Deciphering the role of cuproptosis-related lncRNAs in shaping the lung cancer immune microenvironment: A comprehensive prognostic model.

Cuproptosis plays an important role in cancer, but its role in lung cancer remains unknown. Transcriptional profiles, clinical details and mutation data were acquired from the Cancer Genome Atlas database through a variety of methods. The analysis of this publicly available data was comprehensively performed using R software along with its relevant packages, ensuring a thorough examination of the information. In this study, we conducted a detailed analysis of cuproptosis-related genes and lncRNA co-expression, identifying 129 relevant lncRNAs and establishing a prognostic model with four key lncRNAs (LINC00996, RPARP-AS1, SND1-IT1, TMPO-AS1). Utilizing data from TCGA and GEO databases, the model effectively categorized patients into high- and low-risk groups, showing significant survival differences. Correlation analysis highlighted specific relationships between individual lncRNAs and cuproptosis genes. Our survival analysis indicated a higher survival rate in the low-risk group across various cohorts. Additionally, the model's predictive accuracy was confirmed through independent prognostic analysis and ROC curve evaluations. Functional enrichment analysis revealed distinct biological pathways and immune functions between risk groups. Tumour mutation load analysis differentiated high- and low-risk groups by their mutation profiles. Drug sensitivity analysis and immune infiltration studies using the CIBERSORT algorithm further elucidated the potential treatment responses in different risk groups. This comprehensive evaluation underscores the significance of lncRNAs in cuproptosis and their potential as biomarkers for lung cancer prognosis and immune microenvironment.

Asprosin promotes vascular inflammation via TLR4-NFκB-mediated NLRP3 inflammasome activation in hypertension.

Objective: and design Mild vascular inflammation promotes the pathogenesis of hypertension. Asprosin, a newly discovered adipokine, is closely associated with metabolic diseases. We hypothesized that asprosin might led to vascular inflammation in hypertension via NLRP3 inflammasome formation. This study shows the importance of asprosin in the vascular inflammation of hypertension. Methods: Primary vascular smooth muscle cells (VSMCs) were obtained from the aorta of animals, including spontaneously hypertensive rats (SHR), Wistar-Kyoto rats (WKY), NLRP3-/- and wild-type mice. Studies were performed in VSMCs in vitro, as well as WKY and SHR in vivo. Results: Asprosin expressions were up-regulated in VSMCs and media of arteries in SHR. Asprosin overexpression promoted NLRP3 inflammasome activation via Toll-like receptor 4 (TLR4), accompanied with activation of NFκB signaling pathway in VSMCs. Exogenous asprosin protein showed similar roles in promoting NLRP3 inflammasome activation. Knockdown of asprosin restrained NLRP3 inflammasome and p65-NFκB activation in VSMCs of SHR. NLRP3 inhibitor MCC950 or NFκB inhibitor BAY11-7082 attenuated asprosin-caused VSMC proliferation and migration. Asprosin-induced interleukin-1ß production, proliferation and migration were attenuated in NLRP3-/- VSMCs. Local asprosin knockdown in common carotid artery of SHR attenuated inflammation and vascular remodeling. Conclusions: Asprosin promoted NLRP3 inflammasome activation in VSMCs by TLR4-NFκB pathway, and thereby stimulates VSMCs proliferation, migration, and vascular remodeling of SHR.

Epidemiological characteristics and influencing factors of tuberculosis aggregation in schools in Wuhan, China during 2017-2022.

