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Purpose: PI3K and STAT3 are frequently activated in cancer progression. However, little is known about the underlying mechanisms by which PI3K and STAT3 regulate head and neck squamous cell cancer (HNSCC) growth. The lncRNA HOX transcript antisense RNA (HOTAIR) was found to modulate the progression of HNSCC. In this study, we attempted to establish the correlation of PI3K/STAT3/HOTAIR signaling with the progression of HNSCC and its sensitivity toward platinum-based and targeted anti-EGFR combination therapy.Experimental Design: We first analyzed the STAT3/HOTAIR and PI3K/AKT level in human HNSCC samples. We then activated or suppressed STAT3/HOTAIR and determined the effects on HNSCC cell proliferation in vitro and the growth of UM1 xenograft tumor, an orthotopic model of HNSCC. The sensitivity of HNSCC cells toward cisplatin and cetuximab was determined by in vitro assays.Results: HNSCC samples showed significantly robust expression/activation of STAT3, HOTAIR, PI3K, and AKT, compared with normal squamous epithelium. STAT3 inhibition with WP1066 decreased HOTAIR level and sensitized HNSCC to cisplatin or cetuximab. STAT3 promoted HOTAIR transcription and its interaction with pEZH2-S21, resulting in enhanced growth of HNSCC cells. In addition, overexpression of HOTAIR promoted the growth of UM1 xenograft tumors in vivo.Conclusions: Our results suggest that STAT3 signaling promotes HNSCC progression via regulating HOTAIR and pEZH2-S21 in HNSCC with PI3K overexpression/activation. These findings provide a rationale to target the STAT3/HOTAIR/pEZH2-S21 regulatory axis for treating patients with HNSCC. Clin Cancer Res; 24(11); 2665–77. ©2018 AACR.

Small cell lung cancer (SCLC) has a high degree of plasticity and is characterized by a remarkable response to chemotherapy followed by the development of resistance. Here, we use a mouse SCLC model to show that intratumoral heterogeneity of SCLC is progressively established during SCLC tumorigenesis. YAP/TAZ and Notch are required for the generation of non-neuroendocrine (Non-NE) SCLC tumor cells, but not for the initiation of SCLC. YAP signals through Notch-dependent and Notch-independent pathways to promote the fate conversion of SCLC from NE to Non-NE tumor cells by inducing Rest expression. In addition, YAP activation enhances the chemoresistance in NE SCLC tumor cells, while the inactivation of YAP in Non-NE SCLC tumor cells switches cell death induced by chemotherapy drugs from apoptosis to pyroptosis. Our study demonstrates that YAP plays critical roles in the establishment of intratumoral heterogeneity and highlights the potential of targeting YAP for chemoresistant SCLC.

Lithium-sulfur (Li-S) batteries have attracted widespread attention due to their high theoretical energy density. However, their practical application is still hindered by the shuttle effect and the sluggish conversion of lithium polysulfides (LiPSs). Herein, monodisperse molybdenum (Mo) nanoparticles embedded onto nitrogen-doped graphene (Mo@N-G) were developed and used as a highly efficient electrocatalyst to enhance LiPS conversion. The weight ratio of the electrocatalyst in the catalyst/sulfur cathode is only 9%. The unfilled d orbitals of oxidized Mo can attract the electrons of LiPS anions and form Mo–S bonds during the electrochemical process, thus facilitating fast conversion of LiPSs. Li-S batteries based on the Mo@N-G/S cathode can exhibit excellent rate performance, large capacity, and superior cycling stability. Moreover, Mo@N-G also plays an important role in room-temperature quasi-solid-state Li-S batteries. These interesting findings suggest the great potential of Mo nanoparticles in building high-performance Li-S batteries.

