Amlodipine inhibits the proliferation and migration of esophageal carcinoma cells through the induction of endoplasmic reticulum stress.

BACKGROUND: L-type calcium channels are the only protein channels sensitive to calcium channel blockers, and are expressed in various cancer types. The Cancer Genome Atlas database shows that the mRNA levels of multiple L-type calcium channel subunits in esophageal squamous cell carcinoma tumor tissue are significantly higher than those in normal esophageal epithelial tissue. Therefore, we hypothesized that amlodipine, a long-acting dihydropyridine L-type calcium channel blocker, may inhibit the occurrence and development of esophageal cancer (EC). AIM: To investigate the inhibitory effects of amlodipine on EC through endoplasmic reticulum (ER) stress. METHODS: Cav1.3 protein expression levels in 50 pairs of EC tissues and corresponding paracancerous tissues were examined. Subsequently, the inhibitory effects of amlodipine on proliferation and migration of EC cells in vitro were detected using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide and Transwell assays. In vivo experiments were performed using murine xenograft model. To elucidate the underlying mechanisms, in vitro cell studies were performed to confirm that ER stress plays a role in inhibition proliferation and migration of EC cells treated with amlodipine. RESULTS: The expression level of Cav1.3 in esophageal carcinoma was 1.6 times higher than that in paracancerous tissues. Amlodipine treatment decreased the viability of esophageal carcinoma cells in a dose- and time-dependent manner. In vivo animal experiments also clearly indicated that amlodipine inhibited the growth of EC tumors in mice. Additionally, amlodipine reduces the migration of tumor cells by inhibiting epithelial-mesenchymal transition (EMT). Mechanistic studies have demonstrated that amlodipine induces ER stress-mediated apoptosis and suppresses EMT. Moreover, amlodipine-induced autophagy was characterized by an increase in autophagy lysosomes and the accumulation of light chain 3B protein. The combination of amlodipine with the ER stress inhibitor 4-phenylbutyric acid further confirmed the role of the ER stress response in amlodipine-induced apoptosis, EMT, and autophagy. Furthermore, blocking autophagy increases the ratio of apoptosis and migration. CONCLUSION: Collectively, we demonstrate for the first time that amlodipine promotes apoptosis, induces autophagy, and inhibits migration through ER stress, thereby exerting anti-tumor effects in EC.

Ononin promotes radiosensitivity in lung cancer by inhibiting HIF-1α/VEGF pathway.

BACKGROUND: In our previous study, we provided evidence that Astragalus mongholicus Bunge(AM) and its extracts possess a protective capability against radiation-induced damage, potentially mediated through the reduction of reactive oxygen species (ROS) and nitric oxide (NO). However, we were pleasantly surprised to discover during our experimentation that AM not only offers protection against radiation damage but also exhibits a radiation sensitization effect. This effect may be attributed to a specific small molecule present in AM known as ononin. Currently, radiation sensitizers are predominantly found in nitrazole drugs and nanomaterials, with no existing reports on the radiation sensitization properties of ononin, nor its underlying mechanism. PURPOSE: This study aims to investigate the sensitization effect of the small molecule ononin derived from AM on lung cancer radiotherapy, elucidating its specific molecular mechanism of action. Additionally, the safety profile of combining astragalus small molecule ononin with radiation therapy will be evaluated. METHODS: The effective concentration of ononin was determined through cell survival experiments, and the impact of ononin combined with varying doses of radiation on lung cancer cells was observed using CCK-8 and cell cloning experiments. The apoptotic effect of ononin combined with radiation on lung cancer cells was assessed using Hochester staining, flow cytometry, and WB assay. Additionally, WB and immunofluorescence analysis were conducted to investigate the influence of ononin on HIF-1α/VEGF pathway. Furthermore, Molecular Dynamics Simulation was employed to validate the targeted binding ability of ononin and HIF-1α. A lung cancer cell line was established to investigate the effects of knockdown and overexpression of HIF-1α. Subsequently, the experiment was repeated using tumor bearing nude mice and C57BL/6 mouse models in an in vivo study. Tumor volume was measured using a vernier caliper, while HE, immunohistochemistry, and immunofluorescence techniques were employed to observe the effects of ononin combined with radiation on tumor morphology, proliferation, and apoptosis. Additionally, Immunofluorescence was employed to examine the impact of ononin on HIF-1α/VEGF pathway in vivo, and its effect on liver function in mice was assessed through biochemistry analysis. RESULTS: At a concentration of 25 µM, ononin did not affect the proliferation of lung epithelial cells but inhibited the survival of lung cancer cells. In vitro experiments demonstrated that the combination of ononin and radiation could effectively inhibit the growth of lung cancer cells, induce apoptosis, and suppress the excessive activation of the Hypoxia inducible factor 1 alpha/Vascular endothelial growth factor pathway. In vivo experiments showed that the combination of ononin and radiation reduced the size and proliferation of lung cancer tumors, promoted cancer cell apoptosis, mitigated abnormal activation of the Hypoxia inducible factor 1 alpha pathway, and protected against liver function damage. CONCLUSION: This study provides evidence that the combination of AM and its small molecule ononin can enhance the sensitivity of lung cancer to radiation. Additionally, it has been observed that this combination can specifically target HIF-1α and exert its effects. Notably, ononin exhibits the unique ability to protect liver function from damage while simultaneously enhancing the tumor-killing effects of radiation, thereby demonstrating a synergistic and detoxifying role in tumor radiotherapy. These findings contribute to the establishment of a solid basis for the development of novel radiation sensitizers derived from traditional Chinese medicine.

