A Sweet Synthesis of MXenes.

Two-dimensional transition metal carbides/nitrides (MXenes) have shown great promise in various applications. However, mass production of MXenes suffers from the excessive use of toxic fluorine-containing reagents. Herein, a new method was validated for synthesizing MXenes from five MAX ceramics. The method features a minimized (stoichiometric) dosage of F-containing reagent (NaBF4) and polyols (glycerol, erythritol, and xylitol) as the reaction solvent. Due to the sweetness of polyols and the low environmental impact, we refer to this method as a "sweet" synthesis of MXenes. An in-depth molecular dynamics simulation study, combined with experimental kinetic parameters, further revealed that the diffusion of F- in the confined interplanar space is rate-determining for the etching reaction. The expansion of interlayer spacing by polyols effectively reduces the diffusion activation energy of F- and accelerates the etching reaction.

Formation of Disordered High-Entropy-Alloy Nanoparticles for Highly Efficient Hydrogen Electrocatalysis.

Nanoparticles composed of high-entropy alloys (HEA NPs) exhibit remarkable performance in electrocatalytic processes such as hydrogen evolution and oxidations. In this study, two types of quinary HEA NPs of PtRhPdIrRu, are synthesized, featuring disordered and crystallized nanostructures, both with and without a boiling mixture. The disordered HEA NPs (d-HEA NPs) with a size of 3.5 nm is synthesized under intense boiling conditions, attributed to improved heat and mass transfer during reduction of precursors and particle growth. The disordered HEA NPs displayed an exceptionally high turnover frequency of 33.1 s-1 at an overpotential of 50 mV, surpassing commercial Pt NPs in acidic electrolytes by 5.4 times. Additionally, d-HEA NPs exhibited superior stability at a constant electrolyzing current of 50 mA cm-2 compared to commercial Pt NPs. When employed as the anodic catalyst in an H2-O2 fuel cell, d-HEA NPs demonstrated a remarkable high current power density of 15.3 kW per gram of noble metal. Consequently, these findings highlight the potential of d-HEA NPs in electrochemical applications involving hydrogen.

Kinetic-enhanced carbon fiber for rechargeable zinc-air batteries.

Metal-free catalysts are made by the elements with infinite reserve in nature and, therefore, show the potential for large-scale applications in energy devices including metal-air batteries. The construction of metal-air batteries prefers using self-supporting catalysts with favorable activity as well as fast kinetics. However, it is challenging due to the limited electropositivity of metal-free catalysts for O-O bond formation in oxygen evolution reaction (OER), scaling relationship restrictions between OER and oxygen reduction reaction, and difficulty in porosity construction on the monolith electrode surface. In this contribution, through developing a facile methodology of quenching high-temperature carbon clothes in liquid nitrogen, a self-supported carbon cloth with bifunctional active graphene skin and fast kinetics is well constructed to serve as the air cathode in metal-air batteries. Regulated oxygen species and three-dimensionally hierarchical porosity are well constructed on the carbon fiber surfaces, contributing high intrinsic activity and prominently enhanced kinetics, which leads to favorable performances in aqueous as well as flexible rechargeable zinc-air batteries. The work proposed a promising strategy in the rational design and smart synthesis of fast-kinetic monolith electrodes, which refreshes concepts and strategies of advanced material fabrication, and also bridges material science and practical energy devices.

DNA N6-methyladenine involvement and regulation of hepatocellular carcinoma development.

DNA N6-methyladenine (6 mA) is a new type of DNA methylation identified in various eukaryotic cells. However, its alteration and genomic distribution features in hepatocellular carcinoma (HCC) remain elusive. In this study, we found that N6AMT1 overexpression increased HCC cell viability, suppressed apoptosis, and enhanced migration and invasion, whereas ALKBH1 overexpression induced the opposite effects. Further, 23,779 gain-of-6 mA regions and 11,240 loss-of-6 mA regions were differentially identified in HCC tissues. The differential gain and loss of 6 mA regions were considerably enriched in intergenic regions. Moreover, 7% of the differential 6 mA modifications were associated with tumors, with 60 associated with oncogenes and 57 with tumor suppressor genes (TSGs), and 17 were common to oncogenes and TSGs. The candidate genes affected by 6 mA were filtered by gene ontology (GO) and RNA-seq. Using quantitative polymerase chain reaction (qPCR), BCL2 and PARTICL were found to be correlated with DNA 6 mA in certain HCC processes.

