Bimetal Fluorides with Adjustable Vacancy Concentration Reinforcing Ion Transport in Poly(ethylene oxide) Electrolyte.

The poor ambient ionic transport properties of poly(ethylene oxide) (PEO)-based SPEs can be greatly improved through filler introduction. Metal fluorides are effective in promoting the dissociation of lithium salts via the establishment of the Li-F bond. However, too strong Li-F interaction would impair the fast migration of lithium ions. Herein, magnesium aluminum fluoride (MAF) fillers are developed. Experimental and simulation results reveal that the Li-F bond strength could be readily altered by changing fluorine vacancy (VF) concentration in the MAF, and lithium salt anions can also be well immobilized, which realizes a balance between the dissociation degree of lithium salts and fast transport of lithium ions. Consequently, the Li symmetric cells cycle stably for more than 1400 h at 0.1 mA cm-2 with a LiF/Li3N-rich solid electrolyte interphase (SEI). The SPE exhibits a high ionic conductivity (0.5 mS cm-1) and large lithium-ion transference number (0.4), as well as high mechanical strength owing to the hydrogen bonding between MAF and PEO. The corresponding Li//LiFePO4 cells deliver a high discharge capacity of 160.1 mAh g-1 at 1 C and excellent cycling stability with 100.2 mAh g-1 retaining after 1000 cycles. The as-assembled pouch cells show excellent electrochemical stability even at rigorous conditions, demonstrating high safety and practicability.

Chitosan-Modified AgNPs Efficiently Inhibit Swine Coronavirus-Induced Host Cell Infections via Targeting the Spike Protein.

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has filled a gap in our knowledge regarding the prevention of CoVs. Swine coronavirus (CoV) is a significant pathogen that causes huge economic losses to the global swine industry. Until now, anti-CoV prevention and control have been challenging due to the rapidly generated variants. Silver nanoparticles (AgNPs) with excellent antimicrobial activity have attracted great interest for biosafety prevention and control applications. In this study, we synthesized chitosan-modified AgNPs (Chi-AgNPs) with good biocompatibility to investigate their antiviral effects on swine CoVs. In vitro assays showed that Chi-AgNPs could significantly impaired viral entry. The direct interaction between Chi-AgNPs and CoVs can destroy the viral surface spike (S) protein secondary structure associated with viral membrane fusion, which is caused by the cleavage of disulfide bonds in the S protein. Moreover, the mechanism showed that Chi-AgNPs reduced the virus-induced apoptosis of Vero cells via the ROS/p53 signaling activation pathway. Our data suggest that Chi-AgNPs can serve as a preventive strategy for CoVs infection and provide a molecular basis for the viricidal effect of Chi-AgNPs on CoVs.

Designing a Candidate Multi-Epitope Vaccine against Transmissible Gastroenteritis Virus Based on Immunoinformatic and Molecular Dynamics.

Transmissible gastroenteritis virus (TGEV) is an etiological agent of enteric disease that results in high mortality rates in piglets. The economic impact of the virus is considerable, causing significant losses to the pig industry. The development of an efficacious subunit vaccine to provide promising protection against TGEV is of the utmost importance. The viral antigen, spike glycoprotein (S), is widely regarded as one of the most effective antigenic components for vaccine research. In this study, we employed immunoinformatics and molecular dynamics approaches to develop an 'ideal' multi-epitope vaccine. Firstly, the dominant, non-toxic, highly antigenic T (Th, CTL) and B cell epitopes predicted from the TGEV S protein were artificially engineered in tandem to design candidate subunit vaccines. Molecular docking and dynamic simulation results demonstrate that it exhibits robust interactions with toll-like receptor 4 (TLR4). Of particular significance was the finding that the vaccine was capable of triggering an immune response in mammals, as evidenced by the immune simulation results. The humoral aspect is typified by elevated levels of IgG and IgM, whereas the cellular immune aspect is capable of eliciting the robust production of interleukins and cytokines (IFN-γ and IL-2). Furthermore, the adoption of E. coli expression systems for the preparation of vaccines will also result in cost savings. This study offers logical guidelines for the development of a secure and efficacious subunit vaccine against TGEV, in addition to providing a novel theoretical foundation and strategy to prevent associated CoV infections.

