Multiomics integrated analysis and experimental validation identify TLR4 and ALOX5 as oxidative stress-related biomarkers in intracranial aneurysms.

BACKGROUND: Intracranial aneurysm (IA) is a severe cerebrovascular disease, and effective gene therapy and drug interventions for its treatment are still lacking. Oxidative stress (OS) is closely associated with the IA, but the key regulatory genes involved are still unclear. Through multiomics analysis and experimental validation, we identified two diagnostic markers for IA associated with OS. METHODS: In this study, we first analyzed the IA dataset GSE75436 and conducted a joint analysis of oxidative stress-related genes (ORGs). Differential analysis, functional enrichment analysis, immune infiltration, WGCNA, PPI, LASSO, and other methods were used to identify IA diagnostic markers related to OS. Next, the functions of TLR4 and ALOX5 expression in IA and their potential targeted therapeutic drugs were analyzed. We also performed single-cell sequencing of patient IA and control (superficial temporal artery, STA) tissues. 23,342 cells were captured from 2 IA and 3 STA samples obtained from our center. Cell clustering and annotation were conducted using R software to observe the distribution of TLR4 and ALOX5 expression in IAs. Finally, the expression of TLR4 and ALOX5 were validated in IA patients and in an elastase-induced mouse IA model using experiments such as WB and immunofluorescence. RESULTS: Through bioinformatics analysis, we identified 16 key ORGs associated with IA pathogenesis. Further screening revealed that ALOX5 and TLR4 were highly expressed to activate a series of inflammatory responses and reduce the production of myocytes. Methotrexate (MTX) may be a potential targeted drug. Single-cell analysis revealed a notable increase in immune cells in the IA group, with ALOX5 and TLR4 primarily localized to monocytes/macrophages. Validation through patient samples and mouse models confirmed high expression of ALOX5 and TLR4 in IAs. CONCLUSIONS: Bioinformatics analysis indicated that ALOX5 and TLR4 are the most significant ORGs associated with the pathogenesis of IA. Single-cell sequencing and experiments revealed that the high expression of ALOX5 and TLR4 are closely related to IA. These two genes are promising new targets for IA therapy.

Understanding the differential impact of PFOS and F-53B pollution on reed-mediated soil organic matter decomposition: Insights from rhizosphere priming effect.

Plants affect soil microorganisms through the release of root exudates under pollution stress. This process may affect rhizosphere priming effect (RPE) and alter the rate of soil organic matter decomposition. However, the influence of plants on the decomposition of organic matter in soil subjected to pollution stress remains unclear. We studied the effects of exposure to perfluorooctanesulfonic (PFOS) and its alternative, chlorinated polyfluoroalkyl ether sulfonic (F-53B), at concentrations of 0.1 mg/kg and 50 mg/kg on the RPE of reed. We conducted our experiments in an artificial climate chamber and used the natural 13C tracer method to determine RPE. In the PFOS-exposed groups, the RPE was negative, with values of -11.45 mg C kg-1 soil d-1 in the low PFOS group and -8.04 mg C kg-1 soil d-1 in the high PFOS group. In contrast, in the F-53B-exposed groups, the RPE was positive, with values of 8.26 mg C kg-1 soil d-1 in the low F-53B group and 12.18 mg C kg-1 soil d-1 in the high F-53B group. Exposure of reeds to PFOS/F-53B stress resulted in differential effects on extracellular enzyme activities. The observed positive and negative RPE phenomena could be attributed to variations in extracellular enzyme activities. In conclusion, RPE responded differently under PFOS/F-53B exposure.

From molecular subgroups to molecular targeted therapy in rheumatoid arthritis: A bioinformatics approach.

