Melatonin ameliorates 10-hydroxycamptothecin-induced oxidative stress and apoptosis via autophagy-regulated p62/Keap1/Nrf2 pathway in mouse testicular cells.

10-Hydroxycamptothecin (HCPT) is a widely used clinical anticancer drug but has a significant side effect profile. Melatonin has a beneficial impact on the chemotherapy of different cancer cells and reproductive processes, but the effect and underlying molecular mechanism of melatonin's involvement in the HCPT-induced side effects in cells, especially in the testicular cells, are poorly understood. In this study, we found that melatonin therapy significantly restored HCPT-induced testicular cell damage and did not affect the antitumor effect of HCPT. Further analysis found that melatonin therapy suppressed HCPT-induced DNA damage associated with ataxia-telangiectasia mutated- and Rad3-related and CHK1 phosphorylation levels in the testis. Changes in apoptosis-associated protein levels (Bax, Bcl-2, p53, and Cleaved caspase-3) and in reactive oxygen species-associated proteins (Nrf2 and Keap1) and index (malondialdehyde and glutathione) suggested that melatonin treatment relieved HCPT-induced cell apoptosis and oxidative damage, respectively. Mechanistically, melatonin-activated autophagy proteins (ATG7, Beclin1, and LC3bII/I) may induce p62-dependent autophagy to degrade Keap1, eliciting Nrf2 from Keap1-Nrf2 interaction to promote antioxidant enzyme expression such as HO-1, which would salvage HCPT-induced ROS production and mitochondrial dysfunction. Collectively, this study reveals that melatonin therapy may protect testicular cells from HCPT-induced damage via the activation of autophagy, which alleviates oxidative stress, mitochondrial dysfunction, and cell apoptosis.

Evaluating combustion kinetics and quantifying fuel-N conversion tendency of shoe manufacturing waste.

Combustion is an effective and cost-efficient thermochemical conversion method for solid waste, showing promise for the resource utilization of shoe manufacturing waste (SMW). However, SMW is generally composed of different components, which can lead to unstable combustion and excessive pollutant emissions, especially NOx. To date, combustion characteristics, reaction mechanism and fuel nitrogen (fuel-N) conversion of different SMW components remain unclear. In this work, the combustion behavior of typical SMW components combustion was investigated using Thermogravimetric coupled with Fourier transform infrared spectrum (TG-FTIR). A simplified single-step reaction mechanism was proposed according to the temperature interval to estimate reaction mechanism of SMW. Additionally, the relationship between fuel-N conversion tendency and fuel properties was established. The results indicate that the values for the comprehensive combustion performance index (S) and flammability index (C) range from 1.65 to 0.44 and 3.98 to 1.37, respectively. This demonstrates the significant variability in combustion behavior among different SMW components. Cardboard, leather and sponge have higher values of S and C, suggesting a better ignition characteristic and a stable combustion process. During the combustion of SMW, nitrogen oxides (NO and N2O) are the main nitrogen-containing compounds in the flue gases, with NO being the major contributor, accounting for over 82.97 % of the nitrogen oxides. NO has a negative correlation with nitrogen content, but it is opposite for N2O, HCN and NH3. Furthermore, the conversion of NO, N2O and NH3 is proportional to logarithmic values of O/N, while its conversion to HCN is proportional to logarithmic values of VM/N. These findings facilitate the prediction of the fuel-N conversion of solid waste combustion. This work might shed light on combustion optimization and in-situ pollutant emission control in solid waste combustion.

Computed tomography-based radiomics improves non-invasive diagnosis of Pneumocystis jirovecii pneumonia in non-HIV patients: a retrospective study.

BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) could be fatal to patients without human immunodeficiency virus (HIV) infection. Current diagnostic methods are either invasive or inaccurate. We aimed to establish an accurate and non-invasive radiomics-based way to identify the risk of PCP infection in non-HIV patients with computed tomography (CT) manifestation of pneumonia. METHODS: This is a retrospective study including non-HIV patients hospitalized for suspected PCP from January 2010 to December 2022 in one hospital. The patients were randomized in a 7:3 ratio into training and validation cohorts. Computed tomography (CT)-based radiomics features were extracted automatically and used to construct a radiomics model. A diagnostic model with traditional clinical and CT features was also built. The area under the curve (AUC) were calculated and used to evaluate the diagnostic performance of the models. The combination of the radiomics features and serum ß-D-glucan levels was also evaluated for PCP diagnosis. RESULTS: A total of 140 patients (PCP: N = 61, non-PCP: N = 79) were randomized into training (N = 97) and validation (N = 43) cohorts. The radiomics model consisting of nine radiomic features performed significantly better (AUC = 0.954; 95% CI: 0.898-1.000) than the traditional model consisting of serum ß-D-glucan levels (AUC = 0.752; 95% CI: 0.597-0.908) in identifying PCP (P = 0.002). The combination of radiomics features and serum ß-D-glucan levels showed an accuracy of 95.8% for identifying PCP infection (positive predictive value: 95.7%, negative predictive value: 95.8%). CONCLUSIONS: Radiomics showed good diagnostic performance in differentiating PCP from other types of pneumonia in non-HIV patients. A combined diagnostic method including radiomics and serum ß-D-glucan has the potential to provide an accurate and non-invasive way to identify the risk of PCP infection in non-HIV patients with CT manifestation of pneumonia. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05701631).

TRIM44 Promotes Rabies Virus Replication by Autophagy-Dependent Mechanism.

Tripartite motif (TRIM) proteins are a multifunctional E3 ubiquitin ligase family that participates in various cellular processes. Recent studies have shown that TRIM proteins play important roles in regulating host-virus interactions through specific pathways, but their involvement in response to rabies virus (RABV) infection remains poorly understood. Here, we identified that several TRIM proteins are upregulated in mouse neuroblastoma cells (NA) after infection with the rabies virus using RNA-seq sequencing. Among them, TRIM44 was found to regulate RABV replication. This is supported by the observations that downregulation of TRIM44 inhibits RABV replication, while overexpression of TRIM44 promotes RABV replication. Mechanistically, TRIM44-induced RABV replication is brought about by activating autophagy, as inhibition of autophagy with 3-MA attenuates TRIM44-induced RABV replication. Additionally, we found that inhibition of autophagy with rapamycin reverses the TRIM44-knockdown-induced decrease in LC3B expression and autophagosome formation as well as RABV replication. The results suggest that TRIM44 promotes RABV replication by an autophagy-dependent mechanism. Our work identifies TRIM44 as a key host factor for RABV replication, and targeting TRIM44 expression may represent an effective therapeutic strategy.

Robust adaptive deep brain stimulation control of in-silico non-stationary Parkinsonian neural oscillatory dynamics.

Objective. Closed-loop deep brain stimulation (DBS) is a promising therapy for Parkinson's disease (PD) that works by adjusting DBS patterns in real time from the guidance of feedback neural activity. Current closed-loop DBS mainly uses threshold-crossing on-off controllers or linear time-invariant (LTI) controllers to regulate the basal ganglia (BG) Parkinsonian beta band oscillation power. However, the critical cortex-BG-thalamus network dynamics underlying PD are nonlinear, non-stationary, and noisy, hindering accurate and robust control of Parkinsonian neural oscillatory dynamics.Approach. Here, we develop a new robust adaptive closed-loop DBS method for regulating the Parkinsonian beta oscillatory dynamics of the cortex-BG-thalamus network. We first build an adaptive state-space model to quantify the dynamic, nonlinear, and non-stationary neural activity. We then construct an adaptive estimator to track the nonlinearity and non-stationarity in real time. We next design a robust controller to automatically determine the DBS frequency based on the estimated Parkinsonian neural state while reducing the system's sensitivity to high-frequency noise. We adopt and tune a biophysical cortex-BG-thalamus network model as an in-silico simulation testbed to generate nonlinear and non-stationary Parkinsonian neural dynamics for evaluating DBS methods.Main results. We find that under different nonlinear and non-stationary neural dynamics, our robust adaptive DBS method achieved accurate regulation of the BG Parkinsonian beta band oscillation power with small control error, bias, and deviation. Moreover, the accurate regulation generalizes across different therapeutic targets and consistently outperforms current on-off and LTI DBS methods.Significance. These results have implications for future designs of closed-loop DBS systems to treat PD.

