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Electrocatalytic oxygen reduction reaction (ORR) via two-electron pathway is a promising approach to decentralized and on-site hydrogen peroxide (H2O2) production beyond the traditional anthraquinone process. In recent years, electrochemical H2O2 production in acidic media has attracted increasing attention owing to its stronger oxidizing capacity, superior stability, and higher compatibility with various applications. Here, recent advances of H2O2 electrosynthesis in acidic media are summarized. Specifically, fundamental aspects of two-electron ORR mechanism are firstly presented with an emphasis on the pH effect on catalytic performance. Major categories of promising electrocatalysts are then reviewed, including noble-metal-based materials, non-noble-metal single-atom catalysts, non-noble-metal compounds, and metal-free carbon-based materials. The innovative development of electrochemical devices and in situ/on-site application of electrogenerated H2O2 are also highlighted to bridge the gap between laboratory-scale fundamental research and practically relevant H2O2 electrosynthesis. Finally, critical perspectives on present challenges and promising opportunities for future research are provided.

Two-dimensional (2D) carbon nanostructures play a critical role in energy-related applications, but developing facile and efficient strategies to synthesize these kinds of nanostructures is extreme...

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.

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.

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.

The demand for efficient and environmentally-benign electrocatalysts that help availably harness the renewable energy resources is growing rapidly. In recent years, increasing insights into the design of water electrolysers, fuel cells, and metal–air batteries emerge in response to the need for developing sustainable energy carriers, in which the oxygen evolution reaction and the oxygen reduction reaction play key roles. However, both reactions suffer from sluggish kinetics that restricts the reactivity. Therefore, it is vital to probe into the structure of the catalysts to exploit high-performance bifunctional oxygen electrocatalysts. Spinel-type catalysts are a class of materials with advantages of versatility, low toxicity, low expense, high abundance, flexible ion arrangement, and multivalence structure. In this review, we afford a basic overview of spinel-type materials and then introduce the relevant theoretical principles for electrocatalytic activity, following that we shed light on the structure–property relationship strategies for spinel-type catalysts including electronic structure, microstructure, phase and composition regulation, and coupling with electrically conductive supports. We elaborate the relationship between structure and property, in order to provide some insights into the design of spinel-type bifunctional oxygen electrocatalysts.

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 CO

With the increased energy demand, developing renewable and clean energy technologies becomes more and more significant to mitigate climate warming and alleviate the environmental pollution. The key point is design and synthesis of low cost and efficient materials for a wide variety of electrochemical reactions. Over the past ten years, two-dimensional(2D) nanomaterials that graphene represents have been paid much attention as a class of the most promising candidates for heterogeneous electrocatalysts in electrochemical storage and conversion. Their unique properties, such as good chemical stability, good flexibility, and good electronic properties, along with their nano-sized thickness and large specific area, make them exhibit comprehensively good performances for energy storage and conversion. Here, we present an overview on the recent advances in electrochemical applications of graphene, graphdiyne, transition metal dichalcogenides(TMDs), and MXenes for supercapacitors(SCs), oxygen reduction reaction (ORR), and hydrogen evolution reaction(HER).

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.

Single/dual-atom and cluster metal catalysts, with much higher atom-utilization efficiency, remarkable performance, good recyclability and unique properties, have emerged as a new frontier in energy-related catalysis. In recent years, metal–organic frameworks (MOFs) have demonstrated great potential for the targeted creation of single/dual-atom and cluster catalysts, featuring the distinctive advantages of high metal loadings, porous structures and tailorable catalytic sites. In this review, we discuss the key roles and the critical issues of single/dual-atom and cluster catalysts, and the great opportunities furnished by MOFs for the construction strategy. The accessible characterization techniques for single/dual-atom and cluster catalysts will be showcased. Furthermore, we highlight recent advances in the construction and energy applications of MOF-based single/dual-atom and cluster catalysts by taking advantage of structural features of MOFs. Current issues, promising ideas and future prospects for MOF-based single/dual-atom and cluster catalysts are given.