Defect Engineered Metal-Organic Framework with Accelerated Structural Transformation for Efficient Oxygen Evolution Reaction.

Metal-organic frameworks (MOFs) have been increasingly applied in oxygen evolution reaction (OER), and the surface of MOFs usually undergoes structural transformation to form metal oxyhydroxides to serve as catalytically active sites. However, the controllable regulation of the reconstruction process of MOFs remains as a great challenge. Here we report a defect engineering strategy to facilitate the structural transformation of MOFs to metal oxyhydroxides during OER with enhanced activity. Defective MOFs (denoted as NiFc'x Fc1-x ) with abundant unsaturated metal sites are constructed by mixing ligands of 1,1'-ferrocene dicarboxylic acid (Fc') and defective ferrocene carboxylic acid (Fc). NiFc'x Fc1-x series are more prone to be transformed to metal oxyhydroxides compared with the non-defective MOFs (NiFc'). Moreover, the as-formed metal oxyhydroxides derived from defective MOFs contain more oxygen vacancies. NiFc'Fc grown on nickel foam exhibits excellent OER catalytic activity with an overpotential of 213 mV at the current density of 100 mA cm-2 , superior to that of undefective NiFc'. Experimental results and theoretical calculations suggest that the abundant oxygen vacancies in the derived metal oxyhydroxides facilitate the adsorption of oxygen-containing intermediates on active centers, thus significantly improving the OER activity.

Main-Group Metal Single-Atomic Regulators in Dual-Metal Catalysts for Enhanced Electrochemical CO2 Reduction.

Single-atom sites can not only act as active centers, but also serve as promising catalyst regulators and/or promoters. However, in many complex reaction systems such as electrochemical CO2 reduction reaction (CO2 RR), the introduction of single-atom regulators may inevitably induce the competitive hydrogen evolution reaction (HER) and thus reduce the selectivity. Here, the authors demonstrate that introducing HER-inert main-group metal single atoms adjacent to transition-metal single atoms can modify their electronic structure to enhance the CO2 RR to CO without inducing the HER side reaction. Dual-metal Cu and In single-site atoms anchored on mesoporous nitrogen-doped carbon (denoted as Cu-In-NC) are prepared by the pyrolysis of a multimetallic metal-organic framework. Cu-In-NC shows a high faradic efficiency of 96% toward CO formation at -0.7 V versus reversible hydrogen electrode, superior to that of its monometallic single-atom counterparts. Density functional theory studies reveal that the HER-inert In sites can activate the adjacent Cu sites through electronic modifications, strengthening the binding of *COOH intermediate and thus boosting the electrochemical reduction of CO2 to CO.

Hollow Spherical Superstructure of Carbon Nanosheets for Bifunctional Oxygen Reduction and Evolution Electrocatalysis.

The pyrolysis of metal-organic frameworks (MOFs) is an ingenious way to synthesize carbon-based materials with unique morphology for various applications including electrocatalysis. In this work, we reported a facile morphology regulation strategy for the synthesis of a spherical superstructure of MOF nanosheets. The use of metal hydroxide nanosheets on Zn particles as precursors/templates allowed MOFs with general polyhedron shape to form nanosheets and assemble into a spherical superstructure in the ligand solution. Further, a hollow spherical superstructure of carbon nanosheets decorated with metal-based nanoparticles was fabricated through the pyrolysis of MOF nanosheet superstructures at 950 °C, where the substrate/template Zn particle cores were evaporated away. The obtained composites possess carbon-based superstructures with abundant mesopores and metal-based nanoparticles with rich alloy/oxide interfaces. These features endow this MOF-derived carbon-based material with outstanding bifunctional activity for oxygen reduction/evolution reactions and great performances in Zn-air batteries.

OSCC cell-secreted exosomal CMTM6 induced M2-like macrophages polarization via ERK1/2 signaling pathway.