Cross-Subject Motor Imagery Decoding by Transfer Learning of Tactile ERD.

For Brain-Computer Interface (BCI) based on motor imagery (MI), the MI task is abstract and spontaneous, presenting challenges in measurement and control and resulting in a lower signal-to-noise ratio. The quality of the collected MI data significantly impacts the cross-subject calibration results. To address this challenge, we introduce a novel cross-subject calibration method based on passive tactile afferent stimulation, in which data induced by tactile stimulation is utilized to calibrate transfer learning models for cross-subject decoding. During the experiments, tactile stimulation was applied to either the left or right hand, with subjects only required to sense tactile stimulation. Data from these tactile tasks were used to train or fine-tune models and subsequently applied to decode pure MI data. We evaluated BCI performance using both the classical Common Spatial Pattern (CSP) combined with the Linear Discriminant Analysis (LDA) algorithm and a state-of-the-art deep transfer learning model. The results demonstrate that the proposed calibration method achieved decoding performance at an equivalent level to traditional MI calibration, with the added benefit of outperforming traditional MI calibration with fewer trials. The simplicity and effectiveness of the proposed cross-subject tactile calibration method make it valuable for practical applications of BCI, especially in clinical settings.

Neural Correlates of Motor/Tactile Imagery and Tactile Sensation in a BCI paradigm: A High-Density EEG Source Imaging Study.

Complementary to brain-computer interface (BCI) based on motor imagery (MI) task, sensory imagery (SI) task provides a way for BCI construction using brain activity from somatosensory cortex. The underlying neurophysiological correlation between SI and MI was unclear and difficult to measure through behavior recording. In this study, we investigated the underlying neurodynamic of motor/tactile imagery and tactile sensation tasks through a high-density electroencephalogram (EEG) recording, and EEG source imaging was used to systematically explore the cortical activation differences and correlations between the tasks. In the experiment, participants were instructed to perform the left and right hand tasks in MI paradigm, sensory stimulation (SS) paradigm and SI paradigm. The statistical results demonstrated that the imagined MI and SI tasks differed from each other within ipsilateral sensorimotor scouts, frontal and right temporal areas in α bands, whereas real SS and imagined SI showed a similar activation pattern. The similarity between SS and SI may provide a way to train the BCI system, while the difference between MI and SI may provide a way to integrate the discriminative information between them to enhance BCI performance. The combination of the tasks and its underlying neurodynamic would provide a new approach for BCI designation for a wider application. BCI studies concentrate on the hybrid decoding method combining MI or SI with SS, but the underlining neurophysiological correlates between them were unclear. MI and SI differed from each other within the ipsilateral sensorimotor cortex in alpha bands. This is a first study to investigate the neurophysiological relationship between MI and SI through an EEG source imaging approach from high-density EEG recording.

Revealing unexpected complex encoding but simple decoding mechanisms in motor cortex via separating behaviorally relevant neural signals.

In motor cortex, behaviorally relevant neural responses are entangled with irrelevant signals, which complicates the study of encoding and decoding mechanisms. It remains unclear whether behaviorally irrelevant signals could conceal some critical truth. One solution is to accurately separate behaviorally relevant and irrelevant signals at both single-neuron and single-trial levels, but this approach remains elusive due to the unknown ground truth of behaviorally relevant signals. Therefore, we propose a framework to define, extract, and validate behaviorally relevant signals. Analyzing separated signals in three monkeys performing different reaching tasks, we found neural responses previously considered to contain little information actually encode rich behavioral information in complex nonlinear ways. These responses are critical for neuronal redundancy and reveal movement behaviors occupy a higher-dimensional neural space than previously expected. Surprisingly, when incorporating often-ignored neural dimensions, behaviorally relevant signals can be decoded linearly with comparable performance to nonlinear decoding, suggesting linear readout may be performed in motor cortex. Our findings prompt that separating behaviorally relevant signals may help uncover more hidden cortical mechanisms.