The relationship between false-lumen area ratio and renal replacement therapy after acute aortic dissection repair on bilateral artery cannulation: a cross-sectional study.

Background: Malperfusion poses a serious challenge to organ function in the repair of acute aortic dissection (AAD). The purpose of this study was to explore the segment change of false-lumen area ratio (FLAR; the ratio of the maximal false-lumen area to the total lumen area) in the descending aorta and its relationship with renal replacement therapy (RRT) after total aortic arch (TAA) surgery. Methods: A total of 228 patients with AAD who received TAA using perfusion mode right axillary and femur artery cannulation between March 2013 and March 2022 were included in a cross-sectional study. The descending aorta was divided into 3 segments: the descending thoracic aorta (S1), the abdominal aorta above the ostium of the renal artery (S2), and the abdominal aorta between the ostium of the renal artery and the iliac bifurcation (S3). The primary outcomes were postoperative segmental FLAR changes in the descending aorta, which were observed using computed tomography angiography before the patients were discharged from the hospital. The secondary outcomes were RRT and 30-day mortality. Results: The total potencies in the false lumen were 71.1%, 95.2%, and 88.2% in S1, S2, and S3. The postoperative/preoperative ratio of the FLAR was higher in S2 than that in S1 and S3 (S1: 67%±14%; S2: 80%±8%; S3: 57%±12%; all P values <0.001). For the patients undergoing RRT, there was a higher postoperative/preoperative ratio of the FLAR for the S2 segment (85%±7% vs. 79%±8%; P<0.001) and higher mortality (28.9% vs. 7.7%; P<0.001) after AAD repair compared with patients in the no-RRT group. Conclusions: This study demonstrated there was less attenuation of the FLAR on the abdominal aorta above the ostium of the renal artery in the whole descending aorta after AAD repair with intraoperative right axillary and femur artery perfusion mode. The patients needing RRT were associated with less postoperative/preoperative change of the FLAR and worse clinical outcomes.

Natural Solar Irradiation Produces Fluorescent and Biodegradable Nanoplastics.

Nanoplastics (NPs) have raised global concern owing to their potential health effects. Herein, after simulated and natural solar irradiation, polyethylene, polypropylene, polystyrene, and poly(vinyl chloride) nanoplastics (PVC NPs) were observed to exhibit enhanced fluorescence, particularly PVC NPs. Furthermore, the role of photoaged NPs as a potential fluorescence indicator was evaluated by exposing a model aquatic organism Daphnia magna to these NPs. Our results revealed that photoaged NPs exhibited strong fluorescence owing to the generation of conjugated π bonds, which can achieve π-π* electron transition with low energy consumption. Photogenerated fluorescence also enabled the photoaged NPs to act as efficient fluorescent tracers, which can help track NP migration in various organisms. The results of two-photon laser confocal scanning microscopy revealed that the photoaged NPs could translocate across biological barriers and accumulate in extraintestinal tissues in addition to being ingested and excreted. Moreover, compared with pristine NPs, the photoaged NPs underwent biodegradation more easily, probably because of increased hydrophilicity due to photogenerated oxygen-containing moieties. Therefore, in addition to producing fluorescent NPs without the attachment of external fluorescent dyes, the natural photoaging process can promote the migration and degradation of photoaged NPs in food chains.

Review: Mechanisms and perspective treatment of radioresistance in non-small cell lung cancer.

