Low-intensity ultrasound combined with arsenic trioxide induced apoptosis of glioma via EGFR/AKT/mTOR.

AIMS: This study aimed to explore whether low-intensity ultrasound (LIUS) combined with low-concentration arsenic trioxide (ATO) could inhibit the proliferation of glioma and, if so, to clarify the potential mechanism. MAIN METHODS: The effects of ATO and LIUS alone or in combination on glioma were examined by CCK8, EdU, and flow cytometry assays. Western blot analysis was used to detect changes in expression of apoptosis-related proteins and their effects on the EGFR/AKT/mTOR pathway. The effects of ATO and LIUS were verified in vivo in orthotopic xenograft models, and tumor size, arsenic content in brain tissue, survival, and immunohistochemical changes were observed. KEY FINDINGS: LIUS enhanced the inhibitory effect of ATO on the proliferation of glioma, and EGF reversed the proliferation inhibition and protein changes induced by ATO and LIUS. The anti-glioma effect of ATO combined with LIUS was related to downstream AKT/mTOR pathway changes caused by inhibition of EGFR activation, which enhanced apoptosis of U87MG and U373 cells. In vivo experiments showed significant increases in arsenic content in brain tissue, as well as decreased tumor sizes and longer survival times in the combined treatment group compared with other groups. The trends of immunohistochemical protein changes were consistent with the in vitro results. SIGNIFICANCE: This study showed that LIUS enables ATO to exert anti-glioma effects at a safe dose by inhibiting the activation of EGFR and the downstream AKT/mTOR pathway to regulate apoptosis. LIUS in combination with ATO is a promising novel method for treating glioma and could improve patient prognosis.

Hydrogen production by traditional and novel alkaline water electrolysis on nickel or iron based electrocatalysts.

Hydrogen production through alkaline water electrolysis holds great promise as a scalable solution for renewable energy storage and conversion. The development of non-precious metal-based electrocatalysts with low-overpotential for alkaline water electrolysis is essential to decrease the cost of electrolysis devices. Although the Ni-based and Fe-based electrocatalysts have been commercially employed in the cathodic hydrogen evolution reaction (HER) and anodic oxygen evolution reaction (OER), it is imperative to persistently pursue the advancement of highly efficient electrocatalysts with enhanced current density and fast kinetics. This feature article overviews the progress of NiMo HER cathodes and NiFe OER anodes in the traditional alkaline water electrolysis process for hydrogen production, including the detailed mechanisms, preparation strategies, and structure-function relationship. Moreover, recent advances of Ni-based and Fe-based electrodes in the process of novel alkaline water electrolysis, involving small energetic molecule electro-oxidation and redox mediator decoupled water electrolysis, are also discussed for hydrogen production with low cell voltage. Finally, the perspective of these Ni-based and Fe-based electrodes in the mentioned electrolysis processes is proposed.

Pharyngoesophageal diverticulum mimicking thyroid nodules: Some interesting ultrasonographic signs.

Objective: To analyze the ultrasonographic features of pharyngoesophageal diverticulum (PED) mimicking thyroid nodules and to explore the clinical value of ultrasonography in the diagnosis of PED. Method: The sonographic findings of 68 patients with PED were retrospectively reviewed. According to the diverticulum echo intensity characteristics, the lesions were divided into solid nodular diverticulum, gas-containing nodular diverticulum, liquid-containing nodular diverticulum, and atypical diverticular changes; and the ultrasonographic manifestations were compared among the four groups. Results: 30/68 were solid nodular diverticula. The diverticulum cavity was oval or elliptic with a clear border, and the diverticulum wall suggested exhibited a typical hyper-hypo-hyper-echogenic pattern. The diverticulum wall and esophageal wall were seen to be continuous if multiple sections were scanned, and hypoechoic walls showed punctate blood flow. 29/68 diagnosed with air-containing nodular diverticulum, lesions appeared with gas-like hyper-echogenicity internally, with some amount of gas and change in the tail pattern during swallowing. 6/68 patients were diagnosed with liquid-containing nodular diverticulum, and the main ultrasonic manifestations were an anechoic internal diverticulum cavity that was clearly bounded from the thyroid but continuous with the esophageal wall, with a typical hyper-hypo-echoless pattern from the outside to the inside. Another 3/68 were found to have atypical diverticular changes, regional convexities of the esophageal wall with unfashioned nodules. The convex segment was continuous with the hyper-hypo-echogenic esophageal wall and could be seen on slitting scanning. Conclusion: Overall, PEDs mimicking thyroid nodules have specific ultrasonographic features. Familiarity with them can avoid missed diagnoses and misdiagnoses.

