Epitaxial Growth of Two-Dimensional MoO2-MoSe2 Metal-Semiconductor Heterostructures for Schottky Diodes.

The metal-semiconductor interface fabricated by conventional methods often suffers from contamination, degrading transport performance. Herein, we propose a one-pot chemical vapor deposition (CVD) process to create a two-dimensional (2D) MoO2-MoSe2 heterostructure by growing MoO2 seeds under a hydrogen environment, followed by depositing MoSe2 on the surface and periphery. The ultraclean interface is verified by cross-sectional scanning transmission electron microscopy and photoluminescence. Along with the high work function of semimetallic MoO2 (Ef = -5.6 eV), a high-rectification Schottky diode is fabricated based on this heterostructure. Furthermore, the Schottky diode exhibits an excellent photovoltaic effect with a high open-circuit voltage of 0.26 eV and ultrafast photoresponse, owing to the naturally formed metal-semiconductor contact with suppressed pinning effect. Our method paves the way for the fabrication of an ultraclean 2D metal-semiconductor interface, without defects or contamination, offering promising prospects for future nanoelectronics.

High Power Figure-of-Merit, 10.6-kV AlGaN/GaN Lateral Schottky Barrier Diode with Single Channel and Sub-100-µm Anode-to-Cathode Spacing.

GaN-based lateral Schottky barrier diodes (SBDs) have attracted great attention for high-power applications due to its combined high electron mobility and large critical breakdown field. However, the breakdown voltage (BV) of the SBDs are far from exploiting the material advantages of GaN at present, limiting the desire to use GaN for ultra-high voltage (UHV) applications. Then, a golden question is whether the excellent properties of GaN-based materials can be practically used in the UHV field? Here, UHV AlGaN/GaN SBDs are demonstrated on sapphire with a BV of 10.6 kV, a specific on-resistance (RON,SP ) of 25.8 mΩ cm2 , yielding a power figure-of-merit (P-FOM = BV2 /RON,SP ) of 4.35 GW cm-2 . These devices are designed with single channel and 85-µm anode-to-cathode spacing, without other additional electric field management, demonstrating its great potential for the UHV application in power electronics.

Production of functional recombinant prolyl hydroxylase-2 enzyme in insect cells for small molecule inhibitor screening studies.

Prolyl hydroxylase-2 (PHD2) is a dioxygenase enzyme that specifically hydroxylates the hypoxia inducible factor (HIF) which then targets it for degradation in oxygenated cells. Inhibition of the activity of the PHD2 enzyme under hypoxic environmental conditions acts to upregulate HIF. Thus, PHD2 inhibitors may serve as a promising treatment for HIF-dependent diseases. In this study, recombinant PHD2 protein was successfully expressed using a baculovirus-insect cell expression secretory system. PHD2 was purified and in combination with bacterially expressed functional von Hippel Lindau protein-elongin B-elongin C (VBC) protein complex was used to successfully develop a fluorescence-based PHD2 activity assay. Myricetin was identified as a novel potent PHD2 inhibitor by high-throughput screening of a natural compound library. Further studies showed that treatment of human neuroblastoma SH-SY5Y cells with Myricetin increased HIF-1α protein levels. These results indicate that the insect cell expression system is capable of producing highly active recombinant PHD2 protein from which a fluorescence-based activity assay can be developed for high-throughput screening applications.

Cetrimonium bromide promotes the clearance of lipids by activating the TFEB-mediated autophagosome-lysosome pathway in hepatic cells.

Autophagy plays a key role in the metabolism of macromolecules via the degradative abilities of the lysosome. Transcription factor EB (TFEB) regulates autophagosome biogenesis and lysosome function, and promoting TFEB activity has emerged as a potential strategy for the treatment of metabolic disorders. Herein, we report that cetrimonium bromide (CTAB; a quaternary ammonium compound) promotes autophagy and lysosomal biogenesis by inducing the nuclear translocation of TFEB in hepatic cells. Knockdown of TFEB mediated by short hairpin RNA inhibits CTAB-induced autophagy and lysosomal biogenesis. Mechanistically, CTAB treatment inhibits the Akt-mTORC1 signaling pathway. Moreover, CTAB treatment significantly increases lipid metabolism in both palmitate- and oleate-treated HepG2 cells, and this increase was attenuated by knockdown of TFEB. Collectively, our results indicate that CTAB activates the autophagosome-lysosome pathway via inducing the nuclear translocation of TFEB by inhibiting the mTORC1 signaling pathway. These results add to the collective understanding of TFEB function and provide new insights into CTAB-mediated lipid metabolism.