Background: Wuhan is located in the hinterland of China, in the east of Hubei Province, at the intersection of the Yangtze River and Hanshui River. It is a national historical and cultural city, an important industrial, scientific, and educational base, and a key transportation hub. There are many schools in Wuhan, with nearly a thousand of all kinds. The number of students is ~2.2 million, accounting for nearly one-fifth of the resident population; college or university students account for ~60% of the total student population. The geographical location of these colleges is relatively concentrated, and the population density is relatively high, making it prone to tuberculosis cluster epidemic. Objective: This study analyzed the epidemiological characteristics and influencing factors of tuberculosis aggregation in schools in Wuhan, China, during 2017-2022 to provide the basis for the scientific development of tuberculosis prevention and control strategies and measures in schools. Methods: This study adopted the methods of descriptive epidemiology to analyze the epidemic characteristics of tuberculosis aggregation in schools in Wuhan from January 2017 to December 2022, collecting the relevant data on tuberculosis prevention and control in all kinds of schools in the city using Questionnaire Star, an application of the China network questionnaire survey, and analyze the influencing factors of tuberculosis aggregation by using multifactor logistic regression analysis. Results: From 2017 to 2022, 54 outbreaks of pulmonary tuberculosis aggregation in schools were reported in Wuhan, which involved 37 different schools, including 32 colleges or universities and five senior high schools; 176 cases were reported, among which 73 were positive for pathogens and 18 were rifampicin or izoniazid resistant. The median duration of a single cluster epidemic was 46 (26,368) days. Universities were more prone to cluster outbreaks than middle schools (χ2 = 105.160, P = 0.001), and the incidence rate among male students was higher than that of female students in cluster epidemics (χ2 = 12.970, P = 0.001). The multivariate logistic regression analysis results showed that boarding in school (OR = 7.60) is the risk factor for a tuberculosis cluster epidemic in schools. The small number of students (OR = 0.50), the location of the school in the city (OR = 0.60), carry out physical examinations for freshmen (OR = 0.44), carry out illness absence and cause tracking (OR = 0.05), dormitories and classrooms are regularly ventilated with open windows (OR = 0.16), strict implement the management of sick student's suspension from school (OR = 0.36), and seeking timely medical consultation (OR = 0.32) were the protective factors for a tuberculosis cluster epidemic in schools. Conclusion: We successfully identified the epidemiological characteristics and influencing factors of tuberculosis aggregation in schools in Wuhan. The results revealed the influence and status of various factors and indicated ways for schools to improve their TB prevention and control measures in their daily activities. These measures can effectively help curb the cluster epidemic of tuberculosis in schools.

A dual-energy computed tomography-based radiomics nomogram for predicting time since stroke onset: a multicenter study.

OBJECTIVES: We aimed to develop and validate a radiomics nomogram based on dual-energy computed tomography (DECT) images and clinical features to classify the time since stroke (TSS), which could facilitate stroke decision-making. MATERIALS AND METHODS: This retrospective three-center study consecutively included 488 stroke patients who underwent DECT between August 2016 and August 2022. The eligible patients were divided into training, test, and validation cohorts according to the center. The patients were classified into two groups based on an estimated TSS threshold of ≤ 4.5 h. Virtual images optimized the visibility of early ischemic lesions with more CT attenuation. A total of 535 radiomics features were extracted from polyenergetic, iodine concentration, virtual monoenergetic, and non-contrast images reconstructed using DECT. Demographic factors were assessed to build a clinical model. A radiomics nomogram was a tool that the Rad score and clinical factors to classify the TSS using multivariate logistic regression analysis. Predictive performance was evaluated using receiver operating characteristic (ROC) analysis, and decision curve analysis (DCA) was used to compare the clinical utility and benefits of different models. RESULTS: Twelve features were used to build the radiomics model. The nomogram incorporating both clinical and radiomics features showed favorable predictive value for TSS. In the validation cohort, the nomogram showed a higher AUC than the radiomics-only and clinical-only models (AUC: 0.936 vs 0.905 vs 0.824). DCA demonstrated the clinical utility of the radiomics nomogram model. CONCLUSIONS: The DECT-based radiomics nomogram provides a promising approach to predicting the TSS of patients. CLINICAL RELEVANCE STATEMENT: The findings support the potential clinical use of DECT-based radiomics nomograms for predicting the TSS. KEY POINTS: Accurately determining the TSS onset is crucial in deciding a treatment approach. The radiomics-clinical nomogram showed the best performance for predicting the TSS. Using the developed model to identify patients at different times since stroke can facilitate individualized management.

Relationship between muscle and subcutaneous adipose tissue size and density and proximal femur bone in elderly women with hip fracture.

BACKGROUND: Both osteoporosis and sarcopenia are associated with aging, increasing the likelihood of falls in older adults and consequently raising the risk of hip fractures (HF). AIMS: To explore the relationship between the size and density of muscle and subcutaneous adipose tissue (SAT) and the bone mineral density (BMD) of the proximal femur in elderly women with HF. METHODS: Quantitative computed tomography (QCT) was conducted on the hips of 661 female participants who experienced low-energy acute HFs to measure both areal BMD (aBMD) and volume BMD (vBMD). Measurements were taken for the cross-sectional area (CSA) and density of the muscle around the hip and adjacent SAT. Multivariable linear regression models were applied to assess the relationship between these parameters. RESULTS: Most increases in the density of the gluteus medius and minimus muscle (G.Med/MinM) were correlated with higher BMD in the femoral neck fracture (FNF) group with osteoporosis. In the FNF group, gluteus maximus muscle (G.MaxM) density was negatively associated with the BMD parameters of the proximal femur in individuals with osteoporosis, while they were positively associated with nonosteoporosis. In the intertrochanteric fracture (ITF) group without osteoporosis, both FN aBMD and FN vBMD showed significant correlations with G.Med/MinM density. DISCUSSION: In women with HFs, bone and muscle are closely related. CONCLUSIONS: In older women with HFs, density but not CSA of the G.Med/MinM were associated with BMD parameters of the proximal femur. Osteoporosis may influence the relationship between G.MaxM density and proximal femur BMD in elderly women with FNF.