Numerous experiments have demonstrated that the metal atom is the active center of monoatomic catalysts for hydrogen evolution reaction (HER), while the active sites of nonmetal doped atoms are often neglected. By combining theoretical prediction and experimental verification, we designed a unique ternary Ru-N 4 -P coordination structure constructed by monodispersed Ru atoms supported on N,P dual-doped graphene for highly efficient hydrogen evolution in acid solution. The density functional theory calculations indicate that the charge polarization will lead to the most charge accumulation at P atoms, which results in a distinct nonmetallic P active sites with the moderate H ∗ adsorption energy. Notably, these P atoms mainly supply highly efficient catalytic sites with ultrasmall absorption energy of 0.007 eV. Correspondingly, the Ru-N 4 -P demonstrated outstanding HER performance not only in an acidic condition but also in alkaline environment. Notably, the performance of Ru-NPC catalyst at high current is even superior to the commercial Pt/C catalysts, whether in acidic or alkaline medium. Our in situ synchrotron radiation infrared spectra demonstrate that a P-H ads intermediate is continually emerging on the Ru-NPC catalyst, actively proving the nonmetallic P catalytically active site in HER that is very different with previously reported metallic sites.

Purpose: PI3K and STAT3 are frequently activated in cancer progression. However, little is known about the underlying mechanisms by which PI3K and STAT3 regulate head and neck squamous cell cancer (HNSCC) growth. The lncRNA HOX transcript antisense RNA (HOTAIR) was found to modulate the progression of HNSCC. In this study, we attempted to establish the correlation of PI3K/STAT3/HOTAIR signaling with the progression of HNSCC and its sensitivity toward platinum-based and targeted anti-EGFR combination therapy. Experimental Design: We first analyzed the STAT3/HOTAIR and PI3K/AKT level in human HNSCC samples. We then activated or suppressed STAT3/HOTAIR and determined the effects on HNSCC cell proliferation in vitro and the growth of UM1 xenograft tumor, an orthotopic model of HNSCC. The sensitivity of HNSCC cells toward cisplatin and cetuximab was determined by in vitro assays. Results: HNSCC samples showed significantly robust expression/activation of STAT3, HOTAIR, PI3K, and AKT, compared with normal squamous epithelium. STAT3 inhibition with WP1066 decreased HOTAIR level and sensitized HNSCC to cisplatin or cetuximab. STAT3 promoted HOTAIR transcription and its interaction with pEZH2-S21, resulting in enhanced growth of HNSCC cells. In addition, overexpression of HOTAIR promoted the growth of UM1 xenograft tumors in vivo. Conclusions: Our results suggest that STAT3 signaling promotes HNSCC progression via regulating HOTAIR and pEZH2-S21 in HNSCC with PI3K overexpression/activation. These findings provide a rationale to target the STAT3/HOTAIR/pEZH2-S21 regulatory axis for treating patients with HNSCC. Clin Cancer Res; 24(11); 2665–77. ©2018 AACR.

Atomic intercalation in two-dimensional (2D) layered materials can be used to engineer the electronic structure at the atomic scale and generate tuneable physical and chemical properties which are quite distinct in comparison with the pristine material. Among them, electron-doped engineering induced by intercalation is an efficient route to modulate electronic states in 2D layers. Herein, we demonstrate a semiconducting to metallic phase transition in zirconium diselenide (ZrSe2) single crystals via controllable incorporation of copper (Cu) atoms. Our angle resolved photoemission spectroscopy (ARPES) measurements and first-principles density functional theory (DFT) calculations clearly revealed the emergence of conduction band dispersion at the M/L point of the Brillouin zone due to Cu-induced electron doping in ZrSe2 interlayers. Moreover, electrical measurements in ZrSe2 revealed semiconducting behavior, while the Cu-intercalated ZrSe2 exhibited a linear current–voltage curve with metallic character. The atomic intercalation approach may have high potential for realizing transparent electron-doping systems for many specific 2D-based nanoelectronic applications.