1Background: Rheumatoid Arthritis (RA) is a heterogeneous autoimmune disease with multiple unidentified pathogenic factors. The inconsistency between molecular subgroups poses challenges for early diagnosis and personalized treatment strategies. In this study, we aimed to accurately distinguish RA patients at the transcriptome level using bioinformatics methods. 2Methods: We collected a total of 362 transcriptome datasets from RA patients in three independent samples from the GEO database. Consensus clustering was performed to identify molecular subgroups, and clinical features were assessed. Differential analysis was employed to annotate the biological functions of specifically upregulated genes between subgroups. 3Results: Based on consensus clustering of RA samples, we identified three robust molecular subgroups, with Subgroup III representing the high-risk subgroup and Subgroup II exhibiting a milder phenotype, possibly associated with relatively higher levels of autophagic ability. Subgroup I showed biological functions mainly related to viral infections, cellular metabolism, protein synthesis, and inflammatory responses. Subgroup II involved autophagy of mitochondria and organelles, protein localization, and organelle disassembly pathways, suggesting heterogeneity in the autophagy process of mitochondria that may play a protective role in inflammatory diseases. Subgroup III represented a high-risk subgroup with pathological processes including abnormal amyloid precursor protein activation, promotion of inflammatory response, and cell proliferation. 4Conclusion: The classification of the RA dataset revealed pathological heterogeneity among different subgroups, providing new insights and a basis for understanding the molecular mechanisms of RA, identifying potential therapeutic targets, and developing personalized treatment approaches.

Groenlandicine enhances cisplatin sensitivity in cisplatin-resistant osteosarcoma cells through the BAX/Bcl-2/Caspase-9/Caspase-3 pathway.

Groenlandicine is a protoberberine alkaloid isolated from Coptidis Rhizoma, a widely used traditional Chinese medicine known for its various biological activities. This study aims to validate groenlandicine's effect on both cisplatin-sensitive and cisplatin-resistant osteosarcoma (OS) cells, along with exploring its potential molecular mechanism. The ligand-based virtual screening (LBVS) method and molecular docking were employed to screen drugs. CCK-8 and FCM were used to measure the effect of groenlandicine on the OS cells transfected by lentivirus with over-expression or low-expression of TOP1. Cell scratch assay, CCK-8, FCM, and the EdU assay were utilized to evaluate the effect of groenlandicine on cisplatin-resistant cells. WB, immunofluorescence, and PCR were conducted to measure the levels of TOP1, Bcl-2, BAX, Caspase-9, and Caspase-3. Additionally, a subcutaneous tumor model was established in nude mice to verify the efficacy of groenlandicine. Groenlandicine reduced the migration and proliferation while promoting apoptosis in OS cells, effectively damaging them. Meanwhile, groenlandicine exhibited weak cytotoxicity in 293T cells. Combination with cisplatin enhanced tumor-killing activity, markedly activating BAX, cleaved-Caspase-3, and cleaved-Caspase-9, while inhibiting the Bcl2 pathway in cisplatin-resistant OS cells. Moreover, the level of TOP1, elevated in cisplatin-resistant OS cells, was down-regulated by groenlandicine both in vitro and in vivo. Animal experiments confirmed that groenlandicine combined with cisplatin suppressed OS growth with lower nephrotoxicity. Groenlandicine induces apoptosis and enhances the sensitivity of drug-resistant OS cells to cisplatin via the BAX/Bcl-2/Caspase-9/Caspase-3 pathway. Groenlandicine inhibits OS cells growth by down-regulating TOP1 level.Therefore, groenlandicine holds promise as a potential agent for reversing cisplatin resistance in OS treatment.

A New Method for Scoliosis Screening Incorporating Deep Learning With Back Images.

