MUC1 promotes glioblastoma progression and TMZ resistance by stabilizing EGFRvIII.

Epidermal growth factor receptor variant III (EGFRvIII) is a mutant isoform of EGFR with a deletion of exons 2-7 making it insensitive to EGF stimulation and downstream signal constitutive activation. However, the mechanism underlying the stability of EGFRvIII remains unclear. Based on CRISPR-Cas9 library screening, we found that mucin1 (MUC1) is essential for EGFRvIII glioma cell survival and temozolomide (TMZ) resistance. We revealed that MUC1-C was upregulated in EGFRvIII-positive cells, where it enhanced the stability of EGFRvIII. Knockdown of MUC1-C increased the colocalization of EGFRvIII and lysosomes. Upregulation of MUC1 occurred in an NF-κB dependent manner, and inhibition of the NF-κB pathway could interrupt the EGFRvIII-MUC1 feedback loop by inhibiting MUC1-C. In a previous report, we identified AC1Q3QWB (AQB), a small molecule that could inhibit the phosphorylation of NF-κB. By screening the structural analogs of AQB, we obtained EPIC-1027, which could inhibit the NF-κB pathway more effectively. EPIC-1027 disrupted the EGFRvIII-MUC1-C positive feedback loop in vitro and in vivo, inhibited glioma progression, and promoted sensitization to TMZ. In conclusion, we revealed the pivotal role of MUC1-C in stabilizing EGFRvIII in glioblastoma (GBM) and identified a small molecule, EPIC-1027, with great potential in GBM treatment.

Large-scale and stacked transfer of bilayers MoS2devices on a flexible polyimide substrate.

Two-dimensional transition metal dichalcogenides (TMDs), as flexible and stretchable materials, have attracted considerable attention in the field of novel flexible electronics due to their excellent mechanical, optical, and electronic properties. Among the various TMD materials, atomically thin MoS2has become the most widely used material due to its advantageous properties, such as its adjustable bandgap, excellent performance, and ease of preparation. In this work, we demonstrated the practicality of a stacked wafer-scale two-layer MoS2film obtained by transferring multiple single-layer films grown using chemical vapor deposition. The MoS2field-effect transistor cell had a top-gated device structure with a (PI) film as the substrate, which exhibited a high on/off ratio (108), large average mobility (∼8.56 cm2V-1s-1), and exceptional uniformity. Furthermore, a range of flexible integrated logic devices, including inverters, NOR gates, and NAND gates, were successfully implemented via traditional lithography. These results highlight the immense potential of TMD materials, particularly MoS2, in enabling advanced flexible electronic and optoelectronic devices, which pave the way for transformative applications in future-generation electronics.

Cyclic-AMP signalling, MYC and hypoxia-inducible factor 1α intersect to regulate angiogenesis in B-cell lymphoma.

Angiogenesis and MYC expression associate with poor outcome in diffuse large B-cell lymphoma (DLBCL). MYC promotes neo-vasculature development but whether its deregulation in DLBCL contributes to angiogenesis is unclear. Examination of this relationship may uncover novel pathogenic regulatory circuitry as well as anti-angiogenic strategies in DLBCL. Here, we show that MYC expression positively correlates with vascular endothelial growth factor (VEGF) expression and angiogenesis in primary DLBCL biopsies, independently of dual expressor status or cell-of-origin classification. We found that MYC promotes VEGFA expression, a correlation that was validated in large datasets of mature B-cell tumours. Using DLBCL cell lines and patient-derived xenograft models, we identified the second messenger cyclic-AMP (cAMP) as a potent suppressor of MYC expression, VEGFA secretion and angiogenesis in DLBCL in normoxia. In hypoxia, cAMP switched targets and suppressed hypoxia-inducible factor 1α, a master regulator of VEGFA/angiogenesis in low oxygen environments. Lastly, we used the phosphodiesterase 4b (Pde4b) knockout mouse to demonstrate that the cAMP/PDE4 axis exercises additional anti-angiogenesis by directly targeting the lymphoma microenvironment. In conclusion, MYC could play a direct role in DLBCL angiogenesis, and modulation of cAMP levels, which can be achieved with clinical grade PDE4 inhibitors, has cell and non-cell autonomous anti-angiogenic activity in DLBCL.

