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BackgroundHormones are identified as key biological variables in tumor immunity. However, previous researches mainly focused on the immune effect of steroid hormones, while the roles that thyroid-stimulating hormone (TSH) played in the antitumor response were far from clear.MethodsThe source of TSH was determined using single-cell transcriptomic, histologic, quantitative PCR, and ELISA analysis. The influence of TSH on tumor proliferation, invasion, and immune evasion was evaluated in multiple cell lines of thyroid cancer, glioma, and breast cancer. Then transcriptomic sequencing and cellular experiments were used to identify signaling pathways. TSH receptor (TSHR) inhibitor was injected into homograft mouse tumor models with or without anti-programmed cell death protein-1 antibody.ResultsMonocyte-derived dendritic cells (moDCs) highly expressed TSHα and TSHβ2 and were the primary source of TSH in the tumor microenvironment. TSH released by moDCs promoted proliferation and invasion of tumors with high TSHR expressions, such as thyroid cancers and glioma. TSH also induced tumor programmed death-ligand 1 (PD-L1) expression through the TSHR-AC-PKA-JNK-c-JUN pathway. TSHR inhibitors reversed tumor immune evasion by inhibiting PD-L1 expression in tumor and myeloid cells and enhancing Teff activation.ConclusionsTSH–TSHR axis promotes tumor evasion in thyroid cancers and glioma. TSH suppression therapy is an effective therapeutic strategy for combination in immune checkpoint blockades.

Triple negative breast cancer (TNBC) is characterized by lack of expression of the estrogen and progesterone receptors and HER2, which are common therapeutic targets. CDK4/6 inhibitor Palbociclib has been approved as an anti-cancer agent for breast cancer. However, identifying biomarkers that predict the response to Palbociclib has always been a challenge for molecular targeted therapy. In this study, we identify microRNA as a hallmark in TNBC patients and explore if miR-3613-3p might serve as a tumor suppressor biomarker for triple negative breast cancer patients and if overexpression of miR-3613-3p could enhance the sensitivity of TNBC cells to Palbociclib. We show that the expression of miR3613-3p was down-regulated in TNBC tumors and cells, and the overexpression of miR-3613-3p in patients’ tumor tissues was clinically and pathologically correlated with favorable prognosis, such as smaller tumor size and the lower Ki-67.In vitro, overexpression of miR-3613-3p inhibited cell proliferation, induced G1 cell-cycle arrest, and enhanced the sensitivity of TNBC cells to Palbociclib treatment.In vivostudy revealed that overexpression of miR-3613-3p inhibited TNBC tumorigenesis and exerted a significant inhibitory effect of Palbociclib on MDA-MB-231 cells. Mechanically, SMAD2 and EZH2 were found to be two direct targets of miR-3613-3p and mediate the proliferation of TNBC cells and the sensitivity of the cells to Palbociclib through inducing cellular senescence. Our findings suggested that miR-3613-3p acts as a cancer-suppressor miRNA in TNBC. Moreover, our study showed that miR-3613-3p might be used as a predictive biomarker for the response of TNBC to Palbociclib.

Reliable and controllable synthesis of two-dimensional (2D) hexagonal boron nitride (h-BN) layers is highly desirable for their applications as 2D dielectric and wide bandgap semiconductors. In this work, we demonstrate that the dissolution of carbon into cobalt (Co) and nickel (Ni) substrates can facilitate the growth of h-BN and attain large-area 2D homogeneity. The morphology of the h-BN film can be controlled from 2D layer-plus-3D islands to homogeneous 2D few-layers by tuning the carbon interstitial concentration in the Co substrate through a carburization process prior to the h-BN growth step. Comprehensive characterizations were performed to evaluate structural, electrical, optical, and dielectric properties of these samples. Single-crystal h-BN flakes with an edge length of ∼600 μm were demonstrated on carburized Ni. An average breakdown electric field of 9 MV/cm was achieved for an as-grown continuous 3-layer h-BN on carburized Co. Density functional theory calculations reveal that the interstitial carbon atoms can increase the adsorption energy of B and N atoms on the Co(111) surface and decrease the diffusion activation energy and, in turn, promote the nucleation and growth of 2D h-BN.

