Inhibition of viral suppressor of RNAi proteins by designer peptides protects from enteroviral infection in vivo.

RNA interference (RNAi) is the major antiviral mechanism in plants and invertebrates, but the absence of detectable viral (v)siRNAs in mammalian cells upon viral infection has questioned the functional relevance of this pathway in mammalian immunity. We designed a series of peptides specifically targeting enterovirus A71 (EV-A71)-encoded protein 3A, a viral suppressor of RNAi (VSR). These peptides abrogated the VSR function of EV-A71 in infected cells and resulted in the accumulation of vsiRNAs and reduced viral replication. These vsiRNAs were functional, as evidenced by RISC-loading and silencing of target RNAs. The effects of VSR-targeting peptides (VTPs) on infection with EV-A71 as well as another enterovirus, Coxsackievirus-A16, were ablated upon deletion of Dicer1 or AGO2, core components of the RNAi pathway. In vivo, VTP treatment protected mice against lethal EV-A71 challenge, with detectable vsiRNAs. Our findings provide evidence for the functional relevance of RNAi in mammalian immunity and present a therapeutic strategy for infectious disease.

Cascaded compression of size distribution of nanopores in monolayer graphene.

Monolayer graphene with nanometre-scale pores, atomically thin thickness and remarkable mechanical properties provides wide-ranging opportunities for applications in ion and molecular separations1, energy storage2 and electronics3. Because the performance of these applications relies heavily on the size of the nanopores, it is desirable to design and engineer with precision a suitable nanopore size with narrow size distributions. However, conventional top-down processes often yield log-normal distributions with long tails, particularly at the sub-nanometre scale4. Moreover, the size distribution and density of the nanopores are often intrinsically intercorrelated, leading to a trade-off between the two that substantially limits their applications5-9. Here we report a cascaded compression approach to narrowing the size distribution of nanopores with left skewness and ultrasmall tail deviation, while keeping the density of nanopores increasing at each compression cycle. The formation of nanopores is split into many small steps, in each of which the size distribution of all the existing nanopores is compressed by a combination of shrinkage and expansion and, at the same time as expansion, a new batch of nanopores is created, leading to increased nanopore density by each cycle. As a result, high-density nanopores in monolayer graphene with a left-skewed, short-tail size distribution are obtained that show ultrafast and ångström-size-tunable selective transport of ions and molecules, breaking the limitation of the conventional log-normal size distribution9,10. This method allows for independent control of several metrics of the generated nanopores, including the density, mean diameter, standard deviation and skewness of the size distribution, which will lead to the next leap in nanotechnology.

Ultralow contact resistance between semimetal and monolayer semiconductors.

Advanced beyond-silicon electronic technology requires both channel materials and also ultralow-resistance contacts to be discovered1,2. Atomically thin two-dimensional semiconductors have great potential for realizing high-performance electronic devices1,3. However, owing to metal-induced gap states (MIGS)4-7, energy barriers at the metal-semiconductor interface-which fundamentally lead to high contact resistance and poor current-delivery capability-have constrained the improvement of two-dimensional semiconductor transistors so far2,8,9. Here we report ohmic contact between semimetallic bismuth and semiconducting monolayer transition metal dichalcogenides (TMDs) where the MIGS are sufficiently suppressed and degenerate states in the TMD are spontaneously formed in contact with bismuth. Through this approach, we achieve zero Schottky barrier height, a contact resistance of 123 ohm micrometres and an on-state current density of 1,135 microamps per micrometre on monolayer MoS2; these two values are, to the best of our knowledge, the lowest and highest yet recorded, respectively. We also demonstrate that excellent ohmic contacts can be formed on various monolayer semiconductors, including MoS2, WS2 and WSe2. Our reported contact resistances are a substantial improvement for two-dimensional semiconductors, and approach the quantum limit. This technology unveils the potential of high-performance monolayer transistors that are on par with state-of-the-art three-dimensional semiconductors, enabling further device downscaling and extending Moore's law.

Two-dimensional halide perovskite lateral epitaxial heterostructures.