Designing double freeform surfaces for large ray bending irradiance tailoring of extended LED sources.

Many illumination applications require redistributing the irradiance distributions of LED sources with large ray bending. The problem becomes even more challenging for a compact design where the LED size is no longer ignorable. We tackle this problem by simultaneously designing two freeform optical surfaces. An iterative wavefront tailoring (IWT) method is adapted for obtaining the entrance and exit base freeform surfaces with a predefined ray bending regulation under stereographic coordinates (u, v). The simulated annealing (SA) algorithm is employed for deforming the two base freeform surfaces using the 'uv' polynomials with the purpose of minimizing the relative root-mean-square deviation (RRMSD) between the simulated irradiance distribution and the prescribed one. The optimizations are implemented in an automated workflow which links the optimization engine, 3D modeling software and ray tracing software. The effectiveness of the proposed method is illustrated by designing several double-freeform-surface lenses (central heights: 10 mm) with different ray bending regulated base surfaces and 10-th order uv polynomial departures for generating 500 × 200 mm2 uniform irradiance distributions at a distance of 100 mm from 2 × 2 mm2 and 3 × 3 mm2 sources, respectively.

Esomeprazole inhibits the lysosomal cysteine protease legumain to prevent cancer metastasis.

Legumain is a newly discovered lysosomal cysteine protease that can cleave asparagine bonds and plays crucial roles in regulating immunity and cancer metastasis. Legumain has been shown to be highly expressed in various solid tumors, within the tumor microenvironment and its levels are directly related to tumor metastasis and poor prognosis. Therefore, legumain presents as a potential cancer therapeutic drug target. In this study, we have identified esomeprazole and omeprazole as novel legumain small molecule inhibitors by screening an FDA approved-drug library. These compounds inhibited enzyme activity of both recombinant and endogenous legumain proteins with esomeprazole displaying the highest inhibitory effect. Further molecular docking analysis also indicated that esomeprazole, the S- form of omeprazole had the most stable binding to legumain protein compared to R-omeprazole. Transwell assay data showed that esomeprazole and omeprazole reduced MDA-MB-231 breast cancer cell invasion without effecting cell viability. Moreover, an in vivo orthotopic transplantation nude mouse model study showed that esomeprazole reduced lung metastasis of MDA-MB-231 breast cancer cells. These results indicated that esomeprazole has the exciting potential to be used in anti-cancer therapy by preventing cancer metastasis via the inhibition of legumain enzyme activity. Graphical abstract.

Production of a novel bispecific protein ULBP1×CD19-scFv targeting the NKG2D receptor and CD19 to promote the activation of NK cells.

Natural killer (NK) cells are potent cytotoxic effector cells of the innate immune system and play an important role in tumor immunosurveillance and control. NKG2D is an activating receptor of NK cells. The NKG2D receptor-ligand system has contributed to immune cells recognizing tumor cells and the tumor microenvironment. In order to stretch the application of NK cells on adoptive immunotherapy for B-cell malignancies, we designed and produced a novel bispecific ULBP1×CD19-scFv fusion protein, in which the extracellular domain of NKG2D ligand ULBP1 was fused to a single chain variable fragment (scFv) of anti-CD19. The vector expressing ULBP1×CD19-scFv protein was constructed and expressed in Pichia pastoris. Effects of medium composition, concentration of methanol as the inducer, induction time and broth content in shake flask on the expression of the recombinant protein were investigated. The results showed that the optimized conditions for ULBP1×CD19-scFv expression were 1% methanol induction for 96 h with 15% broth content. The secreted recombinant protein was purified using ammonium sulfate fractionation and Ni-NTA affinity chromatography and the purity is about 93%. The cytotoxicity of NK92-MI cells against CD19+ Raji cells was enhanced in the presence of purified ULBP1×CD19-scFv protein. These results indicated that ULBP1 could be used as an activating element of bispecific killer engagers (BiKEs) and Pichia pastoris yeast might be an alternative expression host for BiKEs production.

Quercetin inhibiting the PD-1/PD-L1 interaction for immune-enhancing cancer chemopreventive agent.

