Abnormal changes in metabolites caused by m6A methylation modification: The leading factors that induce the formation of immunosuppressive tumor microenvironment and their promising potential for clinical application.

BACKGROUND: N6-methyladenosine (m6A) RNA methylation modifications have been widely implicated in the metabolic reprogramming of various cell types within the tumor microenvironment (TME) and are essential for meeting the demands of cellular growth and maintaining tissue homeostasis, enabling cells to adapt to the specific conditions of the TME. An increasing number of research studies have focused on the role of m6A modifications in glucose, amino acid and lipid metabolism, revealing their capacity to induce aberrant changes in metabolite levels. These changes may in turn trigger oncogenic signaling pathways, leading to substantial alterations within the TME. Notably, certain metabolites, including lactate, succinate, fumarate, 2-hydroxyglutarate (2-HG), glutamate, glutamine, methionine, S-adenosylmethionine, fatty acids and cholesterol, exhibit pronounced deviations from normal levels. These deviations not only foster tumorigenesis, proliferation and angiogenesis but also give rise to an immunosuppressive TME, thereby facilitating immune evasion by the tumor. AIM OF REVIEW: The primary objective of this review is to comprehensively discuss the regulatory role of m6A modifications in the aforementioned metabolites and their potential impact on the development of an immunosuppressive TME through metabolic alterations. KEY SCIENTIFIC CONCEPTS OF REVIEW: This review aims to elaborate on the intricate networks governed by the m6A-metabolite-TME axis and underscores its pivotal role in tumor progression. Furthermore, we delve into the potential implications of the m6A-metabolite-TME axis for the development of novel and targeted therapeutic strategies in cancer research.

Investigating autophagy and intricate cellular mechanisms in hepatocellular carcinoma: Emphasis on cell death mechanism crosstalk.

Hepatocellular carcinoma (HCC) stands as a formidable global health challenge due to its prevalence, marked by high mortality and morbidity rates. This cancer type exhibits a multifaceted etiology, prominently linked to viral infections, non-alcoholic fatty liver disease, and genomic mutations. The inherent heterogeneity of HCC, coupled with its proclivity for developing drug resistance, presents formidable obstacles to effective therapeutic interventions. Autophagy, a fundamental catabolic process, plays a pivotal role in maintaining cellular homeostasis, responding to stressors such as nutrient deprivation. In the context of HCC, tumor cells exploit autophagy, either augmenting or impeding its activity, thereby influencing tumorigenesis. This comprehensive review underscores the dualistic role of autophagy in HCC, acting as both a pro-survival and pro-death mechanism, impacting the trajectory of tumorigenesis. The anti-carcinogenic potential of autophagy is evident in its ability to enhance apoptosis and ferroptosis in HCC cells. Pertinently, dysregulated autophagy fosters drug resistance in the carcinogenic context. Both genomic and epigenetic factors can regulate autophagy in HCC progression. Recognizing the paramount importance of autophagy in HCC progression, this review introduces pharmacological compounds capable of modulating autophagy-either inducing or inhibiting it, as promising avenues in HCC therapy.

Demethylases in tumors and the tumor microenvironment: Key modifiers of N6-methyladenosine methylation.

RNA methylation modifications are widespread in eukaryotes and prokaryotes, with N6-methyladenosine (m6A) the most common among them. Demethylases, including Fat mass and obesity associated gene (FTO) and AlkB homolog 5 (ALKBH5), are important in maintaining the balance between RNA methylation and demethylation. Recent studies have clearly shown that demethylases affect the biological functions of tumors by regulating their m6A levels. However, their effects are complicated, and even opposite results have appeared in different articles. Here, we summarize the complex regulatory networks of demethylases, including the most important and common pathways, to clarify the role of demethylases in tumors. In addition, we describe the relationships between demethylases and the tumor microenvironment, and introduce their regulatory mechanisms. Finally, we discuss evaluation of demethylases for tumor diagnosis and prognosis, as well as the clinical application of demethylase inhibitors, providing a strong basis for their large-scale clinical application in the future.

Intramolecular Hydrogen Bond Improved Durability and Kinetics for Zinc-Organic Batteries.