SPACA6P-AS: a trailblazer in breast cancer pathobiology and therapeutics.

OBJECTIVE: The primary objective of this investigation is to delve into the involvement of the long noncoding RNA (lncRNA) SPACA6P-AS in breast cancer (BC) development, focusing on its expression pattern, association with clinical-pathological features, impact on prognosis, as well as its molecular and immunological implications. METHODS: Bioinformatics analysis was conducted utilizing RNA sequencing data of 1083 BC patients from the TCGA database. Functional exploration of SPACA6P-AS was carried out through the construction of survival curves, GO and KEGG enrichment analysis, and single-sample gene set enrichment analysis (ssGSEA). Furthermore, its functionality was validated through in vitro cell experiments and in vivo nude mouse model experiments. RESULTS: SPACA6P-AS showed a remarkable increase in expression levels in BC tissues (p < 0.001) and demonstrated a close relationship to poor prognosis (overall survival HR = 1.616, progression-free interval HR = 1.40, disease-specific survival HR = 1.54). Enrichment analysis revealed that SPACA6P-AS could impact biological functions such as protease regulation, endopeptidase inhibitor activity, taste receptor activity, taste transduction, and maturity-onset diabetes of the young pathway. ssGSEA analysis indicated a negative correlation between SPACA6P-AS expression and immune cell infiltration like dendritic cells and neutrophils, while a positive correlation was observed with central memory T cells and T helper 2 cells. Results from in vitro and in vivo experiments illustrated that silencing SPACA6P-AS significantly inhibited the proliferation, migration, and invasion capabilities of BC cells. In vitro experiments also highlighted that dendritic cells with silenced SPACA6P-AS exhibited enhanced capabilities in promoting the proliferation of autologous CD3 + T cells and cytokine secretion. These discoveries elucidate the potential multifaceted roles of SPACA6P-AS in BC, including its potential involvement in modulating immune cell infiltration in the tumor microenvironment. CONCLUSION: The high expression of lncRNA SPACA6P-AS in BC is closely linked to poor prognosis and may facilitate tumor progression by influencing specific biological processes, signaling pathways, and the immune microenvironment. The regulatory role of SPACA6P-AS positions it as a prospective biomarker and target for therapeutic approaches for BC diagnosis and intervention.

[Ischemic stroke infarct segmentation model based on depthwise separable convolution for multimodal magnetic resonance imaging].

Magnetic resonance imaging (MRI) plays a crucial role in the diagnosis of ischemic stroke. Accurate segmentation of the infarct is of great significance for selecting intervention treatment methods and evaluating the prognosis of patients. To address the issue of poor segmentation accuracy of existing methods for multiscale stroke lesions, a novel encoder-decoder architecture network based on depthwise separable convolution is proposed. Firstly, this network replaces the convolutional layer modules of the U-Net with redesigned depthwise separable convolution modules. Secondly, an modified Atrous spatial pyramid pooling (MASPP) is introduced to enlarge the receptive field and enhance the extraction of multiscale features. Thirdly, an attention gate (AG) structure is incorporated at the skip connections of the network to further enhance the segmentation accuracy of multiscale targets. Finally, Experimental evaluations are conducted using the ischemic stroke lesion segmentation 2022 challenge (ISLES2022) dataset. The proposed algorithm in this paper achieves Dice similarity coefficient (DSC), Hausdorff distance (HD), sensitivity (SEN), and precision (PRE) scores of 0.816 5, 3.668 1, 0.889 2, and 0.894 6, respectively, outperforming other mainstream segmentation algorithms. The experimental results demonstrate that the method in this paper effectively improves the segmentation of infarct lesions, and is expected to provide a reliable support for clinical diagnosis and treatment.

Fibrinogen binding to activated platelets and its biomimetic thrombus-targeted thrombolytic strategies.

