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Abstract Background Recent studies suggest that tumor fusion burden (TFB) is a hallmark of immune infiltration in prostate cancer, the correlation of TFB with immune microenvironment, and genomic patterns in head and neck squamous cell carcinomas (HNSC) remain largely unclear. Methods Gene fusion, genomic, transcriptomic, and clinical data of HNSC patients from the cancer genome atlas (TCGA) database were collected to analyze the correlation of TFB with mutation patterns, tumor immune microenvironment, and survival time in HNSC patients. Results Human papillomavirus (HPV) (−) patients with low TFB exhibited significantly enhanced CD8+ T cells infiltration and cytolysis activity and increased level of interferon‐gamma (IL‐γ), human leukocyte antigen (HLA) class I, and chemokines. Moreover, TFB was positively correlated with TP53 mutation, score of gene copy number, and loss of heterozygosity (LOH), as well as the biological progress of epithelial‐mesenchymal transition (EMT), metastasis, and stem cell characteristics. Further analysis revealed that HPV (−) HNSC patients with low TFB have a better prognosis. Conclusions Our data revealed the correlation of TFB with tumor immune microenvironment and predictive features for immunotherapy, implying tumors with low TFB may be potential candidates for immunotherapeutic agents. Moreover, the TFB low group had prolonged overall survival (OS) in the HPV (−) HNSC cohort.

A thermosensitive optoelectronic upconversion device based on integrated microscale LED and photodiode structures, with temperature dependent of spectral shift and intensity change.

Ferroptosis is an iron-dependent programmed cell death characterized by reactive oxygen species-induced lipid peroxidation and resultant membrane damage. Recent research has elucidated the mechanism of ferroptosis and investigated the relationship between ferroptosis and various diseases, including degenerative diseases, cancer, and inflammation. Ferroptosis is associated with inflammation-related intestinal diseases such as colitis and colitis-associated cancer. New insights into the role of ferroptosis in the pathogenesis of inflammation-related gut diseases have suggested novel therapeutic targets. In this review, we summarize current information on the molecular mechanisms of ferroptosis and describe its emerging role and therapeutic potential in inflammation-related intestinal diseases.

Abstract Background Gastrointestinal stromal tumors rarely occur in children, but when they do, their biological behavior and histopathological patterns differ from those of adults. Case presentation A 13-year-old boy with a gastrointestinal stromal tumor was characterized by a rare genetic mutation. The patient complained of “fatigue with intermittent abdominal pain for 1 month”. According to the preoperative imaging examination, gastroscopy, and gastroscopic biopsy, the patient was diagnosed with a gastric stromal tumor. Postoperative pathology showed that the tumor cells were fusiform and ovoid, and mitotic figures were easily seen. Immunohistochemistry revealed that the tumor was S-100(+), SOX10(−), CD34(+), SMA(partially+), DOG-1(+), CD117(+), KI-67 (positive for 20% + of the subjects and 40% + of the hotspots), and SDHB(−). Genetic tests showed missense mutations in ALK and TSC1. With surgical treatment, the tumor was completely removed. The patient recovered well and was discharged on the ninth day after the operation. He is currently under follow-up. Conclusions In this case involving a patient with a gastrointestinal stromal tumor, immunohistochemistry indicated that the tumor was an "SDH-deficient type", and gene detection showed no KIT or PDGFRA mutation but rare ALK and TSC1 mutations, which adds to the knowledge of the types of gene mutations in children with gastrointestinal stromal tumors.