Targeting the PD-1/PD-L1 immune checkpoints has achieved significant positive results in the treatment of multiple cancers. Quercetin is one of the most abundant dietary flavonoids found in various vegetables and fruits, and has a wide range of biological activities including immunomodulation. Here we report that quercetin dihydrate was screened and shown to inhibit the PD-1/PD-L1 interaction. Treatment with quercetin dihydrate promoted the killing activity of T cells on MDA-MB-231 and NCI-H460 cancer cells. Experiments using the xenograft mouse model showed that the growth rate of tumor volumes and masses in the quercetin dihydrate-treated mice were decreased. Immunohistochemistry of the tumors showed that CD8, GZMB, and IFN-γ were increased in the quercetin dihydrate-treated mice. These results suggest that quercetin dihydrate attenuates the inhibitory effect of PD-L1 on T cells by inhibiting the PD-1/PD-L1 interaction, which has an exciting potential to be used as a cancer chemopreventive agent.

Screening and production of an affibody inhibiting the interaction of the PD-1/PD-L1 immune checkpoint.

An affibody is a 58 amino acids peptide derived from the Z domain of staphylococcal protein A and generally applied in areas such as imaging diagnosis, clinical therapeutics and biotechnology research. To screen for an affibody targeting the immune checkpoint PD-L1, a combinatorial affibody library was generated in yeast using degenerate overlap PCR primers and In-fusion technology. Z-j1 and Z-j2 affibodies targeting the Ig-like V domain of PD-L1 were screened and identified from this combinatorial library using the yeast two hybrid system. The Z-j1 and Z-j2 recombinant affibody proteins were over produced in E.coli and purified. ELISA and GST pull-down assays showed that recombinant Z-j1 and Z-j2 affibody proteins bound with high affinity to PD-L1 and inhibited the interaction of PD-1/PD-L1. Thus, novel affibodies targeting the immune checkpoint PD-1/PD-L1 were identified and produced in this study and have the potential to be used in cancer immunotherapy.

Ultra-narrow multi-band polarization-insensitive plasmonic perfect absorber for sensing.

We theoretically propose a simple ultra-narrow multi-band perfect absorber for sensing applications. The perfect absorber consists of periodically arranged metallic nanodisks etched with regular prismatic holes standing on the dielectric-metal bi-layer films. Multiple ultra-narrow perfect absorption bands are obtained in the near-infrared region with the maximum bandwidth less than 21 nm and the intensity as high as 99.86%. The ultra-narrow multi-band perfect absorption originates from the synergy of localized surface plasmons, propagating surface plasmons and lattice resonances. The perfect absorber also presents other significant advantages, e.g. polarization insensitivity and high sensitivity of surrounding environments. Moreover, the prominent sensing performance for detecting the trace amounts of glucose in water is demonstrated. These features make it a promising candidate with great potential in the fields of perfect absorbers, plasmonic sensors, filters and multiplexing binding bio-molecular detection.

Ultra-broadband perfect absorber utilizing refractory materials in metal-insulator composite multilayer stacks.

We present an ultra-broadband perfect absorber composed of metal-insulator composite multilayer (MICM) stacks by placing the insulator-metal-insulator (IMI) grating on the metal-insulator-metal (MIM) film stacks. The absorber shows over 90% absorption spanning between 570 nm and 3539 nm, with an average absorption of 97% under normal incidence. The ultra-broadband perfect absorption characteristics are achieved by the synergy of guided mode resonances (GMRs), localized surface plasmons (LSPs), propagating surface plasmons (PSPs), and cavity modes. The polarization insensitivity is demonstrated by analyzing the absorption performance over arbitrary polarization angles. The ultra-broadband absorption remains more than 80% over a wide incident angle up to 50°, for both transverse electric (TE) and transverse magnetic (TM) modes. The ultra-broadband perfect absorber has tremendous potential for various applications, such as solar thermal energy harvesting, thermoelectrics, and imaging.

Functional recombinant human Legumain protein expression in Pichia pastoris to enable screening for Legumain small molecule inhibitors.