STUDY DESIGN: Retrospective observational study. OBJECTIVES: Scoliosis is commonly observed in adolescents, with a world0wide prevalence of 0.5%. It is prone to be overlooked by parents during its early stages, as it often lacks overt characteristics. As a result, many individuals are not aware that they may have scoliosis until the symptoms become quite severe, significantly affecting the physical and mental well-being of patients. Traditional screening methods for scoliosis demand significant physician effort and require unnecessary radiography exposure; thus, implementing large-scale screening is challenging. The application of deep learning algorithms has the potential to reduce unnecessary radiation risks as well as the costs of scoliosis screening. METHODS: The data of 247 scoliosis patients observed between 2008 and 2021 were used for training. The dataset included frontal, lateral, and back upright images as well as X-ray images obtained during the same period. We proposed and validated deep learning algorithms for automated scoliosis screening using upright back images. The overall process involved the localization of the back region of interest (ROI), spinal region segmentation, and Cobb angle measurements. RESULTS: The results indicated that the accuracy of the Cobb angle measurement was superior to that of the traditional human visual recognition method, providing a concise and convenient scoliosis screening capability without causing any harm to the human body. CONCLUSIONS: The method was automated, accurate, concise, and convenient. It is potentially applicable to a wide range of screening methods for the detection of early scoliosis.

Morphological and functional abnormalities of ophthalmic artery in patients with ophthalmic vascular accidents.

Background: By observing and comparing the morphological and functional differences of the ophthalmic artery (OA) in patients with ocular vascular accidents (OVAs) due to iatrogenic embolism or non-iatrogenic occlusion, we propose a classification system based on the characteristics of OA on invasive digital subtraction angiography (DSA). Methods: All patients undergoing ophthalmic arterial DSA within 1 week after the OVAs between January 2017 and December 2021 were enrolled and divided into different types, and the differences between iatrogenic embolism and non-iatrogenic occlusion categories were compared. Results: A total of 27 eyes of 27 patients were included in this study. Based on the results of carotid/intracranial arterial DSA, the morphological and functional abnormalities of OA with OVAs can be divided into five types. The proportion of males (7.14%), ocular ischemic syndrome (OIS) (0.00%) and neovascular glaucoma (NVG) (0.00%) in the iatrogenic embolism category was significantly lower than that (84.62, 61.54, and 69.23%, respectively) of the non-iatrogenic occlusion category (p < 0.001, p = 0.001, p < 0.001, respectively). However, the proportion of no light perception (NLP) (100%), anterior segment ischemia (ASI) (71.43%), and orbital involvement (ophthalmoplegia and ptosis, 42.86%) eventually occurring in the former was significantly greater than that in the latter (23.08, 0.00, 0.00%, respectively) (p < 0.001, p < 0.001, p = 0.010, respectively). Conclusion: Ocular vascular accidents can be divided into five types based on the characteristics of OA on DSA.

Albumin corrected anion gap for predicting in-hospital death among patients with acute myocardial infarction: A retrospective cohort study.

OBJECTIVE: To explore the relationship between Anion Gap (AG), Albumin Corrected AG (ACAG), and in-hospital mortality of Acute Myocardial Infarction (AMI) patients and develop a prediction model for predicting the mortality in AMI patients. METHODS: This was a retrospective cohort study based on the Medical Information Mart for Intensive Care (MIMIC)-Ⅲ, MIMIC-IV, and eICU Collaborative Study Database (eICU). A total of 9767 AMI patients who were admitted to the intensive care unit were included. The authors employed univariate and multivariable cox proportional hazards analyses to investigate the association between AG, ACAG, and in-hospital mortality; p < 0.05 was considered statistically significant. A nomogram incorporating ACAG and clinical indicators was developed and validated for predicting mortality among AMI patients. RESULTS: Both ACAG and AG exhibited a significant association with an elevated risk of in-hospital mortality in AMI patients. The C-index of ACAG (C-index = 0.606) was significantly higher than AG (C-index = 0.589). A nomogram (ACAG combined model) was developed to predict the in-hospital mortality for AMI patients. The nomogram demonstrated a good predictive performance by Area Under the Curve (AUC) of 0.763 in the training set, 0.744 and 0.681 in the external validation cohort. The C-index of the nomogram was 0.759 in the training set, 0.756 and 0.762 in the validation cohorts. Additionally, the C-index of the nomogram was obviously higher than the ACAG and age shock index in three databases. CONCLUSION: ACAG was related to in-hospital mortality among AMI patients. The authors developed a nomogram incorporating ACAG and clinical indicators, demonstrating good performance for predicting in-hospital mortality of AMI patients.