Atomically dispersed catalysts have attracted attention in energy conversion applications because their efficiency and chemoselectivity for special catalysis are superior to those of traditional catalysts. However, they have limitations owing to the extremely low metal-loading content on supports, difficulty in the precise control of the metal location and amount as well as low stability at high temperatures. We prepared a highly doped single metal atom hybrid via a single-step thermal pyrolysis of glucose, dicyandiamide, and inorganic metal salts. High-angle annular dark field-scanning transmission electron microscopy (HAADF-STEM) and X-ray absorption fine structure spectroscopy (XAFS) revealed that nitrogen atoms doped into the graphene matrix were pivotal for metal atom stabilization by generating a metal-Nx coordination structure. Due to the strong anchoring effect of the graphene matrix, the metal loading content was over 4 wt.% in the isolated atomic hybrid (the Pt content was as high as 9.26 wt.% in the Pt-doped hybrid). Furthermore, the single iron-doped hybrid (Fe@N-doped graphene) showed a remarkable electrocatalytic performance for the oxygen reduction reaction. The peak power density was ∼199 mW·cm−2 at a current density of 310 mA·cm−2 and superior to that of a commercial Pt/C catalyst when it was used as a cathode catalyst in assembled zinc-air batteries. This work offered a feasible approach to design and fabricate highly doped single metal atoms (SMAs) catalysts for potential energy applications.

In most cases, layered transition metal dichalcogenides (LTMDs), containing metallic phases, show electrochemical behavior different from their semiconductor counterparts. Typically, two-dimensional layered metallic 1T-MoS2 demonstrates better electrocatalytic performance for water splitting compared to its 2H counterpart. However, the characteristics of low metallic phase concentration and poor stability limit its applications in some cases. Herein, we demonstrate a simple and efficient bottom-up wet-chemistry strategy for the large-scale synthesis of nanoscopic ultrathin Mo1–xWxS2 nanosheets with enlarged interlayer spacing and high metallic phase concentration. Our characterizations, including X-ray absorption fine structure spectroscopy (XAFS), high-angle annular dark-fieldscanning transmission electron microscopy (HAADF-STEM), and X-ray photoelectron spectroscopy (XPS) revealed that the metallic ultrathin ternary Mo1–xWxS2 nanosheets exhibited distorted metal–metal bonds and a tunable metallic phase concentration. As a proof of concept, this optimized catalyst, with the highest metallic phase concentration (greater than 90%), achieved a low overpotential of about–155 mV at a current density of –10 mA/cm2, a small Tafel slope of 67 mV/dec, and an increased turnover frequency (TOF) of 1.3 H2 per second at an overpotential of –300 mV (vs. reversible hydrogen electrode (RHE)), highlighting the importance of the metallic phase. More importantly, this study can lead to a facile solvothermal route to prepare stable and high-metallicphase-concentration transition-metal-based two-dimensional materials for future applications.

Rational design and facet-engineering of nanocrystal is an effective strategy to optimize the catalytic performance of abundant and economic semiconductor-based photocatalysts. In this study, we demonstrate a novel ternary Cu2MoS4 nanotube with the {010} facet exposed, synthesized via a hydrothermal method. Compared with two-dimensional Cu2MoS4 nanosheet with the {001} facet exposed, this one-dimensional nanotube exhibits highly enhanced performance of photodegradation and water splitting. Both theoretical calculations and experimental results suggest that the conduction band minimum (CBM) of the {010} facet crystal shows lower potential than that of the {001} facet. In particular, the up-shifted CBM in Cu2MoS4 nanotube is significantly beneficial for the absorption of dye molecules and reduction of H+ to H2. These results may open a new route for realizing high-efficiency photocatalysts based on Cu2MX4 by facet engineering.

Spinel LiNi 0.5 Mn 1.5 O 4 (LNMO) is one of the most promising high voltage cathode materials for future application. Herein, we report a simple method to prepare nanoscale TiO 2 -coated LNMO composites (LNMO-T). The thin TiO 2 coating layer was pasted on the surface of host material, which favors Li + ions diffusions. Compared to the bare LNMO, the surface modified composites LNMO-T shows outstanding rate capability and excellent cycling ability. In particularly, a discharge capacity of 74.5 mAh/g can be still delivered at 15 C and about 88.5% capacity retention at 2 C after 500 cycles. These results suggest that the TiO 2 coating can not only suppress the dissolution of manganese in the electrolyte but also enhance the conductivity of cathode. This study demonstrates that the potential of developing high energy density cathode materials by surface modification with TiO 2 membrane at nanoscale for future applications.