BACKGROUND: CKLF-like MARVEL transmembrane domain-containing 6 (CMTM6) is a critical regulator of tumor immunology among various cancers. However, the role and underlying molecular mechanism of CMTM6 in oral squamous cell carcinoma (OSCC) progression remains unclear. METHODS: The expression of CMTM6, PD-L1 and CD163 in OSCC tissues were detected by immunohistochemistry on tissue microarray. The effect of CMTM6 knockdown on OSCC cells and macrophage polarization were analyzed by CCK-8 assay, apoptotic assay, would-healing assay, transwell assay and qPCR. OSCC cell derived exosomes were obtained by ultracentrifugation and the mechanistic studies were conducted by qPCR and Western Blot. 4-Nitroquinoline N-oxide (4NQO) induced OSCC mice were used for verifying the effect of CMTM6 downregulation on M2 macrophage infiltration and tumor growth. RESULTS: In OSCC samples, higher CMTM6 expression has been obviously associated with higher pathological stage of OSCC patients, CD163 + macrophages infiltration and PD-L1 expression. CMTM6 knockdown of OSCC cells inhibited proliferative, migrative and invasive abilities of OSCC cells, as well as inhibited M2 macrophage polarization in vitro with downregulating PD-L1 expression. Importantly, exosomes from OSCC cells shuttled CMTM6 to macrophages and promoted M2-like macrophage polarization through activating ERK1/2 signaling. In addition, in 4NQO-induced OSCC mice, CMTM6 level was positively associated with CD163, CD206 and PD-L1 as well as M2-like macrophage infiltration. CONCLUSION: OSCC cell-secreted exosomal CMTM6 induces M2-like macrophages polarization to promote malignant progression via ERK1/2 signaling pathway, revealing a novel crosstalk between cancer cells and immune cells in OSCC microenvironment.

MOF-derived electrocatalysts for oxygen reduction, oxygen evolution and hydrogen evolution reactions.

Oxygen reduction reaction (ORR), oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) are three key reactions for the development of green and sustainable energy systems. Efficient electrocatalysts for these reactions are highly desired to lower their overpotentials and promote practical applications of related energy devices. Metal-organic frameworks (MOFs) have recently emerged as precursors to fabricate carbon-based electrocatalysts with high electrical conductivity and uniformly distributed active sites. In this review, the current progress of MOF-derived carbon-based materials for ORR/OER/HER electrocatalysis is presented. Materials design strategies of MOF-derived carbon-based materials are firstly summarized to show the rich possibilities of the morphology and composition of MOF-derived carbon-based materials. A wide range of applications based on these materials for ORR, OER, HER and multifunctional electrocatalysis are discussed, with an emphasis on the required features of MOF-derived carbon-based materials for the electrocatalysis of corresponding reactions. Finally, perspectives on the development of MOF-derived carbon-based materials for ORR, OER and HER electrocatalysis are provided.

High-Power Microbial Fuel Cells Based on a Carbon-Carbon Composite Air Cathode.

Microbial fuel cells (MFCs) can convert organics in wastewater directly to electricity, and improving oxygen reduction reaction (ORR) performance is critical to their development and future applications. Electrocatalytic ORR performance is determined by the intrinsic activity and accessible amounts of active sites. A surface nitrogen-enriched carbon coaxial nanocable (NCCN) is applied as an ORR electrocatalyst and combined with activated carbon (AC) with 80 wt% addition as a carbon-carbon composite air cathode in MFCs. The fully exposed nitrogen active sites of NCCN contribute to the enhanced ORR activity, while the graphitized core affords a rapid pathway for electron transportation. AC serves as a spacer to construct a porous framework with interconnected ion diffusion channels. This cathode thus exhibits a maximum power density of 2090 mW m-2 , 120% higher than commercial Pt/C electrocatalysts, and also 6% higher than the pure NCCN, indicating a synergistic effect between NCCN and AC. A high-performance NCCN-AC air cathode with a great promise for future MFC applications is reported and an effective strategy to bridge the electrocatalytic performance from nanomaterials to practical devices is presented.

Who is who in oral cancer?

Great attention has been attached to explore the association between oral bacteria and oral cancer. Recently, four common inhabitants of oral cavity, Porphyromonas gingivalis, Fusobacterium nucleatum, Treponema denticola and Streptococcus anginosus, have been identified as potential etiologic bacterial agents for oral carcinogenesis. They might promote the oncogenesis and progression of oral cancer by induction of chronic inflammation, enhancement of migration and invasiveness, inhibition of cell apoptosis, augment of cell proliferation, suppression of immune system and production of carcinogenic substances. Thus, this review will focus on the possible mechanisms of these oral bacteria contributing to occurrence and development of oral cancer, and the potential clinical implications of utilizing oral bacteria on the diagnosis, prevention and treatment of oral cancer will be discussed.