Low-intensity ultrasound: A novel technique for adjuvant treatment of gliomas.

Glioma is the most common primary malignant tumor of the central nervous system. Although surgical treatment combined with radiotherapy, chemotherapy, and immunotherapy are commonly used for glioma treatment, the prognosis of glioma is still unsatisfactory. The poor effect of glioma treatment could be due to the blocking effect of blood-brain barrier (BBB) on most drugs and the multidrug resistance in tumor cells. In recent years, preclinical trials have shown that low-intensity ultrasound (LIUS) can reversibly open the BBB, inhibit the proliferation of tumor cells, and improve the delivery of drugs to brain tissue. This technology has also recently been used in clinical trials, and achieved encouraging preliminary results. In this review, the existing research results, the effect of LIUS on the adjuvant therapy of glioma under safe conditions, and the physical and biological mechanisms have been discussed. This review aims to show the potential and prospect of LIUS technique in the clinical treatment of glioma.

Establishment and Validation of a 5 m6A RNA Methylation Regulatory Gene Prognostic Model in Low-Grade Glioma.

Background: The prognosis of low-grade glioma (LGG) is different from that of other intracranial tumors. Although many markers of LGG have been established, few are used in clinical practice. M6A methylation significantly affects the biological behavior of LGG tumors. Therefore, establishment of an LGG prognostic model based on m6A methylation regulatory genes is of great interest. Methods: Data from 495 patients from The Cancer Genome Atlas (TCGA) and 172 patients from the Chinese Glioma Genome Atlas (CGGA) were analyzed. Univariate Cox analysis was used to identify methylation regulatory genes with prognostic significance. LASSO Cox regression was used to identify prognostic genes. Receiver operating characteristic (ROC) and Kaplan-Meier curves were used to verify the accuracy of the model. Gene Set Enrichment Analysis (GSEA) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to identify cellular pathways that were significantly associated with the prognosis of LGG. Results: A glioma prognostic model based on five methylation regulatory genes was established. Compared with low-risk patients, patients identified as high risk had a poorer prognosis. There was a high degree of consistency between the internal training and internal validation CGGA cohorts and the external validation TCGA cohort. Furthermore, KEGG and GSEA analyses showed that the focal adhesion and cell cycle pathways were significantly upregulated in high-risk patients. This signature could be used to distinguish among patients with different immune checkpoint gene expression levels, which may inform immune checkpoint inhibitor (ICI) immunotherapy. Conclusion: We comprehensively evaluated m6A methylation regulatory genes in LGG and constructed a prognostic model based on m6A methylation, which may improve prognostic prediction for patients with LGG.

Long Noncoding RNA LIFR-AS1: A New Player in Human Cancers.

Emerging evidence has indicated that aberrantly expressed long noncoding RNAs (lncRNAs) play a vital role in various biological processes associated with tumorigenesis. Leukemia inhibitory factor receptor antisense RNA1 (LIFR-AS1) is a recently identified lncRNA transcribed in an antisense manner from the LIFR gene located on human chromosome 5p13.1. LIFR-AS1 regulates tumor proliferation, migration, invasion, apoptosis, and drug resistance through different mechanisms. Its expression level is related to the clinicopathological characteristics of tumors and plays a key role in tumor occurrence and development. In this review, we summarize the role of LIFR-AS1 in the development and progression of different cancers and highlight the potential for LIFR-AS1 to serve as a biomarker and therapeutic target for a variety of human cancers.

Curcumin combined with low-intensity ultrasound suppresses the growth of glioma cells via inhibition of the AKT pathway.

