Poor efficacy of immune checkpoint inhibitor treatment in advanced thymic carcinoma patients with liver metastases.

Background: Although immune checkpoint inhibitor treatment for advanced thymic carcinoma exhibits promising efficacy, factors that affect the efficacy and prognosis, including metastases sites, remain uncertain. Objectives: Our study aimed to investigate the determinants of survival among patients with advanced thymic carcinoma who underwent immunotherapy in real-world settings, with implications for clinical practice. Designs: Different therapy regimens of immunotherapy were produced to analyze the influence of liver metastases on survival and prognosis for advanced thymic carcinoma patients. Methods: Data for advanced thymic carcinoma patients receiving immunotherapy and their metastases sites were collected for analysis from seven different hospitals between January 2015 and January 2023. Progression-free survival (PFS) and overall survival (OS) analyses were performed using the Kaplan-Meier method. Cox analysis was used to evaluate factors influencing survival. Results: The present study analyzed 136 advanced thymic carcinoma patients from seven different hospitals.The PFS for all patients receiving immunotherapy was 6.4 months, while the OS was 24.0 months. The objective response rate was different for patients with liver and non-liver metastases (11.9% versus 37.2%, p = 0.003). The disease control rate values were also different between the two groups (47.6% versus 80.9%, p = 0.037). The PFS for patients with liver metastases demonstrated poor immunotherapy efficacy compared to patients with non-liver metastases (3.0 versus 8.0 months, p < 0.0001). The OS was also significantly different between these two patient groups (16.1 versus 29.1 months, p = 0.009). Conclusion: Immunotherapy had poor efficacy in advanced thymic carcinoma patients with liver metastases.

Preclinical study of pachyman inducing ferroptosis against ovarian cancer: Biological targets and underlying mechanisms.

Ferroptosis has gained extreme purpose in targeting cancer treatment. Poria cocos Wolf, a traditional Chinese herb, has potential anticancer properties, but the action and mechanism against ovarian cancer remain undetailed. Pachyman (Poria cocos polysaccharides) refers to the pharmacologically bioactive ingredients rich in Poria cocos. This study aimed to identify the potent actions and the network mechanisms of pachyman against ovarian cancer through preclinical analysis. Online-accessible database or platform was employed to predict candidate genes and core targets associated with ferroptosis in pachyman against ovarian cancer. Enrichment analyses were used to characterize the functional action and signaling mechanism in pachyman to treat ovarian cancer. Molecular docking imitation was conducted for verification of core target proteins. Network analysis uncovered that there were 30 mutual and 13 core genes targeting ferroptosis in pachyman and/against ovarian cancer, and additional enrichment analysis characterized that these core genes may act synergistically through multiple biological processes and molecular pathways associated with ferroptosis, including anti-inflammatory action, immunoregulation, and microenvironment modulation. The strongest affinities in core target proteins between pachyman and sarcoma (SRC), signal transducer, and activator of transcription 3 (STAT3) were further validated using molecular docking method. In conclusion, pachyman may induce antiovarian cancer potentials via regulating ferroptosis-associated biological functions and pharmacological mechanisms based on current bioinformatics findings. We reason that pachyman, the beneficial nutraceuticals, may be used clinically for future application in ovarian cancer treatment.

Ferroptosis-related biotargets and network mechanisms of fucoidan against colorectal cancer: An integrated bioinformatic and experimental approach.

Ferroptosis, a type of iron-dependent cell death, has been linked with the occurrence and progression of malignant tumors, including colorectal cancer (CRC). Fucoidan, an algal fucose-rich molecule, has been discovered preclinically to have an anti-CRC signature. Although some underlying mechanisms are reported, many signaling pathways associated with ferroptosis in fucoidan treatment of CRC are still unidentified. In this study, we applied network pharmacology and molecular docking technologies to unmask and identify the medication targets and pharmaceutical mechanisms involved in ferroptosis in fucoidan-treated CRC. 19 ferroptosis-related core targets were identified and enrichment analysis indicated their contribution to pharmacological actions and mechanisms in fucoidan treatment of CRC, including ferroptosis-related signaling pathways. Additional molecular docking verification confirmed that fucoidan docked well with ranked core targets, including transcription factor p65 (RELA), interleukin-1 beta (IL1B), and interleukin-6 (IL6). These in silico findings were validated experimentally in CRC cells following fucoidan treatment. RELA, IL1B, and IL6 expressed positively in human CRC samples. In conclusion, the pharmacological mechanisms of fucoidan in treating CRC may be achieved through multiple biological targets and multiple molecular pathways associated with ferroptosis. Thus, these preclinical findings have laid a theoretical foundation for further research and clinical treatment of CRC using fucoidan.