Dynamic evolution of the heterochromatin sensing histone demethylase IBM1.

Heterochromatin is critical for maintaining genome stability, especially in flowering plants, where it relies on a feedback loop involving the H3K9 methyltransferase, KRYPTONITE (KYP), and the DNA methyltransferase CHROMOMETHYLASE3 (CMT3). The H3K9 demethylase INCREASED IN BONSAI METHYLATION 1 (IBM1) counteracts the detrimental consequences of KYP-CMT3 activity in transcribed genes. IBM1 expression in Arabidopsis is uniquely regulated by methylation of the 7th intron, allowing it to monitor global H3K9me2 levels. We show the methylated intron is prevalent across flowering plants and its underlying sequence exhibits dynamic evolution. We also find extensive genetic and expression variations in KYP, CMT3, and IBM1 across flowering plants. We identify Arabidopsis accessions resembling weak ibm1 mutants and Brassicaceae species with reduced IBM1 expression or deletions. Evolution towards reduced IBM1 activity in some flowering plants could explain the frequent natural occurrence of diminished or lost CMT3 activity and loss of gene body DNA methylation, as cmt3 mutants in A. thaliana mitigate the deleterious effects of IBM1.

Ultrasonic-assisted nanofiltration separation recovering salvianolic acid B from ethanol wastewater.

The transformation of salvianolic acid B brought on by heat treatment recovery of ethanol eluent, which is a difficult problem in pharmaceutical technology, affects the purity of raw material when the medicinal raw material salvianolic acid B is purified by resin. Ultrasonic-assisted nanofiltration separation (UANS) was first employed to improve efficiency of resource utilization by regulating rejection and separating salvianolic acid B and rosmarinic acid from organic pharmaceutical wastewater. The rejection was related to three variables: ultrasonic power, pH, and ethanol concentration. But there were differences in the effects of variables on the rejections of salvianolic acid B and rosmarinic acid. The rejections of rosmarinic acid and salvianolic acid B showed a decreasing trend with an increase in ultrasonic power or a decrease in pH; however, when the concentration of ethanol was increased from 5 % to 35 %, the salvianolic acid B rejection increased from 84.96 % to 96.60 % and the rosmarinic acid rejection decreased from 35.09 % to 17.51 %. On the basis of response surface methodology (RSM), the optimal UANS parameters for solution conditions involving different ethanol concentrations are as follows: 10 % ethanol solution (ultrasonic power 500 W and pH 6.15), 20 % ethanol solution (ultrasonic power 500 W and pH 6.54), and 30 % ethanol solution (ultrasonic power 460 W and pH 6.34). The molecular proportions of salvianolic acid B were 10.75 %, 7.13 %, and 8.27 % in 10 %, 20 %, and 30 % ethanol wastewater, while the molecular proportions of rosmarinic acid were 40.52 %, 33.83 %, and 69.87 %, respectively. And the recoveries of salvianolic acid B in 10 %, 20 %, and 30 % ethanol wastewater were 93.56 %, 95.04 %, and 97.30 %, respectively, while the recoveries of rosmarinic acid were 3.19 %, 2.27 %, and 0.56 %. The molecular proportion and the rejection are correlated exponentially. In comparison with conventional nanofiltration separation (CNS), UANS is able to resolve the conflict between rosmarinic acid and salvianolic acid B in pharmaceutical wastewater, as well as enhance resource recycling and separation efficiency to prevent pollution of the environment from pharmaceutical wastewater. Experiments using UANS at different power intensities suggest that the ultrasonic at a power intensity of 46-50 W/L and the power density of 0.92-1.00 W/cm2 may resolve the separation conflict between rosmarinic acid and salvianolic acid B. This work suggests that UANS may be a significant advancement in the field of ultrasonic separation and has several potential uses in the water treatment industry.

