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Abstract N6‐methyladenosine (m6A) is the most abundant modification of RNA in eukaryotic cells. Previous studies have shown that m6A is pivotal in diverse diseases especially cancer. m6A corelates with the initiation, progression, resistance, invasion, and metastasis of cancer. However, despite these insights, a comprehensive understanding of its specific roles and mechanisms within the complex landscape of cancer is still elusive. This review begins by outlining the key regulatory proteins of m6A modification and their posttranslational modifications (PTMs), as well as the role in chromatin accessibility and transcriptional activity within cancer cells. Additionally, it highlights that m6A modifications impact cancer progression by modulating programmed cell death mechanisms and affecting the tumor microenvironment through various cancer‐associated immune cells. Furthermore, the review discusses how microorganisms can induce enduring epigenetic changes and oncogenic effect in microorganism‐associated cancers by altering m6A modifications. Last, it delves into the role of m6A modification in cancer immunotherapy, encompassing RNA therapy, immune checkpoint blockade, cytokine therapy, adoptive cell transfer therapy, and direct targeting of m6A regulators. Overall, this review clarifies the multifaceted role of m6A modification in cancer and explores targeted therapies aimed at manipulating m6A modification, aiming to advance cancer research and improve patient outcomes.

According to the latest consensus, many traditional diseases are considered metabolic diseases, such as cancer, type 2 diabetes, obesity, and cardiovascular disease. Currently, metabolic diseases are increasingly prevalent because of the ever-improving living standards and have become the leading threat to human health. Multiple therapy methods have been applied to treat these diseases, which improves the quality of life of many patients, but the overall effect is still unsatisfactory. Therefore, intensive research on the metabolic process and the pathogenesis of metabolic diseases is imperative. N6-methyladenosine (m6A) is an important modification of eukaryotic RNAs. It is a critical regulator of gene expression that is involved in different cellular functions and physiological processes. Many studies have indicated that m6A modification regulates the development of many metabolic processes and metabolic diseases. In this review, we summarized recent studies on the role of m6A modification in different metabolic processes and metabolic diseases. Additionally, we highlighted the potential m6A-targeted therapy for metabolic diseases, expecting to facilitate m6A-targeted strategies in the treatment of metabolic diseases.

M6A is essential for tumor occurrence and progression. The expression patterns of m6A regulators differ in various kinds of tumors. Transcriptomic expression statistics together with clinical data from a database were analyzed to distinguish patients with digestive tract tumors. Based on the expression patterns of diverse m6A regulators, patients were divided into several clusters. Survival analysis suggested significant differences in patient prognosis among the m6A clusters. The results showed overlapping of m6A expression patterns with energy metabolism and nucleotide metabolism. Functional analyses imply that m6A modifications in tumor cells probably drive metabolic reprogramming to sustain rapid proliferation of cancer cells. Our analysis highlights the m6A risk characterizes various kinds of metabolic features and predicts chemotherapy sensitivity in digestive tract tumors, providing evidence for m6A regulators as markers to predict patient outcomes.

How to simultaneously improve the ionic conductivity and mechanical properties is a key problem facing currently used anion-exchange membranes (AEMs). Here, biomass-based bacterial cellulose (BC) was used as a porous template to make TiO2 localized mineralization around the surface of BC nanofibers, and constructed a TiO2-coated BC porous substrate (TiO2@BC) with hierarchical structure. Then, the coated TiO2 nanoparticles was densely grafted by quaternary ammonium groups to obtain high ionic conduction ability. After filling with a polymeric ionic liquid (PIL) with high ion exchange capacity through in situ polymerization and crosslinking, the obtained novel PIL-filled AEM possessed ultrahigh ionic conductivity of 100.5 mS cm−1 at 80 °C, which was 72.1% higher than that of the PIL-filled pure BC membrane (only 58.4 mS cm−1). Moreover, by the aid of the synergistic reinforcement effect of TiO2@BC, the membrane exhibited extremely high dry strength of 95.3 MPa and satisfactory wet strength and flexibility. When at fully hydrate state, the membrane with the size of 1 × 4 cm (width × length) can hang a bottle containing 1000 g of water. The single cell equipped with this membrane output the peak power density of 40.2 mW cm−2, showing its great potential as a high-performance biomass-based AEM.