Large-Area Flexible Memory Arrays of Oriented Molecular Ferroelectric Single Crystals with Nearly Saturated Polarization.

Molecular ferroelectrics (MFs) have been proven to demonstrate excellent properties even comparable to those of inorganic counterparts usually with heavy metals. However, the validation of their device applications is still at the infant stage. The polycrystalline feature of conventionally obtained MF films, the patterning challenges for microelectronics and the brittleness of crystalline films significantly hinder their development for organic integrated circuits, as well as emerging flexible electronics. Here, a large-area flexible memory array is demonstrated of oriented molecular ferroelectric single crystals (MFSCs) with nearly saturated polarization. Highly-uniform MFSC arrays are  prepared on large-scale substrates including Si wafers and flexible substrates using an asymmetric-wetting and microgroove-assisted coating (AWMAC) strategy. Resultant flexible memory arrays exhibit excellent nonvolatile memory properties with a low-operating voltage of <5 V, i.e., nearly saturated ferroelectric polarization (6.5 µC cm-2 ), and long bending endurance (>103 ) under various bending radii. These results may open an avenue for scalable flexible MF electronics with high performance.

Weak localization in graphene sandwiched by aligned h-BN flakes.

Charge carriers in graphene exhibit distinct characteristics from those in other two-dimensional materials because of their chiral nature. Additionally, multiple Dirac cones that emerge in graphene superlattices have been regarded as an interesting point in condensed-matter physics in recent years. Here, we report an investigation of the magneto-conductance in graphene encapsulated on the top and bottom by aligned h-BN. The bottom h-BN is precisely aligned with graphene, while the top h-BN is rotated a very small angle relative to it. Such a heterostructure could spoil the commensurate state existing in precisely aligned graphene while the giant moiré superlattice remains. A clear signature of weak localization and weak anti-localization is observed at multiple Dirac cones. Both the weak (anti)localization and the universal conductance fluctuations exhibit strong dependencies on the carrier density, temperature and channel length. This artificial heterostructure allows one to explore quantum interference in graphene with a wide spectrum of electronic properties.

Cooperative Adaptive Cruise Control and exhaust emission evaluation under heterogeneous connected vehicle network environment in urban city.

With the development of information communication and artificial intelligence, the ICV (intelligent connected vehicle) will inevitably play an important part in future urban transport system. In this paper, we study the car following behaviour under the heterogeneous ICV environment. The time to receive information varies from vehicle to vehicle, since the manual vehicles and autonomous vehicles co-exist on the road. By introducing time-varying lags function, a new car following model is proposed, and the cooperative control strategy of this model is studied. Based on Lyapunov function theory and linear matrix inequality (LMI) approach, the sufficient condition that the existence of the feedback controller is given, which makes the closed-loop system asymptotically stable under mixed traffic flow environment. That is to say, traffic congestion phenomenon under heterogeneous traffic flow can be effectively suppressed, and the feedback controller gain matrix can be obtained via solving linear matrix inequality. Finally, by simulation the method is verified effective in alleviating traffic congestions and reducing fuel consumption and exhaust emissions. It could be a useful reference to Cooperative Vehicle Infrastructure System and Smart City.

Epitaxial Growth of 6 in. Single-Crystalline Graphene on a Cu/Ni (111) Film at 750 °C via Chemical Vapor Deposition.

The future electronic application of graphene highly relies on the production of large-area high-quality single-crystal graphene. However, the growth of single-crystal graphene on different substrates via either single nucleation or seamless stitching is carried out at a temperature of 1000 °C or higher. The usage of this high temperature generates a variety of problems, including complexity of operation, higher contamination, metal evaporation, and wrinkles owing to the mismatch of thermal expansion coefficients between the substrate and graphene. Here, a new approach for the fabrication of ultraflat single-crystal graphene using Cu/Ni (111)/sapphire wafers at lower temperature is reported. It is found that the temperature of epitaxial growth of graphene using Cu/Ni (111) can be reduced to 750 °C, much lower than that of earlier reports on catalytic surfaces. Devices made of graphene grown at 750 °C have a carrier mobility up to ≈9700 cm2 V-1 s-1 at room temperature. This work shines light on a way toward a much lower temperature growth of high-quality graphene in single crystallinity, which could benefit future electronic applications.