Pseudomonas syringae pv. actinidiae Unique Effector HopZ5 Interacts with GF14C to Trigger Plant Immunity.

The bacterial canker of kiwifruit caused by Pseudomonas syringae pv. actinidiae (Psa) is the most devastating disease threatening the global kiwifruit production. This pathogen delivers multiple effector proteins into plant cells to resist plant immune responses and facilitate their survival. Here, we focused on the unique effector HopZ5 in Psa, which previously has been reported to have virulence functions. In this study, our results showed that HopZ5 could cause macroscopic cell death and trigger a serious immune response by agroinfiltration in Nicotiana benthamiana, along with upregulated expression of immunity-related genes and significant accumulation of reactive oxygen species and callose. Subsequently, we confirmed that HopZ5 interacted with the phosphoserine-binding protein GF14C in both the nonhost plant N. benthamiana (NbGF14C) and the host plant kiwifruit (AcGF14C), and silencing of NbGF14C compromised HopZ5-mediated cell death, suggesting that GF14C plays a crucial role in the detection of HopZ5. Further studies showed that overexpression of NbGF14C both markedly reduced the infection of Sclerotinia sclerotiorum and Phytophthora capsica in N. benthamiana, and overexpression of AcGF14C significantly enhanced the resistance of kiwifruit against Psa, indicating that GF14C positively regulates plant immunity. Collectively, our results revealed that the virulence effector HopZ5 could be recognized by plants and interact with GF14C to activate plant immunity.

Sevoflurane promotes neuronal ferroptosis via upregulation of PLIN4 to modulate the hippo signaling pathway.

BACKGROUND: Sevoflurane is a widely used inhalation anesthetic associated with neuronal damage, cognitive impairment and neurodegenerative diseases, with iron overload reported to contribute to these adverse effects. However, the mechanisms of iron-dependent cell death (ferroptosis) in sevoflurane-induced neurotoxicity remain poorly understood. METHODS: The role of PLIN4, a protein associated with neurodegeneration, in sevoflurane-induced neuronal damage was investigated using cultured mouse hippocampal neurons (HT22). PLIN4 knockdown or overexpression was performed through vector transfection, and PLIN4 transcription and expression levels after sevoflurane treatment and knockdown experiments were assessed via RT-qPCR, immunostaining, and western blot to evaluate its impact on ferroptosis. Transmission electron microscopy was used to assess cellular morphology and measure Fe2+ levels. RESULTS: Sevoflurane treatment significantly increased PLIN4 expression in hippocampal neurons and induced ferroptosis. Silencing PLIN4 reduced ferroptosis and partially reversed sevoflurane's inhibition of the Hippo signaling pathway. Specifically, sevoflurane treatment led to a 2.9-fold increase in PLIN4 mRNA levels. Furthermore, higher PLIN4 levels upregulated ferroptosis in hippocampal neurons by inhibiting the Hippo pathway. CONCLUSION: Our study indicates that sevoflurane promotes ferroptosis in neurons by upregulating PLIN4 and modulating the Hippo signaling pathway. These findings provide insights into the potential development of interventions to prevent anesthesia-related cognitive impairments and neurodegeneration.

METTL1-mediated tRNA m7G methylation and translational dysfunction restricts breast cancer tumorigenesis by fueling cell cycle blockade.