The preparation of composite proton exchange membranes (PEMs) by incorporating metal- organic frameworks (MOFs) into polymeric substrates has become a hot research topic in the field of fuel cells in recent years. In this work, ZSC was prepared by in-suit reacted with the precursor of ZIF-8 (Zeolitic Imidazolate Framework 8) and silica coated carbon nanotubes (SiO2@CNTs). The as-prepared ZSC was introduced into sulfonated poly (ether ether ketone) (SPEEK) to fabricate a series of composite proton exchange membranes SPEEK/ZSC-x (where x is the mass percentage between ZSC and SPEEK). The coating treatment of carbon nanotubes (CNTs) by silica not only can avoid the direct contacting among CNTs and enhance the dispersion in SPEEK matrix, but also realize the regulation of nucleation and crystallization process of ZIF-8 particles along the morphology of CNTs. The obtained SPEEK/ZSC composite membranes show improved performance owing to construction of interconnected network architecture and the compositional advantages of the ZSC materials. The proton conductivity of SPEEK/ZSC-0.5 membrane was up to 38.10 mS/cm at 80 °C, which was 1.8 times that of the pure SPEEK membrane (21.12 mS/cm) under the same condition. Moreover, the SPEEK/ZSC-0.5 showed better performance with peak power density of 38.9 mW/cm2 in 2 M methanol solution, which was 1.3 times that of the pure SPEEK membrane of 30.3 mW/cm2, the further stability tests confirmed that the composite film maintained good voltage stability even after 100 h of continuous operation at 80 °C. These results indicate that the strategy of construction MOFs and functional CNTs hybrid materials show promising application prospects in the preparation of high performance PEMs.

How to simultaneously improve the ionic conductivity and mechanical properties is a key problem facing currently used anion-exchange membranes (AEMs). Here, novel AEMs were prepared using quaternized bacterial cellulose (QBC) as a dual-functional substrate and then filled with a polymeric ionic liquid (poly(vinylbenzyl) trimethylammonium chloride, PVD) with high ion-exchange capacity through in situ polymerization and crosslinking. The dense quaternary ammonium groups grafted on the surface of BC nanofibers greatly increased the ionic conductivity, while the special three-dimensional network structure of BC significantly enhanced the tensile strength and chemical stability of the obtained PVD filled quaternized BC (QBC/PVD) membranes. The ionic conductivity of QBC/PVD membrane reached as high as 111 mS cm−1 at 80°C, which was 109% higher than that of the pure BC/PVD membrane (only 53 mS cm−1). Moreover, the QBC/PVD membrane exhibited extremely high dry strength of 72.3 MPa and satisfactory wet strength and flexibility, this membrane can hang a container containing 500 g of water when at fully hydrated state. The alkaline direct methanol fuel cell equipped with QBC/PVD output a peak power density of 64 mW cm−2, showing its great application potential as an AEM.

Abstract Background Gastric cancer (GC) is one of the most pernicious tumors that seriously harm human healthcare. GC metastasis is one of the prime cause of failed cancer treatment, but correlation between N6-methyladenosine (m6A) and GC metastasis was less reported. Methods Methylated RNA immunoprecipitation sequencing (MeRIP-seq) of GC tissues was conducted. Quantitative real-time PCR (qRT-PCR), western blotting and immunohistochemistry (IHC) were taken to determine the expression of ALKBH5 in GC tissues and cell lines. RNA-seq together with MeRIP-qRT-PCR was used to screen the target gene of ALKBH5. RNA pulldown, mass spectrometry and RNA immunoprecipitation (RIP) were used to search the “reader” protein of target gene. The mechanism was also validated via a tail vein injection method for lung metastasis model. Results Decreased expression of ALKBH5 was detected in GC samples, and it was correlated with clinical tumor distal metastasis and lymph node metastasis. ALKBH5 interference promoted metastasis of GC cells and this effect was closely related to the demethylase activity of ALKBH5. PKMYT1, as a downstream target of ALKBH5, promoted invasion and migration in GC. Caused by ALKBH5 knockdown or its demethylase activity mutation, upregulated expression of PKMYT1 indicated that ALKBH5 modulates expression of PKMYT1 in an m6A-dependent manner. IGF2BP3 helped stabilize the mRNA stability of PKMYT1 via its m6A modification site. Conclusions This study established an ALKBH5-PKMYT1-IGF2BP3 regulation system in metastasis, representing a new therapeutic target for GC metastasis.

