Mature Platform Research Articles

Novel, low-cost bioreactor for in vitro electrical stimulation of cardiac cells

IntroductionThe successful implantation of laboratory-grown cardiac tissue requires phenotypically mature cardiomyocytes capable of electrophysiological integration with native heart tissue. Pulsed electrical stimulation (ES) has been identified as a promising strategy for enhancing cardiomyocyte maturation. However, there are discrepancies in the literature as to best practices for promoting cardiac differentiation using ES.MethodsThis study presents a novel, 3D printed bioreactor that delivers in vitro ES to human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), promoting cell maturity and functional readiness for implantation. Finite element analysis and mathematical modeling were used to model the fluid dynamics and to characterize in detail the delivery of pulsatile electrical signals, providing precise control over stimulation parameters such as voltage, current, and charge.ResultsThe bioreactor developed here provides an easy-to-use, inexpensive platform for culturing hiPSC-CMs under the influence of ES and low-shear fluid flow for enhanced nutrient availability, while its “drop-in” design facilitates real-time observation of cultured cells. The electrical stimulation provided is controlled, modeled, and predictable, enabling reproducible experimental conditions and promoting comparability across future studies. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) grown in the bioreactor with ES showed improved differentiation and an enhanced ability to respond to external electrical pacing signals.DiscussionBy offering a standardized platform for ES-based cardiomyocyte maturation, this bioreactor aims to accelerate advancements in cardiac tissue engineering. Future research will explore how variations in ES parameters influence cardiomyocyte phenotype and maturation, contributing to a deeper understanding of cardiac cell development and optimization for therapeutic applications.

A cytoplasmic form of EHMT1N methylates viral proteins to enable inclusion body maturation and efficient viral replication.

Protein lysine methyltransferases (PKMTs) methylate histone and non-histone proteins to regulate biological outcomes such as development and disease including viral infection. While PKMTs have been extensively studied for modulating the antiviral responses via host gene regulation, their role in methylation of proteins encoded by viruses and its impact on host-pathogen interactions remain poorly understood. In this study, we discovered distinct nucleo-cytoplasmic form of euchromatic histone methyltransferase 1 (EHMT1N/C), a PKMT, that phase separates into viral inclusion bodies (IBs) upon cytoplasmic RNA-virus infection (Sendai Virus). EHMT1N/C interacts with cytoplasmic EHMT2 and methylates SeV-Nucleoprotein upon infection. Elevated nucleoprotein methylation during infection correlated with coalescence of small IBs into large mature platforms for efficient replication. Inhibition of EHMT activity by pharmacological inhibitors or genetic depletion of EHMT1N/C reduced the size of IBs with a concomitant reduction in replication. Additionally, we also found that EHMT1 condensation is not restricted to SeV alone but was also seen upon pathogenic RNA viral infections caused by Chandipura and Dengue virus. Collectively, our work elucidates a new mechanism by which cytoplasmic EHMT1 acts as proviral host factor to regulate host-pathogen interaction.

Research on the Application of AIGC in the Film Industry

This paper explores the feasibility of applying artificial intelligence generated content (AIGC) technology in the film industry, analyzes its potential to replace certain positions in the film industry, and explores how to integrate AIGC into different aspects of film production such as script writing, video production, and audio processing through experimental creation. Comparative research and experimental methods are used to explore the feasibility of applying AIGC in the film industry at this stage. The more mature AIGC platforms such as ChatGPT 4.0, Stability AI, Midjourney, and Suno V3.5 are used for research to optimize the film production process and provide some reference for other researchers. The findings suggest that AIGC could redefine industry standards and democratize the filmmaking process, enabling more creators to access sophisticated tools and produce high-quality content. This paper ultimately provides a roadmap for the strategic adoption of AIGC in filmmaking, outlining best practices and future research directions for a sustainable and creative AI-powered film industry.

Bottom Electrode Modification Enables Efficient and Bright Silicon-Based Top-Emission Perovskite Light-Emitting Diodes.