BACKGROUND: RNA modifications of transfer RNAs (tRNAs) are critical for tRNA function. Growing evidence has revealed that tRNA modifications are related to various disease processes, including malignant tumors. However, the biological functions of methyltransferase-like 1 (METTL1)-regulated m7G tRNA modifications in breast cancer (BC) remain largely obscure. METHODS: The biological role of METTL1 in BC progression were examined by cellular loss- and gain-of-function tests and xenograft models both in vitro and in vivo. To investigate the change of m7G tRNA modification and mRNA translation efficiency in BC, m7G-methylated tRNA immunoprecipitation sequencing (m7G tRNA MeRIP-seq), Ribosome profiling sequencing (Ribo-seq), and polysome-associated mRNA sequencing were performed. Rescue assays were conducted to decipher the underlying molecular mechanisms. RESULTS: The tRNA m7G methyltransferase complex components METTL1 and WD repeat domain 4 (WDR4) were down-regulated in BC tissues at both the mRNA and protein levels. Functionally, METTL1 inhibited BC cell proliferation, and cell cycle progression, relying on its enzymatic activity. Mechanistically, METTL1 increased m7G levels of 19 tRNAs to modulate the translation of growth arrest and DNA damage 45 alpha (GADD45A) and retinoblastoma protein 1 (RB1) in a codon-dependent manner associated with m7G. Furthermore, in vivo experiments showed that overexpression of METTL1 enhanced the anti-tumor effectiveness of abemaciclib, a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor. CONCLUSION: Our study uncovered the crucial tumor-suppressive role of METTL1-mediated tRNA m7G modification in BC by promoting the translation of GADD45A and RB1 mRNAs, selectively blocking the G2/M phase of the cell cycle. These findings also provided a promising strategy for improving the therapeutic benefits of CDK4/6 inhibitors in the treatment of BC patients.

Unraveling the Nrf2-ARE Signaling Pathway in the DF-1 Chicken Fibroblast Cell Line: Insights into T-2 Toxin-Induced Oxidative Stress Regulation.

The T-2 toxin (T2) poses a major threat to the health and productivity of animals. The present study aimed to investigate the regulatory mechanism of Nrf2 derived from broilers against T2-induced oxidative damage. DF-1 cells, including those with normal characteristics, as well as those overexpressing or with a knockout of specific components, were exposed to a 24 h treatment of 50 nM T2. The primary objective was to evaluate the indicators associated with oxidative stress and the expression of downstream antioxidant factors regulated by the Nrf2-ARE signaling pathway, at both the mRNA and protein levels. The findings of this study demonstrated a noteworthy relationship between the up-regulation of the Nrf2 protein and a considerable reduction in the oxidative stress levels within DF-1 cells (p < 0.05). Furthermore, this up-regulation was associated with a notable increase in the mRNA and protein levels of antioxidant factors downstream of the Nrf2-ARE signaling pathway (p < 0.05). Conversely, the down-regulation of the Nrf2 protein was linked to a marked elevation in oxidative stress levels in DF-1 cells (p < 0.05). Additionally, this down-regulation resulted in a significant decrease in both the mRNA and protein expression of antioxidant factors (p < 0.05). This experiment lays a theoretical foundation for investigating the detrimental impacts of T2 on broiler chickens. It also establishes a research framework for employing the Nrf2 protein in broiler chicken production and breeding. Moreover, it introduces novel insights for the prospective management of oxidative stress-related ailments in the livestock and poultry industry.

High-fructose corn syrup aggravates colitis via microbiota dysbiosis-mediated Th17/Treg imbalance.

Dietary fructose is widely used in beverages, processed foods, and Western diets as food additives, and is closely related to the increased prevalence of multiple diseases, including inflammatory bowel disease (IBD). However, the detailed mechanism by which high fructose disrupts intestinal homeostasis remains elusive. The present study showed that high-fructose corn syrup (HFCS) administration exacerbated intestinal inflammation and deteriorated barrier integrity. Several in vivo experimental models were utilized to verify the importance of gut microbiota and immune cells in HFCS-mediated dextran sulfate sodium (DSS)-induced colitis. In addition, untargeted metabolomics analysis revealed the imbalance between primary bile acids (PBAs) and secondary bile acids (SBAs) in feces. Hence, high fructose was speculated to modulate gut microbiota community and reduced the relative abundance of Clostridium and Clostridium scindens at genus and species level respectively, followed by a decrease in SBAs, especially isoalloLCA, thereby affecting Th17/Treg cells equilibrium and promoting intestinal inflammation. These findings provide novel insights into the crosstalk between gut flora, bile acids, and mucosal immunity, and highlight potential strategies for precise treatment of IBD.