Abstract With the development of blue laser endoscopy (BLE) technique, it's often used to diagnose early gastric cancer (EGC) by the morphological changes of blood vessels through BLE. However, EGC is still not obvious to identify, resulting in a high rate of missed diagnosis. Molecular imaging can show the changes in early tumors at molecular level, which provides a possibility for diagnosing EGC. Therefore, developing a probe that visually monitors blood vessels of EGC under BLE is particularly necessary. Herein, a bis‐pyrene (BP) based nanoprobe (BP‐FFVLK‐(PEG)‐RGD, M1) is designed, which can target angiogenesis and self‐assemble into fibers in situ, resulting in stable and long‐term retention in tumor. Moreover, M1 probe can emit yellow‐green fluorescence for imaging under BLE. M1 probe is confirmed to steadily remain in tumor for up to 96 hours in mice transplanted subcutaneously. In addition, the M1 probe is able to target angiogenesis for molecular imaging of isolated human gastric cancer tissue under BLE. Finally, M1 probe i.v. injected into primary gastric cancer model rabbits successfully highlighted the tumor site under BLE, which is confirmed by pathological analysis. It's the first time to develop a probe for diagnosing EGC by visualizing angiogenesis under BLE, showing great clinical significance.

Asphaltene extracted from heavy oil was oxidized by a mixture of propionic anhydride and hydrogen peroxide at a low temperature of 50 °C. Elemental analysis, infrared analysis, proton nuclear magnetic resonance analysis, and gas chromatograph/mass spectrometer analysis results indicated that oxygen addition, side chain cleavage, and condensation reactions mainly occurred in the oxidation process. The oxidation products were divided into 28% methanol solubles and 72% methanol insolubles. There were mainly fatty acids and fatty acid esters in the methanol solubles. There were also small amounts of aromatic compounds with low condensation in the methanol solubles, and the alkyl side chains were mostly short ones. The degree of aromatic ring condensation in the methanol insolubles was slightly higher than that of the pristine asphaltene. There were still some long unbroken chains in the methanol insolubles after the low-temperature reaction. The molecular dynamics simulation results show that the distribution of propionic anhydride around the asphaltene molecules can promote the oxidation of asphaltene. This low-temperature oxidation technology can be used to process asphaltenes to improve the profitability of heavy-oil-processing enterprises.

In this paper, mesoporous CuO with a novel architecture was synthesized through a conventional hydrothermal approach followed by a facile sintering procedure. HR-TEM analysis found that mesoporous CuO with an interconnected pore structure has exposed high-energy crystal planes of (002) and (200). Theoretical calculations indicated that the high-energy crystal planes have superior adsorption capacity for H+ ions, which is critical for the excellent adsorption and remarkable photocatalytic activity of the anionic dye. The adsorption capacity of CuO to methyl orange (MO) at 0.4 g/L was approximately 30% under adsorption equilibrium conditions. We propose a state-changing mechanism to analyze the synergy and mutual restraint relation among the catalyst CuO, H+ ions, dye and H2O2. According to this mechanism, the degradation rate of MO can be elevated 3.5 times only by regulating the MO ratio in three states.