Wafer-scale transferred multilayer MoS2 for high performance field effect transistors.

Chemical vapor deposition synthesis of semiconducting transition metal dichalcogenides (TMDs) offers a new route to build next-generation semiconductor devices. But realization of continuous and uniform multilayer (ML) TMD films is still limited by their specific growth kinetics, such as the competition between surface and interfacial energy. In this work, a layer-by-layer vacuum stacking transfer method is applied to obtain uniform and non-destructive ML-MoS2 films. Back-gated field effect transistor (FET) arrays of 1L- and 2L-MoS2 are fabricated on the same wafer, and their electrical performances are compared. We observe a significant increase of field-effect mobility for 2L-MoS2 FETs, up to 32.5 cm2 V-1 s-1, which is seven times higher than that of 1L-MoS2 (4.5 cm2 V-1 s-1). Then we also fabricated 1L-, 2L-, 3L-, and 4L-MoS2 FETs to further investigate the thickness-dependent characteristics of transferred ML-MoS2. Measurement results show a higher mobility but a smaller current on/off ratio as the layer number increases, suggesting that a balance between mobility and current on/off ratio can be achieved in 2L- and 3L-MoS2 FETs. Dual-gated structure is also investigated to demonstrate an improved electrostatic control of the ML-MoS2 channel.

Mucilaginibacter xinganensis sp. nov., a phenanthrene-degrading bacterium isolated from wetland soil.

An aerobic, Gram-stain negative, rod-shaped and non-motile strain, BJC16-A31T, was isolated from the wetland soil sample taken from Daxing'anling, Heilongjiang, People's Republic of China. Strain BJC16-A31T was found to be oxidase- and catalase-positive, and produced light orange colonies on modified R2A agar. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain BJC16-A31T is closely related to Mucilaginibacter gotjawali SA3-7T with 96.54% sequence similarity and it formed a separate lineage in the genus Mucilaginibacter. Strain BJC16-A31T contained menaquinone-7 (MK-7) as the predominant isoprenoid quinine. Anteiso-C15:0, C16:0 and anteiso-C15:0 were the major fatty acids. The major polar lipids were phosphatidylethanolamine, six unidentified polar lipid, two unidentified aminophospholipids and one unidentified aminolipid. The genome is composed of a circular 5,301,339 bp chromosome with average G + C percentage of 42.25%. The Average Nucleotide Identity (ANI) between strain BJC16-A31T and M. gotjawali SA3-7T was 77.51%. Combined phenotypic, chemotaxonomic, phylogenetic and genomic characteristics support the conclusion that strain BJC16-A31T represents a novel species of the genus Mucilaginibacter, for which the name Mucilaginibacter xinganensis sp. nov. is proposed. The type strain is BJC16-A31T (= CGMCC 1.12728T = NBRC 110384T).

Fabrication of Uniform Gold Nanopatterns on Graphene by Using Nanosphere Lithography.

In this study, we have realized controllable fabrication of gold nanopatterns on pristine monolayer graphene by using nanosphere lithography, in which polystyrene (PS) spheres are used as templates. With this method, periodically ordered triangular Au nanopatterns are uniformly formed on graphene surface. Micro-Raman spectroscopy shows that these sacrificial PS templates have no obvious effect on graphene surface structure while the subsequently formed Au nanopatterns are found to enhance Raman intensity of G and 2D bands by surface plasmon resonance. The compressive stress introduced in the metal deposition process leads to an obvious blue shift of 2D band. Besides, the metal-induced doping effect reduces the intensity ratio between 2D and G bands. This uniform arrangement of metal nanostructure is expected to grow other nanomaterials or used as Raman enhancement substrate in biomedicine, catalyzer and optics areas.

Competing Mechanisms for Photocurrent Induced at the Monolayer-Multilayer Graphene Junction.