PSRR: A Web Server for Predicting the Regulation of miRNAs Expression by Small Molecules.

Background: MicroRNAs (miRNAs) play key roles in a variety of pathological processes by interacting with their specific target mRNAs for translation repression and may function as oncogenes (oncomiRs) or tumor suppressors (TSmiRs). Therefore, a web server that could predict the regulation relations between miRNAs and small molecules is expected to achieve implications for identifying potential therapeutic targets for anti-tumor drug development. Methods: Upon obtaining positive/known small molecule-miRNA regulation pairs from SM2miR, we generated a multitude of high-quality negative/unknown pairs by leveraging similarities between the small molecule structures. Using the pool of the positive and negative pairs, we created the Dataset1 and Dataset2 datasets specific to up-regulation and down-regulation pairs, respectively. Manifold machine learning algorithms were then employed to construct models of predicting up-regulation and down-regulation pairs on the training portion of pairs in Dataset1 and Dataset2, respectively. Prediction abilities of the resulting models were further examined by discovering potential small molecules to regulate oncogenic miRNAs identified from miRNA sequencing data of endometrial carcinoma samples. Results: The random forest algorithm outperformed four machine-learning algorithms by achieving the highest AUC values of 0.911 for the up-regulation model and 0.896 for the down-regulation model on the testing datasets. Moreover, the down-regulation and up-regulation models yielded the accuracy values of 0.91 and 0.90 on independent validation pairs, respectively. In a case study, our model showed highly-reliable results by confirming all top 10 predicted regulation pairs as experimentally validated pairs. Finally, our predicted binding affinities of oncogenic miRNAs and small molecules bore a close resemblance to the lowest binding energy profiles using molecular docking. Predictions of the final model are freely accessible through the PSRR web server at https://rnadrug.shinyapps.io/PSRR/. Conclusion: Our study provides a novel web server that could effectively predict the regulation of miRNAs expression by small molecules.

NVP-BEZ235 Inhibits Renal Cell Carcinoma by Targeting TAK1 and PI3K/Akt/mTOR Pathways.

In spite of the promising in vitro and preclinical results, dual PI3K/Akt/mTOR inhibitor NVP-BEZ235, and ATP-competitive mTOR inhibitor PP242 both failed to confirm their inhibitory efficacy against renal cell carcinoma (RCC) in clinical settings. Therefore, a better understanding of the molecular mechanism is essential so as to provide possibilities for their use in combination with other agents. In present study, RCC cell lines (UMRC6, 786-0 and UOK121) were treated with NVP-BEZ235, PP242 or Rapamycin, an mTOR complex 1 (mTORC1)-specific inhibitor. They all suppressed cell proliferation and invasion, induced apoptosis and cell cycle arrest, and the effects were in the order of NVP-BEZ235 > PP242 > Rapamycin. Accordingly, the marked and sustained decrease in speckle-type POZ protein (SPOP) expression and phosphorylation of Akt and mTOR kinases was observed in RCC cells treated with NVP-BEZ235 and PP242, whereas only potent inhibition of mTOR activity was induced in Rapamycin-treated cells. In considering the overactivation of c-Jun and IκB-α in human renal tumor tissue, we next investigated the role of JNK and IKK pathways in the response of RCC cells to these compounds. First of all, transforming growth factor ß activated kinase 1 (TAK1)-dependent activation of JNK/ (activator protein-1) AP-1 axis in RCC cells was proved by the repression of AP-1 activity with TAK1 or JNK inhibitor. Second, the profound inhibition of TAK1/JNK/AP-1 pathway was demonstrated in RCC cells treated with NVP-BEZ235 or PP242 but not Rapamycin, which is manifested as a reduction in activity of TAK1, c-Jun and AP-1. Meanwhile, subsequent to TAK1 inactivation, the activation of IκB-α was also reduced by NVP-BEZ235 and PP242. Likewise, in vivo, treatment with NVP-BEZ235 and PP242 suppressed the growth of xenografts generated from 786-0 and A498 cells, along with decreased expression of phospho-TAK1, phospho-c-Jun, and phospho-IκB-α. In contrast, Rapamycin elicited no significant inhibitory effects on tumor growth and phosphorylation of TAK1, c-Jun and IκB-α. We conclude that besides PI3K/Akt/mTOR signaling, NVP-BEZ235, and PP242 simultaneously target TAK1-dependent pathways in RCC cells. Notably, these effects were more marked in the presence of NVP-BEZ235 than PP242, indicating the potential application of NVP-BEZ235 in combination therapy for RCC.