Male infertility is a widespread health problem affecting approximately 6%–8% of the male population, and hypoxia may be a causative factor. In mammals, two types of hypoxia are known, including environmental and pathological hypoxia. Studies looking at the effects of hypoxia on male infertility have linked both types of hypoxia to poor sperm quality and pregnancy outcomes. Hypoxia damages testicular seminiferous tubule directly, leading to the disorder of seminiferous epithelium and shedding of spermatogenic cells. Hypoxia can also disrupt the balance between oxidative phosphorylation and glycolysis of spermatogenic cells, resulting in impaired self-renewal and differentiation of spermatogonia, and failure of meiosis. In addition, hypoxia disrupts the secretion of reproductive hormones, causing spermatogenic arrest and erectile dysfunction. The possible mechanisms involved in hypoxia on male reproductive toxicity mainly include excessive ROS mediated oxidative stress, HIF-1α mediated germ cell apoptosis and proliferation inhibition, systematic inflammation and epigenetic changes. In this review, we discuss the correlations between hypoxia and male infertility based on epidemiological, clinical and animal studies and enumerate the hypoxic factors causing male infertility in detail. Demonstration of the causal association between hypoxia and male infertility will provide more options for the treatment of male infertility

Thermally conductive and electrically insulating composites are important for the thermal management of new generation integrated and miniaturized electronic devices. A practical and eco−friendly electrostatic self−assembly method was developed to prepare boron nitride−multilayer graphene (BN−MG) hybrid nanosheets. Then, BN−MG was filled into silicone rubber (SR) to fabricate BN−MG/SR composites. Compared with MG/SR composites with the same filler loadings, BN−MG/SR composites exhibit dramatically enhanced electrical insulation properties while still maintaining excellent thermal conductivity. The BN−MG/SR with 10 wt.% filler loading shows a thermal conductivity of 0.69 W·m−1·K−1, which is 475% higher than that of SR (0.12 W·m−1·K−1) and only 9.2% lower than that of MG/SR (0.76 W·m−1·K−1). More importantly, owing to the electron blocking effect of BN, the electron transport among MG sheets is greatly decreased, thus contributing to the high−volume resistivity of 4 × 1011 Ω cm for BN−MG/SR (10 wt.%), which is fourorders higher than that of MG/SR (2 × 107 Ω·cm). The development of BN−MG/SR composites with synergetic properties of high thermal conductivity and satisfactory electrical insulation is supposed to be a promising candidate for practical application in the electronic packaging field.

High human telomerase reverse transcriptase (hTERT) expression is related to severe Colorectal Cancer (CRC) progression and negatively related to CRC patient survival. Previous studies have revealed that hTERT can reduce cancer cellular reactive oxygen species (ROS) levels and accelerate cancer progression; however, the mechanism remains poorly understood. NFE2-related factor 2 (NRF2) is a molecule that plays a significant role in regulating cellular ROS homeostasis, but whether there is a correlation between hTERT and NRF2 remains unclear. Here, we showed that hTERT increases CRC proliferation and migration by inducing NRF2 upregulation. We further found that hTERT increases NRF2 expression at both the mRNA and protein levels. Our data also revealed that hTERT primarily upregulates NRF2 by increasing NRF2 promoter activity rather than by regulating NRF2 mRNA or protein stability. Using DNA pull-down/MS analysis, we found that hTERT can recruit YBX1 to upregulate NRF2 promoter activity. We also found that hTERT/YBX1 may localize to the P2 region of the NRF2 promoter. Taken together, our results demonstrate that hTERT facilitates CRC proliferation and migration by upregulating NRF2 expression through the recruitment of the transcription factor YBX1 to activate the NRF2 promoter. These results provide a new theoretical basis for CRC treatment.

In this paper, owing to the electrostatic interaction between graphene and h-BN, a facile liquid phase exfoliation method was carried out to fabricate h-BN/graphene based van der Waals heterostructure nanocomposites without additional chemical cross-linkers. The physicochemical properties of as-prepared composites were characterized by several electron microscopic and spectroscopic measurements. The h-BN/graphene heterostructure composites were employed to use as the anodes of asymmetric supercapacitor, and exhibited exceptional capacitive performance due to their synergistic effects. It is expected that the as-prepared h-BN/graphene materials can boost scalable heterostructure electrodes in supercapacitors, and our liquid phase exfoliation method can be used for the construction of the other energy storage and electronics.