Thrombosis is associated with various fatal arteriovenous syndromes including ischemic stroke, myocardial infarction, and pulmonary embolism. However, current clinical thrombolytic treatment strategies still have many problems in targeting and safety to meet the thrombolytic therapy needs. Understanding the molecular mechanism that underlies thrombosis is critical in developing effective thrombolytic strategies. It is well known that platelets play a central role in thrombosis and the binding of fibrinogen to activated platelets is a common pathway in the process of clot formation. Based on this, a concept of biomimetic thrombus-targeted thrombolytic strategy inspired from fibrinogen binding to activated platelets in thrombosis was proposed, which could selectively bind to activated platelets at a thrombus site, thus enabling targeted delivery and local release of thrombolytic agents for effective thrombolysis. In this review, we first summarized the main characteristics of platelets and fibrinogen, and then introduced the classical molecular mechanisms of thrombosis, including platelet adhesion, platelet activation and platelet aggregation through the interactions of activated platelets with fibrinogen. In addition, we highlighted the recent advances in biomimetic thrombus-targeted thrombolytic strategies which inspired from fibrinogen binding to activated platelets in thrombosis. The possible future directions and perspectives in this emerging area are briefly discussed.

Maternal Oxidative Balance Score during Pregnancy and Congenital Heart Defects.

The relationship between maternal oxidative balance score (OBS) in pregnancy, representing overall oxidative balance status by integrating dietary and lifestyle factors, and congenital heart defects (CHD) remains unclear; therefore, this study attempted to explore their associations among the Chinese population. We conducted a case-control study including 474 cases and 948 controls in Northwest China. Pregnant women were interviewed to report diets and lifestyles in pregnancy by structured questionnaires. Logistic regression models were used to estimate the adjusted ORs (95%CIs). Maternal OBS ranged from 6 to 34 among cases, and 5 to 37 among controls. Comparing the highest with the lowest tertile group, the adjusted OR for CHD was 0.31 (0.19-0.50). The CHD risk was reduced by 7% (OR = 0.93, 95%CI = 0.90-0.95) in association with per 1 higher score of OBS during pregnancy. The inverse relationship between maternal OBS and CHD risk appeared to be more pronounced among participants in urban areas (OR = 0.89, 95%CI = 0.86-0.93). Maternal OBS during pregnancy showed good predictive values for fetal CHD, with the areas under the receiver operating characteristic curve 0.78 (0.76-0.81). These findings highlighted the importance of reducing oxidative stress through antioxidant-rich diets and healthy lifestyles among pregnant women to prevent fetal CHD.

Intervention of asprosin attenuates oxidative stress and neointima formation in vascular injury.

AIMS: Asprosin, a newly discovered hormone, is linked to insulin resistance. This study shows the roles of asprosin in vascular smooth muscle cells (VSMCs) proliferation, migration, oxidative stress and neointima formation of vascular injury. METHODS: Mouse aortic VSMCs were cultured, and platelet-derived growth factor-BB (PDGF-BB) was used to induce oxidative stress, proliferation and migration in VSMCs. Vascular injury was induced by repeatedly moving a guidewire in the lumen of carotid artery in mice. RESULTS: Asprosin overexpression promoted VSMC oxidative stress, proliferation and migration, which were attenuated by toll-like receptor 4 (TLR4) knockdown, antioxidant NAC, NOX1 inhibitor ML171 or NOX2 inhibitor GSK2795039. Asprosin overexpression increased NOX1/2 expressions, while asprosin knockdown increased heme oxygenase-1 (HO-1) and NADPH quinone oxidoreductase-1 (NQO-1) expressions. Asprosin inhibited Nrf2 nuclear translocation. Nrf2 activator sulforaphane increased HO-1 and NQO-1 expressions, and prevented asprosin-induced NOX1/2 upregulation, oxidative stress, proliferation and migration. Exogenous asprosin protein had similar roles to asprosin overexpression. PDGF-BB increased asprosin expressions. PDGF-BB-induced oxidative stress, proliferation and migration were enhanced by Nrf2 inhibitor ML385, but attenuated by asprosin knockdown. Vascular injury increased asprosin expression. Local asprosin knockdown in the injured carotid artery promoted HO-1 and NQO-1 expressions, but attenuated the NOX1 and NOX2 upregulation, oxidative stress, neointima formation and vascular remodeling in mice. INNOVATION AND CONCLUSION: Asprosin promotes oxidative stress, proliferation and migration of VSMCs via TLR4-Nrf2-mediated redox imbalance. Inhibition of asprosin expression attenuates VSMC proliferation and migration, oxidative stress and neointima formation in the injured artery. Asprosin might be a promising therapeutic target for vascular injury.