Radiotherapy is the major treatment of non-small cell lung cancer (NSCLC). The radioresistance and toxicity are the main obstacles that leading to therapeutic failure and poor prognosis. Oncogenic mutation, cancer stem cells (CSCs), tumor hypoxia, DNA damage repair, epithelial-mesenchymal transition (EMT), and tumor microenvironment (TME) may dominate the occurrence of radioresistance at different stages of radiotherapy. Chemotherapy drugs, targeted drugs, and immune checkpoint inhibitors are combined with radiotherapy to treat NSCLC to improve the efficacy. This article reviews the potential mechanism of radioresistance in NSCLC, and discusses the current drug research to overcome radioresistance and the advantages of Traditional Chinese medicine (TCM) in improving the efficacy and reducing the toxicity of radiotherapy.

TMAO promotes dementia progression by mediating the PI3K/Akt/mTOR pathway.

BACKGROUND: Dementia poses a serious threat to the daily and social abilities of patients, and trimethylamine-N-oxide (TMAO) is a metabolite of the gut microbiota involved in regulating the inflammatory response. However, the role of TMAO in dementia needs further investigation. This study aimed to investigate the effects and possible mechanisms of TMAO on dementia, which may provide ideas for the treatment of dementia. MATERIALS AND METHODS: Dementia mice were induced by D-galactose + AlCl3, and the changes in learning memory capacity, histopathology, inflammatory factors, and PI3K/Akt/mTOR in mice treated with TMAO were analyzed to determine the mechanism of TMAO action on dementia. In addition, the effect of TMAO+PI3K inhibitor treatment on mice was also analyzed to further determine the mechanism of TMAO effect on dementia. RESULTS: The results revealed that the dementia group had significantly higher TMAO levels and a significant hippocampal injury and inflammatory response. TMAO treatment promoted hippocampal injury and promoted the level of inflammatory cytokines. Further study of PI3K/Akt/mTOR signaling pathway showed that the expression of p-PI3K, p-Akt, and p-mTOR was significantly increased in the dementia group, and it was more obvious after TMAO treatment. And hippocampal injury, inflammatory response, and increase of p-PI3K, p-Akt, p-mTOR were reversed by TMAO+PI3K inhibitor. CONCLUSIONS: This study determined that TMAO promotes dementia through the PI3K/Akt/mTOR signaling pathway, suggesting that TMAO may be a potential target for dementia.

[Analysis of the curative effect of triple surgery under endoscope in the treatment of intractable heel pain].

OBJECTIVE: To investigate the clinical effect the treatment of arthroscopy-assisted calcaneal spur resection combined with plantar fascia release and calcaneal decompression in the treatment of the patients with intractable calcaneal pain. METHODS: The clinical data of 50 patients with intractable heel pain from January 2016 to January 2019 were retrospectively analyzed, including 20 males and 30 females;aged from 40 to 68 years old with an average of (50.12±7.35)years old, the medical history ranged from 1 to 4 years. All patients underwent arthroscopy-assisted calcaneal spur resection combined with plantar fascia release and calcaneal decompression, and were followed up, the duration ranged from 24 to 60 months with an average of(42.00±3.28) months. All patients had obvious heel pain before surgery, and X-ray examinations often showed the presence of calcaneal spurs. In addition to the routine foot examination, the changes in the height and angle of the arch of the foot were also measured pre and post-operatively by X-ray, for the evaluation of clinical effect. The VAS system was used to evaluate the degree of foot pain;the AOFAS scoring system was used to comprehensively evaluate the foot pain, voluntary movement, gait and stability. RESULTS: The VAS decreased from (8.75±1.24) before surgery to (5.15±2.35) at 3 months after surgery, (4.07±2.53) at 6 months after surgery, and (3.95±2.44) at the last fllow-up(P<0.05). The AOFAS score increased from (53.46±4.17) before surgery to(92.46±2.53) at 3 months after surgery, (96.33±2.46) at 6 months after surgery, and (97.05±2.37) at the last follow-up(P<0.05). The arch height was (41.54±1.15) mm before operation and (41.49±1.09) mm after the operation, the difference was not statistically significant(P>0.05). The internal arch angle of the foot arch was (121±6)° before operation and (122±7)° after operation. The difference was not statistically significant(P>0.05). CONCLUSION: Arthroscopy-assisted calcaneal bone spurs resection combined with plantar fascia release and calcaneal decompression exhibited great clinical effect for treating intractable heel.

Multiomics Analysis Reveals Cuproptosis-Related Signature for Evaluating Prognosis and Immunotherapy Efficacy in Colorectal Cancer.