Organic compounds have the advantages of green sustainability and high designability, but their high solubility leads to poor durability of zinc-organic batteries. Herein, a high-performance quinone-based polymer (H-PNADBQ) material is designed by introducing an intramolecular hydrogen bonding (HB) strategy. The intramolecular HB (C=O⋯N-H) is formed in the reaction of 1,4-benzoquinone and 1,5-naphthalene diamine, which efficiently reduces the H-PNADBQ solubility and enhances its charge transfer in theory. In situ ultraviolet-visible analysis further reveals the insolubility of H-PNADBQ during the electrochemical cycles, enabling high durability at different current densities. Specifically, the H-PNADBQ electrode with high loading (10 mg cm-2) performs a long cycling life at 125 mA g-1 (> 290 cycles). The H-PNADBQ also shows high rate capability (137.1 mAh g-1 at 25 A g-1) due to significantly improved kinetics inducted by intramolecular HB. This work provides an efficient approach toward insoluble organic electrode materials.

Isolated splenic metastasis from primary fallopian tube carcinoma and the application of laparoscopic splenectomy: a case report and literature review.

Metastases to the spleen from various non-hematologic malignancies are generally not a common clinical event and usually indicate the late dissemination of disease. Solitary splenic metastases from solid neoplasm are extremely uncommon. Furthermore, solitary metastasis to the spleen from primary fallopian tube carcinoma (PFTC) is extremely rare and has not been reported previously. We report a case of isolated splenic metastasis in a 60-year-old woman, occurring 13 months after a total hysterectomy, a bilateral salpingo-oophorectomy, a pelvic lymphadenectomy, a para-aortic lymphadenectomy, an omentectomy, and an appendectomy were performed for PFTC. The patient's serum tumor marker CA125 was elevated to 49.25 U/ml (N < 35.0 U/ml). An abdominal computed tomography (CT) scan revealed a 4.0 × 3.0 cm low-density lesion in the spleen that was potentially malignant, with no lymphadenectasis or distant metastasis. The patient underwent a laparoscopic exploration, and one lesion was found in the spleen. Then, a laparoscopic splenectomy (LS) confirmed a splenic metastasis from PFTC. The histopathological diagnosis showed that the splenic lesion was a high-differentiated serous carcinoma from PFTC metastasis. The patient recovered for over 1 year, with no tumor recurrence. This is the first reported case of an isolated splenic metastasis from PFTC. This case underlines the importance of serum tumor marker assessment, medical imaging examination, and history of malignancy during follow-up, and LS seems to be the optimal approach for isolated splenic metastasis from PFTC.

Study on the mechanism of NOx reduction by NH3-SCR over a ZnXCu1-XFe2O4 catalyst.

Experimental evidence shows that CuFe2O4 exhibits excellent catalytic performance in the SCR reaction. However, there is a lack of in-depth research on its specific reaction mechanism. Our study begins by computing the adsorption model of molecules like NH3 and then goes on to examine the SCR reaction mechanism of NH3 on CuFe2O4 before and after Zn doping. The results indicate that NH3 is chemically adsorbed (-1.26 eV) on the surface and has a strong interaction with the substrate. Importantly, Zn doping provides more favorable reactive sites for NH3 molecules. Subsequent investigation into the NH3 dehydrogenation and SCR reaction processes showed that incorporating Zn can greatly decrease the energy barrier of the most critical step in the reaction (0.58 eV). Additionally, the study also assesses the feasibility of the reaction of adsorbed NO with surface active O atoms to form NO2 (barrier 0.86 eV). Lastly, the sulfur resistance of the catalyst before and after doping is calculated and analyzed, and it is found that Zn doping effectively improves the sulfur resistance. Our study provides valuable theoretical guidance for the development of ferrite spinel and doping modification.

High Photocatalytic Hydrogen Production of Ag@TiO2 with Different Sizes by Simple Chemical Synthesis.

The photocatalytic enhancement of sliver-based metals compounded with semiconductor materials has been demonstrated. However, there are relatively few studies on the effect of particle size in the system on photocatalytic performance. In this paper, silver nanoparticles of two different sizes, 25 and 50 nm, were prepared by a wet chemical method and subsequently sintered to obtain a photocatalyst with a core-shell structure. The photocatalyst Ag@TiO2-50/150 prepared in this study has a hydrogen evolution rate as high as 4538.90 µmol·g-1·h-1. It is interesting to find that when the ratio of silver core size to composite size is 1:3, the hydrogen yield is almost not affected by the silver core diameter, and the hydrogen production rate is basically the same. In addition, the rate of hydrogen precipitation in air for 9 months was still more than 9 times those of previous studies. This provides a new idea for the study of the oxidation resistance and stability of photocatalysts.