IRG1/ACOD1 Promotes Neutrophil Reverse Migration and Alleviates Local Inflammation.

Polymorphonuclear neutrophil (PMN) infiltration at inflammatory site plays a critical role in inflammation. PMN reverse migration (rM) describes the phenomenon that PMNs migrate away from inflammatory site back into the vasculature, and its role within inflammatory scenarios remains to be fully determined. This study aimed to investigate the mechanism underlying PMN rM and its role in inflammation. First, we demonstrated PMN rM in a mouse model of LPS-induced acute lung inflammation. By single-cell RNA sequencing (scRNA-seq), we demonstrated that reverse migrated (rM-ed) PMNs in blood expressed high level of immuneresponsive gene 1 (Irg1), the encoding gene of cis-aconitate decarboxylase (ACOD1). Using a mouse air pouch model, which enables us to directly track rM-ed PMNs in vivo, we detected higher expression of ACOD1 in the rM-ed PMNs in circulation. Furthermore, mice with Irg1 knockout exhibited decreased PMN rM and higher levels of inflammatory cytokine in inflammatory site. Mechanistically, we found that itaconate, the product of ACOD1 catalyzation, decreased PMN ICAM-1 expression at the inflammation site. Furthermore, inflammatory site showed a high level of shed CD11a, the ligand of ICAM-1. Neutralization of either ICAM-1 or CD11a leading to increased PMN rM. These findings suggest that the binding of ICAM-1 and shed CD11a serves as a retaining force to hold PMNs in the site of inflammation, and ACOD1-decreased PMN surface expression of ICAM-1 weakens the retaining force, so promoting PMNs to leave the inflammatory site. These results indicate a regulatory role of IRG1 in PMN rM and subsequent contributions to inflammation resolution.

A Hexanuclear Gadolinium(III)-Based Nanoprobe for Magnetic Resonance Imaging of Tumor Apoptosis.

Magnetic resonance imaging (MRI) is instrumental in the noninvasive evaluation of tumor tissues in patients subjected to chemotherapy, thereby yielding essential diagnostic data crucial for the prognosis of tumors and the formulation of therapeutic strategies. Currently, commercially available MRI contrast agents (CAs) predominantly consist of mononuclear gadolinium(III) complexes. Because there is only one Gd(III) atom per molecule, these CAs often require administration in high doses to achieve the desired contrast quality, which inevitably leads to some adverse events. Herein, we develop a six-nuclei, apoptosis-targeting T1 CA, Gd6-ZnDPA nanoprobe, which consists of a hexanuclear gadolinium nanocluster (Gd6) with an apoptosis-targeting group (ZnDPA). The amplification of Gd(III) by the hexanuclear structure generates its high longitudinal relaxivity (44.67 mM-1 s-1, 1T) and low r1/r2 ratio (0.68, 1T). Based on the Solomon-Bloembergen-Morgan (SBM) theory, this notable improvement is primarily ascribed to a long correlation tumbling time (τR). More importantly, the Gd6-ZnDPA nanoprobe shows excellent tumor apoptosis properties with an enhanced MR signal ratio (∼74%) and a long MRI imaging acquisition time window (∼48 h) in 4T1 tumor-bearing mice. This study introduces an experimental gadolinium-based CA for the potential imaging of tumor apoptosis in the context of MRI.

Nanoarchitectonic Engineering of Thermal-Responsive Magnetic Nanorobot Collectives for Intracranial Aneurysm Therapy.

Stent-assisted coiling is a main treatment modality for intracranial aneurysms (IAs) in clinics, but critical challenges remain to be overcome, such as exogenous implant-induced stenosis and reliance on antiplatelet agents. Herein, an endovascular approach is reported for IA therapy without stent grafting or microcatheter shaping, enabled by active delivery of thrombin (Th) to target aneurysms using innovative phase-change material (PCM)-coated magnetite-thrombin (Fe3O4-Th@PCM) FTP nanorobots. The nanorobots are controlled by an integrated actuation system of dynamic torque-force hybrid magnetic fields. With robust intravascular navigation guided by real-time ultrasound imaging, nanorobotic collectives can effectively accumulate and retain in model aneurysms constructed in vivo, followed by controlled release of the encapsulated Th for rapid occlusion of the aneurysm upon melting the protective PCM (thermally responsive in a tunable manner) through focused magnetic hyperthermia. Complete and stable aneurysm embolization is confirmed by postoperative examination and 2-week postembolization follow-up using digital subtraction angiography (DSA), contrast-enhanced ultrasound (CEUS), and histological analysis. The safety of the embolization therapy is assessed through biocompatibility evaluation and histopathology assays. This strategy, seamlessly integrating secure drug packaging, agile magnetic actuation, and clinical interventional imaging, avoids possible exogenous implant rejection, circumvents cumbersome microcatheter shaping, and offers a promising option for IA therapy.