Cuproptosis is a copper-induced form of mitochondrial cell death which is engaged in the proliferation and migration of a variety of tumors. Nevertheless, the role of cuproptosis in tumor microenvironment (TME) remodeling and antitumor therapy is still poorly understood. We characterized two diverse cuproptosis-associated molecular isoforms in CRC which exhibit distinct prognostic and TME characteristics. Subsequently, we constructed a cuproptosis-associated prognostic model containing five genes and divided the patients into a high CPS-score group and a low CPS-score group. Univariate and multivariate Cox analyses showed that the CPS score could be used as an independent prognostic factor. The nomogram, and its consequent calibration curves, indicated that this prognostic signature had good predictive power for CRC. The analysis of single-cell sequencing data showed the significant expression of HES4 and SPHK1 in various immune and stromal (including fibroblasts) cells. Further studies showed that tumor mutational burden (TMB), high microsatellite instability (MSI-H) ratio, immune checkpoint blockade (ICB), and human leukocyte antigen (HLA) gene expression all positively correlated with the CPS score, predicting a better reaction to immunotherapy in high CPS-core patients. The CPS score constructed from cuproptosis subtypes can be used as a predictive tool to evaluate the prognosis of CRC patients and their response to immunotherapy.

Radiation-Induced Bystander Effect on the Genome of Bone Marrow Mesenchymal Stem Cells in Lung Cancer.

Aims: Radiation by-radiation effect (RIBE) can induce the genomic instability of bone marrow mesenchymal stem cells (BMSCs) adjacent to lung cancer, and this effect not only exists in the short-term, but also accompanies it in the long-term, but its specific mechanism is not clear. Our goal is to explore the similarities and differences in the mechanism of genomic damage in tumor-associated BMSCs induced by short-term and long-term RIBE, and to provide a theoretical basis for adjuvant drugs for protection against RIBE at different clinical time periods. Results: We found that both short- and long-term RIBE induced genomic instability. We could show a high expression of TGF-ß1, TNF-α, and HIF-1α in tumor-associated BMSCs after short-term RIBE whereas only TNF-α and HIF-1α expression was increased in long-term RIBE. We further confirmed that genomic instability is associated with the activation of the HIF-1α pathway and that this is mediated by TNF-α and TGF-ß1. In addition, we found differences in the mechanisms of genomic instability in the considered RIBE windows of analysis. In short-term RIBE, both TNF-α and TGF-ß1 play a role, whereas only TNF-α plays a decisive role in long-term RIBE. In addition, there were differences in BMSC recruitment and genomic instability of different tissues with a more pronounced expression in tumor and bone marrow than compared to lung. Innovation and Conclusion: We could show dynamic changes in the expression of the cytokines TGF-ß1 and TNF-α during short- and long-term RIBE. The differential expression of the two is the key to causing the genomic damage of tumor-associated BMSCs in the considered windows of analysis. Therefore, these results may serve as a guideline for the administration of radiation protection adjuvant drugs at different clinical stages. Antioxid. Redox Signal. 38, 747-767.

Potential mechanism underlying the effect of matrine on COVID-19 patients revealed through network pharmacological approaches and molecular docking analysis.

BACKGROUND: The clinical efficacy of matrine in treating coronavirus disease (COVID-19) has been confirmed; however, its underlying mechanism of action remains unknown. METHODS: TCMSP, SwissTargetPrediction, SEA, GeneCards, CTD, and TTD were used to identify potential targets for matrine in SARS-CoV-2. Cytoscape software was used to determine the target-pathway network for topographical analysis. The online STRING analysis platform and Cytoscape were together used to generate a PPI network and for GO and KEGG pathway enrichment analysis. Finally, molecular docking simulations were performed to study matrine-Mpro, matrine-ACE2, and matrine-RdRp interactions. RESULTS: Ten common matrine targets were obtained, particularly including TNF-α, IL-6, and CASP3. GO and KEGG pathway enrichment analysis revealed five significantly enriched signalling pathways involved in cell proliferation, apoptosis, programmed cell death, and immune responses. CONCLUSIONS: During COVID-19 treatment, matrine regulates viral replication, host cell apoptosis, and inflammation by targeting the TNF-α, IL-6, and CASP3 in the TNF signalling pathway.

Longitudinal Change of Circulating Tumor Cells During Chemoradiation and Its Correlation with Prognosis in Advanced Nonsmall-Cell Lung Cancer Patients.