Enhancing Concrete Mechanical Properties through Basalt Fibers and Calcium Sulfate Whiskers: Optimizing Compressive Strength, Elasticity, and Pore Structure.

To study the effects of basalt fibers (BFs), calcium sulfate whiskers (CSWs), and modified calcium sulfate whiskers (MCSWs) on the compressive strength and dynamic modulus of elasticity of concrete, this paper utilizes Mercury Intrusion Porosimetry (MIP) to measure the microstructure of concrete and calculate the fractal dimension of pore surface area. The results indicate that both CSWs and BFs can increase the compressive strength of concrete. CSWs can enhance the dynamic modulus of elasticity of concrete, while the effect of BFs on the dynamic modulus of elasticity is not significant. The improvement in compressive strength and dynamic modulus of elasticity provided by MCSWs is significantly greater than that provided by CSWs. Both CSWs and BFs can effectively improve the pore structure of concrete and have a significant impact on the surface fractal dimension. CSWs inhibit the formation of ink-bottle pores, while BFs increase the number of ink-bottle pores. Due to the ink-bottle pore effect, the fractal dimension of the capillary pore surface is generally greater than three, lacking fractal characteristics. The compressive strength and dynamic modulus of elasticity of concrete have a good correlation with the fractal dimensions of large pores and transition pores.

On-Demand Optimization of Colorimetric Gas Sensors Using a Knowledge-Aware Algorithm-Driven Robotic Experimental Platform.

Synthesizing the best material globally is challenging; it needs to know what and how much the best ingredient composition should be for satisfying multiple figures of merit simultaneously. Traditional one-variable-at-a-time methods are inefficient; the design-build-test-learn (DBTL) method could achieve the optimal composition from only a handful of ingredients. A vast design space needs to be explored to discover the possible global optimal composition for on-demand materials synthesis. This research developed a hypothesis-guided DBTL (H-DBTL) method combined with robots to expand the dimensions of the search space, thereby achieving a better global optimal performance. First, this study engineered the search space with knowledge-aware chemical descriptors and customized multiobjective functions to fulfill on-demand research objectives. To verify this concept, this novel method was used to optimize colorimetric ammonia sensors across a vast design space of as high as 19 variables, achieving two remarkable optimization goals within 1 week: first, a sensing array was developed for ammonia quantification of a wide dynamic range, from 0.5 to 500 ppm; second, a new state-of-the-art detection limit of 50 ppb was reached. This work demonstrates that the H-DBTL approach, combined with a robot, develops a novel paradigm for the on-demand optimization of functional materials.

Novel Umami Peptides from Mushroom (Agaricus bisporus) and Their Umami Enhancing Effect via Virtual Screening and Molecular Simulation.

This study aimed to identify novel umami peptides in Agaricus bisporus and investigate their umami enhancing effect. We virtually screened 155 potential umami peptides from the ultrasound-assisted A. bisporus hydrolysate according to Q values, iUmami-SCM, Umami_YYDS, and Tastepeptides_DM models, and molecular docking. Five peptides (AGKNTNGSQF, DEAVARGATF, REESDFQSSF, SEETTTGVHH, and WNNDAFQSSTN) were synthesized for sensory evaluation and kinetic analysis. The result showed that the umami thresholds of the five peptides were in the range of 0.21-0.40 mmol/L. Notably, REESDFQSSF, SEETTTGVHH, and WNNDAFQSSTN had low dissociation constant (KD) values and high affinity for the T1R1-VFT receptor. The enhancing effect of the three peptides with MSG or IMP was investigated by sensory evaluation, kinetic analysis, and molecular dynamics simulations. In stable complexes, ARG_277 in T1R1 played a major role in umami peptide binding to T1R1-VFT. These results provide a theoretical basis for future screening of umami peptides and improving the umami taste of food containing mushrooms.