Does Public Service Motivation Affect Teacher Satisfaction From the Perspective of Urban and Rural Dual Structure? Empirical Analysis Based on Estonia TALIS 2018 Data.

In recent years, basic education in Estonia has achieved balanced development despite the imbalance of structure and regional factors, and this phenomenon has made the Estonian educational system a general interest of international scholars. Based on the data from the 2018 Teacher Teaching International Survey (TALIS) database, this research divides 3,004 respondents in Estonia into rural teachers and urban teachers and explores the impact of public service motivation on teacher satisfaction from the perspective of urban-rural dual structure through the grouping and comparison of ordered regression models. The study finds that the three dimensions of public service motivations in Estonia will positively affect teacher satisfaction and that the influence coefficient of contribute to the society and the tendency to participate in education policies on teacher satisfaction is higher in rural areas than in urban areas. In addition, the satisfaction of rural teachers in Estonia will decrease with the age of teachers, and the satisfaction of male teachers will be significantly lower than the satisfaction of female teachers, while the satisfaction of urban teachers will decrease with the improvement of academic qualifications. In terms of the implications, on the one hand, Estonia's education policy attempts to solve the imbalance between the regional and teacher structure through subsidies and incentives; on the other hand, Estonia's education policy uses measures such as multidimensional evaluation, multichannel feedback, and local democratization to increase the teacher's participation as well as their satisfaction.

Effects of Valence States of Working Cations on the Electrochemical Performance of Sodium Vanadate.

Supercapacitors have received much attention as large-scale energy storage devices for high power density and ultralong cycling life. In this work, sodium vanadate Na0.76V6O15/poly(3,4-ethylenedioxythiophene) (PEDOT) nanocables with deficient bridge oxygen at the interface (denoted Vo••-PNVO) have been tailored for supercapacitors through the in situ polymerization of 3,4-ethylenedioxythiophene and studied using three different electrolytes. Experiments and theoretical calculations reveal that all Na+, Zn2+, and Al3+ ions appear as hydrates in aqueous solutions but insert into the crystal structure as Na+ ions and Zn2+-H2O and Al3+-H2O hydrates, respectively. In comparison with the Zn2+-H2O and Al3+-H2O hydrates, Na+ ions with a smaller radius diffuse more quickly in Vo••-PNVO. Thus, Vo••-PNVO delivers better charge storage capability and stability when an electrolyte with Na+ ions is used. The results strongly suggest that an electrostatic interaction is significant in determining transport properties and storage capacities, rather than hydrate radii or valence states.

Recent advances in Cu(II)/Cu(I)-MOFs based nano-platforms for developing new nano-medicines.

With increasing world population, life-span of humans and spread of viruses, myriad of diseases in human beings are becoming more and more common. Because of the interesting chemical and framework versatility and porosity of metal organic frameworks (MOFs) they find application in varied areas viz. catalysis, sensing, metal ion/gas storage, chemical separation, drug delivery, bio-imaging. This subclass of coordination polymers having interesting three-dimensional framework exhibits inordinate potential and hence may find application in treatment and cure of cancer, diabetes Alzheimer's and other diseases. The presented review focuses on the diverse mechanism of action, unique biological activity and advantages of copper-based metal organic framework (MOF) nanomaterials in medicine. Also, different methods used in the treatment of cancer and other diseases have been presented and the applications as well as efficacy of copper MOFs have been reviewed and discussed. Eventually, the current-status and potential of copper based MOFs in the field of anti-inflammatory, anti-bacterial and anti-cancer therapy as well as further investigations going on for this class of MOF-based multifunctional nanostructures in for developing new nano-medicines have been presented.

HDAC3-dependent transcriptional repression of FOXA2 regulates FTO/m6A/MYC signaling to contribute to the development of gastric cancer.