MicroRNA-19a-3p augments TGF-ß1-induced cardiac fibroblast activation via targeting BAMBI.

The main pathogenic factor leading to cardiac remodeling and heart failure is myocardial fibrosis. Recent research indicates that microRNAs are essential for the progress of cardiac fibrosis. Myocardial fibrosis is considered to be alleviated through the bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI), which does this by blocking the transforming growth factor ß1 (TGF-ß1) signaling pathway. Here, this study sought to elucidate the post-transcriptional regulation of miR-19a-3p on BAMBI and its role in TGF-ß1-induced cardiac fibroblast activation. Transverse aortic constriction (TAC) caused both myocardial interstitial and perivascular collagen deposition. RT-PCR showed that miR-19a-3p was upregulated in the myocardial tissue of cardiac fibrosis, and TGF-ß1 induced an increase of miR-19a-3p expression in cardiac fibroblasts. The dual-luciferase reporter test and qRT-PCR confirmed that miR-19a-3p directly combined with BAMBI mRNA 3'UTR, thus reduced BAMBI expression, which diminished the capability of BAMBI to inhibit TGF-ß1. Furthermore, miR-19a-3p mimic increased the activation of TGF-ß1/SMAD2/3 pathway signaling, which supported cardiac fibroblast activation, which blocked by overexpression of BAMBI. These findings imply that miR-19a-3p enhances the activation of TGF-ß1/SMAD2/3 by inhibiting BAMBI, further boosting the activation of cardiac fibroblasts, and may thus offer a novel strategy to tackling myocardial fibrosis.

SOX13 is a novel prognostic biomarker and associates with immune infiltration in breast cancer.

Background: The transcription factor, SOX13 is part of the SOX family. SOX proteins are crucial in the progression of many cancers, and some correlate with carcinogenesis. Nonetheless, the biological and clinical implications of SOX13 in human breast cancer (BC) remain rarely known. Methods: We evaluated the survival and expression data of SOX13 in BC patients via the UNLCAL, GEPIA, TIMER, and Kaplan-Meier plotter databases. Immunohistochemistry (IHC) was used to verify clinical specimens. The gene alteration rates of SOX13 were acquired on the online web cBioportal. With the aid of the TCGA data, the association between SOX13 mRNA expression and copy number alterations (CNA) and methylation was determined. LinkedOmics was used to identify the genes that co-expressed with SOX13 and the regulators. Immune infiltration and tumor microenvironment evaluations were assessed by ImmuCellAI and TIMER2.0 databases. SOX13 correlated drug resistance analysis was performed using the GDSC2 database. Results: Higher SOX13 expression was discovered in BC tissues in comparison to normal tissues. Moreover, increased gene mutation and amplification of SOX13 were found in BC. Patients with increased SOX13 expression levels showed worse overall survival (OS). Cox analysis showed that SOX13 independently served as a prognostic indicator for poor survival in BC. Further, the expression of SOX13 was also confirmed to be correlated with tumor microenvironment and diverse infiltration of immune cells. In terms of drug sensitivity analysis, we found higher expression level of SOX13 predicts a high IC50 value for most of 198 drugs which predicts drug resistance. Conclusion: The present findings demonstrated that high expression of SOX13 negatively relates to prognosis and SOX13 plays an important role in cancer immunity. Therefore, SOX13 may potentially be adopted as a biomarker for predicting BC prognosis and infiltration of immune cells.

Evaluating Oral Probiotic Supplements as Complementary Treatment in Advanced Lung Cancer Patients Receiving ICIs: A Prospective Real-World Study.