Customizable Colorimetric Sensor Array via a High-Throughput Robot for Mitigation of Humidity Interference in Gas Sensing.

One challenge for gas sensors is humidity interference, as dynamic humidity conditions can cause unpredictable fluctuations in the response signal to analytes, increasing quantitative detection errors. Here, we introduce a concept: Select humidity sensors from a pool to compensate for the humidity signal for each gas sensor. In contrast to traditional methods that extremely suppress the humidity response, the sensor pool allows for more accurate gas quantification across a broader range of application scenarios by supplying customized, high-dimensional humidity response data as extrinsic compensation. As a proof-of-concept, mitigation of humidity interference in colorimetric gas quantification was achieved in three steps. First, across a ten-dimensional variable space, an algorithm-driven high-throughput experimental robot discovered multiple local optimum regions where colorimetric humidity sensing formulations exhibited high evaluations on sensitivity, reversibility, response time, and color change extent for 10-90% relative humidity (RH) in room temperature (25 °C). Second, from the local optimum regions, 91 sensing formulations with diverse variables were selected to construct a parent colorimetric humidity sensor array as the sensor pool for humidity signal compensation. Third, the quasi-optimal sensor subarrays were identified as customized humidity signal compensation solutions for different gas sensing scenarios across an approximately full dynamic range of humidity (10-90% RH) using an ingenious combination optimization strategy, and two accurate quantitative detections were attained: one with a mean absolute percentage error (MAPE) reduction from 4.4 to 0.75% and the other from 5.48 to 1.37%. Moreover, the parent sensor array's excellent humidity selectivity was validated against 10 gases. This work demonstrates the feasibility and superiority of robot-assisted construction of a customizable parent colorimetric sensor array to mitigate humidity interference in gas quantification.

hUCMSC-derived exosomes protect against GVHD-induced endoplasmic reticulum stress in CD4+ T cells by targeting the miR-16-5p/ATF6/CHOP axis.

Exosomes generated from mesenchymal stem cells (MSCs) are thought to be a unique therapeutic strategy for several autoimmune deficiency illnesses. The purpose of this study was to elucidate the protective effects of human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exo) on CD4+ T cells dysfunction during graft-versus-host disease (GVHD) and to identify the underlying processes involved. Here, we showed that hUCMSC-Exo treatment can effectively attenuate GVHD injury by alleviating redox metabolism disorders and inflammatory cytokine bursts in CD4+ T cells. Furthermore, hUCMSC-Exo ameliorate ER stress and ATF6/CHOP signaling-mediated apoptosis in CD4+ T cells and promote the development of CD4+IL-10+ T cells during GVHD. Moreover, downregulating miR-16-5p in hUCMSC-Exo impaired their ability to prevent CD4+ T cells apoptosis and weakened their ability to promote the differentiation of CD4+IL-10+ T cells. Collectively, the obtained data suggested that hUCMSC-Exo suppress ATF6/CHOP signaling-mediated ER stress and apoptosis in CD4+ T cells, enhance the differentiation of CD4+IL-10+ T cells, and reverse the imbalance of immune homeostasis in the GVHD process by transferring miR-16-5p. Our study provided further evidence that GVHD patients can benefit from hUCMSC-Exo-mediated therapy.

Isolation of anti-tumor monoclonal antibodies targeting on MICA/B α3 domain by single B cell technology for colon cancer therapy.