Epitaxial heterostructures based on oxide perovskites and III-V, II-VI and transition metal dichalcogenide semiconductors form the foundation of modern electronics and optoelectronics1-7. Halide perovskites-an emerging family of tunable semiconductors with desirable properties-are attractive for applications such as solution-processed solar cells, light-emitting diodes, detectors and lasers8-15. Their inherently soft crystal lattice allows greater tolerance to lattice mismatch, making them promising for heterostructure formation and semiconductor integration16,17. Atomically sharp epitaxial interfaces are necessary to improve performance and for device miniaturization. However, epitaxial growth of atomically sharp heterostructures of halide perovskites has not yet been achieved, owing to their high intrinsic ion mobility, which leads to interdiffusion and large junction widths18-21, and owing to their poor chemical stability, which leads to decomposition of prior layers during the fabrication of subsequent layers. Therefore, understanding the origins of this instability and identifying effective approaches to suppress ion diffusion are of great importance22-26. Here we report an effective strategy to substantially inhibit in-plane ion diffusion in two-dimensional halide perovskites by incorporating rigid π-conjugated organic ligands. We demonstrate highly stable and tunable lateral epitaxial heterostructures, multiheterostructures and superlattices. Near-atomically sharp interfaces and epitaxial growth are revealed by low-dose aberration-corrected high-resolution transmission electron microscopy. Molecular dynamics simulations confirm the reduced heterostructure disorder and larger vacancy formation energies of the two-dimensional perovskites in the presence of conjugated ligands. These findings provide insights into the immobilization and stabilization of halide perovskite semiconductors and demonstrate a materials platform for complex and molecularly thin superlattices, devices and integrated circuits.

Unconventional ferroelectricity in moiré heterostructures.

The constituent particles of matter can arrange themselves in various ways, giving rise to emergent phenomena that can be surprisingly rich and often cannot be understood by studying only the individual constituents. Discovering and understanding the emergence of such phenomena in quantum materials-especially those in which multiple degrees of freedom or energy scales are delicately balanced-is of fundamental interest to condensed-matter research1,2. Here we report on the surprising observation of emergent ferroelectricity in graphene-based moiré heterostructures. Ferroelectric materials show electrically switchable electric dipoles, which are usually formed by spatial separation between the average centres of positive and negative charge within the unit cell. On this basis, it is difficult to imagine graphene-a material composed of only carbon atoms-exhibiting ferroelectricity3. However, in this work we realize switchable ferroelectricity in Bernal-stacked bilayer graphene sandwiched between two hexagonal boron nitride layers. By introducing a moiré superlattice potential (via aligning bilayer graphene with the top and/or bottom boron nitride crystals), we observe prominent and robust hysteretic behaviour of the graphene resistance with an externally applied out-of-plane displacement field. Our systematic transport measurements reveal a rich and striking response as a function of displacement field and electron filling, and beyond the framework of conventional ferroelectrics. We further directly probe the ferroelectric polarization through a non-local monolayer graphene sensor. Our results suggest an unconventional, odd-parity electronic ordering in the bilayer graphene/boron nitride moiré system. This emergent moiré ferroelectricity may enable ultrafast, programmable and atomically thin carbon-based memory devices.

Two-dimensional MoS2-enabled flexible rectenna for Wi-Fi-band wireless energy harvesting.

The mechanical and electronic properties of two-dimensional materials make them promising for use in flexible electronics1-3. Their atomic thickness and large-scale synthesis capability could enable the development of 'smart skin'1,3-5, which could transform ordinary objects into an intelligent distributed sensor network6. However, although many important components of such a distributed electronic system have already been demonstrated (for example, transistors, sensors and memory devices based on two-dimensional materials1,2,4,7), an efficient, flexible and always-on energy-harvesting solution, which is indispensable for self-powered systems, is still missing. Electromagnetic radiation from Wi-Fi systems operating at 2.4 and 5.9 gigahertz8 is becoming increasingly ubiquitous and would be ideal to harvest for powering future distributed electronics. However, the high frequencies used for Wi-Fi communications have remained elusive to radiofrequency harvesters (that is, rectennas) made of flexible semiconductors owing to their limited transport properties9-12. Here we demonstrate an atomically thin and flexible rectenna based on a MoS2 semiconducting-metallic-phase heterojunction with a cutoff frequency of 10 gigahertz, which represents an improvement in speed of roughly one order of magnitude compared with current state-of-the-art flexible rectifiers9-12. This flexible MoS2-based rectifier operates up to the X-band8 (8 to 12 gigahertz) and covers most of the unlicensed industrial, scientific and medical radio band, including the Wi-Fi channels. By integrating the ultrafast MoS2 rectifier with a flexible Wi-Fi-band antenna, we fabricate a fully flexible and integrated rectenna that achieves wireless energy harvesting of electromagnetic radiation in the Wi-Fi band with zero external bias (battery-free). Moreover, our MoS2 rectifier acts as a flexible mixer, realizing frequency conversion beyond 10 gigahertz. This work provides a universal energy-harvesting building block that can be integrated with various flexible electronic systems.