Background: This study investigated the association of circulating tumor cells (CTCs) change during chemoradiation with the treatment response and survival profiles in advanced nonsmall-cell lung cancer (NSCLC) patients. Materials and Methods: Fifty-eight advanced NSCLC patients who underwent concurrent chemoradiation were enrolled; their peripheral blood samples were collected before chemoradiation, and at 1 month postchemoradiation, the CTCs were assayed using a CTC-Biopsy system. Moreover, CTCs were classified as CTCs positive and CTCs negative according to CTCs' count, and change of CTCs was calculated. In addition, response of chemoradiation was evaluated at 1 month postchemoradiation, then progression-free survival (PFS) and overall survival (OS) were assessed. Results: Prechemoradiation CTCs positive were associated with increased TNM stage, but not other clinicopathologic characteristics. After chemoradiation, the CTCs' number [1.0 (0.0-3.0) vs. 4.0 (2.0-10.0)] and the percentage of CTC-positive cases (37.9% vs. 77.6%) were both decreased compared to those before chemoradiation. Regarding treatment response, prechemoradiation CTCs positive were associated with lower partial response; postchemoradiation CTCs positive were associated with reduced disease control rate, while CTCs' change during chemoradiation was not associated with treatment response. Kaplan-Meier curves showed that postchemoradiation CTCs positive and increased CTCs' number during chemoradiation were associated with reduced PFS, then multivariate Cox's regression analysis disclosed that they independently predicted decreased PFS. However, no correlation of CTCs' status or CTCs' change with OS was observed. Conclusions: Prechemoradiation CTCs relate to increased TNM stage and worse prognosis in chemoradiation-treated advanced NSCLC patients.

The expression and prognostic value of transporter 1, ATP binding cassette subfamily B member in clear cell renal cell cancer with experimental validation.

Transporter associated with antigen processing 1(TAP1) serves as a protein to transport antigenic peptides from the surface of the endoplasmic reticulum to the lumen of the endoplasmic reticulum when the antigens are presented by major histocompatibility complex type I (MHC-I), which has been identified to play a critical role in antigen presentation in innate immunity. In tumors, the role of TAP1 seems to remain controversial. On the one hand, given the role of TAP1 in antigen presentation, it is indicated that high TAP1 expression corresponds to the emergence of more neoantigens epitopes that facilitate the recognition for phagocytes, T cells and other cells. On the other hand, the genetic ablation of transporter associated with antigen processing (TAP) results in the presentation of new class I-restricted epitopes encoded in house-keeping products. Opposite result has been revealed by studies in other tumors suggest, which implies a more complex function of TAP1. Therefore, it's significant to clarify the role of TAP1 in clear cell renal cell carcinoma (ccRCC). In this study, we found the elevated expression levels in mRNA and protein of TAP1 in ccRCC tissues, which indicated a relatively worse prognosis. Transwell assay and Scratch assay in vitro demonstrated the promotive role of TAP1 in ccRCC migration as well as a significant role in metastasis. And the increased expression of TAP1 resulted in more immune cells infiltrated in cancer tissues. TAP1 was also demonstrated to be related to immune regulator genes, as gene set enrichment analysis (GSEA) indicated its significant role in immune regulation. The results of CancerSEA indicated the positive association of the high-level TAP1 expression with epithelial-mesenchymal transition (EMT) and the inverse association with Cell Cycle. The effective drugs were also predicted based on TAP1 expression, of which the high level was indeed associated with resistance to multiple drugs, but some effective drugs still identified based on high TAP1 expression. According to the analysis of various databases, the role of TAP1 in ccRCC was explored, especially in relationship of TAP1 with tumor microenvironment. These results indicate that TAP1 can serve as a potential target for treatment of ccRCC.

[Effects of TOFA on growth of Eca109 and KYSE-450 cells in human esophageal squamous cell carcinoma].