Graphene is characterized by demonstrated unique properties for potential novel applications in photodetection operated in the frequency range from ultraviolet to terahertz. To date, detailed work on identifying the origin of photoresponse in graphene is still ongoing. Here, scanning photocurrent microscopy to explore the nature of photocurrent generated at the monolayer-multilayer graphene junction is employed. It is found that the contributing photocurrent mechanism relies on the mismatch of the Dirac points between the monolayer and multilayer graphene. For overlapping Dirac points, only photothermoelectric effect (PTE) is observed at the junction. When they do not coincide, a different photocurrent due to photovoltaic effect (PVE) appears and becomes more pronounced with larger separation of the Dirac points. While only PTE is reported for a monolayer-bilayer graphene junction in the literature, this work confirms the coexistence of PTE and PVE, thereby extending the understanding of photocurrent in graphene-based heterojunctions.

Laser-based white-light source for high-speed underwater wireless optical communication and high-efficiency underwater solid-state lighting.

White light generated by mixing the red, green, and blue laser diodes (RGB LDs) for simultaneous high-speed underwater wireless optical communication (UWOC) and high-efficiency underwater solid-state lighting (SSL) was proposed and demonstrated experimentally for the first time. The allowable maximum real-time data transmission rates of 3.2 Gbps, 3.4 Gbps, and 3.1 Gbps for RGB LDs with corresponding BERs of 3.6 × 10-3, 3.5 × 10-3 and 3.7 × 10-3 were obtained at a 2.3 m underwater transmission distance using an on-off keying (OOK) modulation scheme, respectively. And the corresponding UWOC aggregate data rate of 9.7 Gbps was achieved based on RGB LDs-based wavelength-division multiplexing (WDM) UWOC. Moreover, UWOC and underwater SSL by using RGB LDs mixed white light were investigated at different scenarios over an underwater link of 2.3 m. The RGB LDs mixed white light-based UWOC system without optical diffusers yielded a maximum allowable data rate of 8.7 Gbps with Commission International de l'Eclairage coordinates (CIE) of (0.3154, 0.3354), a correlated color temperature of 6322 K, a color rendering index of 69.3 and a corresponding illuminance of 7084 lux. Furthermore, optical diffusers were employed to provide large-area underwater SSL. The LDs mixed white light-based UWOC system with line and circle optical diffusers implemented data rates of 5.9 Gbps and 6.6 Gbps with CIE coordinates of (0.3183, 0.3269) and (0.3298, 0.3390), respectively. This work suggests the potential of LDs for applications in high-efficiency underwater white-light SSL and high-speed UWOC.

34.5 m underwater optical wireless communication with 2.70 Gbps data rate based on a green laser diode with NRZ-OOK modulation.

To enable high-speed long-distance underwater optical wireless communication (UOWC) supplementing traditional underwater wireless communication, a low-power 520 nm green laser diode (LD) based UOWC system was proposed and experimentally demonstrated to implement maximal communication capacity of up to 2.70 Gbps data rate over a 34.5 m underwater transmission distance by using non-return-to-zero on-off keying (NRZ-OOK) modulation scheme. Moreover, maximum data rates of up to 4.60 Gbps, 4.20 Gbps, 3.93 Gbps, 3.88 Gbps, and 3.48 Gbps at underwater distances of 2.3 m, 6.9 m, 11.5 m, 16.1 m and 20.7 m were achieved, respectively. The light attenuation coefficient of ~0.44 dB/m was obtained and the beam divergence angle is 0.35°, so the aallowable underwater transmission distance can be estimated to be ~90.7 m at a data rate of 0.15 Gbps with a corresponding received light-output power of -33.01 dBm and a bit-error rate (BER) of 2.0 ×10-6. In addition, when the data rate is up to 1 Gbps, the UOWC distance is predicted to be ~62.7 m for our proposed UOWC system. The achievements we make are suitable for applications requiring high-speed long-distance real-time UOWC.

Protein-protein interaction site predictions with minimum covariance determinant and Mahalanobis distance.