Recombinant Human IL-11 Promotes Lung Adenocarcinoma A549 Cell Growth and EMT through Activating STAT3/HIF-1α/EMT Signaling Pathway.

BACKGROUND: Interleukin-11 (IL-11) could promote invasion and metastasis of cancer cells, however, its mechanism is unclear. OBJECTIVE: This study aimed to investigate the effects of recombinant human IL-11 (rhIL-11) on lung cancer cell metastasis and growth. METHODS: Human lung cancer cell, A549, was cultured and subcutaneously injected into mice to establish Xenograft tumor models. Tumor models were divided into control, rhIL-11 transplantation (250 µg/kg/day), and rhIL-11 transplantation (500 µg/kg/day) group. Tumor volumes were recorded and measured 6 times. Hypoxia- Inducible Factor 1α (HIF1α), snail, slug, Signal Transducers/Activators of Transcription-3 (STAT3), E-cadherin, twist, and vimentin levels were evaluated using western blot and Real-Time PCR (RT-PCR). RESULTS: Sizes of subcutaneous tumors increased following measurement time. rhIL-11 treatment significantly enhanced HIF1α and STAT3 expression in rhIL-11 treatment groups compared to the control group (p<0.05). However, no remarkable differences were discovered between rhIL-11 (250 µg/kg/day) and rhIL-11 (500 µg/kg/day) group (p>0.05). rhIL-11 treatments significantly increased twist, and slug expressions compared to control group (p<0.05), especially for rhIL-11 (500 µg/kg/day) treatment, which triggered significantly higher effects on twist and slug expressions compared to those in the control group (p<0.05). Vimentin and snail mRNA levels were significantly up-regulated and E-cadherin level was significantly down-regulated in rhIL-11 treatment groups compared to the control group (p<0.05). Meanwhile, rhIL-11 at a dosage of 500 µg/kg/day triggered remarkably higher effects on vimentin, snail, and E-cadherin expressions compared to those in rhIL-11 (250 µg/kg/day) group (p<0.05). CONCLUSION: rhIL-11 transplantation promoted growth and Epithelial-Mesenchymal Transition (EMT) of A549 cells, which might be associated with STAT3/HIF-1α/EMT signaling pathway activation.

LncRNA DGCR5 regulates the non-small cell lung cancer cell growth, migration, and invasion through regulating miR-211-5p/EPHB6 axis.

Non-small cell lung cancer (NSCLC) accounts for about 80% of lung cancers worldwide. In recent years, importance of noncoding RNAs including long noncoding RNA and microRNA in regulating tumor progression has been appreciated. Abnormally expression of DiGeorge syndrome critical region gene 5 (DGCR5) was found in multiple human cancers but its function in NSCLC is largely unknown. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was conducted to explore DGCR5 expression level in NSCLC. Bioinformatic analyses were conducted to explore the targets of DGCR5. Cell counting kit-8 assay, wound-healing assay, and transwell invasion assay were performed to analyze functions of DGCR5. RT-qPCR revealed that DGCR5 expression in NSCLC cells was significantly lower than in normal cell. DGCR5 overexpression suppresses NSCLC cell growth, migration, and invasion. Online algorithms found EPH receptor B6 (EPHB6) and DGCR5 contains same miR-211-5p binding region. The predicted connections were further validated by luciferase activity reporter assay. Recue experiments showed DGCR5 regulates NSCLC cell behaviors via targeting miR-211-5p/EPHB6. These findings collectively identified DGCR5/miR-211-5p/EPHB6 triple axis in NSCLC, which may novel understanding regarding the tumorigenesis of NSCLC.

Research on the Development of Light Blending Model for Smart LED Lighting.