Objective: To investigate the effects of 5-tetradecanoxy 2-furanic acid (TOFA) on cell proliferation, cell cycle and apoptosis of esophageal squamous cell carcinoma (ESCC) cells. Methods: Eca-109 cells and KYSE-450 cells were divided into control group (DMSO) and experimental group (TOFA), respectively. The cells (4×103 cells/100 µl) were inoculated into 96-well plates with 5 multiple wells at each concentration. After 24 h culture, cells were treated with DMSO or different concentrations (1, 3, 5, 10 µg/ ml) of TOFA for 24, 48 and 72 h. Cell proliferation was detected by MTT, cell cycle and apoptosis were detected by flow cytometry, the expression levels of p21 and Cleaved caspase-3 and modification levels of p-Akt, p-mTOR and p-4EBP1 were detected by Western blot, and intracellular free fatty acids were detected by special kits. Results: MTT results showed that TOFA inhibited the proliferation of Eca109 and KYSE-450 cells in a concentration and time dependent manner (all P<0.05), with IC50 of 4.65 µg/ml and 3.93 µg/ml for 48 h, respectively. Flow cytometry results showed that compared with DMSO group, the percentage of cells in G2/M phase was increased and the apoptosis rate was increased in the experimental group. Western blotting results showed that compared with DMSO group, p21 and Cleaved caspase-3 protein expression levels were up-regulated, and p-AKT, p-mTOR and p-4EBP1 protein expression levels were down-regulated (all P<0.05). Conclusion: TOFA inhibits the proliferation, blocks the cycle progression and promotes apoptosis of ESCC, the mechanism may be related to the AKT/mTOR/4EBP1 signaling pathway.

Frontiers and hotspots of 18F-FDG PET/CT radiomics: A bibliometric analysis of the published literature.

Objective: To illustrate the knowledge hotspots and cutting-edge research trends of 18F-FDG PET/CT radiomics, the knowledge structure of was systematically explored and the visualization map was analyzed. Methods: Studies related to 18F-FDG PET/CT radiomics from 2013 to 2021 were identified and selected from the Web of Science Core Collection (WoSCC) using retrieval formula based on an interview. Bibliometric methods are mainly performed by CiteSpace 5.8.R3, which we use to build knowledge structures including publications, collaborative and co-cited studies, burst analysis, and so on. The performance and relevance of countries, institutions, authors, and journals were measured by knowledge maps. The research foci were analyzed through research of keywords, as well as literature co-citation analysis. Predicting trends of 18F-FDG PET/CT radiomics in this field utilizes a citation burst detection method. Results: Through a systematic literature search, 457 articles, which were mainly published in the United States (120 articles) and China (83 articles), were finally included in this study for analysis. Memorial Sloan-Kettering Cancer Center and Southern Medical University are the most productive institutions, both with a frequency of 17. 18F-FDG PET/CT radiomics-related literature was frequently published with high citation in European Journal of Nuclear Medicine and Molecular Imaging (IF9.236, 2020), Frontiers in Oncology (IF6.244, 2020), and Cancers (IF6.639, 2020). Further cluster profile of keywords and literature revealed that the research hotspots were primarily concentrated in the fields of image, textural feature, and positron emission tomography, and the hot research disease is a malignant tumor. Document co-citation analysis suggested that many scholars have a co-citation relationship in studies related to imaging biomarkers, texture analysis, and immunotherapy simultaneously. Burst detection suggests that adenocarcinoma studies are frontiers in 18F-FDG PET/CT radiomics, and the landmark literature put emphasis on the reproducibility of 18F-FDG PET/CT radiomics features. Conclusion: First, this bibliometric study provides a new perspective on 18F-FDG PET/CT radiomics research, especially for clinicians and researchers providing scientific quantitative analysis to measure the performance and correlation of countries, institutions, authors, and journals. Above all, there will be a continuing growth in the number of publications and citations in the field of 18F-FDG PET/CT. Second, the international research frontiers lie in applying 18F-FDG PET/CT radiomics to oncology research. Furthermore, new insights for researchers in future studies will be adenocarcinoma-related analyses. Moreover, our findings also offer suggestions for scholars to give attention to maintaining the reproducibility of 18F-FDG PET/CT radiomics features.

Advances in the Welding of Aluminum Matrix Composites: A New Open Special Issue in Materials.

"Advances in the Welding of Aluminum Matrix Composites" is a new open Special Issue of Materials that aims to publish original research and review papers on new scientific and applied research and to make great contributions to advances in the field of welding aluminum matrix composites as well as to the related synthesis, fundamentals, characterization, and application of these materials [...].

The novel transcriptomic signature of angiogenesis predicts clinical outcome, tumor microenvironment and treatment response for prostate adenocarcinoma.

