Astragaloside IV-PESV inhibits prostate cancer tumor growth by restoring gut microbiota and microbial metabolic homeostasis via the AGE-RAGE pathway.

BACKGROUND: Prostate cancer (PCa) is becoming the most common malignancy in men worldwide. We investigated the effect of astragaloside IV combined with PESV on the gut microbiota and metabolite of PCa mice and the process of treating PCa. METHODS: Nude mice were genetically modified to develop tumors characteristic of PCa. The treatment of PCa mice involved the administration of a combination of astragaloside IV and peptides derived from scorpion venom (PESV). Feces were collected for both 16 S rDNA and metabolic analysis. Fecal supernatant was extracted and used for fecal transplantation in PCa mice. Tumor development was observed in both PCa mice and nude mice. Tumor histopathology was examined, and the expression of inflammatory factors and the AGE-RAGE axis in PCa tissues were analyzed. RESULTS: PCa mice treated with Astragaloside IV in combination with PESV showed a significant reduction in tumor volume and weight, and stabilization of gut microbiota and metabolites. At the Genus level, significant differences were observed in Porphyromonas, Corynebacterium, Arthromitus and Blautia, and the differential metabolites were PA16_016_0, Astragaloside+, Vitamin A acid, Nardosinone, a-Nortestoster, D-Pantethine, Hypoxanthine, Pregnenolone, cinnamic acid, Pyridoxa, Cirtruline and Xanthurenate. There was a correlation between gut microbiota and metabolites. After the fecal transplantation, tumor growth was effectively suppressed in the PCa mice. Notably, both the mRNA and protein levels of the receptor for advanced glycation end products (RAGE) were significantly decreased. Furthermore, the expression of inflammatory factors, namely NF-κB, TNF-α, and IL-6, in the tumor tissues was significantly attenuated. Conversely, upregulation of RAGE led to increased inflammation and reversed tumor growth in the mice. CONCLUSION: Astragaloside IV combined with PESV could treat PCa by intervening in gut microbiota composition and metabolite by targeting RAGE.

Evaluating the accuracy of the Ophthalmologist Robot for multiple blindness-causing eye diseases: a multicentre, prospective study protocol.

INTRODUCTION: Early eye screening and treatment can reduce the incidence of blindness by detecting and addressing eye diseases at an early stage. The Ophthalmologist Robot is an automated device that can simultaneously capture ocular surface and fundus images without the need for ophthalmologists, making it highly suitable for primary application. However, the accuracy of the device's screening capabilities requires further validation. This study aims to evaluate and compare the screening accuracies of ophthalmologists and deep learning models using images captured by the Ophthalmologist Robot, in order to identify a screening method that is both highly accurate and cost-effective. Our findings may provide valuable insights into the potential applications of remote eye screening. METHODS AND ANALYSIS: This is a multicentre, prospective study that will recruit approximately 1578 participants from 3 hospitals. All participants will undergo ocular surface and fundus images taken by the Ophthalmologist Robot. Additionally, 695 participants will have their ocular surface imaged with a slit lamp. Relevant information from outpatient medical records will be collected. The primary objective is to evaluate the accuracy of ophthalmologists' screening for multiple blindness-causing eye diseases using device images through receiver operating characteristic curve analysis. The targeted diseases include keratitis, corneal scar, cataract, diabetic retinopathy, age-related macular degeneration, glaucomatous optic neuropathy and pathological myopia. The secondary objective is to assess the accuracy of deep learning models in disease screening. Furthermore, the study aims to compare the consistency between the Ophthalmologist Robot and the slit lamp in screening for keratitis and corneal scar using the Kappa test. Additionally, the cost-effectiveness of three eye screening methods, based on non-telemedicine screening, ophthalmologist-telemedicine screening and artificial intelligence-telemedicine screening, will be assessed by constructing Markov models. ETHICS AND DISSEMINATION: The study has obtained approval from the ethics committee of the Ophthalmology and Optometry Hospital of Wenzhou Medical University (reference: 2023-026 K-21-01). This work will be disseminated by peer-review publications, abstract presentations at national and international conferences and data sharing with other researchers. TRIAL REGISTRATION NUMBER: ChiCTR2300070082.

Ring geometric effect on the performance of AlGaN-based deep-ultraviolet light-emitting diodes.