Bimetallic metal–organic frameworks (MOFs) have two different metal ions in the inorganic nodes. According to the metal distribution, the architecture of bimetallic MOFs can be classified into two main categories namely solid solution and core–shell structures. Various strategies have been developed to prepare bimetallic MOFs with controlled compositions and structures. Bimetallic MOFs show a synergistic effect and enhanced properties compared to their monometallic counterparts and have found many applications in the fields of gas adsorption, catalysis, energy storage and conversion, and luminescence sensing. Moreover, bimetallic MOFs can serve as excellent precursors/templates for the synthesis of functional nanomaterials with controlled sizes, compositions, and structures. Bimetallic MOF derivatives show exposed active sites, good stability and conductivity, enabling them to extend their applications to the catalysis of more challenging reactions and electrochemical energy storage and conversion. This review provides an overview of the significant advances in the development of bimetallic MOFs and their derivatives with special emphases on their preparation and applications., This review summarizes the design and synthesis of bimetallic MOFs and their derivatives, with superior performance to their monometallic counterparts in many applications.

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.

Podophyllotoxin (PTOX) is a biologically active compound derived from the podophyllum plant, and both it and its derivatives possess excellent antitumor activity. The PTOX derivatives etoposide (VP-16) and teniposide (VM-26) have been approved by the U.S. Food and Drug Administration (FDA) for cancer treatment, but are far from perfect. Hence, numerous PTOX derivatives have been developed to address the major limitations of PTOX, such as systemic toxicity, drug resistance, and low bioavailability. Regarding their anticancer mechanism, extensive studies have revealed that PTOX derivatives can induce cell cycle G2/M arrest and DNA/RNA breaks by targeting tubulin and topoisomerase II, respectively. However, few studies are dedicated to exploring the interactions between PTOX derivatives and downstream cancer-related signaling pathways, which is reasonably important for gaining insight into the role of PTOX. This review provides a comprehensive analysis of the role of PTOX derivatives in the biological behavior of tumors and potential molecular signaling pathways, aiming to help researchers design and develop better PTOX derivatives.

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.

CXCR5 played critical roles in tumorigenesis and metastasis. Nevertheless, little was known about the involvement of CXCR5 in perineural invasion (PNI) of salivary adenoid cystic carcinoma (SACC). Here, we confirmed upregulation of CXCR5 in SACC specimens and cells and identified that CXCR5 exhibited a significant positive correlation with PNI. Functionally, knockdown of CXCR5 suppressed SACC cells migration, invasion and PNI ability, whereas CXCR5 overexpression displayed the opposite effects. Moreover, CXCR5 downregulated microRNA (miR)-187, which could competitively sponge S100A4. The PNI-inhibitory effect of CXCR5 knockdown or miR-187 overexpression could be reversed by elevated expression of S100A4. Conjointly, our data revealed that CXCR5 facilitated PNI through downregulating miR-187 to disinhibit S100A4 expression in SACC.

To satisfy the rapid development of gas-involving electrocatalysis (O2, CO2, N2, etc.), nanostructured electrocatalysts with favorably regulated electronic structure and surface nanostructures are urgently required. Herein, we highlighted a core-branch hydroxysulfide as a significantly enhanced oxygen evolution reaction electrocatalyst. This hydroxysulfide was facilely fabricated via a versatile interfacial reaction in S2− inorganic solution at room temperature for a designed period. The moderative growth kinetics contributed to the growth of interconnected hydroxysulfide nanosheets with high-sulfur contents on the hydroxide precursor substrates, resulting in a hierarchical nanostructure with multifunctional modifications, including regulated electronic structure, rapid electron highway, excellent accessibility, and facilitated mass transfer. Such synthetic methodology can be generalized and facilely governed by regulating the temperature, concentration, duration, and solvent for targeted nanostructures. Contributed to the favorably regulated electronic structure and surface nanostructure, the as-obtained core-branch Co2NiS2.4(OH)1.2 sample exhibits superior OER performance, with a remarkably low overpotential (279 mV required for 10.0 mA cm−2), a low Tafel slope (52 mV dec−1), and a favorable long-term stability. This work not only presents a promising nanostructured hydroxysulfide for excellent OER electrocatalysis, but also shed fresh lights on the further rational development of efficient electrocatalysts.