Angiogenesis plays the critical roles in promoting tumor progression, aggressiveness, and metastasis. Although few studies have revealed some angiogenesis-related genes (ARGs) could serve as prognosis-related biomarkers for the prostate cancer (PCa), the integrated role of ARGs has not been systematically studied. The RNA-sequencing data and clinical information of prostate adenocarcinoma (PRAD) were downloaded from The Cancer Genome Atlas (TCGA) as discovery dataset. Twenty-three ARGs in total were identified to be correlated with prognosis of PRAD by the univariate Cox regression analysis, and a 19-ARG signature was further developed with significant correlation with the disease-free survival (DFS) of PRAD by the least absolute shrinkage and selection operator (LASSO) Cox regression with tenfold cross-validation. The signature stratified PRAD patients into high- and low-ARGs signature score groups, and those with high ARGs signature score were associated with significantly poorer outcomes (median DFS: 62.71 months vs unreached, p < 0.0001). The predicting ability of ARGs signature was subsequently validated in two independent cohorts of GSE40272 & PRAD_MSKCC. Notably, the 19-ARG signature outperformed the typical clinical features or each involved ARG in predicting the DFS of PRAD. Furthermore, a prognostic nomogram was constructed with three independent prognostic factors, including the ARGs signature, T stage and Gleason score. The predicted results from the nomogram (C-index = 0.799, 95%CI = 0.744-0.854) matched well with the observed outcomes, which was verified by the calibration curves. The values of area under receiver operating characteristic curve (AUC) for DFS at 1-, 3-, 5-year for the nomogram were 0.82, 0.83, and 0.83, respectively, indicating the performance of nomogram model is of reasonably high accuracy and robustness. Moreover, functional enrichment analysis demonstrated the potential targets of E2F targets, G2M checkpoint pathways, and cell cycle pathways to suppress the PRAD progression. Of note, the high-risk PRAD patients were more sensitive to immune therapies, but Treg might hinder benefits from immunotherapies. Additionally, this established tool also could predict response to neoadjuvant androgen deprivation therapy (ADT) and some chemotherapy drugs, such as cisplatin, paclitaxel, and docetaxel, etc. The novel ARGs signature, with prognostic significance, can further promote the application of targeted therapies in different stratifications of PCa patients.

Seed oil of Rosa roxburghii Tratt against non-alcoholic fatty liver disease in vivo and in vitro through PPARα/PGC-1α-mediated mitochondrial oxidative metabolism.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), characterized by hepatic steatosis and hepatocyte injury, is an obesity-induced metabolic dysregulation with few available therapeutic options. Enhancement of the mitochondrial function was considered as an effective treatment for NALFD. Unsaturated fatty acids (UFAs) have been shown to have beneficial effects on metabolic syndrome disease such as hyperlipidemia, coronary artery disease and cardiovascular diseases. The seed oil of Rosa roxburghii Tratt (ORRT) was of high quality in terms of its high amount of unsaturated fatty acids. However, the effects of ORRT on NALFD have not been reported so far. PURPOSE: The study aimed to evaluate the protective effects and molecular mechanism of ORRT for the treatment of NAFLD in vivo and in vitro. METHODS: The beneficial effects, especially improving the mitochondrial function, and the potential mechanism of ORRT on NAFLD were studied both in vivo and in vitro. Lipid levels were determined by triglyceride (TG), total cholesterol (TC), and Oil Red O staining. Oxidative stress and inflammation were assessed by detecting antioxidant enzyme activity, MDA content, and ELISA assay. Blood TG, TC, HDL-c and LDL-c levels were measured in HFD mice. Western blot analyses were used to determine the levels of the protein involved in fatty acid oxidation, oxidative metabolism, and mitochondria biogenesis and function. The mitochondrial membrane potential level was measured by JC-1 staining to teste the effect of ORRT on mitochondrial function in vitro. GW6471 (inhibitor of PPARα) was used to confirm the relationship between PPARα and PGC-1α. RESULTS: ORRT significantly restrained NAFLD progression by attenuating lipid accumulation, oxidative stress and inflammatory response. Furthermore, ORRT upregulated thermogenesis-related gene expressions, such as uncoupling protein 1 (UCP1) and p38 mitogen-activated protein kinase (p38 MAPK). The results showed that the expression of key genes involved in fatty acid oxidation (e.g., CPT-1α, ACADL, PPARα) and in mitochondrial biogenesis and function (e.g., TFAM, NRF1, PGC-1α, and COX IV) was significantly increased. Together with the observed MMP improvement, these findings suggested that ORRT activated the mitochondrial oxidative pathway. Additionally, GW6471 inhibited the ORRT on promoting the expression of PGC-1α, CPT-1α, and ACADL. In conclusion, ORRT possessed the potential to prevent lipid accumulation via the PPARα/PGC-1α signaling pathway, which could be developed as a natural health-promoting oil against NAFLD.

Halide salts induced the photodegradation of a fat-burning compound 2, 4-dinitrophenol by iron-montmorillonite.