Boosting Monolayer Transition Metal Dichalcogenides Growth by Hydrogen-Free Ramping during Chemical Vapor Deposition.

The controlled vapor-phase synthesis of two-dimensional (2D) transition metal dichalcogenides (TMDs) is essential for functional applications. While chemical vapor deposition (CVD) techniques have been successful for transition metal sulfides, extending these methods to selenides and tellurides often faces challenges due to uncertain roles of hydrogen (H2) in their synthesis. Using CVD growth of MoSe2 as an example, this study illustrates the role of a H2-free environment during temperature ramping in suppressing the reduction of MoO3, which promotes effective vaporization and selenization of the Mo precursor to form MoSe2 monolayers with excellent crystal quality. As-synthesized MoSe2 monolayer-based field-effect transistors show excellent carrier mobility of up to 20.9 cm2/(V·s) with an on-off ratio of 7 × 107. This approach can be extended to other TMDs, such as WSe2, MoTe2, and MoSe2/WSe2 in-plane heterostructures. Our work provides a rational and facile approach to reproducibly synthesize high-quality TMD monolayers, facilitating their translation from laboratory to manufacturing.

Cav-1 regulates the bile salt export pump on the canalicular membrane of hepatocytes by PKCα-associated signalling under cholesterol stimulation.

BACKGROUND AND AIMS: The secretion of bile salts transported by the bile salt export pump (BSEP) is the primary driving force for the generation of bile flow; thus, it is closely related to the formation of cholesterol stones. Caveolin-1 (Cav-1), an essential player in cell signalling and endocytosis, is known to co-localize with cholesterol-rich membrane domains. This study illustrates the role of Cav-1 and BSEP in cholesterol stone formation. METHODS: Adult male C57BL/6 mice were used as an animal model. HepG2 cells were cultured under different cholesterol concentrations and BSEP, Cav-1, p-PKCα and Hax-1 expression levels were determined via Western blotting. Expression levels of BSEP and Cav-1 mRNA were detected using real-time PCR. Immunofluorescence and immunoprecipitation assays were performed to study BSEP and Hax-1 distribution. Finally, an ATPase activity assay was performed to detect BSEP transport activity under different cholesterol concentrations in cells. RESULTS: Under low-concentration stimulation with cholesterol, Cav-1 and BSEP protein and mRNA expression levels significantly increased, PKCα phosphorylation significantly decreased, BSEP binding capacity to Hax-1 weakened, and BSEP function increased. Under high-concentration stimulation with cholesterol, Cav-1 and BSEP protein and mRNA expression levels decreased, PKCα phosphorylation increased, BSEP binding capacity to Hax-1 rose, and BSEP function decreased. CONCLUSION: Cav-1 regulates the bile salt export pump on the canalicular membrane of hepatocytes via PKCα-associated signalling under cholesterol stimulation.

Heterozygous CAPZA2 mutations cause global developmental delay, hypotonia with epilepsy: a case report and the literature review.

CAPZA2 encodes the α2 subunit of CAPZA, which is vital for actin polymerization and depolymerization in humans. However, understanding of diseases associated with CAPZA2 remains limited. To date, only three cases have been documented with neurodevelopmental abnormalities such as delayed motor development, speech delay, intellectual disability, hypotonia, and a history of seizures. In this study, we document a patient who exhibited seizures, mild intellectual disability, and impaired motor development yet did not demonstrate speech delay or hypotonia. The patient also suffered from recurrent instances of respiratory infections, gastrointestinal and allergic diseases. A novel de novo splicing variant c.219+1 G > A was detected in the CAPZA2 gene through whole-exome sequencing. This variant led to exon 4 skipping in mRNA splicing, confirmed by RT-PCR and Sanger sequencing. To our knowledge, this is the third study on human CAPZA2 defects, documenting the fourth unambiguously diagnosed case. Furthermore, this splicing mutation type is reported here for the first time. Our research offers additional support for the existence of a CAPZA2-related non-syndromic neurodevelopmental disorder. Our findings augment our understanding of the phenotypic range associated with CAPZA2 deficiency and enrich the knowledge of the mutational spectrum of the CAPZA2 gene.

