Metabolic switch and epithelial-mesenchymal transition cooperate to regulate pluripotency.

Both metabolic switch from oxidative phosphorylation to glycolysis (OGS) and epithelial-mesenchymal transition (EMT) promote cellular reprogramming at early stages. However, their connections have not been elucidated. Here, when a chemically defined medium was used to induce early EMT during mouse reprogramming, a facilitated OGS was also observed at the same time. Additional investigations suggested that the two events formed a positive feedback loop via transcriptional activation, cooperated to upregulate epigenetic factors such as Bmi1, Ctcf, Ezh2, Kdm2b, and Wdr5, and accelerated pluripotency induction at the early stage. However, at late stages, by over-inducing glycolysis and preventing the necessary mesenchymal-epithelial transition, the two events trapped the cells at a new pluripotency state between naïve and primed states and inhibited further reprogramming toward the naïve state. In addition, the pluripotent stem cells at the new state have high similarity to epiblasts from E4.5 and E5.5 embryos, and have distinct characteristics from the previously reported epiblast-like or formative states. Therefore, the time-dependent cooperation between OGS and EMT in regulating pluripotency should extend our understanding of related fields.

NAT10 Overexpression Promotes Tumorigenesis and Epithelial-Mesenchymal Transition Through AKT Pathway in Gastric Cancer.

BACKGROUND: N-acetyltransferase 10 (NAT10), the only RNA cytosine acetyltransferase known in humans, contributes to cancer tumorigenesis and progression. This study aims to investigate the effect of NAT10 on the malignant biological properties of gastric cancer (GC) and its underlying mechanism. METHODS: The expression and prognostic significance of NAT10 in GC were analyzed using The Cancer Genome Atlas (TCGA) and Sun Yat-sen University (SYSU) cohorts. The influence of NAT10 on the malignant biological behaviors of GC was detected by Cell Counting Kit-8 (CCK-8) assay, plate colony formation assay, 5-ethynyl-2'-deoxyuridine (EdU), Transwell migration and invasion assays, scratch wound assay, flow cytometric analysis, and animal studies. The overall level of N4 acetylcytidine (ac4C) in GC was detected by liquid chromatography with tandem mass spectrometry (LC-MS/MS). The downstream signal pathways of NAT10 were analyzed by Gene Set Enrichment Analysis (GSEA) and verified by Western blot (WB) and immunofluorescence (IF). RESULTS: The significant upregulation of NAT10 expression in GC was associated with a poor prognosis. The knockdown of NAT10 markedly suppressed GC cell proliferation, migration, invasion, and cell cycle progression. Downregulating NAT10 reduced ac4C levels and inhibited AKT phosphorylation and epithelial-mesenchymal transition (EMT) in GC. CONCLUSIONS: NAT10 functions as an oncogene and may provide a new therapeutic target in GC.

Accelerated Microbial Corrosion by Magnetite and Electrically Conductive Pili through Direct Fe0 -to-Microbe Electron Transfer.

Electrobiocorrosion, the process in which microbes extract electrons from metallic iron (Fe0 ) through direct Fe0 -microbe electrical connections, is thought to contribute to the costly corrosion of iron-containing metals that impacts many industries. However, electrobiocorrosion mechanisms are poorly understood. We report here that electrically conductive pili (e-pili) and the conductive mineral magnetite play an important role in the electron transfer between Fe0 and Geobacter sulfurreducens, the first microbe in which electrobiocorrosion has been rigorously documented. Genetic modification to express poorly conductive pili substantially diminished corrosive pitting and rates of Fe0 -to-microbe electron flux. Magnetite reduced resistance to electron transfer, increasing corrosion currents and intensifying pitting. Studies with mutants suggested that the magnetite promoted electron transfer in a manner similar to the outer-surface c-type cytochrome OmcS. These findings, and the fact that magnetite is a common product of iron corrosion, suggest a potential positive feedback loop of magnetite produced during corrosion further accelerating electrobiocorrosion. The interactions of e-pili, cytochromes, and magnetite demonstrate mechanistic complexities of electrobiocorrosion, but also provide insights into detecting and possibly mitigating this economically damaging process.

The Underlying Function and Structural Organization of the Intracellular Protein Corona on Graphdiyne Oxide Nanosheet for Local Immunomodulation.