As one of the deadliest malignancies, gastric cancer (GC) is often accompanied by a low 5-year survival following initial diagnosis, which accounts for a substantial proportion of cancer-related deaths each year worldwide. Altered epigenetic modifications of cancer oncogenes and tumor suppressor genes emerge as novel mechanisms have been implicated the pathogenesis of GC. In the current study, we aim to elucidate whether histone deacetylase 3 (HDAC3) exerts oncogenic role in GC, and investigate the possible mechanism. Initially, we collected 64 paired cancerous and noncancerous tissues surgically resected from GC patients. Positive expression of HDAC3, FTO, and MYC in the tissues was measured using Immunohistochemistry. Meanwhile, GC cell line BGC-823/AGS was selected and treated with lentivirus vectors for alteration of HDAC3, FTO, or FOXA2 expressions, followed by detection on mRNA and protein levels of HDAC3, FOXA2, FTO, and MYC using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot assays. The results demonstrated that the expressions of HDAC3, FTO and MYC were upregulated, while FOXA2 expression was downregulated in GC tissues and cells. After that, the cell viability, migration, and invasion of GC cells were assessed by CCK-8 and Transwell assays, revealing that HDAC3 accelerated GC cell viability, migration and invasion by degrading FOXA2. Subsequently, the binding relationship among HDAC3, FOXA2, FTO, and MYC was assessed by assays of immunoprecipitation, dual-luciferase reporter gene, and chromatin immunoprecipitation assay. Methylation of m6A mRNA in GC cells was detected via gene-specific m6A qPCR and dot-blot assays. The transcription factor FOXA2 was found to bind to the FTO gene promoter and decreased its expression, while FTO stabilized MYC mRNA by reducing m6A methylation of MYC in GC cells. In addition, HDAC3 was observed to maintain the FTO/m6A/MYC signaling and regulated GC progression, which was also supported by in vivo animal study data of GC cell tumorigenesis in nude mice. These key observations uncover the tumor-initiating activities of HDAC3 in GC through its regulation on FOXA2-mediated FTO/m6A/MYC axis, highlighting the potential of therapeutically targeting epigenetic modifications to combat GC.

HBXIP promotes gastric cancer via METTL3-mediated MYC mRNA m6A modification.

Gastric cancer (GC) is one of the most common malignancies worldwide with limited treatment options and distinct geographical distribution even in countries such as China. Genetic alterations during its carcinogenesis need urgent elucidation. In this study, we propose an intriguing hypothesis that the hepatitis B X-interacting protein (HBXIP) may function as an oncogene in GC. We harvested 45 GC tissues and matched the paracancerous tissues. The c-myc proto-oncogene (MYC) N6-methyladenosine (m6A) mRNA methylation was detected by m6A RNA immunoprecipitation and dot-blot assays. Expressions of HBXIP, methyltransferase like 3 (METTL3) and MYC were all determined to be upregulated in both GC tissues and cells. Silencing HBXIP led to a decreased expression of METTL3, which inhibited GC cell proliferation, migration and invasion while promoting their apoptosis. Furthermore, METTL3 enhanced MYC m6A methylation and increased MYC translation, which could potentiate the proliferation, migration and invasion of GC cells. Finally, the HBXIP knockdown impeded the tumorigenicity of GC cells in vivo. Based on the findings of this study, we conclude that HBXIP plays an oncogenic role in GC via METTL3-mediated MYC mRNA m6A modification. The study offers a comprehensive understanding of HBXIP as a potential therapeutic target to limit GC progression.

In situ interfacial engineering of nickel tungsten carbide Janus structures for highly efficient overall water splitting.

Regulating chemical bonds to balance the adsorption and disassociation of water molecules on catalyst surfaces is crucial for overall water splitting in alkaline solution. Here we report a facile strategy for designing Ni2W4C-W3C Janus structures with abundant Ni-W metallic bonds on surfaces through interfacial engineering. Inserting Ni atoms into the W3C crystals in reaction progress generates a new Ni2W4C phase, making the inert W atoms in W3C be active sites in Ni2W4C for overall water splitting. The Ni2W4C-W3C/carbon nanofibers (Ni2W4C-W3C/CNFs) require overpotentials of 63 mV to reach 10 mA cm-2 for hydrogen evolution reaction (HER) and 270 mV to reach 30 mA cm-2 for oxygen evolution reaction (OER) in alkaline electrolyte, respectively. When utilized as both cathode and anode in alkaline solution for overall water splitting, cell voltages of 1.55 and 1.87 V are needed to reach 10 and 100 mA cm-2, respectively. Density functional theory (DFT) results indicate that the strong interactions between Ni and W increase the local electronic states of W atoms. The Ni2W4C provides active sites for cleaving H-OH bonds, and the W3C facilitates the combination of Hads intermediates into H2 molecules. The in situ electrochemical-Raman results demonstrate that the strong absorption ability for hydroxyl and water molecules and further demonstrate that W atoms are the real active sites.