The thermal decomposition behavior of ammonium perchlorate (AP) directly influences the combustion performance of the composite solid propellants (CSPs). To enhance the effective thermal decomposition of AP, a highly active catalyst was prepared by entrapping Ni nanoparticles (NPs) inside three-dimensional hierarchically ordered porous carbon (3D HOPC). The obtained HOPC/Ni nanohybrid possessed interconnected porous structures, a high specific surface area (996 m2 g-1), large pore volume (1.43 cm3 g-1), and highly dispersed Ni NPs. To investigate the catalytic activity of the HOPC/Ni nanohybrid for AP thermal decomposition, an AP/HOPC/Ni nanocomposite was synthesized by homogeneously confining AP nanocrystals into the HOPC/Ni nanohybrid to form a high contact area. Because of the synergistic effect between the 3D HOPC and Ni NPs as well as the size effect of the AP nanocrystals, the HOPC/Ni nanohybrid decreased the high-temperature decomposition (HTD) peak temperature of AP by 136.1 °C and increased the heat release from 371 to 2681 J g-1, demonstrating better catalytic activity than the individual 3D HOPC and Ni NPs components. It can be foreseen that the HOPC/Ni nanohybrid may be a promising, highly active catalyst that meets the development needs of AP-based CSPs.

BackgroundDespite the effectiveness of chemotherapy and targeted therapy for colorectal cancer, drug resistance drives therapy failure and tumor relapse. Increasing evidence has suggested that cancer cells can enter a reversible drug-tolerant persister state to survive chemotherapy or targeted agents. However, the traits and treatable vulnerabilities of anti-colorectal cancer drug-tolerant persister cells is not yet known.MethodsIn this study, we established 5-fluorouracil and AZ628-tolerant persister cell models in two colorectal cancer cell lines, namely HCT116 and SW620, and revealed the characteristics of colorectal cancer persister cells by cell viability assay and flow cytometry. We investigated the efficacy and mechanism of ferroptosis inducers RSL3 and FIN56 on persister cells, which are glutathione peroxidase 4 inhibitors. In the xenograft mouse model, we further evaluated the inhibitory effect of RSL3 on tumor regrowth.ResultsColorectal cancer persister cells, which were enriched in the residual cancer cell population, exhibited reduced drug sensitivity, were largely quiescent and expressed high levels of stem cell-related genes and mesenchymal markers but not epithelial markers. The persister cells were more sensitive and underwent ferroptosis induced by glutathione peroxidase 4 inhibitors. Mechanistically, glutathione peroxidase 4 and ferrous iron, which are pivotal ferroptosis regulators, were upregulated in residual cells or tumors, and were hence potential therapeutic targets of persister cells. In the xenograft model, we confirmed that inhibition of glutathione peroxidase 4 restrained tumor regrowth after discontinuation of anti-cancer drug treatment. Moreover, biopsies obtained from patients with colorectal cancer undergoing neoadjuvant chemoradiotherapy revealed upregulated glutathione peroxidase 4 and ferritin heavy chain 1. High glutathione peroxidase 4 expression correlates with a worse prognosis in colorectal cancer patients.ConclusionsOur work reveals that the upregulated glutathione peroxidase 4 and ferrous iron in anti-colorectal cancer drug-tolerant persister cells were potential therapeutic targets. Glutathione peroxidase 4 inhibition combined with chemotherapy or targeted therapy may be a promising therapy for colorectal cancer.

BackgroundThe difficulties of early diagnosis of colorectal cancer (CRC) result in a high mortality rate. The ability to predict the response of a patient to surgical resection or chemotherapy may be of great value for clinicians when planning CRC treatments. Metabolomics is an emerging tool for biomarker discovery in cancer research. Previous reports have indicated that the metabolic profile of individuals can be significantly altered between CRC patients and healthy controls. However, metabolic changes in CRC patients at different treatment stages have not been explored.MethodsTo this end, we performed nuclear magnetic resonance (NMR)-based metabolomic analysis to determine metabolite aberrations in CRC patients before and after surgical resection or chemotherapy. In general, a total of 106 urine samples from four clinical groups, namely, healthy volunteers (n = 31), presurgery CRC patients (n = 25), postsurgery CRC patients (n = 25), and postchemotherapy CRC patients (n = 25), were collected and subjected to further analysis.ResultsIn the present study, we identified five candidate metabolites, namely, N-phenylacetylglycine, succinate, 4-hydroxyphenylacetate, acetate, and arabinose, in CRC patients compared with healthy individuals, three of which were reported for the first time. Furthermore, approximately ten metabolites were uniquely identified at each stage of CRC treatment, serving as good candidates for biomarker panel selection.ConclusionIn summary, these potential metabolite candidates may provide promising early diagnostic and monitoring approaches for CRC patients at different anticancer treatment stages.