Nanomaterial-biology interaction is the critical step in the fate of biomedical nanomedicines, influencing the consequent biological outcomes. Herein, we present two-dimensional carbon-based nanomaterials-graphdiyne oxide (GDYO) nanosheets that interact with an intracellular protein corona consisting of signal transducer and activator of transcription 3 (STAT3), inducing the reeducation of immunosuppressive macrophages. The interaction at the GDYO-STAT3 interface, driven by structure matching, hydrogen bonding, and salt bridges, simultaneously triggers the immune response in the tumor microenvironment, facilitating cancer immunotherapy. For the first time, our data reveal an interaction mechanism between the nanoparticle-protein interfaces inevitably formed inside the cells that determines the macrophage phenotype. Our results suggest that GDYO nanosheets could be applied for local immunomodulation due to their function and structural organization of the intracellular protein corona occurred inside macrophages.

Graphdiyne:Structure of Fluorescent Quantum Dots.

Graphdiyne (GDY) as an emerging two-dimensional carbon allotrope exhibits excellent performance in energy chemistry, catalytic chemistry, optoelectronics, electronics, etc. because of the unique structure combining an sp- and sp2 -hybrid carbon network. However, the poor solubility of pristine GDY is a major obstacle to its applications in many fields. Proposed here is a facile strategy to control the preparation of GDY quantum dots (GDY-Py QDs), in which pyrene groups are covalently linked to GDY by using a Sonogashira cross-coupling reaction. The as-prepared GDY-Py QDs, with an average diameter of about 3±0.1 nm, show superior dispersibility in many organic solvents and water. The GDY-Py QDs display not only bright fluorescent with a high relative quantum yield (QY) of 42.82 %, but they are also well-behaved as contrast agents in cell imaging. The GDY-Py QDs are bestowed with high stability and non-cytotoxicity, and exhibit long fluorescent times, and have potential for optical imaging and biomedical applications.

Corrosion Resistance of Plasma Electrolytic Oxidation Coatings on LD7 Alloy in Oxalate and Dihydrogen Phosphate Electrolytes.

Two plasma electrolytic oxidation (PEO) coatings were fabricated on LD7 aluminum alloy in oxalate and dihydrogen phosphate electrolytes. The phase composition, morphology and corrosion resistant of the two PEO coatings were analyzed by X-ray diffraction (XRD), scanning electron microscopy (SEM) and electrochemical test. Both PEO coatings presented three-layer structure, i.e., a porous outer layer, a relative dense intermediate layer with nano-size micro-pores and an inner nanoscale barrier layer at the coating/substrate interface. It was found that the porosity of the coating in oxalate electrolyte was lower than that in dihydrogen phosphate electrolyte. The small quantity of the nanosize micro-pores might be attributed to the appearance of "soft spark" in oxalate electrolyte, whereas the large number of micro-pores and cracks should be related to intensive micro-discharges in dihydrogen phosphate electrolyte during PEO process. The compact coating with nano-size micropores in oxalate electrolyte provided better protection than that in dihydrogen phosphate electrolyte from corrosion.

Preparation of a Duplex Nanocrystalline Coating by Magnetron Sputtering and Its Oxidation Performance.

A duplex nanocrystalline coating was prepared in this study by magnetron sputtering on N5 single-crystal super alloy (Ni: Bal, Co: 7.5, Cr: 7.0, Al: 6.2, Ta: 6.5, Re: 3.0, Mo: 1.5 and W: 5.0, wt%). The novel nanocrystalline coating consists of two layers, the inner layer having the same composition with the alloy substrate for avoiding elements inter diffusion while the outer layer has 7.6 wt% higher Al to quickly ensure the formation of a protective Al2O3 layer. Both two layers were deposited within one magnetron sputtering apparatus that contained two targets. The main target was having the same alloy substrate in composition and secondary target with pure Al. The difference in Al content between the two layers was achieved by controlling the secondary target during sputtering. This study revealed a way for preparing a series of similar coatings with varying compositions and improving performance. After oxidation at 1050 °C, a protective Al2O3 layer was quickly formed on the duplex nanocrystalline coating and no TCP phases were detected in the alloy substrate.

Passive DNA demethylation preferentially up-regulates pluripotency-related genes and facilitates the generation of induced pluripotent stem cells.