EZH2 promotes invasion and tumour glycolysis by regulating STAT3 and FoxO1 signalling in human OSCC cells.

The enhancer of zeste homolog 2 (EZH2), known as a member of the polycomb group (PcG) proteins, is an oncogene overexpressed in a variety of human cancers. Here, we found that EZH2 correlated with poor survival of oral squamous cell carcinoma (OSCC) patients using immunohistochemistry staining. EZH2 overexpression led to a significant induction in tumour glycolysis, Epithelial-mesenchymal transition (EMT), migration and invasion of OSCC cells. Conversely, silencing of EZH2 inhibited tumour glycolysis, EMT, migration and invasion in OSCC cells. Ectopic overexpression of EZH2 increased phosphorylation of STAT3 at pY705 and decreased FoxO1 expression, and FoxO1 expression was enhanced when inhibiting STAT3. In addition, EZH2 overexpression led to a significant decrease in FoxO1 mRNA levels in nude mice xenograft. These results indicated that regulation of EZH2 might have the potential to be targeted for OSCC treatment.

MIF promotes perineural invasion through EMT in salivary adenoid cystic carcinoma.

Macrophage migration inhibitory factor (MIF) is a prominent orchestrator during the onset and progression of cancer. Recently, MIF was detected in salivary adenoid cystic carcinoma (SACC). However, its functional effect in perineural invasion (PNI) of SACC remained unknown. To illuminate the effect of MIF in genesis of PNI in SACC, we examined the expression of MIF, epithelial-to-mesenchymal transition (EMT)-related markers, and Schwann cell markers by immunohistochemical analysis in 158 cases of SACC samples. Meanwhile, the correlation between MIF and PNI of SACC species was analyzed. Our data indicated that MIF expression was associated with PNI of SACC significantly. In vitro, the silence and overexpression experiments of MIF were performed in SACC cell lines. The ability of migration, invasion and PNI could be inhibited significantly by siRNA-mediated MIF silence, and the occurrence of EMT and Schwann-like cell differentiation was also inhibited by MIF silence in SACC-LM cells. Overexpression of MIF in SACC-83 cells using expressive plasmid showed the opposite effects. Our findings identified that an association between PNI and MIF expression existed. MIF may promote PNI of SACC by participating in cytoskeletal reorganization and pseudo foot formation induced by EMT and the Schwann-like cell differentiation of SACC cells.

Multiscale Principles To Boost Reactivity in Gas-Involving Energy Electrocatalysis.

Various gas-involving energy electrocatalysis, including oxygen reduction reaction (ORR), oxygen evolution reaction (OER), and hydrogen evolution reaction (HER), has witnessed increasing concerns recently for the sake of clean, renewable, and efficient energy technologies. However, these heterogeneous reactions exhibit sluggish kinetics due to multistep electron transfer and only occur at triple-phase boundary regions. Up to now, tremendous attention has been attracted to develop cost-effective and high-performance electrocatalysts to boost the electrocatalytic activities as promising alternatives to noble metal counterparts. In addition to the prolific achievements in materials science, the advances in interface chemistry are also very critical in consideration of the complex phenomena proceeded at triple-phase boundary regions, such as mass diffusion, electron transfer, and surface reaction. Therefore, insightful principles and effective strategies for a comprehensive optimization, ranging from active sites to electrochemical interface, are necessary to fully enhance the electrocatalytic performance aiming at practical device applications. In this Account, we give an overview of our recent attempts toward efficient gas-involving electrocatalysis with multiscale principles from the respect of electronic structure, hierarchical morphology, and electrode interface step by step. It is widely accepted that the intrinsic activity of individual active sites is directly influenced by their electronic structure. Heteroatom doping and topological defects are demonstrated to be the most effective strategies for metal-free nanocarbon materials, while the cationic (e.g., Ni, Fe, Co, Sn) and anionic (e.g., O, S, OH) regulation is revealed to be a promising method for transition metal compounds, to alter the electronic structure and generate high activity. Additionally, the apparent activity of the whole electrocatalyst is significantly impacted by its hierarchical morphology. The active sites of nanocarbon materials are expected to be enriched on the surface for a full exposure and utilization; the hybridization of other active components with nanocarbon materials should achieve a uniform dispersion in nanoscale and a strongly coupled interface, thereby ensuring the electron transfer and boosting the activity. Furthermore, steady and favorable electrochemical interfaces are strongly anticipated in working electrodes for optimal reaction conditions. The powdery electrocatalysts are suggested to be constructed into self-supported electrodes for more efficient and stable catalysis integrally, while the local microenvironment can be versatilely modified by ionic liquids with more beneficial gas solubility and hydrophobicity. Collectively, with the all-round regulation of the electronic structure, hierarchical morphology, and electrode interface, the electrocatalytic performances are demonstrated to be comprehensively facilitated. Such multiscale principles stemmed from the in-depth insights on the structure-activity relationship and heterogeneous reaction characteristics will no doubt pave the way for the future development of gas-involving energy electrocatalysis, and also afford constructive inspirations in a broad range of research including CO2 reduction reaction, hydrogen peroxide production, nitrogen reduction reaction, and other important electrocatalytic activation of small molecules.