HIF means hypoxia-inducible factor gene family, and it could regulate various biological processes, including tumor development. In 2021, the FDA approved the new drug Welireg for targeting HIF-2a, and it is mainly used to treat von Hippel-Lindau syndrome, which demonstrated its good prospects in tumor therapy. As the fourth deadliest cancer worldwide, gastric cancer endangers the health of people all across the world. Currently, there are various treatment methods for patients with gastric cancer, but the five-year survival rate of patients with advanced gastric cancer is still not high. Therefore, here we reviewed the regulatory role and target role of HIF in gastric cancer, and provided some references for the treatment of gastric cancer.

As nitric oxide (NO) plays significant roles in a variety of physiological processes, the capability for real-time and accurate detection of NO in live organisms is in great demand. Traditional assessments of NO rely on indirect colorimetric techniques or electrochemical sensors that often comprise rigid constituent materials and can hardly satisfy sensitivity and spatial resolution simultaneously. Here, we report a flexible and highly sensitive biosensor based on organic electrochemical transistors (OECTs) capable of continuous and wireless detection of NO in biological systems. By modifying the geometry of the active channel and the gate electrodes of OECTs, devices achieve optimum signal amplification of NO. The sensor exhibits a low response limit, a wide linear range, high sensitivity, and excellent selectivity, with a miniaturized active sensing region compared with a conventional electrochemical sensor. The device demonstrates continuous detection of the nanomolar range of NO in cultured cells for hours without significant signal drift. Real-time and wireless measurement of NO is accomplished for 8 d in the articular cavity of New Zealand White rabbits with anterior cruciate ligament (ACL) rupture injuries. The observed high level of NO is associated with the onset of osteoarthritis (OA) at the later stage. The proposed device platform could provide critical information for the early diagnosis of chronic diseases and timely medical intervention to optimize therapeutic efficacy. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the mechanisms underlying microRNA (miRNA)-mediated regulation of chondrogenic differentiation. Mouse embryo-derived stem cells C3H10T1/2 were cultured and chondrogenic differentiation was induced using transforming growth factor-β3 (TGF-β3). In addition, miRNA expression profiles were detected via miRNA array analysis, and quantitative polymerase chain reaction was performed to verify the differentially expressed miRNAs. Furthermore, bioinformatics software was used to predict the putative targets and the prediction was validated by dual-luciferase reporter assays and western blot analysis. In addition, cell proliferation and glycosaminoglycans were measured by a direct cell count method and alcian blue staining, respectively. Compared with the control group, 86 miRNAs were identified as differentially expressed in TGF-β3-induced cells and the expression levels of 28 miRNAs were increased while the remaining 58 miRNAs exhibited a decline in expression. Amongst the differentially expressed miRNAs, miR-30b expression was observed to have significantly decreased during chondrogenic differentiation. SOX9 is a target gene of miR-30b, and miR-30b inhibits SOX9 expression during chondrogenic differentiation. Furthermore, the alcian blue staining results demonstrated that miR-30b inhibited early chondrogenic differentiation. However, the data of the present study indicated that miR-30b had no influence on C3H10T1/2 cell line proliferation. In conclusion, miR-30b is a key negative regulator of TGF-β3-induced C3H10T1/2 cell chondrogenic differentiation, which functions by directly targeting SOX9. [ABSTRACT FROM AUTHOR]