OBJECTIVE: To evaluate the effectiveness of oral probiotic supplements in patients undergoing immune checkpoint inhibitors (ICIs) for the treatment of advanced lung cancer. METHODS: This prospective real-world study enrolled patients with advanced lung cancer who were receiving ICIs as part of their treatment. The patients were divided into 2 groups: Group OPS received oral probiotic supplements along with ICIs, while Group C did not. The primary endpoint was progression-free survival (PFS). The secondary outcome measure was the objective response rate (ORR). RESULTS: A total of 253 patients were included in the study, with 71 patients in Group OPS and 182 patients in the control group (Group C). No significant differences were observed in the median PFS between the 2 groups for all patients. However, for small cell lung cancer (SCLC) patients, the median PFS was significantly better in the Group OPS compared to the Group C (11.1 months vs 7.0 months, P = .049). No significant differences were observed in median PFS for the non-small cell lung cancer (NSCLC) cohort between the 2 groups, but a trend towards better median PFS in Group OPS was noticed (16.5 months vs 12.3 months, P = .56). The ORR for the entire cohort was 58.0%. CONCLUSION: Oral probiotics supplements in combination with ICIs included regimen may improve the outcome in patients with advanced SCLC. The above points should be proved by further study.

This study examined whether the addition of oral probiotic supplements to ICIs could enhance the treatment of advanced lung cancer. A total of 253 patients with advanced lung cancer were involved in the study, with some receiving probiotics in combination with ICIs and others not. The findings revealed that patients with SCLC who took probiotics had significantly better PFS compared to those who did not. Additionally, there was a tendency towards enhanced PFS in NSCLC patients who received probiotics. In conclusion, the study indicates that incorporating oral probiotics with ICIs may lead to better outcomes for patients with advanced SCLC, although further research is necessary to validate these results.This real world study explores whether oral probiotic supplements along with immune checkpoint inhibitors (ICIs) can help treat advanced lung cancer. The study included 253 patients with advanced lung cancer receiving ICIs treatment, part of them taking probiotics along with ICIs. The results showed that patients with small cell lung cancer (SCLC) who took probiotics had better progression-free survival (PFS) compared to those who didn't. There was also a trend towards better PFS in non-small cell lung cancer (NSCLC) patients who took probiotics. Overall, the study suggests that taking oral probiotics along with ICIs may improve outcomes for patients with advanced SCLC, but more research is needed to confirm these findings.

circLIFR-007 reduces liver metastasis via promoting hnRNPA1 nuclear export and YAP phosphorylation in breast cancer.

Cancer metastasis is the major cause of death in patients with breast cancer (BC). The liver is a common site of breast cancer metastasis, and the 5-year survival rate of patients with breast cancer liver metastases (BCLMs) is only about 8.5 %. CircRNAs are involved in a variety of cancer-related pathological behaviors, and their unique structure and resistance to RNA degradation enable them to serve as ideal diagnostic biomarkers and therapeutic targets. Therefore, it is important to investigate the role and molecular mechanism of circRNAs in cancer metastasis. CircLIFR-007 was identified as a critical circular RNA in BC metastasis by circRNAs microarray and qRT-PCR experiment. Cell function assays were performed to explore the effect of circLIFR-007 in breast cancer cells. Experiments in vivo validated the function of circLIFR-007. Several molecular assays were performed to investigate the underlying mechanisms. We found that circLIFR-007 acted as a negative controller in breast cancer liver metastasis. CircLIFR-007 upregulates the phosphorylation level of YAP by exporting hnRNPA1 to promote the combination between hnRNPA1 and YAP in the cytoplasm. Overexpression of circLIFR-007 suppressed the expression of liver metastasis-related proteins, SREBF1 and SNAI1, which were regulated by transcription factor YAP. Functionally, circLIFR-007 inhibits the proliferation and metastasis of breast cancer cells both in vivo and in vitro.

GLP-1 in the Hypothalamic Paraventricular Nucleus Promotes Sympathetic Activation and Hypertension.

Glucagon-like peptide-1 (GLP-1) and its analogs are widely used for diabetes treatment. The paraventricular nucleus (PVN) is crucial for regulating cardiovascular activity. This study aims to determine the roles of GLP-1 and its receptors (GLP-1R) in the PVN in regulating sympathetic outflow and blood pressure. Experiments were carried out in male normotensive rats and spontaneously hypertensive rats (SHR). Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded. GLP-1 and GLP-1R expressions were present in the PVN. PVN microinjection of GLP-1R agonist recombinant human GLP-1 (rhGLP-1) or EX-4 increased RSNA and MAP, which were prevented by GLP-1R antagonist exendin 9-39 (EX9-39) or GLP-1R antagonist 1, superoxide scavenger tempol, antioxidant N-acetylcysteine, NADPH oxidase (NOX) inhibitor apocynin, adenylyl cyclase (AC) inhibitor SQ22536 or protein kinase A (PKA) inhibitor H89. PVN microinjection of rhGLP-1 increased superoxide production, NADPH oxidase activity, cAMP level, AC, and PKA activity, which were prevented by SQ22536 or H89. GLP-1 and GLP-1R were upregulated in the PVN of SHR. PVN microinjection of GLP-1 agonist increased RSNA and MAP in both WKY and SHR, but GLP-1 antagonists caused greater effects in reducing RSNA and MAP in SHR than in WKY. The increased superoxide production and NADPH oxidase activity in the PVN of SHR were augmented by GLP-1R agonists but attenuated by GLP-1R antagonists. These results indicate that activation of GLP-1R in the PVN increased sympathetic outflow and blood pressure via cAMP-PKA-mediated NADPH oxidase activation and subsequent superoxide production. GLP-1 and GLP-1R upregulation in the PVN partially contributes to sympathetic overactivity and hypertension.