Partially PEG-Grafted Poly(Terphenyl Piperidinium) Anion Exchange Membranes with Balanced Properties for Alkaline Fuel Cells.

Poly(ethylene glycol) (PEG) or oligo (ethylene glycol) (OEG) grafted anion exchange membranes (AEMs) exhibit improved ionic conductivity, high alkaline stability, and subsequent boosted AEM fuel cell performance, but too much PEG/OEG side chains may can result in a reduction in the ion exchange capacity (IEC), which can have adverse effects on ion transport. Here, a series of partially PEG-grafted poly(terphenyl piperidinium) with different side chain length are synthesized using simple postpolymerization modification to produce AEMs with balanced properties. The polar and flexible PEG side chains are responsible for the controlled water uptake and swelling, superior hydroxide conductivity (122 mS cm-1 at 80 °C with an IEC of 1.99 mmol g-1), and enhanced alkaline stability compared to the reference sample without PEG grafts (PTP). More importantly, the performance of AEM fuel cell (AEMFC) with the membrane containing partial PEG side chains surpasses that with PTP membrane, demonstrating a highest peak power density of 1110 mW cm-2 at 80 °C under optimized conditions. This work provides a novel approach to the fabrication of high-performance AEM materials with balanced properties for alkaline fuel cell application.

Bilateral axial length growth patterns of myopic anisometropes undergoing sequential monocular to binocular orthokeratology treatment.

PURPOSE: To investigate bilateral axial length (AL) growth patterns and interactions of myopic eyes in anisometropic children during unilateral orthokeratology (OK) treatment in their singularly myopic eyes (Eyes1), followed by bilateral treatment when their second eyes (Eyes2) developed myopia. METHODS: This study enrolled 94 eyes from 47 anisometropes (20 males). All patients had undergone monocular OK treatment for > 1 year followed by binocular treatment for > 1 year. Axial growth of Eyes1 and Eyes2 during the first year of monocular treatment (Stage 1), average annual axial elongation during the monocular treatment period, and axial elongation during the first year of binocular treatment (Stage 2) were respectively termed: S1E1 and S1E2, Annual E1 and Annual E2, and S2E1 and S2E2. Associations between AL growth and age, sex, interval time, and ocular parameters were analysed using correlation and generalised estimating equation (GEE) analysis. RESULTS: During the monocular period, Eyes1 showed less AL growth (S1E1: 0.05 ± 0.18 mm; Annual E1: 0.05 ± 0.21 mm) than Eyes2 (S1E2: 0.51 ± 0.24 mm; Annual E2: 0.52 ± 0.25 mm) (all p < 0.001). During the binocular period, there was no significant difference between S2E1 and S2E2(0.21 ± 0.14 mm v. 0.19 ± 0.17 mm, p = 0.951). Between monocular and binocular periods, Eyes1 had significantly higher S2E1 compared to S1E1 and Annual E1 (both p < 0.001), and Eyes2 had significantly lower S2E2 than S1E2 and Annual E2 (both p < 0.001). In the GEE model, spherical equivalent refraction (SER) and between periods interval time showed independently significant associations with AL growth after adjusting for age and sex. CONCLUSION: Orthokeratology can significantly control AL growth in unilateral myopia. AL growth of the initial myopic OK-treated eyes accelerated relative to the monocular period when contralateral eyes developed myopia and assumed OK treatment. During the binocular treatment phase, OK lenses showed moderate and comparable effects on AL retardation across both eyes.

DreamAnime: Learning Style-Identity Textual Disentanglement for Anime and Beyond.