Legumain (LGMN) is a lysosomal protease that can specifically hydrolyze proteins after carboxyl-terminal asparagine residues. It has been reported that Legumain is highly expressed in many human tumors and promotes the migratory and invasive activity of cancer cells. Due to the limitation of an abundant and affordable source of endogenous active Legumain for further function studies, we produced the recombinant protein in Pichia pastoris. The pPICZα-LGMN expression plasmid was constructed and transformed into Pichia pastoris strain and positive recombinants were identified. Fermentation conditions were optimized and it was found that Legumain was most highly expressed under pH 6 culture conditions. In addition, the enzyme activity of the purified Legumain was tested using a fluorogenic substrate (Z-Ala-Ala-Asn-AMC) assay and the optimum pH for the autocatalytic activation of recombinant Legumain was very acidic at a pH value of 3. The recombinant protein was then used to screen a library of compounds and small molecule 1773 (Terramycin) was shown to effectively inhibit Legumain enzyme activity. These results indicate that the Pichia pastoris expression system can produce highly active recombinant Legumain protein allowing it to be used for High-throughput screening (HTS) applications.

Low density lipoprotein receptor class A domain containing 4 (LDLRAD4) promotes tumorigenesis of hepatic cancer cells.

LDLRAD4 was previously identified and shown to be connected with psychiatric disorders. The structure of LDLRAD4 protein is similar to that of TMEPAI protein, which is overexpressed in many tumors. However, it is still unknown whether LDLRAD4 is involved in tumorigenesis. In this study, the potential role of LDLRAD4 in tumorigenesis was investigated. LDLRAD4 is elevated in hepatic cancer cells and tumor tissues, and expression of LDLRAD4 promotes hepatic cancer cell HepG2 and SMMC-7721 proliferation and migration. LDLRAD4 interacts Nedd4 to promote cell proliferation and migration and negatively regulates the TGF-ß signaling. Furthermore, immunofluorescence microscopy analysis indicates that LDLRAD4 is localized to the lysosome and association with Nedd4 is necessary for its intracellular transport to the lysosome. In addition, depletion of LDLRAD4 in HepG2 liver cancer cells inhibited tumorigenesis in nude mice. These results reveal an oncogenic role of LDLRAD4 in tumorigenesis through its association with Nedd4.

Saponin fraction isolated from Conyza blinii H.Lév. demonstrates strong anti-cancer activity that is due to its NF-κB inhibition.

CBS (Conyza blinii saponin) is the total triterpenoidal saponins of Conyza blinii H.Lév which is a type of traditional Chinese medicine (TCM). We have discovered that CBS has a profound cytostatic activity against a range of solid tumour cells in a time- and dose-dependent manner. We also confirm that the cytostatic activity of CBS originates from its apoptosis induction effect. Additionally, we use immunoblot to find out that the apoptosis induction effect of CBS is attributable to the activation of mitochondrial pathway. Mechanistic study demonstrates that CBS is an effective NF-κB inhibitor. It inhibits p65 nuclear translocation and NF-κB downstream gene expression, including XIAP, survivin, Bcl-xL, COX-2, cyclin D1, MMP-2, MMP-9 in HeLa cells. Tumour xenografted animal models verify the anti-cancer efficacy in vivo. Tumour growth is significantly repressed in two CBS-treated groups compared with the controls (P < 0.001). CBS treatment (i.g.) leads to a 48.5% and 57.0% reduction in terms of tumour weight for the 10 and 20 mg/kg dosed groups respectively. Also no apparent observable adverse effects can be seen. These results suggest that CBS obliterate tumour, at least in part due to its NF-κB inhibition, which creates potential for CBS to be developed as a practical cancer treatment.

Lysosome Inhibitors Enhance the Chemotherapeutic Activity of Doxorubicin in HepG2 Cells.

The lysosome inhibitors bafilomycin A1 and chloroquine have both lysosomotropic properties and autophagy inhibition ability, and are promising clinical agents to be used in combination with anticancer drugs. In order to investigate this combination effect, HepG2 cells were treated with bafilomycin A1, chloroquine, or/and doxorubicin, and their proliferative ability, induction of apoptosis, and the changes of lysosomal membrane permeabilization and mitochondrial membrane potential were studied. The results demonstrate that treatment with bafilomycin A1 or chloroquine alone at a relatively low concentration promotes the inhibitory effect of doxorubicin on cell growth and apoptosis. Further studies reveal that bafilomycin A1 and chloroquine promote lysosomal membrane permeabilization and the reduction of mitochondrial membrane potential induced by doxorubicin. Our findings suggest that bafilomycin A1 and chloroquine potentiate the anticancer effect of doxorubicin in hepatic cancer cells and that supplementation of conventional chemotherapy with lysosome inhibitors may provide a more efficient anticancer therapy.

A dual-channel detection of mercuric ions using a label free G-quadruplex-based DNAzyme molecule.