Colon cancer (CC) is one of the most common gastrointestinal malignancies. Effectiveness of the existing therapies is limited. Immunotherapy is a promising complementary treatment approach for CC. Major histocompatibility complex class I-related protein A and B (MICA/B) are ligands for NK cells. Shedding of MICA/B from the surface of tumor cells by cleavage of MICA/B at the membrane proxial region in MICA/B α3 structural domain is one of immune evasion strategies leading to escape of cancer cells from immunosurveillance. In this study, we generated a panel of MICA/B monoclonal antibodies (mAbs) and identified one of mAbs, mAb RDM028, that had high binding affinity to MICA/B and recognized a site on MICA/B α3 structural domain that is critically important for cleavage of MICA/B. Our study has further demonstrated that RDM028 augmented the surface expression of MICA/B on HCT-116 human CC cells by inhibiting the MICA/B shedding resulting in the enhanced cyotoxicity of NK cells against HCT-116 human CC cells and mediated anti-tumor activity in nude mouse model of colon cancer. These results indicate that mAb RDM028 could be explored for developing as an effective immuno therapy against CC by targeting the MICA/B α3 domain to promot immunosurveillance mediated by MICA/B-NKG2D interaction.

Synchronously in vivo real-time monitoring bacterial load and temperature with evaluating immune response to decipher bacterial infection.

Determining the precise course of bacterial infection requires abundant in vivo real-time data. Synchronous monitoring of the bacterial load, temperature, and immune response can satisfy the shortage of real-time in vivo data. Here, we conducted a study in the joint-infected mouse model to synchronously monitor the bacterial load, temperature, and immune response using the second near-infrared (NIR-II) fluorescence imaging, infrared thermography, and immune response analysis for 2 weeks. Staphylococcus aureus (S. aureus) was proved successfully labeled with glucose-conjugated quantum dots in vitro and in subcutaneous-infected model. The bacterial load indicated by NIR-II fluorescence imaging underwent a sharp drop at 1 day postinfection. At the same time, the temperature gap detected through infrared thermography synchronously brought by infection reached lowest value. Meanwhile, the flow cytometry analysis demonstrated that immune response including macrophage, neutrophil, B lymphocyte, and T lymphocyte increased to the peak at 1 day postinfection. Moreover, both M1 macrophage and M2 macrophage in the blood have an obvious change at ~ 1 day postinfection, and the change was opposite. In summary, this study not only obtained real-time and long-time in vivo data on the bacterial load, temperature gap, and immune response in the mice model of S. aureus infection, but also found that 1 day postinfection was the key time point during immune response against S. aureus infection. Our study will contribute to synchronously and precisely studying the complicated complex dynamic relationship after bacterial infection at the animal level.

Neoadjuvant toripalimab combined with axitinib in patients with locally advanced clear cell renal cell carcinoma: a single-arm, phase II trial.

BACKGROUND: A combination of axitinib and immune checkpoint inhibitors (ICIs) demonstrated promising efficacy in the treatment of advanced renal cell carcinoma (RCC). This study aims to prospectively evaluate the safety, efficacy, and biomarkers of neoadjuvant toripalimab plus axitinib in non-metastatic clear cell RCC. METHODS: This is a single-institution, single-arm phase II clinical trial. Patients with non-metastatic biopsy-proven clear cell RCC (T2-T3N0-1M0) are enrolled. Patients will receive axitinib 5 mg twice daily combined with toripalimab 240 mg every 3 weeks (three cycles) for up to 12 weeks. Patients then will receive partial (PN) or radical nephrectomy (RN) after neoadjuvant therapy. The primary endpoint is objective response rate (ORR). Secondary endpoints include disease-free survival, safety, and perioperative complication rate. Predictive biomarkers are involved in exploratory analysis. RESULTS: A total of 20 patients were enrolled in the study, with 19 of them undergoing surgery. One patient declined surgery. The primary endpoint ORR was 45%. The posterior distribution of πORR had a mean of 0.44 (95% credible intervals: 0.24-0.64), meeting the predefined primary endpoint with an ORR of 32%. Tumor shrinkage was observed in 95% of patients prior to nephrectomy. Furthermore, four patients achieved a pathological complete response. Grade ≥3 adverse events occurred in 25% of patients, including hypertension, hyperglycemia, glutamic pyruvic transaminase/glutamic oxaloacetic transaminase (ALT/AST) increase, and proteinuria. Postoperatively, one grade 4a and eight grade 1-2 complications were noted. In comparison to patients with stable disease, responders exhibited significant differences in immune factors such as Arginase 1(ARG1), Melanoma antigen (MAGEs), Dendritic Cell (DC), TNF Superfamily Member 13 (TNFSF13), Apelin Receptor (APLNR), and C-C Motif Chemokine Ligand 3 Like 1 (CCL3-L1). The limitation of this trial was the small sample size. CONCLUSION: Neoadjuvant toripalimab combined with axitinib shows encouraging activity and acceptable toxicity in locally advanced clear cell RCC and warrants further study. TRIAL REGISTRATION NUMBER: clinicaltrials.gov, NCT04118855.