Natural montmorillonite clay and anthropogenic organic pollutants frequently coexist in the estuarine environment where freshwater from rivers mixes with saltwater from the ocean. In this environment, the sharply changed aqueous chemistry especially salt content could significantly alter the photochemical behaviors of pollutants. However, this process was rarely investigated. In this study, the photodegradation of a representative anthropogenic weight-loss compound 2,4-dinitrophenol in the presence of Fe3+-montmorillonite and different halide salts was systematically investigated. Results show that 2,4-dinitrophenol was resistant to photodegradation by Fe3+-montmorillonite alone, but the presence of NaCl, NaBr, and sea salts in the system can evoke significant 2,4-dinitrophenol degradation. The enhancement effect was further elucidated as the replacement reaction between the clay associated Fe3+ and Na + which leads to the release of more interlayer Fe3+ from montmorillonite, resulting in increased production of high active hydroxyl radicals (˙OH) that can substantially damage 2,4-dinitrophenol molecule. In addition, halogen radicals from the reaction of halide ions with ˙OH were also confirmed to participate in 2,4-dinitrophenol degradation. Overall, this study implied that the changed salty condition in the estuarine water could induce the rapid transformation of organic pollutants that move from freshwater and have relatively stable photochemical properties.

Survival in Metastatic Renal Cell Carcinoma Patients Treated With Sunitinib With or Without Cryoablation.

BACKGROUND: Percutaneous cryoablation (PCA) has emerged as an alternative to extirpative management of small renal masses in select patients. In recent years, the use of targeted therapies has become mainstream, while the role of PCA in treating primary tumor is not well established among patients with metastatic renal cell carcinoma (mRCC). We sought to evaluate how mRCC patients react to PCA in combination with sunitinib. METHODS: We retrospectively identified patients with mRCC (primary tumor diameter ≤ 7 cm) treated with sunitinib between 2013 and 2019. These patients were categorized by initial treatment (cryoablation followed by sunitinib versus sunitinib only). Oncological outcomes and rate of adverse events were compared. RESULTS: Of the 178 patients analyzed, 65 underwent PCA prior to sunitinib. The median overall survival (OS) in the PCA-sunitinib group was 31.7 months (95% CI; 26.1-37.3), better than the sunitinib-only group, which reported a median OS of 19.8 months (95% CI; 17.1-22.4) (p < 0.001). The median progression-free survival (PFS) in patients treated with PCA-sunitinib versus sunitinib alone was 13.8 months (95% CI; 10.0-17.6) versus 7.2 months (95% CI: 6.1-8.3) (p < 0.005). No significant differences in adverse events were observed (p > 0.05). CONCLUSIONS: PCA combined with sunitinib is associated with better survival outcomes than sunitinib alone in patients with mRCC. Careful patient selection remains warranted. These results should inform future prospective trials.

Clinical Observation of Prophylactic Extended-Field Intensity-Modulated Radiation Therapy with Synchronous Chemotherapy in Locally Advanced Cervical Cancer.

BACKGROUND We aimed to evaluate the value of prophylactic extended-field intensity-modulated radiation therapy (IMRT) in the treatment of locally advanced cervical cancer with multiple pelvic lymph node metastases (≥2) and negative common iliac and paraaortic lymph nodes. MATERIAL AND METHODS Thirty-four patient with newly diagnosed cervical cancer (IB1-IVA) and multiple pelvic lymph node metastases (≥2) confirmed by computed tomography and magnetic resonance imaging were randomly divided into an extended-field group (17 patients) and a pelvic-field group (17 patients). In the extended-field group, we added the drainage area of paraaortic lymph nodes on the pelvic field. The pelvic field was administered Dt 45.0 to 50.4 Gy, while the drainage area of paraaortic lymph nodes was administered Dt 40.0 to 45.0 Gy. Both groups were given Irl92 intracavitary radiotherapy after 3 weeks of external irradiation. The total dose of point A was 25.0 to 30.0 Gy, fractional 6.0 to 7.0 Gy. All patients had concurrent platinum-based chemotherapy once weekly until the end of radiotherapy. RESULTS No paraaortic lymph node metastasis was found in the extended-field group (P=0.0184), and disease-free survival (DFS) was prolonged (P=0.0286). Adverse effects in patients with III-IV degree myelosuppression were increased in the extended-field group (P=0.0324). However, all patients recovered after symptomatic treatment. CONCLUSIONS Prophylactic extended-field IMRT with chemotherapy reduced the metastasis rate of paraaortic lymph nodes and prolonged the DFS in patients with locally advanced cervical cancer and multiple pelvic lymph node metastases (≥2), while the toxic adverse effects were tolerated.