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.

Different kinds of 2D materials can be well hybridized by constructing van der Waals heterostructures of them. Among various kinds of 2D materials, graphene has caught the most attention attributed to its superior electronic and mechanical features. To fully maintain and demonstrate their intrinsic features, 3D nanostructured graphene materials are proposed and can be realized by the in-situ curving of graphene layers or the post-assembly of graphene nanosheets. Furthermore, by the integration of 3D graphene framework and other 2D materials, graphene-based 3D van der Waals hybrids can be obtained with superior performances and promising applications in various energy fields. In this review, recent advances on graphene-based 3D van der Waals hybrids for energy applications were summarized, highlighting the hybrids between graphene and transition-metal dichalcogenides, other transition metal compounds, metal-free 2D materials, and multiple 2D materials. We hope this review can inspire more innovative insights into this emerging topic in energy materials.

The rational development of effective energy materials is crucial to the sustainable growth of society. Here, 3D hierarchical porous graphene (hpG)-based materials with micro-, meso-, and macroporous features have recently attracted extensive research efforts due to unique porosities, controllable synthesis, versatile functionalization, favorable mass/electron transport, and superior performances in which corresponding electrochemical performances are strongly dependent on the nature of the building blocks and structural hierarchy of the assemblies. In this review, recent achievements in the controllable synthesis, versatile functionalization, and device application of 3D hpG-based energy materials will be summarized, including controllable and facile synthesis through chemical vapor deposition on 3D porous templates, post-assembly/treatment of graphene oxide nanosheets, and templated polymerization. In addition, graphene material functionalization through heteroatom doping, spatially confined decoration of active nanoparticles, and surface hybridization of graphene-analogous components to enhance electrochemical properties will be discussed. Furthermore, applications of 3D hpG materials in various electrochemical energy storage and conversion systems will be summarized, including lithium-ion batteries, lithium-sulfur batteries, lithium metal anodes, oxygen reduction reaction, oxygen evolution reaction, hydrogen evolution reaction, and nitrogen reduction reaction. Overall, this review will comprehensively present the property advantages, design principles and synthesis strategies of 3D hpG-based energy materials and provide guidance in the development of various 2D graphene-analogous materials and nanomaterials for advanced electrochemical energy storage and conversion systems.

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.

Cathepsin B (CTSB) has been reported to be involved in cancer metastasis by altering extracellular matrix (ECM) remodeling and facilitating invasion. However, the contribution of CTSB to collective cell invasion in salivary adenoid cystic carcinoma (SACC) and the underlying mechanisms remain unclear. The present study demonstrated that collective cell invasion is commonly observed in SACC without a complete epithelial‑mesenchymal transition signature. CTSB was found to be overexpressed in the invasive front of SACC compared to the tumor center, and was associated with a poor prognosis of patients with SACC. Subsequently, a 3D spheroid invasion assay was established in order to recapitulate the collective cell invasion of SACC and the results revealed that CTSB was only expressed in leader cells. The knockdown of CTSB by siRNA inhibited the migration and invasion of SACC‑83 cells and impaired the formation of leader cells. CTSB knockdown also disrupted cytoskeletal organization, altered cell morphology and inhibited ECM remodeling by downregulating matrix metalloproteinase‑9, focal adhesion kinase and Rho/ROCK function. Therefore, the present study provides evidence that CTSB may define leader cells in SACC and is required for collective cell invasion as a potential key regulator of ECM remodeling.