Selective binding of cationic fibrinogen-mimicking chitosan nanoparticles to activated platelets and efficient drug release for antithrombotic therapy.

Thrombosis is the main cause of catastrophic events including ischemic stroke, myocardial infarction and pulmonary embolism. Acetylsalicylic acid (ASA) therapy offers a desirable approach to antithrombosis through a reduction of platelet reactivity. However, major bleeding complications, severe off-target side effects, and resistance or nonresponse to ASA greatly attenuate its clinical outcomes. Herein, we report a cationic fibrinogen-mimicking nanoparticle, denoted as ASA-RGD-CS@TPP, to achieve activated-platelet-targeted delivery and efficient release of ASA for safer and more effective antithrombotic therapy. This biomimetic antithrombotic system was prepared by one-pot ionic gelation between cationic arginine-glycine-aspartic acid (RGD)-grafted chitosan (RGD-CS) and anionic tripolyphosphate (TPP). The platform exhibited selective binding to activated platelets, leading to efficient release of ASA and subsequent attenuation of platelet functions, including the remarkable inhibition of platelet aggregation through a potent blockage of cyclooxygenase-1 (COX-1). After intravenous administration, ASA-RGD-CS@TPP displayed significantly prolonged circulation time and successful prevention of thrombosis in a mouse model. ASA-RGD-CS@TPP was demonstrated to significantly enhance antithrombotic therapy while showing minimal coagulation and hemorrhagic risks and excellent biocompatibility in vivo as compared to free ASA. This platform provides a simple, safe, effective and targeted strategy for the development of antithrombotic nanomedicines.

Development and Validation of a Deep Learning Model to Reduce the Interference of Rectal Artifacts in MRI-based Prostate Cancer Diagnosis.

Purpose To develop an MRI-based model for clinically significant prostate cancer (csPCa) diagnosis that can resist rectal artifact interference. Materials and Methods This retrospective study included 2203 male patients with prostate lesions who underwent biparametric MRI and biopsy between January 2019 and June 2023. Targeted adversarial training with proprietary adversarial samples (TPAS) strategy was proposed to enhance model resistance against rectal artifacts. The automated csPCa diagnostic models trained with and without TPAS were compared using multicenter validation datasets. The impact of rectal artifacts on the diagnostic performance of each model at the patient and lesion levels was compared using the area under the receiver operating characteristic curve (AUC) and the area under the precision-recall curve (AUPRC). The AUC between models was compared using the DeLong test, and the AUPRC was compared using the bootstrap method. Results The TPAS model exhibited diagnostic performance improvements of 6% at the patient level (AUC: 0.87 vs 0.81, P < .001) and 7% at the lesion level (AUPRC: 0.84 vs 0.77, P = .007) compared with the control model. The TPAS model demonstrated less performance decline in the presence of rectal artifact-pattern adversarial noise than the control model (ΔAUC: -17% vs -19%, ΔAUPRC: -18% vs -21%). The TPAS model performed better than the control model in patients with moderate (AUC: 0.79 vs 0.73, AUPRC: 0.68 vs 0.61) and severe (AUC: 0.75 vs 0.57, AUPRC: 0.69 vs 0.59) artifacts. Conclusion This study demonstrates that the TPAS model can reduce rectal artifact interference in MRI-based csPCa diagnosis, thereby improving its performance in clinical applications. Keywords: MR-Diffusion-weighted Imaging, Urinary, Prostate, Comparative Studies, Diagnosis, Transfer Learning Clinical trial registration no. ChiCTR23000069832 Supplemental material is available for this article. Published under a CC BY 4.0 license.