Protein-protein interaction site (PPIS) prediction must deal with the diversity of interaction sites that limits their prediction accuracy. Use of proteins with unknown or unidentified interactions can also lead to missing interfaces. Such data errors are often brought into the training dataset. In response to these two problems, we used the minimum covariance determinant (MCD) method to refine the training data to build a predictor with better performance, utilizing its ability of removing outliers. In order to predict test data in practice, a method based on Mahalanobis distance was devised to select proper test data as input for the predictor. With leave-one-validation and independent test, after the Mahalanobis distance screening, our method achieved higher performance according to Matthews correlation coefficient (MCC), although only a part of test data could be predicted. These results indicate that data refinement is an efficient approach to improve protein-protein interaction site prediction. By further optimizing our method, it is hopeful to develop predictors of better performance and wide range of application.

Ino80 is essential for proximal-distal axis asymmetry in part by regulating Bmp4 expression.

BACKGROUND: Understanding how embryos specify asymmetric axes is a major focus of biology. While much has been done to discover signaling pathways and transcription factors important for axis specification, comparatively little is known about how epigenetic regulators are involved. Epigenetic regulators operate downstream of signaling pathways and transcription factors to promote nuclear processes, most prominently transcription. To discover novel functions for these complexes in axis establishment during early embryonic development, we characterized phenotypes of a mouse knockout (KO) allele of the chromatin remodeling Ino80 ATPase. RESULTS: Ino80 KO embryos implant, but fail to develop beyond the egg cylinder stage. Ino80 KO embryonic stem cells (ESCs) are viable and maintain alkaline phosphatase activity, which is suggestive of pluripotency, but they fail to fully differentiate as either embryoid bodies or teratomas. Gene expression analysis of Ino80 KO early embryos by in situ hybridization and embryoid bodies by RT-PCR shows elevated Bmp4 expression and reduced expression of distal visceral endoderm (DVE) markers Cer1, Hex, and Lefty1. In culture, Bmp4 maintains stem cell pluripotency and when overexpressed is a known negative regulator of DVE differentiation in the early embryo. Consistent with the early embryo, we observed upregulated Bmp4 expression and down-regulated Cer1, Hex, and Lefty1 expression when Ino80 KO ESCs are differentiated in a monolayer. Molecular studies in these same cells demonstrate that Ino80 bound to the Bmp4 promoter regulates its chromatin structure, which correlates with enhanced SP1 binding. These results in combination suggest that Ino80 directly regulates the chromatin structure of the Bmp4 promoter with consequences to gene expression. CONCLUSIONS: In contrast to Ino80 KO differentiated cells, our experiments show that undifferentiated Ino80 KO ESCs are viable, but fail to differentiate in culture and in the early embryo. Ino80 KO ESCs and the early embryo up-regulate Bmp4 expression and down-regulate the expression of DVE markers Cer1, Hex and Lefty1. Based on this data, we propose a model where the Ino80 chromatin remodeling complex represses Bmp4 expression in the early embryo, thus promoting DVE differentiation and successful proximal-distal axis establishment. These results are significant because they show that epigenetic regulators have specific roles in establishing embryonic axes. By further characterizing these complexes, we will deepen our understanding of how the mammalian embryo is patterned by epigenetic regulators.

Stable and Fast-Response Capacitive Humidity Sensors Based on a ZnO Nanopowder/PVP-RGO Multilayer.

In this paper, capacitive-type humidity sensors were prepared by sequentially drop-coating the aqueous suspensions of zinc oxide (ZnO) nanopowders and polyvinyl pyrrolidone-reduced graphene oxide (PVP-RGO) nanocomposites onto interdigitated electrodes. Significant improvements in both sensitivity and linearity were achieved for the ZnO/PVP-RGO sensors compared with the PVP-RGO/ZnO, PVP-RGO, and ZnO counterparts. Moreover, the produced ZnO/PVP-RGO sensors exhibited rather small hysteresis, fast response-recovery time, and long-term stability. Based on morphological and structural analyses, it can be inferred that the excellent humidity sensing properties of the ZnO/PVP-RGO sensors may be attributed to the high surface-to-volume ratio of the multilayer structure and the supporting roles of the PVP-RGO nanocomposites. The results in this work hence provide adequate guidelines for designing high-performance humidity sensors that make use of the multilayer structure of semiconductor oxide materials and PVP-RGO nanocomposites.