EIF4A3-mediated circ_0042881 activates the RAS pathway via miR-217/SOS1 axis to facilitate breast cancer progression.

Breast cancer (BC) is one of the most frequent cancer-related deaths in women worldwide. Studies have shown the potential impact of circRNAs in multiple human tumorigeneses. Research on the vital signaling pathways and therapeutic targets of circRNAs is indispensable. Here, we aimed to investigate the clinical implications and underlying mechanisms of circ_0042881 in BC. RT-qPCR validated circ_0042881 was notably elevated in BC tissues and plasma, and closely associated with BC clinicopathological features. Functionally, circ_0042881 significantly accelerated the proliferation, migration, and invasion of BC cells in vitro and tumor growth and metastasis in vivo. Mechanistically, circ_0042881 promoted BC progression by sponging miR-217 to relieve its inhibition effect in son of sevenless 1 (SOS1), which further activated RAS protein and initiated downstream signaling cascades, including MEK/ERK pathway and PI3K/AKT pathway. We also demonstrated that treatment of BAY-293, an inhibitor of SOS1 and RAS interaction, attenuated BC progression induced by circ_0042881 overexpression. Furthermore, Eukaryotic initiation factor 4A-III (EIF4A3) could facilitate circ_0042881 circularization. Altogether, we proposed a novel signaling network in which circ_0042881, induced by EIF4A3, influences the process of BC tumorigenesis and metastasis by miR-217/SOS1 axis.

N6-methyladenosine modification of REG1α facilitates colorectal cancer progression via ß-catenin/MYC/LDHA axis mediated glycolytic reprogramming.

Aerobic glycolysis has been considered as a hallmark of colorectal cancer (CRC). However, the potential functional regulators of glycolysis in CRC remains to be elucidated. In the current study, we found that Regenerating islet-derived protein 1-alpha (REG1α) was significantly increased in both CRC tissues and serum, and positively associated with CRC patients' lymph node metastasis, advanced tumor stage, and unfavorable prognosis. Ectopic expression of REG1α contributed to various tumorigenic properties, including cell proliferation, cell cycle, migration, invasion, and glycolysis. In contrast, REG1α deficiency in CRC cells attenuated malignant properties and glucose metabolism. Mechanically, REG1α promoted CRC proliferation and metastasis via ß-catenin/MYC axis-mediated glycolysis upregulation. Moreover, the malignant behaviors governed by REG1α could be effectively abolished by silencing of Wnt/ß-catenin/MYC axis or glycolysis process using specific inhibitors. Besides, REG1α expression was mediated by METTL3 in an m6A-dependent manner. Overall, our work defines a novel regulatory model of the METTL3/REG1α/ß-catenin/MYC axis in CRC, which indicates that REG1α could function as a novel biomarker and a potential therapeutic target for patients with CRC.

Deciphering the Hazardous Effects of AFB1 and T-2 Toxins: Unveiling Toxicity and Oxidative Stress Mechanisms in PK15 Cells and Mouse Kidneys.

In China, animal feeds are frequently contaminated with a range of mycotoxins, with Aflatoxin B1 (AFB1) and T-2 toxin (T-2) being two highly toxic mycotoxins. This study investigates the combined nephrotoxicity of AFB1 and T-2 on PK15 cells and murine renal tissues and their related oxidative stress mechanisms. PK15 cells were treated with the respective toxin concentrations for 24 h, and oxidative stress-related indicators were assessed. The results showed that the combination of AFB1 and T-2 led to more severe cellular damage and oxidative stress compared to exposure to the individual toxins (p < 0.05). In the in vivo study, pathological examination revealed that the kidney tissue of mice exposed to the combined toxins showed signs of glomerular atrophy. The contents of oxidative stress-related indicators were significantly increased in the kidney tissue (p < 0.05). These findings suggest that the combined toxins cause significant oxidative damage to mouse kidneys. The study highlights the importance of considering the combined effects of mycotoxins in animal feed, particularly AFB1 and T-2, which can lead to severe nephrotoxicity and oxidative stress in PK15 cells and mouse kidneys. The findings have important implications for animal feed safety and regulatory policy.