Graphene has attracted a great deal of interest due to its fascinating properties and a wide variety of potential applications. Several methods have been used to achieve high-quality graphene films on different substrates. However, there have been only a few studies on graphene growth on iron (Fe) and the growth mechanism remains unclear. This paper systematically investigates temperature-dependent growth of graphene on Fe substrate by gas-source molecular beam epitaxy. Two-dimensional (2D), large-area graphene samples were grown on Fe thin films, and characterized by Raman, X-ray photoelectron spectroscopy, X-ray diffraction, optical microscopy, transmission electron microscopy and atomic force microscopy. It is found that graphene flakes can be grown on Fe at a growth temperature as low as 400 °C and the optimized large-area graphene growth temperature is relatively low between 500 °C and 550 °C. The graphene growth on Fe that undergoes the formation and decomposition of iron carbide is discussed.

One of the low-dimensional Boron Nitride (BN) forms, namely, cubic-BN (c-BN) nanodots (NDs), offers a variety of novel opportunities in battery, biology, deep ultraviolet light emitting diodes, sensors, filters, and other optoelectronic applications. To date, the attempts towards producing c-BN NDs were mainly performed under extreme high-temperature/high-pressure conditions and resulted in c-BN NDs with micrometer sizes, mixture of different BN phases, and containing process-related impurities/contaminants. To enhance device performance for those applications by taking advantage of size effect, pure, sub-100 nm c-BN NDs are necessary. In this paper, we report self-assembled growth of c-BN NDs on cobalt and nickel substrates by plasma-assisted molecular beam epitaxy. It is found that the nucleation, formation, and morphological properties of c-BN NDs can be closely correlated with the nature of substrate including catalysis effect, lattice-mismatch-induced strain, and roughness, and growth conditions, in particular, growth time and growth temperature. The mean lateral size of c-BN NDs on cobalt scales from 175 nm to 77 nm with the growth time. The growth mechanism of c-BN NDs on metal substrates is concluded to be Volmer-Weber (VW) mode. A simplified two-dimensional numerical modeling shows that the elastic strain energy plays a key role in determining the total formation energy of c-BN NDs on metals.

Two-dimensional (2D) hexagonal boron nitride (h-BN), which has a similar honeycomb lattice structure to graphene, is promising as a dielectric material for a wide variety of potential applications based on 2D materials. Synthesis of high-quality, large-size and single-crystalline h-BN domains is of vital importance for fundamental research as well as practical applications. In this work, we report the growth of h-BN films on mechanically polished cobalt (Co) foils using plasma-assisted molecular beam epitaxy. Under appropriate growth conditions, the coverage of h-BN layers can be readily controlled by growth time. A large-area, multi-layer h-BN film with a thickness of 5~6 nm is confirmed by Raman spectroscopy, scanning electron microscopy, X-ray photoelectron spectroscopy and transmission electron microscopy. In addition, the size of h-BN single domains is 20~100 μm. Dielectric property of as-grown h-BN film is evaluated by characterization of Co(foil)/h-BN/Co(contact) capacitor devices. Breakdown electric field is in the range of 3.0~3.3 MV/cm, which indicates that the epitaxial h-BN film has good insulating characteristics. In addition, the effect of substrate morphology on h-BN growth is discussed regarding different domain density, lateral size, and thickness of the h-BN films grown on unpolished and polished Co foils.

Van der Waals materials have received a great deal of attention for their exceptional layered structures and exotic properties, which can open up various device applications in nanoelectronics. However, in situ epitaxial growth of dissimilar van der Waals materials remains challenging. Here we demonstrate a solution for fabricating van der Waals heterostructures. Graphene/hexagonal boron nitride (h-BN) heterostructures were synthesized on cobalt substrates by using molecular beam epitaxy. Various characterizations were carried out to evaluate the heterostructures. Wafer-scale heterostructures consisting of single-layer/bilayer graphene and multilayer h-BN were achieved. The mismatch angle between graphene and h-BN is below 1°.