Brucella melitensis is a facultative intracellular bacterium that replicates within macrophages. The ability of brucellae to survive and multiply in the hostile environment of host macrophages is essential to its virulence. The RNA-binding protein Hfq is a global regulator that is involved in stress resistance and pathogenicity. Here we demonstrate that Hfq is essential for stress adaptation and intracellular survival in B. melitensis. A B. melitensis hfq deletion mutant exhibits reduced survival under environmental stresses and is attenuated in cultured macrophages and mice. Microarray-based transcriptome analyses revealed that 359 genes involved in numerous cellular processes were dysregulated in the hfq mutant. From these same samples the proteins were also prepared for proteomic analysis to directly identify Hfq-regulated proteins. Fifty-five proteins with significantly affected expression were identified in the hfq mutant. Our results demonstrate that Hfq regulates many genes and/or proteins involved in metabolism, virulence, and stress responses, including those potentially involved in the adaptation of Brucella to the oxidative, acid, heat stress, and antibacterial peptides encountered within the host. The dysregulation of such genes and/or proteins could contribute to the attenuated hfq mutant phenotype. These findings highlight the involvement of Hfq as a key regulator of Brucella gene expression and facilitate our understanding of the role of Hfq in environmental stress adaptation and intracellular survival of B. melitensis.

We report the photoelectrochemical (PEC) oxidation of glucose at tungsten trioxide nanoplate (WO3NP) electrode for glucose sensing application and photo fuel cell (PFC) application. The WO3-based PEC sensor shows high sensitivity of 68.15 μA cm-2 mM-1 in glucose detection for the concentrations in the range of 0.1~0.5 mMand displays good selectivity toward the interferents of ascorbic acid (AA) and uric acid (UA).Moreover, electricity can be extracted from photo-oxidizing of glucose onWO3NP electrode in a PFC device and the output strongly depends on the concentration of glucose fuel. In addition, the power performance of PFC obtained under irradiation shows 60-fold higher than that of achieved in the dark, indicating that photo-oxidation of glucose on the WO3NP anode is the essence for this fuel cell electricity generation. The work expands the application of WO3 in the field of glucose analysis and provides a possible way to detect glucose without inputting external power. [ABSTRACT FROM AUTHOR]

Chalkiness and grain shape are two important appearance traits of milled rice (Oryza sativa L.), and grain shape is generally considered to greatly affect chalkiness of endosperm. This study was conducted to validate and fine map an important multifunction region located on the long arm of rice chromosome 10, qPCG10/ qDC10, conferring grain shape and chalkiness that has not been well characterized. The quantitative trait loci validations were first performed using BC2F2 and BC2F2:3 populations derived from indica maternal line Teqing and recurrent paternal line IR24. Plants with overlapping heterozygous segments in the interval of RM3773 to RM6673 were selected from the BC4F2 population to develop nearisogenic lines for fine mapping of qPCG10/ qDC10. Using two-way ANOVA of phenotypic variance among three genotype groups in each near-isogenic line set, qPCG10/qDC10 was delimited to a 93.4-kb region flanked by RM25828 and RM3123 and showed significant effects on grain width, grain length, 1000-grain weight, percentage of chalky grain, and degree of chalkiness. We speculated that the multifunction region may harbor a novel gene causing chalkiness and grain shape. The present study will facilitate the cloning of qPCG10/qDC10 and the exploration of the molecular mechanisms underlying rice grain chalkiness. [ABSTRACT FROM AUTHOR]