The color of the LED smart light is tunable by its inner equipped micro-processing systems. Therefore, it could provide significant improvement for the smart lighting conditions, such as museum lighting and home lighting. At present, the limitation of the current lighting blending technology remarkably affects the application of smart lighting technology and people could not make full use of the adjustability of the smart luminaries. In this research, a novel light blending model was proposed based on BP neural network and active set algorithm. The models could effectively simulate the nonlinear relationship between the device control values of the smart light and the output radiance spectrum of the light. Particularly, a BP neural network-based forward model for LED light blending was firstly proposed, which could accurately calculate the spectral radiance power distribution from the device control values. Afterwards, based on forward model, an active set algorithm-based backward model was developed, which could precisely predict the device control values from the desired spectral radiance power distribution. The experimental result indicates that the proposed method could accurately achieve the light blending controlling of smart LED light, with a CIEUCS Duv value of 0.002 7, which is significantly smaller than the just noticeable difference value of human vision. The authors believe that the proposed method will provided effective support for the development of smart LED lighting in near future.

Self-assembled 3D flower-like Ni2+-Fe3+ layered double hydroxides and their calcined products.

This paper describes a facile solvothermal method to synthesize self-assembled three-dimensional (3D) Ni2+-Fe3+ layered double hydroxides (LDHs). Flower-like Ni2+-Fe3+ LDHs constructed of thin nanopetals were obtained using ethylene glycol (EG) as a chelating reagent and urea as a hydrolysis agent. The reaction mechanism and self-assembly process are discussed. After calcinating the as-prepared LDHs at 450 degrees C in nitrogen gas, porous NiO/NiFe2O4 nanosheets were obtained. This work resulted in the development of a simple, cheap, and effective route for the fabrication of large area Ni2+-Fe3+ LDHs as well as porous NiO/NiFe2O4 nanosheets.

Nanocrystalline CdS/ZnO thin films: fabrication and application to solar cells.

In this paper we reported the preparation and characterization of the nanostrutured CdS/ZnO nanoarray thin film, based on the free-standing ZnO nanorod-array. The method was simple and low-cost. The ZnO nanorod-arrays were synthesized on F-doped tin oxide glass (TCO) substrate by hydrothermal method, then coated with CdS nanoparticles closely via chemical bath deposition method. The resulting thin films showed better photoelectrochemical performances than those of CdS/ZnO nanoparticles thin films. Under the illumination of AM 1.5 simulated sunlight (30 mW/cm2), the photocurrent of the samples achieved to 0.72 mA/cm2.

Room temperature fabrication of single crystal nanotubes of CaSn(OH)6 through sonochemical precipitation.

CaSn(OH)(6) nanotubes were fabricated by sonochemical precipitation method at room temperature. A direct rolling process from nanosheets to nanotubes was expected for the synthesis of CaSn(OH)(6) nanotubes. The transient CaSn(OH)(6) nanosheets are formed as intermediates produced by the spontaneous self-assembly and transformation of amorphous colloid clusters. During the crystallization process of intermediate nanosheets, the relaxation of surface strain in the nanosheet interfaces can induce the nanosheets to roll up to form nanotubes under ultrasonic conditions. In this synthesis, the addition of Na(2)CO(3) seems to play an important role in the formation, size, and shape control of the nanotubes. Investigations into the stability performance of the nanotubes indicate that the morphologies are very sensitive to pH and temperature. The method suggests a general strategy for the design and fabrication of functional single-crystalline nanotubes through an intermediate nanosheet rolling process. The in vitro fabrication of such single crystal nanotubes could shed light on fundamental mechanisms for closed hollow nanostructures. Furthermore, nanotubes produced in high yield and at low cost are envisioned to have applications in areas ranging from medicine to pharmaceuticals through to materials science.

Synthesis of CdSnO(3).3H(2)O nanocubes via ion exchange and their thermal decompositions to cadmium stannate.

Uniform crystalline CdSnO3.3H2O nanocubes with a 28-35 nm edge length have been obtained via the ion-exchange reaction of Na2Sn(OH)6 in a CdSO4 aqueous solution, assisted by ultrasonic treatment. Precursor Na2Sn(OH)6 crystals were prepared via hydrothermal treatment in an ethanol/water solution. The formation of CdSnO3.3H2O nanocubes resulted from the strain during the ion-exchange process. The influences of reaction conditions, such as ion-exchange (ultrasonic treatment) duration, solvent constitutes, surfactant, and pH on the formation of CdSnO3.3H2O crystals were described. Crystalline CdSnO3 and Cd2SnO4 have been obtained by thermal treatment at 300 and 500 degrees C, respectively, for 5 h under an inert-gas protecting condition using CdSnO3.3H2O nanocubes as the precursor. The cube shape of CdSnO3.3H2O was sustained after thermal decomposition to CdSnO3.