Ultrafine noble metal nanoparticles decorated on onion-like carbon (OLC) were successfully prepared without any reductant or surfactant. Particularly, the as-prepared Pt–OLC nanocomposite not only exhibited superior electrocatalytic activity and stability for the hydrogen evolution reaction as compared with the commercial 20% Pt/C, but also showed enhanced supercapacitor performance with a specific capacitance almost four times larger than that of OLC. Notably, the C–O functional groups on the surface of OLC will increase after the reaction because of the oxidation by O2 and chloroplatinic acid, which is very useful for the reuse of OLC and helpful for the decoration of noble metal nanoparticles on OLC. This work provides a simple and straightforward method for the facile preparation of metal composite nanocatalysts with high catalytic activity.

Tumor metastasis regulated by epithelial‑mesenchymal transition (EMT) plays a significant role in the development of human cancers, whereas the molecular mechanisms of this process in head and neck squamous cell carcinoma (HNSCC) remain elusive. In this study, we found that inhibition of enhancer of zeste homolog 2 (EZH2) resulted in suppressed EMT in HNSCC in vitro and in vivo. We reported that signal transducer and activator of transcription factor 3 (STAT3)/vascular endothelial growth factor receptor 2 (VEGFR2) axis served as the downstream signaling of EZH2 and mediated EMT in HNSCC. EZH2 inhibition downregulated the expression of key molecules of the STAT3/VEGFR2 axis and EMT‑related markers, while the expression of E‑cadherin was upregulated in HNSCC cells. Targeting the EZH2/STAT3/VEGFR2 axis significantly reduced motility of HNSCC cells. Furthermore, EZH2 knockdown reduced the growth of xenograft HNSCC tumors via inhibiting the EZH2/STAT3/VEGFR2 axis. In conclusion, we proposed that EZH2 regulates EMT and tumor invasion and metastasis in HNSCC by governing the STAT3/VEGFR2 axis. These findings provide a rationale for developing novel strategies to treat invasive and metastatic HNSCC via targeting the EZH2/STAT3/VEGFR2 pathway.

Aberrant expression and activation of signal transducer and activator of transcription 3 (STAT3) is implicated in several malignancies, including glioblastoma, and is correlated with poor outcomes in patients with glioblastoma, rendering STAT3 a potential therapeutic target. However, few STAT3 inhibitors have been approved for clinical use. We recently developed an orally active small-molecule compound with anti-STAT3 activity, HJC0152. This study aimed to test the effect of this novel drug on glioblastoma cell lines, and provide possibility to improve clinic prognosis of patients with glioblastoma in the future. In the present study, we aimed to determine the effects of HJC0152 on the growth, proliferation, and chemosensitivity of glioblastoma cell lines and xenograft tumors. We found that HJC0152 inactivated STAT3 via inhibiting phosphorylation of the Tyr705 residue. In vitro, HJC0152 suppressed the proliferation and motility of glioblastoma cells, induced apoptosis, and enhanced the chemosensitivity of glioblastoma cells. Furthermore, HJC0152 inhibited the growth of glioblastoma xenograft tumors in vivo. This study provides a rationale for developing HJC0152 as a STAT3-targeting therapy for treating human glioblastoma in the future.

Layered tungsten disulfide (WS2) is a potential electrode material for electric double layer capacitance (EDLC) and hydrogen evolution reaction (HER). However, the electrochemical performance of WS2 has been hindered by the semiconducting nature and poor active sites. Herein, we have demonstrated a bottom-up hydrothermal approach to fabricate metallic 1T-WS2 nanoislands in situ grown on flexible single-walled carbon nanotube nonwovens (1T-WS2@SWCNT). The robust hybrids with a tight interface possess nanoscopic few-layered WS2 pieces with an abundance of exposed sites, along with a unique woven-architecture originating from the high conductive carbon nanotube network. The in situ-growing enhanced interface between metallic WS2 nanoislands and SWCNTs provides a relatively strong electrical coupling integrity, which facilitates charge transfer during electrochemical reactions. The merits of rich active sites, excellent conductivity and well bonding-interactions are significantly beneficial to improve the electrochemical performance. Particularly, in contrast to the pure material, the as-obtained hybrids are found to exhibit higher EDLC capacity (226 mF cm−2), almost 646-fold higher than pure 1T-WS2, smaller Tafel slope (57 mV per decade) and lower HER overpotential (∼25 mV) than any WS2-based materials reported so far.