Exploring ischemic core growth rate and endovascular therapy benefit in large core patients.

After stroke onset, ischemic brain tissue will progress to infarction unless blood flow is restored. Core growth rate measures the infarction speed from stroke onset. This multicenter cohort study aimed to explore whether core growth rate influences benefit from the reperfusion treatment of endovascular thrombectomy in large ischemic core stroke patients. It identified 134 patients with large core volume >70 mL assessed on brain perfusion image within 9 hours of stroke onset. Of 134 patients, 71 received endovascular thrombectomy and 63 did not receive the treatment. Overall, poor outcomes were frequent, with 3-month severed disability or death rate at 56% in treatment group and 68% in no treatment group (p = 0.156). Patients were then stratified by core growth rate. For patients with 'ultrafast core growth' of >70 mL/hour, rates of poor outcome were especially high in patients without endovascular thrombectomy (n = 13/14, 93%) and relatively lower in patients received the treatment (n = 12/20, 60%, p = 0.033). In contrast, for patients with core growth rate <70 mL/hour, there was not a large difference in poor outcomes between patients with and without the treatment (55% vs. 61%, p = 0.522). Therefore, patients with 'ultrafast core growth' might stand to benefit the most from endovascular treatment.

LncRNA RP11-10E18.7 cooperates with lncRNA RP11-481C4.2 to affect the overall survival of breast cancer patients: a TCGA-based retrospective study.

Background: As either oncogenes or tumor suppressor genes, long non-coding RNAs (lncRNAs) have a major role in both tumorigenesis and progression of human cancers, including breast cancer (BC). However, the statistical correlation between the lncRNA-lncRNA interaction and prognosis of BC remains unclear. Methods: We analyzed the fragments per kilobase per million (FPKM) lncRNA expression data in tumor tissue samples from 890 female patients with BC in The Cancer Genome Atlas (TCGA) between May 2021 and October 2022. The Cox proportional hazards model adjusted for age, race, clinical stage, neoadjuvant therapy, estrogen receptor (ER), and progesterone receptor (PR) was adopted to evaluate the lncRNA-lncRNA interaction regarding overall survival (OS) of BC. The multiple comparison was corrected by Bonferroni method. Results: RP11-10E18.7×RP11-481C4.2 was significantly associated with OS of BC patients [hazard ratio (HR)interaction =1.04, 95% confidence interval (CI): 1.03-1.06, P=3.35×10-9]. Then, gene-gene interaction analysis was performed for genes co-expressed with lncRNAs. FOXA1×U2SURP (HRinteraction =1.49, 95% CI: 1.28-1.73, P=2.16×10-7) was found to have a similar interactive pattern to RP11-10E18.7×RP11-481C4.2. after classifying the patients by intersection (3.47), we observed that the effect of FOXA1 opposite in patients with different U2SURP expression level (HRhigh vs. low =0.58, 95% CI: 0.34-0.99, P=0.046 in low expression of U2SURP; HRhigh vs. low =1.56, 95% CI: 1.18-2.87, P=0.029 in high expression of U2SURP). Conclusions: Our comprehensive study identified RP11-10E18.7×RP11-481C4.2 as a potential biomarker of BC prognosis. The results play an essential role in the impact of lncRNA-lncRNA interaction on BC survival. Our findings elucidated potential molecular mechanisms of BC progression under complex association patterns and provided potential dynamic and reversible therapeutic targets for BC patients.