Background Patients were prone to have poor prognosis once dormant tumor cells being reactivated. However, the molecular mechanism of tumor cell dormancy remains poorly understood. This study aimed to investigate the function of DEC2 in the dormancy of salivary adenoid cystic carcinoma (SACC) in vitro and vivo. Methods The function of DEC2 in tumor dormancy of SACC was investigated in nude mice by establishing primary and lung metastasis model. Meanwhile, the interaction between hypoxia and SACC dormancy and the role of DEC2 were demonstrated through CoCl2 induced hypoxia–mimicking microenvironments. Furthermore, the expression of DEC2 was detected by immunohistochemical staining in primary SACC samples with and without recurrence. Results In the primary SACC, DEC2 overexpression inhibited cell proliferation, increased cell population arrested in G0/G1 phase, and participated in dormancy regulation, which limited tumor growth. Intriguingly, in the model of lung metastasis, the level of DEC2 was reduced significantly and resulted in dormancy exit and growth resumption of SACC cells. Then, we found that DEC2 may associate with hypoxia in contributing to tumor dormancy, which might provide a possible cue to explain the different roles of DEC2 in primary and metastasis lesions. And overexpression of DEC2 induced dormancy and promoted migration and invasion through activating EMT program. Finally, DEC2 positive expression was shown to be significantly correlated with recurrence and dormancy of SACC patients. Conclusions These findings provide a novel insight into the role of DEC2 gene in tumor dormancy and metastasis.

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.

Additional file 2: Supplementary Table 1. Real-Time RT-PCR primer sequences.

Background: Patients were prone to have poor prognosis once dormant tumor cells being reactivated. However, the molecular mechanism of tumor cell dormancy remains poorly understood. This study aimed to investigate the function of DEC2 in the dormancy of salivary adenoid cystic carcinoma (SACC) in vitro and vivo. Methods: The function of DEC2 in tumor dormancy of SACC was investigated in nude mice by establishing primary and lung metastasis model. Meanwhile, the interaction between hypoxia and SACC dormancy and the role of DEC2 were demonstrated through CoCl2 induced hypoxia–mimicking microenvironments. Furthermore, the expression of DEC2 was detected by immunohistochemical staining in primary SACC samples with and without recurrence. Results: In the primary SACC, DEC2 overexpression inhibited cell proliferation, increased cell population arrested in G0/G1 phase, and participated in dormancy regulation, which limited tumor growth. Intriguingly, in the model of lung metastasis, the level of DEC2 was reduced significantly and resulted in dormancy exit and growth resumption of SACC cells. Then, we found that DEC2 may associate with hyoxia in contributing to tumor dormancy, which might provide a possible cue to explain the different roles of DEC2 in primary and metastasis lesions. And overexpression of DEC2 induced dormancy and promoted migration and invasion through activating EMT program. Finally, DEC2 positive expression was shown to be significantly correlated with recurrence and dormancy of SACC patients. Conclusions: These findings provide a novel insight into the role of DEC2 gene in tumor dormancy and metastasis.

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. 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. 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. 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.

Purpose The tumor-related myeloid derived suppressor cells (MDSCs), important immunosuppressive cells in tumor microenvironment, play an important role in the cancer progression. This study is aimed to investigate the crosstalk between MDSCs and oral squamous cell carcinoma (OSCC) cells and their role in the malignant progression of OSCC. Methods Immunochemistry (IHC) was used to investigate the expression of CD33 in 200 OSCC, 36 premalignant. CD33+ MDSCs were sorted and enriched via magnetic-activated cell sorting (MACS) from OSCC patients or health donor, and their phenotypes were identified by flow cytometry. With a co-culture system of MDSCs and OSCC, the effects of MDSCs on OSCC proliferation, apoptosis, migration invasion, epithelial-mesenchymal transition (EMT), and vasculogenic mimicry formation (VM) formation were assessed, respectively. Besides, peripheral blood mononuclear cells (PBMCs) from health donor were cultured with OSCC supernatant, the level of MDSCs and expressions of Arginase (Arg-1) and inducible nitric oxide synthase (iNOS) were measured. Results The number of MDSCs was increased in tumor tissues of OSCC patients, and was positively related to the T stage, pathological grade, lymph node metastasis and poor prognosis. Tumor-related MDSCs of the co-culture system promoted OSCC progression by contributing to cell proliferation, migration and invasion as well as inducing EMT and VM. In turn, OSCC cells had potential to induce MDSCs differentiation from PBMCs and increase the expression of Arg-1 and iNOS. Conclusion These indicated that the crosstalk between MDSCs and tumor cells facilitated the malignant progression of OSCC cells and the immune suppressive properties of MDSCs, which may provide new insights into tumor treatment on targeting tumor-associated immunosuppressive cells.