Malignant glioma is the most lethal form of brain cancer, and effective therapeutic modalities remain unavailable to date. We aim to investigate whether low-dose curcumin combined with low-intensity ultrasound (LIUS) effectively suppresses the growth of glioma cells and elucidate the underlying mechanisms. Glioma cells were treated with LIUS and curcumin. Subsequently, the effects of LIUS and curcumin on glioma cells were determined by CCK-8 assay, EdU assay, and flow cytometry analysis, respectively. Western blot analysis was performed to examine the levels of apoptosis-associated proteins and the proteins related to the AKT pathway. The proliferation assay showed that combined treatment with LIUS and curcumin synergistically decreased proliferation in glioma cells. And cell apoptosis was promoted after LIUS-curcumin combination treatment, characterized by the occurrence of more apoptotic cells and a significant increase in Bax level and attenuated Bcl-2 expression. Moreover, the role of LIUS-curcumin combination in downregulation of the AKT pathway was observed. The AKT pathway activator SC79 reversed apoptosis and anti-proliferation induced by combined treatment with LIUS and curcumin. Our findings show that LIUS in combination with low-dose curcumin synergistically suppresses the growth of glioma cells via inhibition of the AKT pathway. LIUS plus curcumin may be a promising therapeutic strategy for preventing glioma growth.

Highly efficient hamburger-like nanostructure of a triadic Ag/Co3O4/BiVO4 photoanode for enhanced photoelectrochemical water oxidation.

The combination of a semiconductor heterojunction and oxygen evolution cocatalyst (OEC) is an important strategy to improve photoelectrochemical (PEC) water oxidation. Herein, a novel hamburger-like nanostructure of a triadic photoanode composed of BiVO4 nanobulks, Co3O4 nanosheets and Ag nanoparticles (NPs), that is, Ag/Co3O4/BiVO4, was designed. In our study, an interlaced 2D ultrathin p-type Co3O4 OEC layer was introduced onto n-type BiVO4 to form a p-n Co3O4/BiVO4 heterojunction with an internal electric field (IEF) in order to facilitate charge transport. Then the modification with Ag NPs can significantly facilitate the separation and transport of photogenerated carriers through the surface plasma resonance (SPR) effect, inhibiting the electron-hole recombination. The resulting Ag/Co3O4/BiVO4 photoanodes exhibit largely enhanced PEC water oxidation performance: the photocurrent density of the ternary photoanode reaches up to 1.84 mA cm-2 at 1.23 V vs. RHE, which is 4.60 times higher than that of the pristine BiVO4 photoanode. The IPCE value is 2.83 times higher than that of the pristine BiVO4 at 400 nm and the onset potential has a significant cathodic shift of 550 mV for the ternary well-constructed photoanode.

Diagnostic Accuracy of Contrast-Enhanced Ultrasonography in Papillary Thyroid Microcarcinoma Stratified by Size.

We explored the diagnostic accuracy of ultrasonography (US) in papillary thyroid microcarcinoma (PTMC), studying nodular growths according to size via 3-D color Doppler US (3-DCDUS) and contrast-enhanced US (CEUS). A total of 109 patients undergoing CEUS and surgery of thyroid nodules at the First Hospital of China Medical University between January 2017 and December 2018 were selected for the study, including 77 with post-operative pathologically confirmed PTMC (test group) and 32 with nodular goiter (controls). All nodules were ≤1.0 cm in maximum diameter. After 3-DCDUS, each patient underwent Thyroid Imaging Reporting and Data System (TI-RADS) grading. In both groups, receiver operating characteristic curve analysis of anteroposterior (AP) nodule diameters was conducted, establishing a cutpoint for probable malignancy by CEUS. In the test group (n = 77), grading was as follows: TI-RADS 4a, 23; TI-RADS 4b, 40; TI-RADS 4c, 14. More patients had heterogeneous enhancement or hypo-enhancement (n = 55) than uniform hyper-enhancement or uniform iso-enhancement (n = 22) by contrast-enhanced ultrasonography (CEUS). Control group (n = 32) grading was as follows: TI-RADS 3, 1; TI-RADS 4, 21; TI-RADS 4b, 10. Fewer patients had heterogeneous enhancement or hypo-enhancement (n = 12) than uniform hyper-enhancement or uniform iso-enhancement (n = 20) by CEUS. The diagnostic accuracy of 3-DCDUS or CEUS differed significantly from that of 3-DCD-US + CEUS (p < 0.05), whereas 3-DCDUS and CEUS performed similarly (p > 0.05). At AP diameters of 0.66 cm, the Youden index for diagnosing malignancy by CEUS was maximal. When nodules below this threshold were excluded, both CEUS and 3-DCDUS + CEUS improved significantly in diagnostic accuracy (p < 0.05). CEUS is useful in determining the status (benign vs. malignant) of thyroid nodules, with significantly better accuracy at AP diameters ≥0.66 cm.