A high proliferation rate has been observed to facilitate somatic cell reprogramming, but the pathways that connect proliferation and reprogramming have not been reported. DNA methyltransferase 1 (DNMT1) methylates hemimethylated CpG sites produced during S phase and maintains stable inheritance of DNA methylation. Impairing this process results in passive DNA demethylation. In this study, we show that the cell proliferation rate positively correlated with the expression of Dnmt1 in G1 phase. In addition, as determined by whole-genome bisulfate sequencing and high-performance liquid chromatography, global DNA methylation of mouse embryonic fibroblasts was significantly higher in G1 phase than in G2/M phase. Thus, we suspected that high cellular proliferation requires more Dnmt1 expression in G1 phase to prevent passive DNA demethylation. The methylation differences of individual CpG sites between G1 and G2/M phase were related to the methylation status and the positions of their surrounding CpG sites. In addition, larger methylation differences were observed on the promoters of pluripotency-related genes; for example, Oct4, Nanog, Sox2, Esrrb, Cdh1, and Epcam When such methylation differences or passive DNA demethylation accumulated with Dnmt1 suppression and proliferation acceleration, DNA methylation on pluripotency-related genes was decreased, and their expression was up-regulated, which subsequently promoted pluripotency and mesenchymal-epithelial transition, a necessary step for reprogramming. We infer that high cellular proliferation rates promote generation of induced pluripotent stem cells at least partially by inducing passive DNA demethylation and up-regulating pluripotency-related genes. Therefore, these results uncover a connection between cell reprogramming and DNA methylation.

Mesenchymal stem cells tune the development of monocyte-derived dendritic cells toward a myeloid-derived suppressive phenotype through growth-regulated oncogene chemokines.

Mesenchymal stem/stromal cells (MSCs) are promising potential candidates for the treatment of immunological diseases because of their immunosuppressive functions. However, the molecular mechanisms that mediate MSCs' immunosuppressive activity remain elusive. In this article, we report for the first time, to our knowledge, that secreted growth-regulated oncogene (GRO) chemokines, specifically GRO-γ, in human MSC-conditioned media have an effect on the differentiation and the function of human monocyte-derived dendritic cells. The monocyte-derived dendritic cells were driven toward a myeloid-derived suppressor cell (MDSC)-like phenotype by the GRO chemokines. GRO-γ-treated MDSCs had a tolerogenic phenotype that was characterized by an increase in the secretion of IL-10 and IL-4, and a reduction in the production of IL-12 and IFN-γ. We have also shown that the mRNA expression levels of the arginase-1 and inducible NO synthase genes, which characterize MDSCs, were upregulated by GRO-γ-primed mouse bone marrow cells. In addition, the ability of GRO-γ-treated bone marrow-derived dendritic cells to stimulate the OVA-specific CD8(+) T (OT-1) cell proliferation and the cytokine production of IFN-γ and TNF-α were significantly decreased in vivo. Our findings allow a greater understanding of how MDSCs can be generated and offer new perspectives to exploit the potential of MDSCs for alternative approaches to treat chronic inflammation and autoimmunity, as well as for the prevention of transplant rejection.

Harnessing active biofilm for microbial corrosion protection of carbon steel against Geobacter sulfurreducens.

Microbiologically influenced corrosion (MIC) caused by corrosive microorganisms poses significant economic losses and safety hazards. Conventional corrosion prevention methods have limitations, so it is necessary to develop the eco-friendly and long-term effective strategies to mitigate MIC. This study investigated the inhibition of Vibrio sp. EF187016 biofilm on Geobacter sulfurreducens on carbon steel. Vibrio sp. EF187016 biofilm reduced the corrosion current density and impeded pitting corrosion. A thick and uniform Vibrio sp. EF187016 biofilm formed on the coupon surfaces, acting as a protective layer against corrosive ions and electron acquisition by G. sulfurreducens. The pre-grown mature Vibrio sp. EF187016 biofilms, provided enhanced protection against G. sulfurreducens corrosion. Additionally, the extracellular polymeric substances from Vibrio sp. EF187016 was confirmed to act as a green corrosion inhibitor to mitigate microbial corrosion. This study highlights the potential of active biofilms for eco-friendly corrosion protection, offering a novel perspective on material preservation against microbial corrosion.

Combatting cyanobacteria: unraveling the potency of 316L-Cu stainless steel in inhibiting Microcystis aeruginosa growth.