The integration of perovskites with mature silicon platform has emerged as a promising approach in the development of efficient on-chip light sources and high-brightness displays. However, the performance of Si-based green perovskite light-emitting diodes (PeLEDs) still falls significantly short compared to their red and near-infrared counterparts. In this study, it is revealed that the high work function Au, widely employed in Si-based top-emission PeLEDs as the reflective bottom electrode, exhibits considerably lower reflectivity in the green spectrum than in the longer wavelengths. Consequently, Ag electrode is introduced to replace Au to enhance the green light reflectivity, and the ultrathin MoO3 and self-assembled monolayers (SAMs) are sequentially deposited for surface modification. These results indicate that the MoO3 layer removes the energy barrier at Ag/polymer hole transport layer interface, enhancing the hole injection efficiency; while the SAMs firmly anchor onto the MoO3 layer, effectively preventing interfacial defect formation. Benefited from this organic/inorganic dual-layer modification strategy, Si-based green PeLEDs with an impressive peak external quantum efficiency of 18.2% and a maximum brightness of 81931 cd m-2 are successfully fabricated, on par with those of the red and near-infrared counterparts. This achievement marks an advancement in developing high-performance Si-based PeLEDs with full-spectrum output.

Dual mature microRNA-responsive logic biosensing platform based on CRISPR/Cas12a and DNA nanocage

Mature microRNAs play crucial roles in tumorigenesis and progression. However, their potential as cancer biomarkers is limited by the sequence interference of precursor microRNAs and the occurrence of false positive signals mediated by single microRNAs. Herein, we reported a dual mature microRNA-responsive second-order (YES-AND) logic biosensing platform for accurate cancer diagnosis. Specifically, DNA nanocages were conceived as the first stage of “YES” gates, capable of signal transduction through strand displacement reactions, and realizing size-selective discrimination of mature microRNAs and pre-microRNAs. Subsequently, CRISPR/Cas12a system served as the second stage of “AND” gate, wherein dual activators cooperatively triggered trans-cleavage. As a proof-of-concept, this second-order logic biosensing platform was successfully applied to detect non-small cell lung cancer-related mature microRNA in clinical serum, and showed remarkable sensitivity (Lod = 100 pM) and trueness (recovery ≥90 %). Our study represents a significant step forward in the development of intelligent biosensors capable of performing complex computations within pathological networks, and opens up broader possibilities for applications in biological science study and clinic disease diagnosis.

The social shaping of biotechnological innovation. The case of Covid-19 protein vaccine in Cuba and the US

AbstractLike other technologies, vaccines are socially shaped by socio-economic, political and organisational factors. Property rights, value capture strategies and public innovation policies guide research teams in the biochemical design of vaccines, with inevitable consequences for their price and accessibility. The Covid-19 pandemic provided an opportunity to analyse this institutional shaping process and its consequences for global public health from a political economy perspective. Indeed, the same type of invention, a recombinant protein vaccine, was simultaneously and originally developed in the US and Cuban biopharmaceutical industries and in the field of philanthropic Open Innovation. The article shows, through empirical research that collected direct testimony from scientists and privileged observers of the vaccine development fields, how certain norms and values characteristic of the US industry (financialization, assetization and de-risk) created a path dependency in the use of proprietary and experimental biotechnologies that made the US vaccine Nuvaxovid more expensive and complex to produce, but no more effective and safe than Abdala, Soberana 02 and Corbevax. In addition, the institutional constraints of the US biopharmaceutical industry on radical innovation, even within a mature biotechnology platform such as protein vaccines, would have resulted in a competitive disadvantage for Nuvaxovid, which was as expensive as an mRNA vaccine but less rapid to market and less reliable in delivery. The case of protein vaccines against Covid-19 thus shows how the institutional architectures of techno-scientific capitalism create not only inequalities but also inefficiencies, and that an innovation path with excellent results is possible even in competition where the market is not the dominant order of worth.