Effects of a UV absorber in silica-loaded resin on DLP silica fiber preform fabrication.

3D printing technologies have distinguished advantages in manufacturing arbitrary shapes and complex structures that have attracted us to use digital light processing (DLP) technology for specialty silica optical fiber preforms. One of the main tasks is to develop an appropriate recipe for DLP resin that is UV sensitive and loaded with silica nanoparticles. In this work, the effects of a UV absorber in highly silica-loaded resin on DLP printing are experimentally investigated. Spot tests and DLP printing are carried out on resins with varying dosages of a typical UV absorber, Sudan Orange G. Based on the experimental results, the UV absorber can significantly improve the resolution of DLP printed green bodies while requiring a larger exposure dose.

Designing artificial two-dimensional landscapes via atomic-layer substitution.

Technology advancements in history have often been propelled by material innovations. In recent years, two-dimensional (2D) materials have attracted substantial interest as an ideal platform to construct atomic-level material architectures. In this work, we design a reaction pathway steered in a very different energy landscape, in contrast to typical thermal chemical vapor deposition method in high temperature, to enable room-temperature atomic-layer substitution (RT-ALS). First-principle calculations elucidate how the RT-ALS process is overall exothermic in energy and only has a small reaction barrier, facilitating the reaction to occur at room temperature. As a result, a variety of Janus monolayer transition metal dichalcogenides with vertical dipole could be universally realized. In particular, the RT-ALS strategy can be combined with lithography and flip-transfer to enable programmable in-plane multiheterostructures with different out-of-plane crystal symmetry and electric polarization. Various characterizations have confirmed the fidelity of the precise single atomic layer conversion. Our approach for designing an artificial 2D landscape at selective locations of a single layer of atoms can lead to unique electronic, photonic, and mechanical properties previously not found in nature. This opens a new paradigm for future material design, enabling structures and properties for unexplored territories.

New sesquiterpenoids from Biscogniauxia sp.

Five new sesquiterpenoids, including a campherenane-type (1), a bergamotane-type (2), a drimane-type (3), and two bisabolane-type (5-6) sesquiterpenoids have been isolated from Biscogniauxia sp. 71-10-1-1. Their structures were determined by spectroscopic analyses, quantum chemical ECD calculations,13C chemical shifts calculations, and X-ray crystallography. This is the first report of campherenane-type and drimane-type sesquiterpenoids from Biscogniauxia. Furthermore, the anti-inflammatory assays of all compounds are evaluated, and the results showed that compounds 3 and 7 exhibited the effects against the production of the pro-inflammatory cytokine TNF-α.

High-Performance Complementary Circuits from Two-Dimensional MoTe2.

Two-dimensional (2D) materials hold great promise for future complementary metal-oxide semiconductor (CMOS) technology. However, the lack of effective methods to tune the Schottky barrier poses a challenge in constructing high-performance complementary circuits from the same material. Here, we reveal that the polarity of pristine MoTe2 field-effect transistors (FETs) with minimized air exposure is n-type, irrespective of the metal contact type. The fabricated n-FETs with palladium contact can reach electron currents up to 275 µA/µm at VDS = 2 V. For p-FETs, we introduce a novel nitric oxide doping strategy, allowing a controlled transition of MoTe2 FETs from n-type to unipolar p-type. By doping only in the contact region, we demonstrate hole currents up to 170 µA/µm at VDS= -2 V with preserved Ion/Ioff ratios of 105. Finally, we present a complementary inverter circuit comprising the high-performance n- and p-type FETs based on MoTe2, promoting the application of 2D materials in future electronic systems.

Effect of Twist Angle on Interfacial Thermal Transport in Two-Dimensional Bilayers.