NR2F1 contributes to cancer cell dormancy, invasion and metastasis of salivary adenoid cystic carcinoma by activating CXCL12/CXCR4 pathway.

BACKGROUND: Salivary adenoid cystic carcinoma (SACC) can recur after removal of the primary tumor and treatment, where they can keep no clinical symptoms and dormant state for 10-15 years. NR2F1 has been demonstrated to regulate the tumor cell dormancy in various malignant tumors and has a potential impact on recurrence and metastasis of carcinoma. However, the role and significance of NR2F1 in SACC dormancy still remain unknown. METHODS: A total number of 59 patients with a diagnosis of SACC were included to detected expression of NR2F1, Ki-67 by immunohistochemical (IHC) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick and labeling (TUNEL). Fisher's exact test was used to examine the NR2F1 expression and clinicopathologic parameters of SACC. In vitro, SACC cell lines were transfected NR2F1 and knockdown NR2F1 respectively. CCK-8, flow cytometry, wound healing assay and transwell invasion determined SACC cell proliferation, apoptosis, cell cycle, migration and invasion respectively. Chromatin immunoprecipitation (ChIP) assays were utilized to demonstrate the potential role of NR2F1 in SACC invasion via CXCL12/CXCR4 axis. In vivo, xenografts of nude mice via subcutaneous injection or tail vein injection were used to testify the results in vitro. RESULTS: Among the 59 patients with SACC, 23.73% (14/59) were positive to NR2F1 expression, a lower rate of expression compared with 60% (6/10) in normal salivary gland samples. NR2F1 was correlated with metastasis, relapse and dormancy of SACC. SACC cells with transfected NR2F1 remained dormant, as well as enhanced invasion and metastasis. Knockdown of NR2F1 via siRNA after NR2F1 overexpression restored the proliferation and the cell number in G2/M phases, and reduced the abilities of migration and invasion. In addition, NR2F1 promoted the expression of CXCL12 and CXCR4, and overexpression of CXCL12 at least partly rescued the proliferation, migration, and invasion activities induced by NR2F1 silencing. CONCLUSIONS: NR2F1 may be an underlying mechanism of SACC recurrence and metastasis via regulating tumor cell dormancy through CXCL12/CXCR4 pathway.

Cancer-associated fibroblasts-derived CXCL1 activates DEC2-mediated dormancy in oral squamous cell carcinoma.