Dynamic Color-Switching of Hydrogel Micropillar Array under Ethanol Vapor for Optical Encryption.

Responsive structural colors from artificially engineered micro/nanostructures are critical to the development of anti-counterfeiting, optical encryption, and intelligent display. Herein, the responsive structural color of hydrogel micropillar array is demonstrated under the external stimulus of ethanol vapor. Micropillar arrays with full color are fabricated via femtosecond laser direct writing by controlling the height and diameter of the micropillars according to the FDTD simulation. Color-switching of the micropillar arrays is achieved in <1 s due to the formation of liquid film among micropillars. More importantly, the structural color blueshift of the micropillar arrays is sensitive to the micropillar diameter, instead of the micropillar height. The micropillar array with a diameter of 772 nm takes 400 ms to complete blueshift under ethanol vapor, while that with a diameter of 522 nm blueshifts at 2400 ms. Microscale patterns are realized by employing the size-dependent color-switching of designed micropillar arrays under ethanol vapor. Moreover, Morse code and directional blueshift of structural colors are realized in the micropillar arrays. The advantages of controllable color-switching of the hydrogel micropillar array would be prospective in the areas of optical encryption, dynamic display, and anti-counterfeiting.

Dual-Stimuli Cooperative Responsive Hydrogel Microactuators Via Two-Photon Lithography.

With the development of bionics as well as materials science, intelligent soft actuators have shown promising applications in many fields such as soft robotics, sensing, and remote manipulation. Microfabrication technologies have enabled the reduction of the size of responsive soft actuators to the micron level. However, it is still challenging to construct microscale actuators capable of responding to different external stimuli in complex and diverse conditions. Here, this work demonstrates a dual-stimuli cooperative responsive hydrogel microactuator by asymmetric fabrication via femtosecond laser direct writing. The dual response of the hydrogel microstructure is achieved by employing responsive hydrogel with functional monomer 2-(dimethylamino)ethyl methacrylate. Raman spectra of the hydrogel microstructures suggest that the pH and temperature response of the hydrogel is generated by the changes in tertiary amine groups and hydrogen bonds, respectively. The asymmetric hydrogel microstructures show opposite bending direction when being heated to high temperature or exposed to acid solution, and can independently accomplish the grasp of polystyrene microspheres. Moreover, this work depicts the cooperative response of the hydrogel microactuator to pH and temperature at the same time. The dual-stimuli cooperative responsive hydrogel microactuators will provide a strategy for designing and fabricating controllable microscale actuators with promising applications in microrobotics and microfluidics.

Clay-Originated Two-Dimensional Holey Silica Separator for Dendrite-Free Lithium Metal Anode.

Lithium metal anode is the ultimate choice to obtain next-generation high-energy-density lithium batteries, while the dendritic lithium growth owing to the unstable lithium anode/electrolyte interface largely limits its practical application. Separator is an important component in batteries and separator engineering is believed to be a tractable and effective way to address the above issue. Separators can play the role of ion redistributors to guide the transport of lithium ions and regulate the uniform electrodeposition of Li. The electrolyte wettability, thermal shrinkage resistance, and mechanical strength are of importance for separators. Here, clay-originated two-dimensional (2D) holey amorphous silica nanosheets (ASN) to develop a low-cost and eco-friendly inorganic separator is directly adopted. The ASN-based separator has higher porosity, better electrolyte wettability, much higher thermal resistance, larger lithium transference number, and ionic conductivity compared with commercial separator. The large amounts of holes and rich surface oxygen groups on the ASN guide the uniform distribution of lithium-ion flux. Consequently, the Li//Li cell with this separator shows stable lithium plating/stripping, and the corresponding Li//LiFePO4 , Li//LiCoO2, and Li//NCM523 full cells also show high capacity, excellent rate performance, and outstanding cycling stability, which is much superior to that using the commercial separator.