[Distribution of diatoms in Chuanyang River of Pudong new area of Shanghai and its forensic application].

OBJECTIVE: To investigate the quantity and species distribution of diatoms in Chuanyang River of Pudong new area of Shanghai and provide references for the invesitigation of water body in forensic practice. METHODS: The water samples collected from 15 areas in Chuanyang River of Pudong new area in September 2012 were examined by microscope to identify the species of diatoms. RESULTS: Cyclotella and Pinnularia were found to be the dominant species within the 12 species of diatoms in Chuanyang River, which showed differences in species among the sections of Huangpu River, the center and the East China Sea. CONCLUSION: The differences in subsectional distribution of diatom species in Chuanyang River may provide a new foundation for forensic identification in drowning cases especially in the determination of falling location.

High-Performance Contact-Doped WSe2 Transistors Using TaSe2 Electrodes.

Two-dimensional (2D) transitional metal dichalcogenides (TMDs) have garnered significant attention due to their potential for next-generation electronics, which require device scaling. However, the performance of TMD-based field-effect transistors (FETs) is greatly limited by the contact resistance. This study develops an effective strategy to optimize the contact resistance of WSe2 FETs by combining contact doping and 2D metallic electrode materials. The contact regions were doped using a laser, and the metallic TaSe2 flakes were stacked on doped WSe2 as electrodes. Doping the contact areas decreases the depletion width, while introducing the TaSe2 contact results in a lower Schottky barrier. This method significantly improves the electrical performance of the WSe2 FETs. The doped WSe2/TaSe2 contact exhibits an ultralow Schottky barrier height of 65 meV and a contact resistance of 11 kΩ·µm, which is a 50-fold reduction compared to the conventional Cr/Au contact. Our method offers a way on fabricating high-performance 2D FETs.

A simple iterative method to optimize protein-ligand-binding residue prediction.

This article describes an iterative method (IM) for improving protein-ligand-binding residue prediction. Through modifying the binding residue definition in every iteration, this method, step by step, increased the performance of the classifiers used. Using a balanced assessment index (BAI), the classifier optimized by the IM achieved a value of 80.4 that is bigger than the one (66.9) of the initial classifier. According to mean per-instance BAI scores, a direct comparison of methods has been carried out along with an analysis of statistical significance of the differences in performance. The results show that the iterative method (IM) does achieve a higher mean score than the threshold-altering method (TAM) used in our previous study and there is a statistically significant difference between the two methods. The IM has a significant advantage that it is independent of the concrete residue characterization models and learning algorithms, and more extensively applicable. These results indicate that optimizing the binding residue definition is also an effective approach to improve protein-ligand-binding residue prediction.

Revealing the origin of PL evolution of InSe flake induced by laser irradiation.

Two-dimensional InSe has been considered as a promising candidate for novel optoelectronic devices owing to large electron mobility and a near-infrared optical band gap. However, its widespread applications suffer from environmental instability. A lot of theoretical studies on the degradation mechanism of InSe have been reported whereas the experimental proofs are few. Meanwhile, the role of the extrinsic environment is still obscure during the degradation. As a common technique of studying the degradation mechanism of 2D materials, laser irradiation exhibits many unique advantages, such as being fast, convenient, and offering in situ compatibility. Here, we have developed a laser-treated method, which involves performing repeated measurements at the same point while monitoring the evolution of the resulting PL, to systematically study the photo-induced degradation process of InSe. Interestingly, we observe different evolution behavior of PL intensity under weak irradiation and strong irradiation. Our experimental results indicate the vacancy passivation and degrading effect simultaneously occurring in InSe under a weak laser irradiation, resulting in the PL increasing first and then decreasing during the measurement. Meanwhile we also notice that the passivation has a stronger effect on the PL than the degrading effect of weak oxidation. In contrast, under a strong laser irradiation, the InSe suffers serious destruction caused by excess heating and intense oxidation. This leads to a direct decrease of PL and corresponding oxidative products. Our work provides a reliable experimental supplement to the photo oxidation study of InSe and opens up a new avenue to regulate the PL of InSe.