Text-to-image generation models have significantly broadened the horizons of creative expression through the power of natural language. However, navigating these models to generate unique concepts, alter their appearance, or reimagine them in unfamiliar roles presents an intricate challenge. For instance, how can we exploit language-guided models to transpose an anime character into a different art style, or envision a beloved character in a radically different setting or role? This paper unveils a novel approach named DreamAnime, designed to provide this level of creative freedom. Using a minimal set of 2-3 images of a user-specified concept such as an anime character or an art style, we teach our model to encapsulate its essence through novel "words" in the embedding space of a pre-existing text-to-image model. Crucially, we disentangle the concepts of style and identity into two separate "words", thus providing the ability to manipulate them independently. These distinct "words" can then be pieced together into natural language sentences, promoting an intuitive and personalized creative process. Empirical results suggest that this disentanglement into separate word embeddings successfully captures a broad range of unique and complex concepts, with each word focusing on style or identity as appropriate. Comparisons with existing methods illustrate DreamAnime's superior capacity to accurately interpret and recreate the desired concepts across various applications and tasks. Code is available at https://github.com/chnshx/DreamAnime.

Engeletin alleviates depressive-like behaviours by modulating microglial polarization via the LCN2/CXCL10 signalling pathway.

Microglial polarization and associated inflammatory activity are the key mediators of depression pathogenesis. The natural Smilax glabra rhizomilax derivative engeletin has been reported to exhibit robust anti-inflammatory activity, but no studies to date have examined the mechanisms through which it can treat depressive symptoms. We showed that treatment for 21 days with engeletin significantly alleviated depressive-like behaviours in chronic stress social defeat stress (CSDS) model mice. T1-weighted imaging (T1WI), T2-weighted imaging (T2WI) imaging revealed no significant differences between groups, but the bilateral prefrontal cortex of CSDS mice exhibited significant increases in apparent diffusion coefficient and T2 values relative to normal control mice, with a corresponding reduction in fractional anisotropy, while engeletin reversed all of these changes. CSDS resulted in higher levels of IL-1ß, IL-6, and TNF-a production, enhanced microglial activation, and greater M1 polarization with a concomitant decrease in M2 polarization in the mPFC, whereas engeletin treatment effectively abrogated these CSDS-related pathological changes. Engeletin was further found to suppress the LCN2/C-X-C motif chemokine ligand 10 (CXCL10) signalling axis such that adeno-associated virus-induced LCN2 overexpression ablated the antidepressant effects of engeletin and reversed its beneficial effects on the M1/M2 polarization of microglia. In conclusion, engeletin can alleviate CSDS-induced depressive-like behaviours by regulating the LCN2/CXCL10 pathway and thereby altering the polarization of microglia. These data suggest that the antidepressant effects of engeletin are correlated with the polarization of microglia, highlighting a potential avenue for future design of antidepressant strategies that specifically target the microglia.

Arctic amplification-induced decline in West and South Asia dust warrants stronger antidesertification toward carbon neutrality.

Dust loading in West and South Asia has been a major environmental issue due to its negative effects on air quality, food security, energy supply and public health, as well as on regional and global weather and climate. Yet a robust understanding of its recent changes and future projection remains unclear. On the basis of several high-quality remote sensing products, we detect a consistently decreasing trend of dust loading in West and South Asia over the last two decades. In contrast to previous studies emphasizing the role of local land use changes, here, we attribute the regional dust decline to the continuous intensification of Arctic amplification driven by anthropogenic global warming. Arctic amplification results in anomalous mid-latitude atmospheric circulation, particularly a deepened trough stretching from West Siberia to Northeast India, which inhibits both dust emissions and their downstream transports. Large ensemble climate model simulations further support the dominant role of greenhouse gases induced Arctic amplification in modulating dust loading over West and South Asia. Future projections under different emission scenarios imply potential adverse effects of carbon neutrality in leading to higher regional dust loading and thus highlight the importance of stronger anti-desertification counter-actions such as reforestation and irrigation management.

Silver-coated hollow fiber surface plasmon resonance sensor for glucose detection with enhanced limit of detection.