On the Status Quo, Problems and Countermeasures of Crowdfunding Publishing in China

Abstract Under the background of the Internet, many new publishing methods have been developed, and crowdfunding publishing is one of them. Crowdfunding publishing breaks the one-way static publishing environment of traditional publishing, and at the same time extends the traditional publishing industry chain, injecting new vitality into China’s publishing industry. By analyzing the larger crowdfunding platforms and crowdfunding publishing cases in China, this paper focuses on the development status and problems of crowdfunding publishing in China and tries to provide effective suggestions on the problems. Crowdfunding publishing has been developing in China for ten years, has attracted widespread attention in the industry from the very beginning. Moreover, it has developed rapidly in the context of crowdfunding economy, forming a relatively mature crowdfunding platform and model, with an increasing number of successful crowdfunding publishing projects demonstrating a certain degree of influence. However, China’s crowdfunding publishing is still in the early stage of development due to the imperfect laws and regulations of crowdfunding publishing, the profit model has not yet been successfully explored, and individual self-marketing is greater than quality content production. Only by strengthening the operation and construction of comprehensive crowdfunding platforms, striving to build vertical specialized crowdfunding platforms, and focusing on the publications themselves and content innovation, can China’s crowdfunding publishing break through and grow?

Abstract We007: High Throughput 3D-Printed Human Engineered Heart Tissues for Cardiac Disease Modeling

While cell models have been used to study cardiac diseases, there is currently no standardization or fully mature in vitro system. Obtaining a mature cardiomyocyte (CM) phenotype is necessary to create a physiologically relevant environment and accurately model and study cardiac diseases. Increased success in maturation of human induced pluripotent stem cell derived CMs (hiPS-CMs) has been achieved in 3D in vitro models in the form of engineered heart tissues (EHTs). Digital light processing (DLP) offers a high throughput and efficient method to fabricate hydrogels that recapitulate properties of native tissues. In this study, we use DLP-printed EHTs to seed and mature differentiated hiPS-CMs and test their potential for modeling pathological cardiac hypertrophy. To further encourage maturity of CMs, we utilized a low glucose maturation medium supplemented with fatty acids. DLP-printed EHTs displayed high reproducibility and increased CM maturity. To determine degree of maturity of our system, we performed RT-qPCR, western blot analysis, and immunofluorescence (IF) microscopy. We found increased expression of fatty-acid transport and beta oxidation genes and improved sarcomere alignment compared to 2D hiPS-CMs. To model pathological cardiac hypertrophy, we used two different approaches: 1. acute adrenergic agonism with isoproterenol and phenylephrine; 2. chronic culturing of EHTs in pathologically stiff conditions. To assess pathology, we conducted RT-qPCR, western blot, ELISA, IF microscopy, and functional analyses. We found that agonist-treated EHTs displayed increased pathology-associated gene expression compared to standard 2D hiPS-CMs. Both agonist-treated and stiff EHTs had increased secreted B-Type Natriuretic Peptide (BNP) and phosphorylation of proteins involved in pathological remodeling, including ERK and P38. Additionally, we observed increased nuclear area, increased calcium handling, and increased contractile force in the treatment groups. In conclusion, we have established a high throughput, reproducible, mature EHT platform that can be used to model pathological cardiac hypertrophy. This platform can be easily adopted by other laboratories to study a wide array of cardiac diseases.

Integrated Resonant Electro‐Optic Comb Enabled by Platform‐Agnostic Laser Integration

AbstractThe field of integrated photonics has significantly impacted numerous fields including communication, sensing, and quantum physics owing to the efficiency, speed, and compactness of its devices. However, the reliance on off‐chip bulk lasers compromises the compact nature of these systems. While silicon photonics and III‐V platforms have established integrated laser technologies, emerging demands for ultra‐low optical loss, wider bandgaps, and optical nonlinearities necessitate other platforms. Developing integrated lasers on less mature platforms is arduous and costly due to limited throughput or unconventional process requirements. In response, a novel platform‐agnostic laser integration technique is proposed, utilizing a singular design and process flow, applicable without modification to a diverse range of platforms. Leveraging a two‐step micro‐transfer printing method, nearly identical laser performance is achieved across platforms with refractive indices between 1.7 and 2.5. Experimental validation demonstrates strikingly similar laser characteristics between devices processed on lithium niobate and silicon nitride platforms. Furthermore, the integration of a laser with a resonant electro‐optic comb generator on the thin‐film lithium niobate platform is showcased, producing over 80 comb lines spanning 12 nm. This versatile technique transcends platform‐specific limitations, facilitating applications like microwave photonics, handheld spectrometers, and cost‐effective Lidar systems, across multiple platforms.