In this study, we fabricated and characterized various parallel flip-chip AlGaN-based deep-ultraviolet (DUV) micro-ring LEDs, including changes in ring dimensions as well as the p-GaN-removed region widths at the outer micro-ring, respectively (PRM LEDs). It is revealed that the LED chips with smaller mesa withstand higher current density and deliver considerably higher light output power density (LOPD), under the same proportion of the hole to the entire mesa column (before it is etched into ring) within the limits of dimensions. However, as the ring-shaped mesa decreases, the LOPD begins to decline because of etching damage. Subsequently, at the same external diameter, the optical performance of micro-ring LEDs with varied internal diameters is studied. Meanwhile, the influence of different structures on light extraction efficiency (LEE) is studied by employing a two-dimensional (2D)-finite-difference time-domain (FDTD) method. In addition, the expand of the p-GaN-removed region at the outer micro-ring as well as the corresponding effective light emission region have some influence to LOPD. The PRM-23 LED (with an external diameter of 90 µm, an internal diameter of 22 µm, and a p-GaN-removed region width of 8 µm) has an LOPD of 53.36 W/cm2 with a current density of 650 A/cm2, and an external quantum efficiency (EQE) of 6.17% at 5 A/cm2. These experimental observations provide a comprehensive understanding of the optical and electrical performance of DUV micro-LEDs for future applications.

Single-Atom Alloys Materials for CO2 and CH4 Catalytic Conversion.

The catalytic conversion of greenhouse gases CH4 and CO2 constitutes an effective approach for alleviating the greenhouse effect and generating valuable chemical products. However, the intricate molecular characteristics characterized by high symmetry and bond energies, coupled with the complexity of associated reactions, pose challenges for conventional catalysts to attain high activity, product selectivity, and enduring stability. Single-atom alloys (SAAs) materials, distinguished by their tunable composition and unique electronic structures, confer versatile physicochemical properties and modulable functionalities. In recent years, SAAs materials demonstrate pronounced advantages and expansive prospects in catalytic conversion of CH4 and CO2. This review begins by introducing the challenges entailed in catalytic conversion of CH4 and CO2 and the advantages offered by SAAs. Subsequently, the intricacies of synthesis strategies employed for SAAs are presented and characterization techniques and methodologies are introduced. The subsequent section furnishes a meticulous and inclusive overview of research endeavors concerning SAAs in CO2 catalytic conversion, CH4 conversion, and synergy CH4 and CO2 conversion. The particular emphasis is directed toward scrutinizing the intricate mechanisms underlying the influence of SAAs on reaction activity and product selectivity. Finally, insights are presented on the development and future challenges of SAAs in CH4 and CO2 conversion reactions.

Establish a novel tumor budding-related signature to predict prognosis and guide clinical therapy in colorectal cancer.

Tumor budding is a long-established independent adverse prognostic marker for colorectal cancer (CRC), yet assessment of tumor budding was not reproducible. Therefore, development of precise diagnostic approaches to tumor budding is in demand. In this study, we first performed bioinformatic analysis in our single-center CRC patients' cohort (n = 84) and identified tumor budding-associated hub genes using the weighted gene co-expression network analysis (WGCNA). A machine learning methodology was used to identify hub genes and construct a prognostic signature. Nomogram model was used to identified hub genes score for tumor budding, and the receiver operating characteristic (ROC) curve and calibration plot indicated high accuracy and stability of hub gene score for predicted the prognosis of CRC. The association between budding-associated hub genes and score and prognosis of CRC were further verified in TCGA CRC cohort (n = 342). Then gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were applied to explore the signaling pathways related to the tumor budding and validated by immunohistochemistry (IHC) of our clinical samples. Subsequently, immune infiltration analysis demonstrated that there was a high correlation between hub genes score and M2-like macrophages infiltrated in tumor tissue. In addition, somatic mutation and chemotherapeutic response prediction were analyzed based on the risk signature. In summary, we established a tumor budding diagnostic molecular model, which can improve tumor budding assessment and provides a promising novel molecular marker for immunotherapy and prognosis of CRC.

Luteolin induces ferroptosis in prostate cancer cells by promoting TFEB nuclear translocation and increasing ferritinophagy.