A fiber-optic surface plasmon resonance (SPR) biosensor based on a silver-coated hollow fiber (HF) structure for glucose detection is presented. The sensor surface was immobilized with 4-mercaptophenylboronic acid (PMBA) acting as a glucose recognition monolayer. Then, gold nanoparticles (AuNPs) modified with 2-aminoethanethiol (2-AET) and PMBA were introduced onto the sensor surface after glucose was captured to enhance the wavelength shift of the SPR phenomenon excited by the light transmitted in the wall of the HF sensor. Instead of the conventional one-step sensitization pretreatment commonly used in the deposition process of silver films for fiber-optic SPR sensors, a sensitization-activation two-step activation method was adopted in the fabrication of the proposed sensor. Experiments for glucose detection were performed on the fabricated sensors in the concentration range of 1 nM-1 mM. Results showed that the sensor fabricated by the two-step activation method has a much larger shift of resonance wavelength than the sensor fabricated using the one-step sensitization method. The resonance wavelength shift was found to be linear to the logarithm of the concentration in the range of 1 nM-1 mM. The sensor achieved a limit of detection (LOD) of as low as 1 nM, which is at least an order of magnitude lower than that of other fiber-optic sensors for glucose detection reported previously. The presented HF glucose sensor has the potential for biosensing applications and provides a large reference value in the study of optical fiber SPR sensors for biosensing.

LncRNA CTBP1-AS inhibits TP63-mediated activation of S100A14 during prostate cancer progression.

Long noncoding RNAs (lncRNAs) have emerged as important molecules and potential new targets for human cancers. This study investigates the function of lncRNA CTBP1 antisense RNA (CTBP1-AS) in prostate cancer (PCa) and explores the entailed molecular mechanism. Aberrantly expressed genes potentially correlated with PCa progression were probed using integrated bioinformatics analyses. A cohort of 68 patients with PCa was included, and their tumor and para-cancerous tissues were collected. CTBP1-AS was highly expressed in PCa tissues and cells and associated with poor patient prognosis. By contrast, tumor protein p63 (TP63) and S100 calcium binding protein A14 (S100A14) were poorly expressed in the PCa tissues and cells. CTBP1-AS did not affect TP63 expression; however it blocked the TP63-mediated transcriptional activation of S100A14, thereby reducing its expression. CTBP1-AS silencing suppressed proliferation, apoptosis resistance, migration, invasion, and tumorigenicity of PCa cell lines, while its overexpression led to inverse results. The malignant phenotype of cells was further weakened by TP63 overexpression but restored following artificial S100A14 silencing. In conclusion, this study demonstrates that CTBP1-AS plays an oncogenic role in PCa by blocking TP63-mediated transcriptional activation of S100A14. This may provide insight into the management of PCa.

YAP1 Regulates the YAP1/AR/PSA Axis through Autophagy in Castration-Resistant Prostate Cancer and Mediates T-Cell Immune and Inflammatory Cytokine Infiltration.

The emergence of castration-resistant prostate cancer (CRPC) following androgen deprivation therapy (ADT) is associated with increased malignancy and limited treatment options. This study aims to investigate potential connections between immune cell infiltration and inflammatory cytokines with the YAP1/AR/PSA axis by exploring their interactions with autophagy. Our research reveals heightened levels of Yes-associated protein 1 (YAP1) expression in CRPC tissues compared with tissues from androgen-dependent prostate cancer (ADPC) and benign prostate hyperplasia (BPH). Additionally, a correlation was observed between YAP1 and PSA expressions in CRPC tissues, suggesting that YAP1 may exert a regulatory influence on PSA expression within CRPC. Enhanced YAP1 expression in C4-2 cells resulted in the upregulation of androgen receptor (AR) nuclear translocation and intracellular prostate-specific antigen (PSA) levels. Conversely, the suppression of YAP1 led to a decrease in PSA expression, suggesting that YAP1 may positively regulate the PSA in castration-resistant prostate cancer (CRPC) by facilitating AR nuclear import. The modulation of the autophagy activity exerts a significant impact on the expression levels of YAP1, the AR, and the PSA. Moreover, recent advancements in immunity and inflammation studies present promising avenues for potential therapies targeting prostate cancer (PC).