Thanks to its larger surface and free volume, hollow nanostructure and nanomaterials are one kind of highly desirable electrodes for efficiently enhancing sodium-ion battery performance, especially at high rate. Herein, we demonstrate a design of hierarchical semi-open hollow structure, assembling with molybdenum selenide (MoSe2) nanosheets embedded on the nitrogen doped carbon matrix. The unique hollow structure can not only enable sufficient electrode/electrolyte interaction and fast electron transportation, but also suppress volume expansion during the insertion/extraction of sodium ion. As a direct outcome, the MoSe2/carbon anode exhibits excellent cycling and rate performance with a specific capacity of 431 mAh g−1 at 200 ​mA ​g−1, maintaining 87.7% capacity after 120 cycles. Notably, a discharge capacity of 199.1 mAh g−1 can be achieved even at an ultra-high current density of 20 ​A ​g−1, indicating quick Na+ storage ability. The results may open a new way to realize high-rate anode for ion battery applications.

Despite the fact that two-dimensional layered magnetic materials hold immense potential applications in the field of spintronic devices, tunable magnetism is still a challenge due to the lack of controllable synthesis. Herein, high-quality single crystals MPS3 (M= Mn, Fe) of millimeter size were synthesized through the chemical vapor transport method. After systemic structural characterizations, magnetic properties were studied on the bulk MPS3 layers through experiments, along with first principle theoretical calculations. The susceptibilities as well as the EPR results evidently revealed unique isotropic and anisotropic behavior in MnPS3 and FePS3 crystals, respectively. It is worth noting that both of these materials show antiferromagnetic states at measured temperatures. The estimated antiferromagnetic transition temperature is 78 K for bulk MnPS3 and 123 K for FePS3 crystals. The spin polarized density functional theory calculations confirmed that the band gap of the antiferromagnetic states could be generated owing to asymmetric response all over the energy range. The ferromagnetic state in MnPS3 and FePS3 is less stable as compared to the antiferromagnetic state, resulting in antiferromagnetic behavior. Additionally, frequency-dependent dielectric functions for parallel and perpendicular electric field component vectors, along with the absorption properties of MPS3, are thoroughly investigated.

Abnormal activation of signal transducer and activator of transcription 3 (STAT3) serves a pivotal role in oral squamous cell carcinoma (OSCC) tumor cell invasion into normal tissues or distant organs. However the downstream regulatory network of STAT3 signaling remains unclear. The present study aimed to investigate the potential mechanism underlying how STAT3 triggers enhancer of zeste homolog 2 (EZH2) expression and inhibits microRNA (miR)-200a/b/429 expression in SCC25 and SCC15 cells in vitro and in vivo. Western blotting and reverse transcription-quantitative polymerase chain reaction were performed to detect expression, and numerous functional tests were conducted to explore cancer metastasis. The results indicated that when STAT3 signaling activity was attenuated by Stattic or enhanced with a STAT3 plasmid, the EZH2/miR-200 axis was markedly altered, thus resulting in modulation of the invasion and migration of OSCC cell lines. In addition, loss of function of EZH2 compromised the oncogenic role of STAT3 in both cell lines. F-actin morphology and the expression of epithelial-mesenchymal transition markers were also altered following disruption of the STAT3/EZH2/miR-200 axis. An orthotopic tumor model derived from SCC15 cells was used to confirm that targeting STAT3 or EZH2 suppressed OSCC invasion in vivo. In conclusion, the EZH2/miR-200 axis was revealed to mediate antitumor effects by targeting STAT3 signaling; these findings may provide a novel therapeutic strategy for the treatment of OSCC.