BACKGROUND: As the second most common cancer in men and the leading cause of cancer-related death, prostate cancer (PCa) could potentially be treated by inducing ferroptosis. In this study, we aimed to investigate whether luteolin could induce ferroptosis in PCa cells through the transcription Factor EB (TFEB). METHODS: Different concentrations of luteolin were applied to treat normal prostate epithelial cells RWPE-1 and PCa cell lines DU145, PC-3, VCaP, and LNcaP. Ferrostatin-1 (Fer-1), Necrostain-1 (Nec-1), 3-methyladenine (3-MA), chloroquine (CQ), and the apoptosis inhibitor benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (Z-VAD-FMK) were added to treat DU145 and PC-3 cells. Additionally, we knocked down TFEB and performed in vitro cell experiments. Finally, tumor-forming experiments in nude mice were conducted to verify luteolin mechanism in PCa after knocking down TFEB. RESULTS: There was no significant difference in RWPE-1 at 12, 24, and 48 h after treatment with 60 µM luteolin. However, a significant difference was observed between DU145 and PC-3 cells. Luteolin exhibited a promoting effect on PCa cell death. After treatment with luteolin, cell viability, and Ki67 expression were decreased, and AnV-PI-positive dead cells were increased. Fer-1, Nec-1, 3-MA, and Z-VAD-FMK reversed luteolin effects on DU145 and PC-3 cell viability, proliferation, and AnV-PI-positive dead cells. Among them, Fer-1 and 3-MA were more effective. Luteolin-induced increased autophagy and ferroptosis in DU145 and PC-3 cells. Moreover, luteolin promoted ferroptosis by inducing increased autophagy in DU145 and PC-3 cells. However, knockdown of TFEB reversed the ability of luteolin to induce lysosome degradation of ferritin. In addition, luteolin promoted PCa ferroptosis by inducing ferritinophagy in vivo. CONCLUSIONS: Luteolin-induced ferroptosis in PCa cells by promoting TFEB nuclear translocation and increasing ferritinophagy.

Real-world analysis of survival benefit of surgery and adjuvant therapy in elderly patients with colorectal cancer.

Treatment guidelines for colorectal cancer (CRC) in elderly patients remain unclear. This study aimed to investigate whether elderly patients (≥ 70 years) with CRC benefit from surgery and adjuvant therapy. A total of 90,347 eligible CRC patients older than 70 years were collected from the Surveillance, Epidemiology, and End Results (SEER) database and divided into a surgery group and a no-surgery group. After being matched by propensity score matching at a 1:1 ratio, 23,930 patients were included in our analysis. The Kaplan‒Meier method and log-rank test were applied to compare overall survival (OS) and cancer-specific survival (CSS). Univariate and multivariate Cox regression analyses were utilized to confirm independent prognostic factors for OS and CSS. In age-stratified analysis (70-74; 75-79; 80-84; ≥ 85), the OS and CSS rates of patients in the surgery group were significantly higher than those of patients in the no-surgery group (all P < 0.001). Adjuvant therapy was an independent prognostic factor for OS and CSS in elderly patients with CRC (all P < 0.001). Further analysis showed that elderly colon cancer patients with stage III and stage IV disease gained a survival benefit from adjuvant chemotherapy. Adjuvant chemoradiotherapy can significantly improve OS and CSS in elderly rectal cancer patients with stage II, III, and IV disease. In conclusion, among CRC patients aged ≥ 70 years reported in the SEER database, treatment with surgical resection is significantly associated with improved OS and CSS. Moreover, adjuvant therapy led to a significant prognostic advantage for elderly advanced CRC patients who underwent surgery.

Long-term storage protocol of reagent red blood cells treated with 0.01M dithiothreitol (DTT) for pre-transfusion testing of patients receiving anti-CD38 therapy, daratumumab.

OBJECTIVE: Use red blood cell stabilizer to store the antibody screening and antibody identification reagent red blood cells (RBCs) treated with 0.01 mol/L DTT and investigate its value in the pre-transfusion examinations of patients treated with daratumumab. METHOD: Determined the optimal incubation time for the 0.01 mol/L DTT-treated RBCs method by evaluating the effect of treatment at different time points. Added ID-CellStab to store DTT-treated RBCs, determined the maximum shelf life of reagent RBCs by monitoring the hemolysis index, and assessed changes in the antigenicity of blood group antigens on the surface of RBCs during storage with antibody reagents. RESULT: A protocol for long-term storage of reagent red blood cells treated with the 0.01 mol/L DTT method was established. The optimal incubation time was 40-50 min. RBCs could be stored stably for 18 days after adding ID-CellStab. The protocol was able to eliminate pan-agglutination caused by daratumumab, with no significant changes in the antigens of most blood group systems, except for some attenuation of K antigen and Duffy blood group system antigens during the storage period. CONCLUSION: The storage protocol of reagent RBCs based on the 0.01 mol/L DTT method does not affect the detection of most blood group antibodies and retains a certain degree of detection ability for anti-K antibodies, allowing patients treated with daratumumab to quickly perform pre-transfusion examinations, making up for the shortcomings of currently commercial reagent RBCs.