Harmful algal blooms, particularly those of Microcystis aeruginosa, present significant ecological and health risks. To address this issue, this study utilized a custom static algal growth assessment apparatus to investigate the anti-algal performance of a copper-alloyed 316L stainless steel (SS), named 316L-Cu SS. This material was compared with traditional 316L SS, which is widely utilized in freshwater systems for its corrosion resistance. Algal growth dynamics were monitored through optical density (OD) and chlorophyll A concentration measurements. Notably, 316L-Cu SS exhibited superior inhibitory effects on Microcystis aeruginosa growth compared to 316L SS and control groups. Inductively coupled plasma mass spectrometry (ICP-MS) confirmed that the copper ion release from 316L-Cu SS played a critical role in this algal suppression, which interfered with photosynthesis, induced oxidative stress, and damaged algal cell membranes. In contrast, other metal ions (Ni, Cr, Fe) had a negligible impact on algal growth. The study highlights 316L-Cu SS as a promising material for mitigating harmful algal blooms, thereby offering potential benefits for both aquatic ecosystem conservation and public health protection.

Influence of Ultraviolet Light and Alternating Wet-Dry Environments on the Corrosion Behavior of Weathering Steels.

The corrosion behaviors of two bridge steels (Q345q and Q500q) under simulated ultraviolet irradiation and a wet-dry alternating (UVWD) environment were studied. Weight loss measurement, stereomicroscope observation, SEM, XRD, and electrochemical impedance spectroscopy (EIS) were performed to investigate the influence of the coupled environment. The results revealed that the corrosion rates of Q345q and Q500q were significantly accelerated by the synergistic effect of UV light exposure and alternating wet-dry conditions. Numerous voids and cracks could be observed throughout the thickened rust layers, enabling the corrosive substances to easily penetrate through the rust layer. Q500q exhibited better corrosion resistance than Q345q due to the addition of Mo, Cr, and Ni as corrosion-resistant elements, which tended to transform the rust layer into α-FeOOH rather than γ-FeOOH during later stages of corrosion.

The identification of arsenic species produced in the dissolution of crystalline orpiment under anoxic conditions: XAS evidence.

The orpiment (As2S3) is an important secondary mineral in the geochemical process of arsenic (As) in the environment. The dissolution of orpiment has a close relationship with the migration and transformation of As. The dissolved species of As2S3 is closely related to sulfide (S-II) in the anoxic and sulfidic environment. This paper focuses on the various As species formed when As2S3 dissolved in the presence and absence of excess S-II under anoxic conditions with simulation tests via X-ray absorption spectroscopy (XAS), liquid chromatography with (hydride generation) atomic fluorescence spectrophotometry, and Raman spectroscopy. The results showed that the As produced when As2S3 dissolved in the excess S-II contained a mixture of arsenite and thioarsenite (ThioAsIII). Based on the linear combination fitting, ThioAsIII is the dominant As species (88.2 %) with arsenite as the leftover component. However, the percentage of ThioAsIII decreased to 43.7 % if As2S3 dissolved in the absence of excess S-II, indicting ThioAsIII favored under sulfidic conditions. The findings may give further insights about the role and formation mechanism of ThioAsIII in the dissolution process of As2S3. ENVIRONMENTAL IMPLICATION: The dissolution of crystallization orpiment has a close relationship with the transport of As in the environment. Qualitatively and quantitatively identification of the dissolved species of As2S3 in the presence and absence of excess S-II may be helpful for a better understanding and predicting the fate of As. The formed trithioarsenite was the dominant dissolved species compared to arsenite in the sulfidic system. It has higher mobility than AsV and AsIII, and has been found in many As-related adsorption/desorption and redox reactions. Therefore, great cautions should be given when choosing technologies to remediate the As contaminated soils and waters.

The long-term transformation of FeIII-AsV coprecipitates at room temperature under oxic conditions: New insights for the fate and the speciation of As.

The long-term stability of FeIII-AsV coprecipitates, a typically hydrometallurgical or naturally produced As-bearing wastes in tailings or in other environments, is critical to evaluating the As risk caused by them. A wide pH range, different Fe/As molar ratios, reaction media, and neutralization reagents were considered in order to find the mechanisms controlling the fate of As during the 1640 days of transformation at 25 °C. The results indicated that at pH 4 and 12, As continuously released from the solid phase. The components and their proportions determined the fate of As at pH 4. However, at pH 12, crystalline calcium carbonates (CCA) formed due to the CO2 in the air and this combined with the adsorption capacity of As on the 2-line ferrihydrite controlling the fate of As. If pH changed to 8 and 10, yukonite formed after the release of As. The CCA also appeared in the presence of Ca. Therefore, these two processes controlled the fate of As at this pH range. These findings are important for understanding and predicting the transport of As under various environmental conditions. The technology chosen for As remediation in soils and As removal from waste waters will also be benefit from these results.

The Galvanic Corrosion of AM60B Coupled with DC01 in Simulated Environments with Varying Water Salinity.