When N7-methyladenosine modification meets cancer: Emerging frontiers and promising therapeutic opportunities.

N7-methylguanosine (m7G) methylation, one of the most common RNA modifications in eukaryotes, has recently gained considerable attention. The biological functions of m7G modification in RNAs, including tRNA, rRNA, mRNA, and miRNA, remain largely unknown in human diseases. Owing to rapid advances in high-throughput technologies, increasing evidence suggests that m7G modification plays a critical role in cancer initiation and progression. As m7G modification and hallmarks of cancer are inextricably linked together, targeting m7G regulators may provide new possibilities for future cancer diagnoses and potential intervention targets. This review summarizes various detection methods for m7G modification, recent advances in m7G modification and tumor biology regarding their interplay and regulatory mechanisms. We conclude with an outlook on the future of diagnosing and treating m7G-related diseases.

Performance of 2D-shear wave elastography in autoimmune hepatitis-primary biliary cholangitis overlap syndrome.

PURPOSE: To evaluate the diagnostic values of liver stiffness (LS) measured by 2D-SWE, fibrosis index based on the four factors (FIB-4), aspartate aminotransferase to platelet ratio index (APRI), and GGT to PLT ratio (GPR) for assessing liver fibrosis and high-risk esophageal varices (EVs) in patients with autoimmune hepatitis-primary biliary cholangitis (AIH-PBC) overlap syndrome. METHODS: Data of 141 patients were retrospectively collected. Liver fibrosis was staged according to the Scheuer scoring system. The Spearman correlation coefficient was used for correlation analysis. Receiver operating characteristic (ROC) curves were plotted to evaluate the diagnostic performance. RESULTS: LS and FIB-4 were positively correlated with the fibrosis stage (r = 0.555 and 0.198, respectively). LS had significantly higher areas under the ROC curves (AUROCs) values than FIB-4 for predicting advanced fibrosis (0.818 vs. 0.567, P < 0.001), cirrhosis (0.879 vs. 0.637, P < 0.001), whereas LS and FIB-4 similarly predicted significant fibrosis (0.748 vs. 0.638, P = 0.071) and high-risk EVs (0.731 vs. 0.659, P = 0.303). The optimal cut-off values of 2D-SWE for detecting significant fibrosis, advanced fibrosis, cirrhosis, and high-risk EVs were 8.7 kPa, 12.8 kPa, 14.0 kPa, and 11.0 kPa, respectively. LS values were influenced by fibrosis stage, serum GGT, albumin, and total bilirubin levels. The overall concordance rate of the liver stiffness vs. Scheuer stages was 49.65%. CONCLUSIONS: 2D-SWE shows significantly greater diagnostic accuracy than serum fibrosis indexes for diagnosing advanced fibrosis and cirrhosis in patients with AIH-PBC overlap syndrome.

Salidroside alleviates ulcerative colitis via inhibiting macrophage pyroptosis and repairing the dysbacteriosis-associated Th17/Treg imbalance.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by flora disequilibrium and mucosal immunity disorder. Here, we report that salidroside effectively restricts experimental colitis from two aspects of intestinal macrophage pyroptosis and dysbacteriosis-derived colonic Th17/Treg imbalance. In innate immunity, the upregulated TREM1 and pyroptosis-related proteins in inflamed colons were inhibited by salidroside administration and further experiments in vitro showed that salidroside suppressed LPS/ATP-induced bone marrow-derived macrophages (BMDMs) pyroptosis evident by the decline of LDH and IL-1ß release as well as the protein level of NLRP3, caspase-1, and GSDMD p30. Moreover, the TREM1 inhibitor weakened the effect of salidroside on BMDMs pyroptosis, whereas salidroside still could downregulate TREM1 when NLRP3 was inhibited. In adaptive immunity, salidroside improved the gut microflora diversity and Th17/Treg ratio in DSS-induced mice, especially promoting the abundance of Firmicutes. Clearance of the gut flora blocked the benefit of salidroside on colonic inflammation and Th17/Treg adaptive immunity, but transplanting salidroside-treated foecal bacterium into flora-depleted wild mice reproduced the resistance of salidroside to gut inflammation. Taken together, our data demonstrated that salidroside protected experimental colitis via skewing macrophage pyroptosis and Th17/Treg balance, indicating its potential effect on UC and other immune disorders.