[Explore the mechanism of astragaloside IV-PESV on proliferation, migration, and autophagy of prostate cancer cells based on the PI3K/AKT signaling pathway].

OBJECTIVE: Explore the effects of Astragaloside IV and Scorpion Venom Peptide on the activity, migration, apoptosis, cell cycle, autophagy, and the expression of proteins related to the PI3K/AKT signaling pathway in prostate cancer cells. METHODS: The human prostate cancer cell lines LNCaP and PC-3 were randomly divided into blank control group, Astragaloside IV group, Scorpion Venom Peptide group, Astragaloside IV-Scorpion Venom Peptide group, and rapamycin (positive drug group). After corresponding drug treatments for 24 hours, logarithmic growth phase tumor cells were collected for testing. Cell proliferation was assessed using a Cell Counting Kit-8 (CCK-8) assay, Transwell assay, apoptosis assay, cell cycle assay, and immunofluorescence analysis were performed to detect the activity and migration capacity of prostate cancer cells in each group, as well as their effects on apoptosis, cell cycle, and the autophagy target LC3. Western blot analysis was employed to measure the protein expression levels of p-PI3K, p-Akt, p-mTOR, Beclin1, LC3, and P62. RESULTS: Compared to the blank control group, the Astragaloside IV-Scorpion Venom Peptide group exhibited a significant decrease in the activity of prostate cancer cells (P<0.05) and a reduction in the cell invasion ability (migration capacity) (P<0.05). The early apoptosis rate (LR), late apoptosis rate (UR), and total apoptosis rate all increased (P<0.05). The proportion of cells in the G1 phase increased (P<0.05), while the proportion in the G2+S phase decreased (P<0.05). The immunofluorescence expression of LC3 significantly increased (P<0.05). The expression of LC3Ⅱ and Beclin1 proteins in prostate cancer cells LNCaP and PC-3 was upregulated (P<0.05), while the expression of P62, p-PI3K, p-AKT, and p-mTOR proteins was downregulated (P<0.05).Astragaloside IV-Scorpion Venom Peptide is superior to the Astragaloside IV group or Scorpion Venom Peptide group alone in inhibiting the activity and migration capacity of prostate cancer cells, suppressing cell mitosis, promoting early apoptosis, upregulating the expression level of LC3, and inhibiting the PI3K/AKT pathway while promoting autophagy (P<0.05). CONCLUSION: The mechanism by which Astragaloside IV-Scorpion Venom Peptide inhibits the proliferation and migration of prostate cancer cells, suppresses cell mitosis, promotes early apoptosis, and enhances autophagy may be related to the inhibition of the PI3K/AKT pathway.

Four types of RNA modification writers predict the prognosis of prostate cancer.

RNA modification is an important part of epigenetic regulation. However, the relationship between RNA modification writers and prostate cancer (PCa) remains unclear. We obtained transcriptome data from The Cancer Genome Atlas; the expression of writers for four RNA modifications (N6-methyladenosine, N1-methyladenosine, alternative polyadenylation and adenosine-to-inosine RNA editing) was altered in PCa tissue when compared with normal tissue. RNA modification writers affect the expression of immune checkpoints. Gene ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that the RNA modification was related to the cell cycle. Hub genes were screened using machine learning, and a risk score model was established using multivariate Cox analysis. Univariate and multivariate Cox analyses showed that a risk score model based on RNA modification writers could be an independent prognostic factor for PCa. In conclusion, our study showed that RNA modification writers are differentially expressed in PCa and might influence the development of PCa by regulating immune checkpoints and the cell cycle. The risk score model of RNA modification writers is predicted to be an independent prognostic factor for PCa. Thus, RNA modification writers might be used as potential indicators for the clinical diagnosis of PCa.

A case report on mixed pulmonary infection of Nocardia nova, Mycobacterium tuberculosis, and Aspergillus fumigatus based on metagenomic next-generation sequencing.