The effect of novel linguistic-based review features on review helpfulness through information ecosystem and ELM theories: Heterogeneity analysis across platforms

Although online review helpfulness has been extensively discussed, examining it at the platform level can still yield new insights. Drawing on ELM and information ecosystem theories, this study identifies heterogeneity in review features and their impact on helpfulness across platforms through a multimethod analysis of 82,130 reviews on JD and TikTok. Econometric analysis revealed that reviews on mature platforms contain richer objective content, more diverse language styles, and stronger semantic associations. In terms of content, objective content diversity positively affects helpfulness on emerging platforms, while it has the opposite effect on mature platforms. Negative sentiment significantly affects helpfulness only on mature platforms, and positive sentiment has no significant effect on either platform. In terms of language style, the analysis indicated that language style diversity positively impacts the helpfulness of emerging platforms. However, four specific styles (figurative, comparative, interrogative and exaggerative) negatively affect helpfulness on emerging platforms, with only comparative style having a significant negative effect on mature platforms. In terms of semantic association, the results show a more substantial positive impact on emerging platforms. Machine learning-based performance analysis corroborates the core findings of the econometric analysis. This study provides novel findings to the existing literature and provides managerial implications for different platforms.

Solution for Accelerator Wall of HPC with HBM Integrated Packages

With 4 billion-scaled daily-online- population in digital world, it becomes that the driving force of global economic is increasing the capital expenditure on cloud infrastructure deployed. As the architecture of high performance computing (HPC) is the trending on heterogeneous interconnection package (HIP) and three-dimension stacked platform as one of direction to migrate the accelerator wall. The routing path out of memory-bank is majority index reflecting on computing performance at band-width, data-rate latency, and power efficiency with rephrasing the Moore¡¦s Law on logic cell development. The numbers of packaged platform options is pop-up in semiconductor industry, momentum growing at on-and-off die scale packaging platform. The catalogue in industry is divided by three group: silicon bridge interposer, fan-out routed technology, substrate-selective replaced by silicon bridge die. In-depth reviewing the HIP packaging profile: First, silicon bridge interposer is strength on the surface of three-dimension thermal dissipation flow and equipping the less than 1/1 um L/S capability but mineral cost of silicon manufacturing is jeopardizing the ROI issue on expensive for consuming the deployed routed area. Second, fan-out routed technology is deploying the routing capability ranging from 2/2 um to 10/10 um L/S outline profile as flexible connection platform. Third, substrate-selective replaced by silicon bridge die is to leverage mature flip chip platform, it did provide the competitive pricing solution but the embedded die bridge technology is to constrain the power and computing at horizon scalable out deployment. This paper is to present the electrical metrics on HBM Integrated Packages at industry benchmark catalogue by simulation software analysis. The software modeling is to render the transportation performance of bit source deployed at high speed memory bank connection, and communicate the through-hole-via routing at fan-out scalable area, then reach to another logic cell chip bank. The strength is grouping the diversity transistor layout power-supplied at three-dimension building for avoiding the horizon transistor current constrain. The raised-module solution is key to jump across the accelerator wall with the advocating on bit-per-joule and ROI for next high performance computing.

Starch digestibility: How single, double, and multiple physicochemical modifications change nutritional attributes of starch?

AbstractThe ever‐increasing ranges of starch applications have been restricted by some of its inherent adverse characteristics like retrogradability, gel opacity, low resistibility to variations of pH, and elevated shear/temperatures. Starch modification through various physical, chemical, and enzymatic methods has been proposed as the most mature platform to tackle such drawbacks. Along with their outstanding potential in enhancing the starch's technofunctional characteristics, physicochemical modifications could remarkably customize starch nutritional/digestibility attributes. For instance, physical modifications could remarkably change starch digestibility by manipulating the granular architecture while chemical approaches change it by altering the chemical structure of starch molecules, making them unrecognizable to digestive enzymes. Such alterations could even be more challenging upon applying a combination of starch modifications. The changes in starch digestibility through its modification via single, double, and multiple modifications have been overviewed in this review.