The galvanic corrosion performance of AM60B coupled to DC01 was characterized in simulated environments with varying water salinity. The results showed that the coupled DC01 effectively accelerated the corrosion rate of AM60B, and the increased salt concentration had a significant effect on the deterioration process. The corrosion of AM60B mainly exhibits metal dissolution, and the formed Mg(OH)2 has weak a protective effect on the alloy substrate. Furthermore, the distributions of the corrosion potential and the corrosion current density of the AM60B/DC01 couple were simulated and intensively discussed.

Robust Chiral Metal-Organic Framework Coatings for Self-Activating and Sustainable Biofouling Mitigation.

Surface coatings are designed to mitigate pervasive biofouling herald, a new era of surface protection in complex biological environments. However, existing strategies are plagued by persistent and recurrent biofilm attachment, despite the use of bactericidal agents. Herein, a chiral metal-organic framework (MOF)-based coating with conformal microstructures to enable a new anti-biofouling mode that involves spontaneous biofilm disassembly followed by bacterial eradication is developed. A facile and universal metal-polyphenol network (MPN) is designed to robustly anchor the MOF nanoarmor of biocidal Cu2+ ions and anti-biofilm d-amino acid ligands to a variety of substrates across different material categories and surface topologies. Incorporating a diverse array of chiral amino acids endows the resultant coatings with widespread signals for biofilm dispersal, facilitating copper-catalyzed chemodynamic reactions and inherent mechano-bactericidal activities. This synergistic mechanism yields unprecedented anti-biofouling efficacy elucidated by RNA-sequencing transcriptomics analysis, enhancing broad-spectrum antibacterial activities, preventing biofilm formation, and destroying mature biofilms. Additionally, the chelation-directed amorphous/crystalline coatings can activate photoluminescent properties to inhibit the settlement of microalgae biofilms. This study provides a distinctive perspective on chirality-enhanced antimicrobial behaviors and pioneers a rational pathway toward developing next-generation anti-biofouling coatings for diverse applications.

The role of a novel secretory peptidoglycan recognition protein with antibacterial ability from the Chinese Oak Silkworm Antheraea pernyi in humoral immunity.

Peptidoglycan recognition proteins (PGRPs) are a family of pattern recognition receptors that play a critical role in the immune response of invertebrates and vertebrates. Herein, the short ApPGRP-D gene was cloned from the model lepidopteran Antheraea pernyi. Quantitative PCR (qPCR) confirmed that ApPGRP-D is an immune-related protein and that the expression of ApPGRP-D can be induced by microorganisms. ApPGRP-D is a broad-spectrum pattern recognition protein that activates the prophenoloxidase cascade activation system and promotes the agglutination of microbial cells. Likely due to its amidase activity, ApPGRP-D can inhibit the growth of E. coli and S. aureus. In addition, we demonstrated for the first time that zinc ions, as important metal coenzymes, could promote multiple functions of ApPGRP-D but not its amidase activity.

Corrosive Pseudomonas aeruginosa detection by measuring pyocyanin with a lab-on-fiber optical surface plasmon resonance biosensor in aquatic environments.

Oceanic facilities and equipment corrosion present considerable economic and safety concerns, predominantly due to microbial corrosion. Early detection of corrosive microbes is pivotal for effective monitoring and prevention. Yet, traditional detection methods often lack specificity, require extensive processing time, and yield inaccurate results. Hence, the need for an efficient real-time corrosive microbe monitoring technology is evident. Pseudomonas aeruginosa, a widely distributed microorganism in aquatic environments, utilizes its production of quinone-like compounds, specifically pyocyanin (PYO), to corrode metals. Here, we report a novel fiber optic surface plasmon resonance (SPR) sensor modified by the C-terminal of BrlR protein (BrlR-C), which is a specific receptor of PYO molecule, to detect P. aeruginosa in aquatic environments. The results showed that the sensor had a good ability to recognize PYO in the concentration range of 0-1 µg/mL, and showed excellent sensing performance in real-time monitoring the growth status of P. aeruginosa. With a strong selectivity of PYO, the sensor could clearly detect P. aeruginosa against other bacteria in seawater environment, and exhibited excellent anti-interference ability against variations in pH, temperature and pressure and other interfering substances. This study provides a useful tool for monitoring corrosive P. aeruginosa biofilm in aquatic environments, which is a first of its kind example that serves as a laboratory model for the application of fiber optic technology in real-world scenarios to monitoring biofilms in microbial corrosion and biofouling.