Background: Pulmonary infection is one of the common complications of long-term use of glucocorticoids. Severe infections not only increase the length of hospital stay and treatment costs but also cause progression or recurrence of the primary disease. Case description: Herein, we reported a case of mixed pulmonary infection secondary to glucocorticoid use. Rare pathogens such as Nocardia nova, Mycobacterium tuberculosis, Aspergillus fumigatus, and cytomegalovirus were detected by metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid and lung puncture tissue. Combining the results of conventional pathogen detection and clinical symptoms, the patient was diagnosed with mixed pulmonary infection by multiple pathogens. After timely targeted medication, the patient was finally discharged with a good prognosis. Conclusion: To our knowledge, this is the first case report on mixed pulmonary infection with pathogens including Nocardia nova, Mycobacterium tuberculosis, Aspergillus fumigatus, and human cytomegalovirus. As a new clinical diagnostic method, mNGS has great advantages in diagnosis of diseases such as mixed infections.

Astragalus-Scorpion Drug Pair Inhibits the Development of Prostate Cancer by Regulating GDPD4-2/PI3K/AKT/mTOR Pathway and Autophagy.

Objective: Prostate cancer (PCa) is an epithelial malignancy of the prostate that currently lacks effective treatment. Traditional Chinese medicine (TCM) can play an anticancer role through regulating the immune system, anti-tumor angiogenesis, regulating tumor cell apoptosis, autophagy dysfunction, and other mechanisms. This study attempted to explore the active ingredients and potential mechanism of action of the Astragalus-Scorpion (A-S) drug pair in PCa, in order to provide new insights into the treatment of PCa. Methods: Network pharmacology was used to analyze the A-S drug pair and PCa targets. Bioinformatics analysis was used to analyze the LncRNAs with significant differences in PCa. The expression of LC3 protein was detected by immunofluorescence. CCK8 was used to detect cell proliferation. The expressions of GDPD4-2, AC144450.1, LINC01513, AC004009.2, AL096869.1, AP005210.1, and BX119924.1 were detected by RT-qPCR. The expression of the PI3K/AKT/mTOR pathway and autophagy-related proteins were detected by western blot. LC-MS/MS was used to identify the active components of Astragalus and Scorpion. Results: A-S drug pair and PCa have a total of 163 targets, which were mainly related to the prostate cancer and PI3K/AKT pathways. A-S drug pair inhibited the formation of PCa, promoted the expression of LC3Ⅱ and Beclin1 proteins, and inhibited the expression of P62 and PI3K-AKT pathway proteins in PCa mice. Astragaloside IV and polypeptide extract from scorpion venom (PESV) were identified as the main active components of the A-S drug pair. GDPD4-2 was involved in the treatment of PCa by Astragaloside IV-PESV. Silencing GDPD4-2 reversed the therapeutic effects of Astragaloside IV-PESV by regulating the PI3K/AKT/mTOR pathway. Conclusion: Astragaloside IV-PESV is the main active components of A-S drug pair treated PCa by regulating the GDPD4-2/PI3K-AKT/mTOR pathway and autophagy.

Quercetin in Tonglong Qibi decoction ameliorates testosterone-induced benign prostatic hyperplasia in rats by regulating Nrf2 signalling pathways and oxidative stress.

Benign prostatic hyperplasia (BPH) is a common urological disease in older males. Existing pharmacotherapy shows several side effects, and the exploration of new therapeutic strategies is of high significance. Tonglong Qibi (TQ) decoction was proved to ameliorate BPH, while the underlying mechanisms are still unclear. In the current study, we explored the anti-BPH effects of TQ in vivo and identified its main therapeutic component and the underlying mechanisms in vitro. We demonstrated that TQ mitigated BPH in rats and showed no toxicity to the liver and reproductive system. Network pharmacology identified quercetin as the main component in TQ treating BPH. Quercetin reduced proliferation, oxidative stress, and increased Nrf2 expression in hyperplastic prostate epithelial cells. These findings indicate that quercetin in TQ alleviates BPH via inhibiting oxidative stress and activating the Nrf2 signalling pathway.

Personalized image enhancement method for color deficient observers.