IGF2BP2-induced circRUNX1 facilitates the growth and metastasis of esophageal squamous cell carcinoma through miR-449b-5p/FOXP3 axis.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common digestive malignancies with relatively high morbidity and mortality. Emerging evidence suggests circular RNAs (circRNAs) play critical roles in tumor cell malignancy. However, the biological function and clinical significance of many circRNAs in ESCC remain elusive. METHODS: The expression level and clinical implication of circRUNX1 in ESCC tissues were evaluated using qRT-PCR. In vitro and in vivo functional studies were conducted to investigate the underlying biological effects of circRUNX1 on ESCC cell growth and metastasis. Moreover, bioinformatics analysis, RNA sequencing (RNA-seq), RNA immunoprecipitation (RIP) assays, dual-luciferase reporter assays, and rescue experiments were performed to explore the relationships between circRUNX1, miR-449b-5p, Forkhead box protein P3 (FOXP3), and insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). RESULTS: CircRUNX1 was found to be significantly up-regulated in ESCC tissues and associated with TNM stage and differentiation grade. Functionally, circRUNX1 promoted ESCC cell proliferation and metastasis in vitro and in vivo. CircRUNX1 enhanced FOXP3 expression by competitively sponging miR-449b-5p. Notably, both miR-449b-5p mimics and FOXP3 knockdown restored the effects of circRUNX1 overexpression on cell proliferation and metastasis. Furthermore, IGF2BP2 binding to circRUNX1 prevented its degradation. CONCLUSIONS: IGF2BP2 mediated circRUNX1 functions as an oncogenic factor to facilitate ESCC progression through the miR-449b-5p/FOXP3 axis, implying that circRUNX1 has the potential to be a promising diagnostic marker and therapeutic target for ESCC patients.

Novel insights into m6A modification of coding and non-coding RNAs in tumor biology: From molecular mechanisms to therapeutic significance.

Accumulating evidence has revealed that m6A modification, the predominant RNA modification in eukaryotes, adds a novel layer of regulation to the gene expression. Dynamic and reversible m6A modification implements sophisticated and crucial functions in RNA metabolism, including generation, splicing, stability, and translation in messenger RNAs (mRNAs) and non-coding RNAs (ncRNAs). Furthermore, m6A modification plays a determining role in producing various m6A-labeling RNA outcomes, thereby affecting several functional processes, including tumorigenesis and progression. Herein, we highlighted current advances in m6A modification and the regulatory mechanisms underlying mRNAs and ncRNAs in distinct cancer stages. Meanwhile, we also focused on the therapeutic significance of m6A regulators in clinical cancer treatment.

Current advances and future perspectives on the functional roles and clinical implications of circular RNAs in esophageal squamous cell carcinoma: more influential than expected.

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive gastrointestinal cancers with high incidence and mortality. Therefore, it is necessary to identify novel sensitive and specific biomarkers for ESCC detection and treatment. Circular RNAs (circRNAs) are a type of noncoding RNAs featured by their covalently closed circular structure. This special structure makes circRNAs more stable in mammalian cells, coupled with their great abundance and tissue specificity, suggesting circRNAs may present enormous potential to be explored as valuable prognostic and diagnostic biomarkers for tumor. Mounting studies verified the critical roles of circRNAs in regulating ESCC cells malignant behaviors. Here, we summarized the current progresses in a handful of aberrantly expressed circRNAs, and elucidated their biological function and clinical significance in ESCC, and introduced a series of databases for circRNA research. With the improved advancement in high-throughput sequencing and bioinformatics technique, new frontiers of circRNAs will pave the path for the development of precision treatment in ESCC.