Cancer-associated fibroblasts (CAFs) are known to play an important role in cancer progression, but their effects on tumor cell dormancy and the underlying mechanisms remain to be explored. Here, we aimed to dissect the intercellular communication between CAFs and oral squamous cell carcinoma (OSCC) cells under cellular dormancy. In this study, we investigated 61 OSCC patients and found that low expression of Differentiated Embryonic Chondrocyte gene 2 (DEC2) was closely associated with tumor recurrence, cisplatin chemotherapy administration, and infiltration of CAFs. Overexpression of DEC2 promoted the invasion and migration ability of OSCC cells but inhibited their proliferation and glucose metabolism, and characterized them as dormant and cisplatin-resistant cells. C-X-C motif ligand 1 (CXCL1) from CAFs was found to down-regulate DEC2 expression in OSCC cells, ultimately awakening dormant cells and leading to tumor recurrence, which was validated in vitro and in vivo. In conclusion, CAFs-derived CXCL1 downregulated DEC2 and "interrupted" DEC2-mediated OSCC cell dormancy, which may be a mechanism by which CAFs modulate OSCC cell dormancy and contribute to the development of new therapies for OSCC.

A Janus heteroatom-doped carbon electrocatalyst for hydrazine oxidation.

The trade-off between the intrinsic activity and electronic conductivity of carbon materials is a major barrier for electrocatalysis. We report a Janus-type carbon material combining electrically conductive nitrogen-doped carbon (NC) and catalytically active boron, nitrogen co-doped carbon (BNC). The integration of NC with BNC can not only ensure high electronic conductivity of the hybrid, but also achieve an enhancement in the intrinsic activity of the BNC side due to the electron redistribution on their coupling interfaces. In the electrocatalytic hydrazine oxidation reaction (HzOR), the Janus carbon electrocatalyst exhibits superior activity than their single counterparts and simple physical mixtures. Density functional theory calculations reveal that the NC/BNC interfaces simultaneously promote efficient electron transport and decrease the free energy of the rate-determining step in the HzOR process.

Hypermethylation of PRKCZ Regulated by E6 Inhibits Invasion and EMT via Cdc42 in HPV-Related Head and Neck Squamous Cell Carcinoma.

PURPOSE: To study the role of target genes with aberrant DNA methylation in HPV+ HNSCC. METHODS: A HumanMethylation450 BeadChip array (Illumina) was used to identify differentially methylated genes. CCK-8, flow cytometry, wound healing, and cell invasion assays were conducted to analyze the biological roles of PRKCZ. Western blot, qRT-PCR, immunohistochemistry, and animal studies were performed to explore the mechanisms underlying the functions of PRKCZ. RESULTS: We selected PRKCZ, which is associated with HPV infection, as our target gene. PRKCZ was hypermethylated in HPV+ HNSCC patients, and PRKCZ methylation status was negatively related to the pathological grading of HNSCC patients. Silencing PRKCZ inhibited the malignant capacity of HPV+ HNSCC cells. Mechanistically, HPV might promote DNMT1 expression via E6 to increase PRKCZ methylation. Cdc42 was required for the PRKCZ-mediated mechanism of action, contributing to the occurrence of epithelial-mesenchymal transition (EMT) in HPV+ HNSCC cells. In addition, blocking PRKCZ delayed tumor growth in HPV16-E6/E7 transgenic mice. Cdc42 expression was decreased, whereas E-cadherin levels increased. CONCLUSION: We suggest that PRKCZ hypermethylation induces EMT via Cdc42 to act as a potent tumor promoter in HPV+ HNSCC.

A Gas-Steamed MOF Route to P-Doped Open Carbon Cages with Enhanced Zn-Ion Energy Storage Capability and Ultrastability.

Carbon micro/nanocages have received great attention, especially in electrochemical energy-storage systems. Herein, as a proof-of-concept, a solid-state gas-steamed metal-organic-framework approach is designed to fabricate carbon cages with controlled openings on walls, and N, P dopants. Taking advantage of the fabricated carbon cages with large openings on their walls for enhanced kinetics of mass transport and N, P dopants within the carbon matrix for favoring chemical adsorption of Zn ions, when used as carbon cathodes for advanced aqueous Zn-ion hybrid supercapacitors (ZHSCs), such open carbon cages (OCCs) display a wide operation voltage of 2.0 V and an enhanced capacity of 225 mAh g-1 at 0.1 A g-1 . Also, they exhibit an ultralong cycling lifespan of up to 300 000 cycles with 96.5% capacity retention. Particularly, such OCCs as electrode materials lead to a soft-pack ZHSC device, delivering a high energy density of 97 Wh kg-1 and a superb power density of 6.5 kW kg-1 . Further, the device can operate in a wide temperature range from -25 to + 40 °C, covering the temperatures for practical applications in daily life.