A personalized image enhancement method is proposed to improve color vision in hereditary color vision deficiency (CVD). It is divided into two stages: evaluation of CVD and gamut mapping for image enhancement. These two separate stages are connected via a psychophysical experiment, through which the deficiency test result expressed using the C-index can be further transformed into a physical parameter, namely the wavelength shift of the cone fundamental. Experiments conducted by the color-deficient observers (CDOs) validated this proposed method, and it is emphasized that the proposed method is just serving as a template for image enhancement. A more advanced simulation model, a more accurate assessment method, or a more sophisticated gamut mapping algorithm can yield a better result.

Application of magnetic bead method in detecting coagulation function.

BACKGROUND: Blood samples indicative of jaundice, lipemia, hemolysis, and others are often encountered in the laboratory, and such features impact greatly on the detection of coagulation items. To understand the anti-interference ability of the magnetic bead method automatic coagulation instrument and the optical method automatic coagulation instrument against jaundice, lipemia, and hemolysis, anti-interference experiments of prolonged prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (FIB) were conducted using ExC810 (magnetic bead method) and CS5100 (optical method). METHODS: Interference samples were prepared with bilirubin, hemoglobin, and lipids, while control samples were prepared with NaOH and distilled water. The samples contained different values of PT, APTT, TT, and FIB and were detected by magnetic bead method and optical method, respectively. The relative deviation was calculated according to the formula. RESULTS: In the anti-interference experiment of PT, APTT, TT, and FIB (jaundice, lipemia, hemolysis), the deviation between the test results and the control results with the addition of interfering substances tested by ExC810 was lower overall than that of CS5100. However, after the addition of interfering substances, most of the items were not detected by CS5100 in the anti-lipidemia experiment. CONCLUSIONS: When testing coagulation function, the magnetic bead method has better anti-interference recognition of jaundice, lipemia, and hemolysis than the optical method, and its anti-lipemic interference has a particularly obvious advantage.

Application of network pharmacology and molecular docking to elucidate the potential mechanism of Astragalus-Scorpion against prostate cancer.

The present study aimed to investigate the molecular mechanism of the Astragalus-Scorpion drug pair in the treatment of prostate cancer (PCa). We employed network pharmacology and molecular docking technology to retrieving the active ingredients and corresponding targets of Astragalus-Scorpion by using TCMSP, BATMAN-TCM, TCMID and Swiss Target Prediction Databases. The targets related to PCa were retrieved through GeneCards. Cytoscape software was used to construct the 'active ingredient-target disease' network, and GO and KEGG enrichment analyses were performed on the common targets. Autodock software was used for molecular docking verification. In total, 26 active ingredients, 340 potential targets related to active ingredients and 122 common targets were screened from Astragalus-Scorpion drug pair. The core targets of the protein-protein interaction (PPI) network were JUN, AKT1, IL6, MAPK1 and RELA, whereas the core active ingredients were quercetin, kaempferol, formononetin, 7-o-methylisomucronulatol and calycosin. Nearly 762 GO entries and 154 pathways were obtained by using the pathway enrichment analysis. Molecular docking results revealed that quercetin and kaempferol bind to AKT1 and formononetin binds to RELA, all of which were found to be stable bounds.

Characterization of the inhomogeneity of Pt/CeO x /Pt resistive switching devices prepared by magnetron sputtering.

There are unrevealed factors that bring about the performance variations of resistive switching devices. In this work, Pt/CeO x /Pt devices prepared by magnetron sputtering showed rectification in their asymmetrical current-voltage (I-V) curves during voltage sweeps. X-ray photoelectron spectroscopy showed that the deposited CeO x film had an inhomogeneous composition, and more oxygen vacancies existed in CeO x near the top electrode. The asymmetrical resistance change of the Pt/CeO x /Pt devices can be explained by the presence of more charged oxygen vacancies in CeO x near the top electrode, along with the Schottky conduction mechanism. This work reveals that the compositional inhomogeneity is inevitable in the magnetron sputtering of oxide targets like CeO2 and can be an important source of device-to-device and cycle-to-cycle variations of memristors.

Enhancement of anticancer activity of docetaxel by combination with Fuzheng Yiliu decoction in a mouse model of castration-resistant prostate cancer.