Bacterial small non-coding RNAs (sRNAs) are gene expression modulators respond to environmental changes, stressful conditions, and pathogenesis. In this study, by using a combined bioinformatic and experimental approach, eight novel sRNA genes were identified in intracellular pathogen Brucella melitensis. BSR0602, one sRNA that was highly induced in stationary phase, was further examined and found to modulate the intracellular survival of B. melitensis. BSR0602 was present at very high levels in vitro under stresses similar to those encountered during infection in host macrophages. Furthermore, BSR0602 was found to be highly expressed in the spleens of infected mice, suggesting its potential role in the control of pathogenesis. BSR0602 targets the mRNAs coding for gntR, a global transcriptional regulator, which is required for B. melitensis virulence. Overexpression of BSR0602 results in distinct reduction in the gntR mRNA level. B. melitensis with high level of BSR0602 is defective in bacteria intracellular survival in macrophages and defective in growth in the spleens of infected mice. Therefore, BSR0602 may directly inhibit the expression of gntR, which then impairs Brucellae intracellular survival and contributes to Brucella infection. Our findings suggest that BSR0602 is responsible for bacterial adaptation to stress conditions and thus modulate B. melitensis intracellular survival. [ABSTRACT FROM AUTHOR]

New acid-base polymer blends based on sulfonated poly(phenylene oxide) (SPPO) as the proton-conducting component and poly(ether imide) (PEI) as the basic component were considered for use as proton-exchange membranes (PEM). The obtained blend membranes had a higher thermal stability and a higher glass transition temperature (Tg) than the pure SPPO, as revealed by TGA and DSC. The morphology of blend membranes indicated that PEI was highly compatible with SPPO polymers because of the formation of hydrogen bonds between the sulfonated acid and PEI. Although the blend membranes exhibited a lower water uptake and lower proton conductivity than the pure SPPO membrane, the PEI component improved the dimensional stability, mechanic properties, and especially inhibited methanol permeation. The methanol permeability coefficient of the blend membrane with 30 wt.% PEI content was 9.68×10-8 cm2/s, which is lower than that of the pure SPPO and just one tenth of that of Nafion® 112. This considerable reduction in methanol crossover revealed the feasibility of the blend membranes as promising electrolytes for direct methanol fuel cells. [ABSTRACT FROM AUTHOR]

A series of sulfonated poly(ether sulfone) (SPES)/silica composite membranes were prepared by sol–gel method using tetraethylorthosilicate (TEOS) hydrolysis. Physico–chemical properties of the composite membranes were characterized by thermogravimetric analysis (TGA), X‐ray diffraction (XRD), scanning electron microscope–energy dispersive X‐ray (SEM–EDX), and water uptake. Compared to a pure SPES membrane, SiO2doping in the membranes led to a higher thermal stability and water uptake. SEM–EDX indicated that SiO2particles were uniformly embedded throughout the SPES matrix. Proper silica loadings (below 5 wt %) in the composite membranes helped to inhibit methanol permeation. The permeability coefficient of the composite membrane with 5 wt % SiO2was 1.06 × 10−7cm2/s, which was lower than that of the SPES and just one tenth of that of Nafion® 112. Although proton conductivity of the composite membranes decreased with increasing silica content, the selectivity (the ratio of proton conductivity and methanol permeability) of the composite membrane with 5 wt % silica loading was higher than that of the SPES and Nafion® 112 membrane. This excellent selectivity of SPES/SiO2composite membranes could indicate a potential feasibility as a promising electrolyte for direct methanol fuel cell. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010 [ABSTRACT FROM AUTHOR]

An investigation on the effect of sulfonic group on solubility parameters and solubility behavior of poly(2,6?dimethyl?1,4?phenylene oxide) (PPO) is presented. Sulfonated PPO (SPPO) was prepared using chlorosulfonic acid as a sulfonating agent. The structure of SPPO was confirmed by FT?IR, and the ion exchange capacity (IEC) of SPPO was accurately determined by conductometric titration and 1H?NMR. The three?dimensional solubility parameters of SPPO defined by Hansen were estimated by group contribution, and this approach was used to obtain the three coordinates of a solubility parameter in terms of: a dispersion part ?d, a polar part ?p and a hydrogen bonding part ?h. The theoretical predications of solubility behavior were characterized using “soluble sphere” in three?dimensional space. The estimated results were in accordance with the solubility experiments in different solvents. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]