Observation of a Brillouin dynamic grating in silicon nitride waveguides

Brillouin enhanced four wave mixing in the form of a Brillouin dynamic grating (BDG) enables a uniquely tunable filter whose properties can be tuned by purely optical means. This makes the BDG a valuable tool in microwave photonics (MWP). BDGs have been studied extensively in fibers, but the only observation in an integrated platform required exotic materials. Unlocking BDG in a standard and mature platform will enable its integration into large-scale circuits. Here, we demonstrate the first observation of a BDG in a silicon nitride (Si3N4) waveguide. We also present a new and optimized design, which will enhance the BDG response of the waveguide, unlocking the path to large-scale integration into MWP circuits.

Efficient Spiking Neural Networks With Radix Encoding.

Spiking neural networks (SNNs) have advantages in latency and energy efficiency over traditional artificial neural networks (ANNs) due to their event-driven computation mechanism and the replacement of energy-consuming weight multiplication with addition. However, to achieve high accuracy, it usually requires long spike trains to ensure accuracy, usually more than 1000 time steps. This offsets the computation efficiency brought by SNNs because a longer spike train means a larger number of operations and larger latency. In this article, we propose a radix-encoded SNN, which has ultrashort spike trains. Specifically, it is able to use less than six time steps to achieve even higher accuracy than its traditional counterpart. We also develop a method to fit our radix encoding technique into the ANN-to-SNN conversion approach so that we can train radix-encoded SNNs more efficiently on mature platforms and hardware. Experiments show that our radix encoding can achieve 25× improvement in latency and 1.7% improvement in accuracy compared to the state-of-the-art method using the VGG-16 network on the CIFAR-10 dataset.

Protection of the receptor binding domain (RBD) dimer against SARS-CoV-2 and its variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants achieved immune escape and became less virulent and easily transmissible through rapid mutation in the spike protein, thus the efficacy of vaccines on the market or in development continues to be challenged. Updating the vaccine, exploring compromise vaccination strategies, and evaluating the efficacy of candidate vaccines for the emerging variants in a timely manner are important to combat complex and volatile SARS-CoV-2. This study reports that vaccines prepared from the dimeric receptor-binding domain (RBD) recombinant protein, which can be quickly produced using a mature and stable process platform, had both good immunogenicity and protection in vivo and could completely protect rodents from lethal challenge by SARS-CoV-2 and its variants, including the emerging Omicron XBB.1.16, highlighting the value of dimeric recombinant vaccines in the post-COVID-19 era.

Defect-engineered graphene-on-silicon-carbide platform for magnetic field sensing at greatly elevated temperatures

High-temperature electrical properties of p-type hydrogen-intercalated quasi-free-standing epitaxial Chemical Vapor Deposition graphene on semi-insulating vanadium-compensated on-axis 6H-SiC(0001) and high-purity on-axis 4H-SiC(0001) originate from the double-carrier system of spontaneous-polarization-induced holes in graphene and thermally-activated electrons in the substrate. In this study, we pre-epitaxially modify SiC by implanting hydrogen (H+) and helium (He+) ions with energies ranging from 20 keV to 50 keV to reconstruct its post-epitaxial defect structure and suppress the thermally-developed electron channel. Through a combination of dark current measurements and High-Resolution Photo-Induced Transient Spectroscopy between 300 K and 700 K, we monitor the impact of ion bombardment on the transport properties of SiC and reveal activation energies of the individual deep-level defects. We find that the ion implantation has a negligible effect on 6H-SiC. Yet in 4H-SiC, it shifts the Fermi level from ∼600 meV to ∼800 meV below the minimum of the conduction band and reduces the electron concentration by two orders of magnitude. Specifically, it eliminates deep electron traps related to silicon vacancies in the charge state (2-/-) occupying the h and k sites of the 4H-SiC lattice. Finally, we directly implement the protocol of deep-level defect engineering in the technology of amorphous-aluminum-oxide-passivated Hall effect sensors and introduce a mature sensory platform with record-linear current-mode sensitivity of approximately 80 V/AT with -0.03-%/K stability in a broad temperature range between 300 K and 770 K, and likely far beyond 770 K.

