraction recovery, and short run time. The results showed that legubicin was present in the circulation in vivo mainly in a protein-bound form with larger AUC values and lower clearance and distribution, and essentially released small amounts of doxorubicin. Compared to administration of equimolar doses of doxorubicin, legubicin showed increased exposure of the active drug in the tumor and decreased the level of the active drug in the heart and kidney. This study provides valuable information on the pharmacokinetics and tissue distribution of legubicin, implicating its potential as a novel and effective drug candidate for anti-cancer therapies.

Development strategy of early childhood music education industry: An IFS-AHP-SWOT analysis based on dynamic social network.

Early childhood music education has garnered recognition for its unique contribution to cognitive, emotional, and social development in children. Nevertheless, the industry grapples with numerous challenges, including a struggle to adapt traditional educational paradigms to new curriculum reforms, and an excessive emphasis on skill training at the expense of nurturing a love for music and aesthetics in children. To navigate these challenges and explore growth strategies for the early childhood music education industry, we initiated a comprehensive approach that involved distributing surveys to practitioners and parents and engaging experts for insightful discussions. Consequently, we proposed an analytical method based on dynamic social networks in conjunction with Intuitionistic Fuzzy Sets (IFS), Analytic Hierarchy Process (AHP), and Strengths, Weaknesses, Opportunities, and Threats (SWOT) analysis, collectively referred to as IFS-AHP-SWOT. This integrated methodology synergizes the capabilities of dynamic social networks, IFS, AHP, and SWOT analysis to offer a nuanced perspective on industry development strategies. The findings underscore that institutions within the early childhood music education industry need to adopt a development strategy that leverages their strengths and opportunities to foster sustainable growth. Ultimately, this research aims to provide critical decision-making support for industry practitioners, policymakers, and researchers, contributing significantly to the ongoing discourse on strategic development in the early childhood music education industry.

Attention gate and dilation U-shaped network (GDUNet): an efficient breast ultrasound image segmentation network with multiscale information extraction.

Background: In recent years, computer-aided diagnosis (CAD) systems have played an important role in breast cancer screening and diagnosis. The image segmentation task is the key step in a CAD system for the rapid identification of lesions. Therefore, an efficient breast image segmentation network is necessary for improving the diagnostic accuracy in breast cancer screening. However, due to the characteristics of blurred boundaries, low contrast, and speckle noise in breast ultrasound images, breast lesion segmentation is challenging. In addition, many of the proposed breast tumor segmentation networks are too complex to be applied in practice. Methods: We developed the attention gate and dilation U-shaped network (GDUNet), a lightweight, breast lesion segmentation model. This model improves the inverted bottleneck, integrating it with tokenized multilayer perceptron (MLP) to construct the encoder. Additionally, we introduce the lightweight attention gate (AG) within the skip connection, which effectively filters noise in low-level semantic information across spatial and channel dimensions, thus attenuating irrelevant features. To further improve performance, we innovated the AG dilation (AGDT) block and embedded it between the encoder and decoder in order to capture critical multiscale contextual information. Results: We conducted experiments on two breast cancer datasets. The experiment's results show that compared to UNet, GDUNet could reduce the number of parameters by 10 times and the computational complexity by 58 times while providing a double of the inference speed. Moreover, the GDUNet achieved a better segmentation performance than did the state-of-the-art medical image segmentation architecture. Conclusions: Our proposed GDUNet method can achieve advanced segmentation performance on different breast ultrasound image datasets with high efficiency.

S-adenosylmethionine attenuates angiotensin II-induced aortic dissection formation by inhibiting vascular smooth muscle cell phenotypic switch and autophagy.

It is well known that aortic dissection (AD) is a very aggressive class of vascular diseases. S-adenosylmethionine (SAM) is an autophagy inhibitor with anti-inflammatory and anti-oxidative stress effects; however, the role of SAM in AD is unknown. In this study, we constructed an animal model of AD using subcutaneous minipump continuous infusion of AngII-induced ApoE-/-mice and a cytopathic model using AngII-induced primary vascular smooth muscle cells (VSMCs) to investigate the possible role of SAM in AD. The results showed that mice in the AngII + SAM group had significantly lower AD incidence, significantly prolonged survival, and reduced vascular elastic fiber disruption compared with mice in the AngII group. In addition, SAM significantly inhibited autophagy in vivo and in vitro. Meanwhile, SAM also inhibited the cellular phenotypic switch, mainly by up regulating the expression levels of contractile marker proteins [α-smooth muscle actin (α-SMA) and smooth muscle 22α (SM22α)] and down regulating the expression levels of synthetic marker proteins [osteoblast protein (OPN), matrix metalloproteinase-2 (MMP2), and matrix metalloproteinase-9 (MMP9)]. Molecularly, SAM inhibited AD formation mainly by activating the PI3K/AKT/mTOR signaling pathway. Using a PI3K inhibitor (LY294002) significantly reversed the protective effect of SAM in AngII-induced mice and VSMCs.Our study demonstrates the protective effect of SAM on mice under AngII-induced AD for the first time. SAM prevented AD formation mainly by inhibiting cellular phenotypic switch and autophagy, and activation of the PI3K/AKT/mTOR signaling pathway is a possible molecular mechanism. Thus, SAM may be a novel strategy for the treatment of AD.