In order to obtain a deep red emitting Mn4+ doped phosphor for applications in white LEDs, we choose Mg7Ga2GeO12 with AO6 polyhedra favoring the emission of Mn4+ ions as host and design a novel Mg7Ga2GeO12:Mn4+ phosphor by solid state method at 1400 °C in air. The photoluminescence properties were investigated in conjunction with a structural analysis. The crystallographic occupancy of Mn4+ ion in the Mg7Ga2GeO12 host was studied based on the Rietveld refinement results and the crystal chemistry rules as well as luminescence properties. It reveals that the Mn4+ ion occupies the trivalent Ga site in GaO6 polyhedra, resulting in efficient emission of Mn4+ ion. The excitation spectrum exhibits a broad peak at 420 nm due to the characteristic 4A2g→4T2g transitions of Mn4+ ions, and it indicates that this Mg7Ga2GeO12:Mn4+ material can be availably excited in 400–450 nm region. Upon excitation at 420 nm, the composition-optimized Mg7Ga2GeO12:0.5 mol%Mn4+ sample shows broad deep red emission band (2Eg→4A2g transition) in 600–750 nm with the CIE chromaticity (x = 0.7133, y = 0.2866). An analysis of the thermal quenching shows that the emission intensity of the optimal Mg7Ga2GeO12:Mn4+ sample at 250 °C is 78% of their initial intensity at room temperature. Therefore, the Mg7Ga2GeO12:Mn4+ material could serve as a potential red phosphor for white LEDs.

Patients suffered from head and neck squamous cell carcinoma (HNSCC) have an overall poor prognosis owing to proliferation and resistance to treatment. Hence, mining the underlying mechanism of malignancies above and translating the bench outcomes to clinical practice are in urgent need. Previous studies found that the epidermal growth factor receptor (EGFR) increases and co-expresses with EGFRvIII in HNSCC tissues, which indicates poor prognosis of HNSCC patients. Here, we clarify that compared with EGFRwt, EGFRwt/vIII enhances the capability of proliferation and colony formation in HNSCC cells in vitro, and reduces the sensitivity to cisplatin. Furthermore, EGFRwt/vIII induces nuclear translocation of the M2 isoform of pyruvate kinase (PKM2) in a time-dependent manner. The aberrant expression of PKM2 in HNSCC suggests unfavorable outcome. Especially, nuclear PKM2 determines the activation of β-catenin signaling and regulates the proliferation and chemo-sensitivity of HNSCC cells. Together, our findings demonstrate that EGFRwt/vIII-PKM2-β-catenin cascade controls the proliferation and chemo-sensitivity of HNSCC, thereby providing a promising strategy for diagnosis and therapy of HNSCC.

The electronic performance of graphene is largely related to its morphology, surface, size and various synthesis conditions, mainly because of the presence of grain boundary. Better understanding on the relationship between the size and electronic property is very important for graphene's applications in potential electronics. Herein, we selectively synthesized single-crystal graphene using a chemical vapor deposition (CVD) method. The obtained CVD-graphene exhibited various sizes, ranging from 20 μm to 120 μm. Our measurements of field effect transistor devices revealed that the charge carrier mobility of CVD-graphene could increase from 17.8 to 720 cm 2 V −1 s −1 with the size decreasing. The better electronic performance in comparable smaller-size graphene was ascribed to less grain boundary compared with the bigger one, which was further confirmed by our observations from scanning tunneling microscope/spectroscopy (STM/STS).

In this work we directly synthesized molybdenum disulfide (MoS2) nanosheets on carbon nanotube film (MoS2@CNT) via a two-step chemical vapor deposition method (CVD). By etching the obtained MoS2@CNT into 10% wt HNO3, the morphology of MoS2 decorated on CNT bundles was modulated, resulting in more catalytic active MoS2 edges being exposed for significantly enhanced electrochemical performance. Our results revealed that an 8 h acid etching sample exhibited the best performance for the oxygen evolution reaction, i.e., the current density reached 10 mA/cm2 under 375 mV over-potential, and the tafel slope was as low as 94 mV/dec. The enhanced behavior was mainly originated from the more catalytic sites in MoS2 induced by the acid etching treatment and the higher conductivity from the supporting CNT films. Our study provides a new route to produce two-dimensional layers on CNT films with tunable morphology, and thus may open a window for exploring its promising applications in the fields of catalytic-, electronic-, and electrochemical-related fields.