Docetaxel (Doc) is the gold standard of care for castration-resistant prostate cancer (CRPC) patients, although the therapeutic effects are modest. Fuzheng Yiliu decoction (FZYL) comprises multiple herbs, and has been used for >10 years to treat various cancers, including hepatocellular tumors, malignant gastrointestinal tumors, and prostate cancer. In the study reported, we evaluated the anticancer effects of FZYL and of a combination of Doc and FZYL in CRPC tumor-bearing mice, and explored the underlying mechanisms. PC-3 tumor-bearing mice were treated with FZYL, Doc, Doc + FZYL or vehicle solution. Tumor volume was monitored, and tumor weight, proliferation and apoptosis of tumor tissues were measured. Deep sequencing was used to profile the miRNA expression patterns in tumor tissues. Our results suggested that FZYL alone could depress tumor growth, and the combination of Doc and FZYL treatment exhibited enhanced anticancer effects. Doc + FZYL regulated the expression of 10 miRNAs: miR-34b-5p, miR-674-3p, miR-140-3p, miR-342-3p, miR-214-3p, miR-149-5p, miR-378c, miR-29b-3p, miR-218-5p, and miR-378a-3p, involving in the PI3K-Akt pathway in the treatment of CRPC.

FOXM1 promotes the growth and metastasis of colorectal cancer via activation of ß-catenin signaling pathway.

PURPOSE: Our previous study proved that FOXM1 regulates colorectal cancer (CRC) cell metastasis through epithelial-mesenchymal transition program. The aim of this study is to further explore the underlying mechanism of FOXM1 in CRC. MATERIALS AND METHODS: In this study, we detected the mRNA and protein expressions of FOXM1 and ß-catenin in CRC tissues and their corresponding normal-appearing tissues (NATs) by quantitative reverse transcription-PCR and western blot analysis, respectively. Then the potential link between FOXM1 and ß-catenin in CRC tissues was analyzed. Furthermore, we systematically analyzed the biological functions of FOXM1 in CRC cells after reconstitution of FOXM1 expression in vitro. Moreover, the mechanism of FOXM1-promoted CRC progression by improving ß-catenin nuclear translocation was also discussed. RESULTS: Our data demonstrated that FOXM1 and ß-catenin were upregulated in CRC tissues compared with the corresponding NATs (P<0.05). Clinicopathologic analysis revealed that increased FOXM1 (or ß-catenin) expression positively correlated with some clinicopathologic features, such as tumor size, TNM stage, lymphatic metastasis, and distant metastasis (P<0.05). Meanwhile, the possible relationships between FOXM1 and ß-catenin in CRC samples were evaluated using SPSS software, and a significant positive correlation was found (P<0.05). In vitro data demonstrate that elevated FOXM1 expression exerted oncogenic effects on CRC via activation of ß-catenin signaling pathway. The inhibition of ß-catenin by siRNAs significantly attenuates FOXM1-induced malignant activities. CONCLUSION: The data suggested that FOXM1/ß-catenin is critical for malignancy of CRC, which may constitute a potential therapeutic strategy for CRC.

Early changes of volume and spatial location in target and normal tissues caused by IMRT for cervical cancer.

AIMS: To investigate the early changes of volume and spatial location in target and normal tissues caused by intensity-modulated radiotherapy (IMRT) for cervical cancer. METHODS: Forty patients with cervical cancer were included in this study and treated by IMRT. Computed tomography (CT) was performed before radiotherapy and when the patient had received 27 Gy in 15 fractions. After image registration, the volume of interest (VOI) for the targets and organs at risk was delineated by clinicians on the CT images. Changes of volume, spatial location and Dice similarity were calculated for all VOIs. RESULTS: There were significant changes in gross tumor volume (GTV) in the primary tumor (GTV-T) with t = 8.304 (p<0.01) and visible pelvic lymph nodes (GTV-N) with t = 4.996 (p<0.01) caused by IMRT. The mean volume differences for GTV-T and GTV-N were 38.64% ± 19.50% (range 3.16%-86.49%) and 42.49% ± 25.68% (range 2.79%-87.42%), respectively. Among the organs at risk, the bladder had the greatest volume change with 55.13% ± 33.40% (range 3.25%-116.01%). The Dice similarity for GTV-T and GTV-N was 0.50 ± 0.18 (range 0.10-0.85) and 0.31 ± 0.20 (range 0.00-0.71), respectively. The rectum had the least Dice similarity among the normal tissues, with a mean value of 0.57 ± 0.14 (range 0.18-0.76). CONCLUSIONS: There were significant changes in volume and spatial location of the target and normal tissues after 27 Gy IMRT. In order to maintain the radiation dose to the targets and minimize the radiation to normal tissues, it is necessary to modify the radiotherapy planning.