Rechargeable flexible Zn–air batteries have attracted great attentions as promising next-generation energy storage devices for portable and wearable electronics. Bifunctional oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) electrocatalysts on the air electrode are critical for improving the energy storage performance of Zn–air batteries. Free-standing electrocatalysts with superb OER/ORR reactivity render promising flexible power sources for the wearable and stretchable devices. In this contribution, a metal-free electrocatalyst based on surface modification of flexible carbon cloth is proposed. A coaxial cable-like structure with carbon fiber skeleton coated by nanostructured porous and defect-rich graphene skin is in situ fabricated through a facile H2 etching approach. With abundant heteroatoms and defects as active sites, the nanocarbon shells coated carbon cloth exhibits excellent OER/ORR bifunctional activity. The OER and ORR current densities on graphene skin modified carbon fiber are 20 and 3 times higher than those of pristine carbon cloth, respectively. This emerging carbon cloth derived electrocatalyst with porous graphene skin also serves as the air electrode in a rechargeable flexible solid-state Zn air battery with polymer gel electrolyte, and demonstrates stable charge/discharge cycling even under bending. This strategy of constructing nanostructures directly on carbon fibers benefits the rational design of flexible and functionalized materials for electrocatalytic energy applications.

Metal-free electrocatalyst is an emerging energy material to replace precious metal for effective oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) in a working electrochemical energy conversion device. Developing an effective bifunctional catalyst with abundant highly active sites and full exposure to reactants is strongly considered. Herein a nitrogen-doped mesoporous graphene framework (NMGF) was proposed with intrinsic N/O heteroatoms and abundant topological defects for metal-free ORR/OER. The NMGF was fabricated by direct chemical vapor deposition on MgO template. The as-obtained NMGF exhibited high porosity with a large specific surface area of 1440 m 2 g −1 as well as a high electrical conductivity of 57.0 S cm −1 . This unique structure is demonstrated to possess several advantages, including plentiful active centers due to defects and heteroatoms, improved utilization efficiency by very high electrochemically active surface area and hydrophilic surface, facilitated ion diffusion through interconnected pores and smooth electron transportation in the highly conductive 3D framework, thereby leading to superior ORR and OER bifunctional activity. The ORR half-wave potential was 0.714 V, and the potential to reach 10.0 mA cm −2 OER current density was 1.664 V with the potential gap of 0.95 V. This bifunctional performance was better than routine precious metal-based catalysts ( e.g. Pt/C and IrO 2 ) for oxygen redox reaction.

Head and neck squamous cell carcinomas (HNSCCs) are closely linked with immunosuppression, accompanied by complex immune cell functional activities. The abnormal competition between costimulatory and coinhibitory signal molecules plays an important role in the malignant progression of HNSCC. This review will summarize the features of costimulatory molecules (including CD137, OX40 as well as CD40) and coinhibitory molecules (including CTLA-4, PD-1, LAG3, and TIM3), analyze the underlying mechanism behind these molecules' regulation of the progression of HNSCC, and introduce the clinic application. Vaccines, such as those targeting STING while working synergistically with monoclonal antibodies, are also discussed. A deep understanding of the tumor immune landscape will help find new and improved tumor immunotherapy for HNSCC.

Non-coding RNAs (NcRNAs), a family of functional RNA molecules that cannot translate into proteins but control specific gene expression programs, have been shown to be implicated in various biological processes, including fatty acid metabolism. Fast-growing tumor cells rewire their fatty acid metabolic circuitry in order to meet the needs of energy storage, membrane proliferation, and the generation of signaling molecules, which is achieved by regulating a variety of key enzymes along with related signaling pathways in fatty acid metabolism. This review presents an update of our knowledge about the regulatory network of ncRNAs-specifically, microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs)-in this metabolic shift and discusses the possibility of ncRNA-based therapeutics being applied to the restoration of cancer-related fatty acid metabolism.