Advances in two-dimensional (2D) devices require innovative approaches for manipulating transport properties. Analogous to the electrical and optical responses, it has been predicted that thermal transport across 2D materials can have a similar strong twist-angle dependence. Here, we report experimental evidence deviating from this understanding. In contrast to the large tunability in electrical transport, we measured an unexpected weak twist-angle dependence of interfacial thermal transport in MoS2 bilayers, which is consistent with theoretical calculations. More notably, we confirmed the existence of distinct regimes with weak and strong twist-angle dependencies for thermal transport, where, for example, a much stronger change with twist angles is expected for graphene bilayers. With atomic simulations, the distinct twist-angle effects on different 2D materials are explained by the suppression of long-wavelength phonons via the moiré superlattice. These findings elucidate the unique feature of 2D thermal transport and enable a new design space for engineering thermal devices.

Two-Terminal MoS2 Memristor and the Homogeneous Integration with a MoS2 Transistor for Neural Networks.

Memristors are promising candidates for constructing neural networks. However, their dissimilar working mechanism to that of the addressing transistors can result in a scaling mismatch, which may hinder efficient integration. Here, we demonstrate two-terminal MoS2 memristors that work with a charge-based mechanism similar to that in transistors, which enables the homogeneous integration with MoS2 transistors to realize one-transistor-one-memristor addressable cells for assembling programmable networks. The homogenously integrated cells are implemented in a 2 × 2 network array to demonstrate the enabled addressability and programmability. The potential for assembling a scalable network is evaluated in a simulated neural network using obtained realistic device parameters, which achieves over 91% pattern recognition accuracy. This study also reveals a generic mechanism and strategy that can be applied to other semiconducting devices for the engineering and homogeneous integration of memristive systems.

Revealing Variable Dependences in Hexagonal Boron Nitride Synthesis via Machine Learning.

Wafer-scale monolayer two-dimensional (2D) materials have been realized by epitaxial chemical vapor deposition (CVD) in recent years. To scale up the synthesis of 2D materials, a systematic analysis of how the growth dynamics depend on the growth parameters is essential to unravel its mechanisms. However, the studies of CVD-grown 2D materials mostly adopted the control variate method and considered each parameter as an independent variable, which is not comprehensive for 2D materials growth optimization. Herein, we synthesized a representative 2D material, monolayer hexagonal boron nitride (hBN), on single-crystalline Cu (111) by epitaxial chemical vapor deposition and varied the growth parameters to regulate the hBN domain sizes. Furthermore, we explored the correlation between two growth parameters and provided the growth windows for large flake sizes by the Gaussian process. This new analysis approach based on machine learning provides a more comprehensive understanding of the growth mechanism for 2D materials.

Low-Temperature Vapor-Phase Growth of 2D Metal Chalcogenides.

2D metal chalcogenides (MCs) have garnered significant attention from both scientific and industrial communities due to their potential in developing next-generation functional devices. Vapor-phase deposition methods have proven highly effective in fabricating high-quality 2D MCs. Nevertheless, the conventionally high thermal budgets required for synthesizing 2D MCs pose limitations, particularly in the integration of multiple components and in specialized applications (such as flexible electronics). To overcome these challenges, it is desirable to reduce the thermal energy requirements, thus facilitating the growth of various 2D MCs at lower temperatures. Numerous endeavors have been undertaken to develop low-temperature vapor-phase growth techniques for 2D MCs, and this review aims to provide an overview of the latest advances in low-temperature vapor-phase growth of 2D MCs. Initially, the review highlights the latest progress in achieving high-quality 2D MCs through various low-temperature vapor-phase techniques, including chemical vapor deposition (CVD), metal-organic CVD, plasma-enhanced CVD, atomic layer deposition (ALD), etc. The strengths and current limitations of these methods are also evaluated. Subsequently, the review consolidates the diverse applications of 2D MCs grown at low temperatures, covering fields such as electronics, optoelectronics, flexible devices, and catalysis. Finally, current challenges and future research directions are briefly discussed, considering the most recent progress in the field.

Enoxacin Shows Broad-Spectrum Antiviral Activity against Diverse Viruses by Enhancing Antiviral RNA Interference in Insects.