TCF21 inhibits proliferation and chemoresistance through the AKT pathway in human gastric cancer.

In a previous study, we showed that transcription factor 21 (TCF21) is methylated and downregulated in human gastric cancer samples and serves as an independent prognostic factor. However, its biological role and potential mechanism in gastric cancer cells remain unexplored. In the current study, we examined TCF21 expression in 6 gastric cancer cell lines. The BGC-823 and SGC-7901 cell lines were selected for small interfering RNA and plasmid transfection, respectively. The results of the Cell Counting Kit-8 assay demonstrated that TCF21 inhibited gastric cancer cell proliferation. Cell cycle analysis suggested that TCF21 inhibited cell cycle progression in gastric cancer cells. The Matrigel invasion assay demonstrated that TCF21 negatively regulated invasion. The cell adhesion assay showed that TCF21 increased cell adhesion. Gastric cancer cells were treated with cisplatin to explore the role of TCF21 in chemoresistance. Cell Counting Kit-8 assay and AnnexinV/propidium iodide analyses showed that TCF21 overexpression sensitized SGC-7901 cells to cisplatin, whereas its depletion reduced sensitivity in BGC-823 cells. JC-1 staining was performed to measure the effect of TCF21 on mitochondrial potential. TCF21 downregulated mitochondrial membrane potential after treatment with cisplatin. Western blot analysis showed that TCF21 overexpression negatively regulated Bcl-xL, phosphorylated extracellular signal regulated kinase, and phosphorylated AKT expression and induced caspase 3 cleavage. LY294002, an AKT inhibitor, blocked the effect of TCF21 on Bcl-xL, caspase 3 and CDDP-induced apoptosis. Nude mice experiments demonstrated that TCF21 inhibited gastric cancer growth in vivo. In conclusion, our results suggest that TCF21 inhibits gastric cancer growth and chemoresistance possibly through the AKT signaling pathway.

Zinc finger antisense 1: A long noncoding RNA with complex roles in human cancers.

Zinc finger antisense 1 (ZFAS1), a newly identified long non-coding RNA, is a transcript antisense to the 5' end of the protein-coding gene zinc finger NFX1-type containing 1 which hosts three C/D-box small nucleolar RNAs (SNORDs) within sequential introns: Snord12, Snord12b, and Snord12c. ZFAS1 is dysregulated and acts as either an oncogene or a tumor suppressor in different human malignancies. ZFAS1 has been implicated in many aspects of carcinogenesis, including proliferation, invasion, metastasis, apoptosis, cell cycle, and drug resistance. The mechanisms underlying the effects of ZFAS1 are complex and involve multiple signaling pathways. In this review, the multiple pathological functions of ZFAS1 in diverse malignancies are systematically reviewed to elucidate the molecular basis of its biological roles and to provide new directions for future research.

X-inactive-specific transcript: A long noncoding RNA with complex roles in human cancers.

The X-inactive-specific transcript (XIST/Xist) is one of the first long non-coding RNAs discovered in mammals and plays an essential role in X chromosome inactivation. XIST is dysregulated and acts as an oncogene or a tumor suppressor in different human malignancies. XIST is implicated in many aspects of carcinogenesis including tumor initiation, invasion, metastasis, apoptosis, cell cycle, stemness, autophagy, and drug resistance. This review focuses on research progress on the roles of XIST in tumor development. The multiple pathological functions of XIST in various cancers are systematically reviewed to elucidate the molecular basis of its biological roles and to provide new directions for future research.

Clinical value of hepatitis C virus core antigen levels in monitoring acute hepatitis C spontaneous clearance or treatment-induced clearance.