Quantum Computing: Principles and Applications

People are witnessing quantum computing revolutions nowadays. Progress in the number of qubits, coherence times and gate fidelities is happening. Although quantum error correction era has not arrived, the research and development of quantum computing have inspired insights and breakthroughs in quantum technologies, both in theories and in experiments. In this review, we introduce the basic principles of quantum computing and the multilayer architecture for a quantum computer. There are different experimental platforms for implementing quantum computing. In this review, based on a mature experimental platform, the Nuclear Magnetic Resonance (NMR) platform, we introduce the basic steps to experimentally implement quantum computing, as well as the common challenges and techniques.

(Invited) Multimodality Sensing and Actuation Using Nanocarbons

My team’s efforts are focused on the development and engineering of nanocarbons-based flexible platforms to interrogate and affect the properties of cells and tissue, with a specific goal to understand signal transduction (chemical or electrical) in tissue or complex 3D cellular assemblies. Our highly flexible bottom-up nanomaterials synthesis capabilities allow us to form unique hybrid-nanomaterials that can be used in various input/output bioelectrical interfaces, i.e., bioelectrical platforms for chemical and physical sensing and actuation. We have developed several approaches for monitoring (and affecting) the complex signal transduction in 3D cellular assemblies toward an organ-on-an-electronic-chip (organ-on-e-chip) platform for tissue maturation and disease progression investigations. Utilizing graphene, a two-dimensional (2D) atomically thin carbon allotrope, we can simultaneously record the intracellular electrical activity of multiple excitable cells with ultra-microelectrodes that can be as small as an axon (ca. 2µm). The outstanding electrochemical properties of the synthesized hybrid-nanomaterials allow us to develop highly efficient catalysts, that can be deployed as electrical sensors and (chemical) actuators. We demonstrated sensors capable of exploring brain chemistry and sensors/actuators that are deployed in a large volumetric muscle loss animal model. Finally, using the unique optical properties of nanocarbons in the form of graphene-based hybrid-nanomaterials and 2D nanocarbides (MXene), we have formed remote, non-genetic bioelectrical interfaces with excitable cells and modulated cellular and network activity with low needed energy and high precision. In summary, the exceptional synthetic control and flexible assembly of nanomaterials provide powerful tools for fundamental studies and applications in life science and potentially seamlessly merge nanomaterials-based platforms with cells, fusing nonliving and living systems together.

Photophysics of Intrinsic Single‐Photon Emitters in Silicon Nitride at Low Temperatures

AbstractA robust process for fabricating intrinsic single‐photon emitters in silicon nitride is recently established. These emitters show promise for quantum applications due to room‐temperature operation and monolithic integration with technologically mature silicon nitride photonics platforms. Here, the fundamental photophysical properties of these emitters are probed through measurements of optical transition wavelengths, linewidths, and photon antibunching as a function of temperature from 4.2 to 300 K. Important insight into the potential for lifetime‐limited linewidths is provided through measurements of inhomogeneous and temperature‐dependent broadening of the zero‐phonon lines. At 4.2 K, spectral diffusion is found to be the main broadening mechanism, while spectroscopy time series reveal zero‐phonon lines with instrument‐limited linewidths.

Thickness-Dependent Superconductivity in a Layered Electride on Silicon.

Layered materials exhibit a plethora of fascinating properties. The challenge is to make the materials into epitaxial films, preferably integrated with mature technological platforms to facilitate their potential applications. Progress in this direction can establish the film thickness as a valuable parameter to control various phenomena, superconductivity in particular. Here, a synthetic route to epitaxial films of SrAlSi, a layered superconducting electride, on silicon is designed. A set of films ranging in thickness is synthesized employing a silicene-based template. Their structure and superconductivity are explored by a combination of techniques. Two regimes of TC dependence on the film thickness are identified, the coherence length being the crossover parameter. The results can be extended to syntheses of other honeycomb-lattice ternary compounds on Si or Ge exhibiting superconducting, magnetic, and other properties.