We carried out a systematic study of hexagonal boron nitride/graphene (h-BN/G) heterostructure growth by introducing high incorporation of a carbon (C) source on a heated cobalt (Co) foil substrate followed by boron and nitrogen sources in a molecular beam epitaxy system. With the increase of C incorporation in Co, three distinct regions of h-BN/G heterostructures were observed from region (1) where the C saturation was not attained at the growth temperature (900 °C) and G was grown only by precipitation during the cooling process to form a 'G network' underneath the h-BN film; to region (2) where the Co substrate was just saturated by C atoms at the growth temperature and a part of G growth occurs isothermally to form G islands and another part by precipitation, resulting in a non-uniform h-BN/G film; and to region (3) where a continuous layered G structure was formed at the growth temperature and precipitated C atoms added additional G layers to the system, leading to a uniform h-BN/G film. It is also found that in all three h-BN/G heterostructure growth regions, a 3 h h-BN growth at 900 °C led to h-BN film with a thickness of 1-2 nm, regardless of the underneath G layers' thickness or morphology. Growth time and growth temperature effects have been also studied.

Research on graphene/hexagonal boron nitride (h-BN) heterostructures has attracted much attention for band engineering and device performance optimization of graphene. However, the growth of graphene/h-BN heterostructure is still challenging, which usually requires high growth temperature and long growth duration. In this paper, we demonstrate graphene/h-BN heterostructures by growing graphene onto the substrates which consist of exfoliated h-BN flakes on Co thin films using molecular beam epitaxy. The heterostructure samples grown at different temperatures and growth times were characterized by Raman, optical microscopy, atomic force microscopy, microwave impedance microscopy, and scanning tunneling microscopy. It is found that the graphene/h-BN heterostructures were formed by the formation of graphene underneath rather than on top of the h-BN flakes. The growth mechanism is discussed.

Graphene/hexagonal boron nitride (G/h-BN) heterostructures have attracted a great deal of attention because of their exceptional properties and wide variety of potential applications in nanoelectronics. However, direct growth of large-area, high-quality, and stacked structures in a controllable and scalable way remains challenging. In this work, we demonstrate the synthesis of h-BN/graphene (h-BN/G) heterostructures on cobalt (Co) foil by sequential deposition of graphene and h-BN layers using plasma-assisted molecular beam epitaxy. It is found that the coverage of h-BN layers can be readily controlled on the epitaxial graphene by growth time. Large-area, uniform-quality, and multi-layer h-BN films on thin graphite layers were achieved. Based on an h-BN (5–6 nm)/G (26–27 nm) heterostructure, capacitor devices with Co(foil)/G/h-BN/Co(contact) configuration were fabricated to evaluate the dielectric properties of h-BN. The measured breakdown electric field showed a high value of ∼2.5–3.2 MV/cm. Both I-V and C-V characteristics indicate that the epitaxial h-BN film has good insulating characteristics.

We incorporate single-crystal Fe${}_{3}$O${}_{4}$ thin films into a gated device structure and demonstrate the ability to control the Verwey transition with static electric fields. The Verwey transition temperature (${T}_{V}$) increases for both polarities of the electric field, indicating that the effect is not driven by changes in carrier concentration. The energetics of induced electric polarization and/or strain within the Fe${}_{3}$O${}_{4}$ film provide a possible explanation for this behavior. Electric field control of the Verwey transition leads directly to a large magnetoelectric effect with coefficient of 585 pT m/V.

Hexagonal boron nitride (h-BN) single-crystal domains were grown on cobalt (Co) substrates at a substrate temperature of 850–900 °C using plasma-assisted molecular beam epitaxy. Three-point star shape h-BN domains were observed by scanning electron microscopy, and confirmed by Raman and X-ray photoelectron spectroscopy. The h-BN on Co template was used for in situ growth of multilayer graphene, leading to an h-BN/graphene heterostructure. Carbon atoms preferentially nucleate on Co substrate and edges of h-BN and then grow laterally to form continuous graphene. Further introduction of carbon atoms results in layer-by-layer growth of graphene on graphene and lateral growth of graphene on h-BN until it may cover entire h-BN flakes.