BACKGROUND AND AIM: To observe the clinical value of hepatitis C virus (HCV) core antigen (HCcAg) levels in monitoring acute HCV infection in patients with spontaneous clearance (SC) or clearance induced by antiviral therapy. METHODS: Patients with iatrogenic HCV infection (n = 104) were enrolled at the Shengjing Hospital, China Medical University, between 5 February 2013 and 3 April 2013. All cases were diagnosed with acute HCV infection, enrolled within 90 days of infection, and followed for 12 to 16 weeks. Blood was collected every month. HCV RNA and HCcAg levels were detected. From week 16, patients without SC were treated with pegylated-interferon and the HCV RNA and HCcAg levels were observed monthly. Follow-up was 7.5 (5.0 to 10.4) months. The Spearman correlation analysis was performed to determine the correlation between HCV RNA and HCcAg. Logistic regression analysis was used to determine the association of baseline HCV RNA and HCcAg levels with SC. RESULTS: Ten patients (9.62%) showed SC, with a negative conversion time of 57 (14 to 143) days. During follow-up, HCV RNA and HCcAg expression levels were positively correlated for each patient (except on the sixth month), but the levels of HCV RNA and HCcAg were not associated with HCV infection SC. CONCLUSIONS: HCcAg levels could be of value for monitoring the course early HCV infection, but could not predict SC of HCV infection.

Multiple biological functions of transcription factor 21 in the development of various cancers.

Transcription factor 21 (TCF21) is a basic helix-loop-helix transcription factor that binds to DNA and regulates cell differentiation and cell fate specification through mesenchymal-epithelial transition during development. The TCF21 gene is epigenetically inactivated in many types of human cancers and exerts a wide variety of functions, including the regulation of epithelial-mesenchymal transition, invasion, metastasis, cell cycle, and autophagy. This review focuses on research progress in relation to the roles of TCF21 in tumor development. We systematically consider multiple pathological functions of TCF21 in various cancers, revealing the molecular bases of its diverse biological roles and providing new directions for future research.

NRAGE confers poor prognosis and promotes proliferation, invasion, and chemoresistance in gastric cancer.

Neurotrophin receptor-interacting melanoma antigen-encoding protein (NRAGE) is a type II melanoma-associated antigen that plays an essential role in various processes, including cell differentiation and apoptosis. NRAGE has been shown to act as a cancer-related protein, with complex and apparently contradictory functions in a variety of cancers. In the current study, we examined the expression of NRAGE protein in 169 gastric cancer samples. NRAGE upregulation was correlated with advanced TNM stage, local invasion, and poor survival. Importantly, NRAGE could serve as an independent prognostic factor in patients with gastric cancer. We also examined the expression of NRAGE protein in GES-1 normal gastric epithelial cells and in six gastric cancer cell lines. Inhibition of NRAGE expression by transfection with small interfering RNA reduced the proliferation and invasion of MGC-803 and HGC-27 cells, as demonstrated by CCK-8 and Matrigel invasion assays. NRAGE depletion also sensitized HGC-27 and MGC-803 cells to cisplatin, as shown by CCK-8 and Annexin V/propidium iodide analyses. Western blot analysis also showed that NRAGE depletion negatively regulated Bcl-2 and p-ERK and upregulated ZO-1 and p27 expression levels. In conclusion, our results suggest that NRAGE acts as a tumor promoter in gastric cancer by facilitating cancer invasion and chemoresistance, possibly through regulation of p-ERK and Bcl-2.

The application of nanoparticles in biochips.

A nanoparticle is a microscopic particle with at least one dimension less than 100 nm, which plays an important role in the area of intense scientific research. In recent years, the application of gold nanoparticles instead of fluorescence dyes and enzyme-conjugation in biochips is very common. For example, Au nanoparticles labeling method was applied in many DNA-detection methods, and a novel readout scheme for gold nanoparticle-based DNA microarrays was studied relying on "Laser-Induced Scattering around a nanoAbsorber" and nanogold electrode, and the colorimetric detection using gold label plus silver stain was also developed. The technology is a good combination of gene technology and nanotechnology. At the same time, a number of scientists from different countries have paid more attention to the application of nanoparticles in biochips and gotten some new patents for it.