RNA interference (RNAi) functions as the major host antiviral defense in insects, while less is understood about how to utilize antiviral RNAi in controlling viral infection in insects. Enoxacin belongs to the family of synthetic antibacterial compounds based on a fluoroquinolone skeleton that has been previously found to enhance RNAi in mammalian cells. In this study, we show that enoxacin efficiently inhibited viral replication of Drosophila C virus (DCV) and cricket paralysis virus (CrPV) in cultured Drosophila cells. Enoxacin promoted the loading of Dicer-2-processed virus-derived small interfering RNA (siRNA) into the RNA-induced silencing complex, thereby enhancing the antiviral RNAi response in infected cells. Moreover, enoxacin treatment elicited RNAi-dependent in vivo protective efficacy against DCV or CrPV challenge in adult fruit flies. In addition, enoxacin also inhibited the replication of flaviviruses, including dengue virus and Zika virus, in Aedes mosquito cells in an RNAi-dependent manner. Together, our findings demonstrate that enoxacin can enhance RNAi in insects, and enhancing RNAi by enoxacin is an effective antiviral strategy against diverse viruses in insects, which may be exploited as a broad-spectrum antiviral agent to control the vector transmission of arboviruses or viral diseases in insect farming. IMPORTANCE RNAi has been widely recognized as one of the most broadly acting and robust antiviral mechanisms in insects. However, the application of antiviral RNAi in controlling viral infections in insects is less understood. Enoxacin is a fluoroquinolone compound that was previously found to enhance RNAi in mammalian cells, while its RNAi-enhancing activity has not been assessed in insects. Here, we show that enoxacin treatment inhibited viral replication of DCV and CrPV in Drosophila cells and adult fruit flies. Enoxacin promoted the loading of Dicer-generated virus-derived siRNA into the Ago2-incorporated RNA-induced silencing complex and in turn strengthened the antiviral RNAi response in the infected cells. Moreover, enoxacin displayed effective RNAi-dependent antiviral effects against flaviviruses, such as dengue virus and Zika virus, in mosquito cells. This study is the first to demonstrate that enhancing RNAi by enoxacin elicits potent antiviral effects against diverse viruses in insects.

Tuning colour centres at a twisted hexagonal boron nitride interface.

The colour centre platform holds promise for quantum technologies, and hexagonal boron nitride has attracted attention due to the high brightness and stability, optically addressable spin states and wide wavelength coverage discovered in its emitters. However, its application is hindered by the typically random defect distribution and complex mesoscopic environment. Here, employing cathodoluminescence, we demonstrate on-demand activation and control of colour centre emission at the twisted interface of two hexagonal boron nitride flakes. Further, we show that colour centre emission brightness can be enhanced by two orders of magnitude by tuning the twist angle. Additionally, by applying an external voltage, nearly 100% brightness modulation is achieved. Our ab initio GW and GW plus Bethe-Salpeter equation calculations suggest that the emission is correlated to nitrogen vacancies and that a twist-induced moiré potential facilitates electron-hole recombination. This mechanism is further exploited to draw nanoscale colour centre patterns using electron beams.

Remote epitaxy through graphene enables two-dimensional material-based layer transfer.

Epitaxy-the growth of a crystalline material on a substrate-is crucial for the semiconductor industry, but is often limited by the need for lattice matching between the two material systems. This strict requirement is relaxed for van der Waals epitaxy, in which epitaxy on layered or two-dimensional (2D) materials is mediated by weak van der Waals interactions, and which also allows facile layer release from 2D surfaces. It has been thought that 2D materials are the only seed layers for van der Waals epitaxy. However, the substrates below 2D materials may still interact with the layers grown during epitaxy (epilayers), as in the case of the so-called wetting transparency documented for graphene. Here we show that the weak van der Waals potential of graphene cannot completely screen the stronger potential field of many substrates, which enables epitaxial growth to occur despite its presence. We use density functional theory calculations to establish that adatoms will experience remote epitaxial registry with a substrate through a substrate-epilayer gap of up to nine ångströms; this gap can accommodate a monolayer of graphene. We confirm the predictions with homoepitaxial growth of GaAs(001) on GaAs(001) substrates through monolayer graphene, and show that the approach is also applicable to InP and GaP. The grown single-crystalline films are rapidly released from the graphene-coated substrate and perform as well as conventionally prepared films when incorporated in light-emitting devices. This technique enables any type of semiconductor film to be copied from underlying substrates through 2D materials, and then the resultant epilayer to be rapidly released and transferred to a substrate of interest. This process is particularly attractive in the context of non-silicon electronics and photonics, where the ability to re-use the graphene-coated substrates allows savings on the high cost of non-silicon substrates.