We have constructed a 'turn-off' and label free bio-sensor using a DNAzyme molecule. This facile bio-sensor is capable of selective detection of mercuric ions with a high sensitivity and satisfactory dynamic range. More importantly, it is able to generate both fluorescent and colourimetric signals for detection. This dual-channel bio-sensor is expected to afford high detection confidence and overcome false-positive readout especially when assaying complex biological samples.

Expression and purification of active recombinant human bone morphogenetic 7-2 dimer fusion protein.

Bone morphogenetic proteins (BMPs) have been applied in bone regeneration therapy due to their significant osteogenic activity, however, the complicated processing and high cost in producing recombinant BMP have limited their use in the clinic. In this study, we have developed a simple method to prepare recombinant human BMP7-BMP2 fusion protein with a flexible peptide linker (rhBMP7-2). The rhBMP7-2 protein is expressed efficiently in Escherichia coli, and the denatured protein purified by anion exchange chromatography then refolded by dialysis. The yield was about 6.8 mg per gram of wet cell weight. The bioactivity of re-folded rhBMP7-2 was measured by alkaline phosphatase assay and alizarin red staining using both C2C12 and MC3T3-E1 cells, and also using the rat subcutaneous ectopic bone formation model. High level osteogenic activity was found in all the assays tested demonstrating the production of corrected folded and active rhBMP7-2 protein.

Semantic segmentation of UAV remote sensing images based on edge feature fusing and multi-level upsampling integrated with Deeplabv3.

Deeplabv3+ currently is the most representative semantic segmentation model. However, Deeplabv3+ tends to ignore targets of small size and usually fails to identify precise segmentation boundaries in the UAV remote sensing image segmentation task. To handle these problems, this paper proposes a semantic segmentation algorithm of UAV remote sensing images based on edge feature fusing and multi-level upsampling integrated with Deeplabv3+ (EMNet). EMNet uses MobileNetV2 as its backbone and adds an edge detection branch in the encoder to provide edge information for semantic segmentation. In the decoder, a multi-level upsampling method is designed to retain high-level semantic information (e.g., the target's location and boundary information). The experimental results show that the mIoU and mPA of EMNet improved over Deeplabv3+ by 7.11% and 6.93% on the dataset UAVid, and by 0.52% and 0.22% on the dataset ISPRS Vaihingen.

TMEPAI promotes degradation of the NF-κB signaling pathway inhibitory protein IκBα and contributes to tumorigenesis.

The transmembrane prostate androgen-induced protein (TMEPAI) is known to be highly expressed in various types of cancer and promoted oncogenic abilities. However, the mechanisms whereby TMEPAI facilitates tumorigenesis are not fully understood. Here we reported that expression of TMEPAI activated the NF-κB signaling. TMEPAI showed direct interaction with NF-κB pathway inhibitory protein IκBα. Though ubiquitin ligase Nedd4 (neural precursor cell expressed, developmentally down-regulated 4) did not interact with IκBα directly, TMEPAI recruited Nedd4 for ubiquitination of IκBα, leading to IκBα degradation through the proteasomal and lysosomal pathway, and promoted activation of NF-κB signaling. Further study indicated NF-κB signaling is involved in TMEPAI-induced cell proliferation and tumor growth in immune deficient mice. This finding helps to further understand the mechanism of TMEPAI on tumorigenesis and suggests TMEPAI is potential target for cancer treatment.

The Study on the Lasing Modes Modulated by the Dislocation Distribution in the GaN-Based Microrod Cavities.

Low-threshold lasing under pulsed optical pumping is demonstrated in GaN-based microrod cavities at room temperature, which are fabricated on the patterned sapphire substrates (PSS). Because the distribution of threading dislocations (TDs) is different at different locations, a confocal micro-photoluminescence spectroscopy (µ-PL) was performed to analyze the lasing properties of the different diameter microrods at the top of the triangle islands and between the triangle islands of the PSS substrates, respectively. The µ-PL results show that the 2 µm-diameter microrod cavity has a minimum threshold of about 0.3 kW/cm2. Whispering gallery modes (WGMs) in the microrod cavities are investigated by finite-difference time-domain simulation. Combined with the dislocation distribution in the GaN on the PSS substrates, it is found that the distribution of the strongest lasing WGMs always moves to the region with fewer TDs. This work reveals the connection between the lasing modes and the dislocation distribution, and can contribute to the development of low-threshold and high-efficiency GaN-based micro-lasers.