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In this work, the variations of the electrical properties and trapping effects of p-GaN gate high-electron-mobility transistors (HEMTs) under 1-MeV electron irradiation were investigated systematically. When the irradiation fluence was increased, the drain-source current and the gate leakage current also uprose, but the threshold voltage shifted toward the negative direction. Specifically, after final irradiation, traps in these devices were identified via the current-transient method, and alteration of the trapping effects near the drain and gate could be observed, respectively, by applying different filling voltages. According to the time constant spectra (TCS) and differential amplitude spectra (DAS), six types of detrapping behaviors could be identified. When compared with the results during the pristine stage, the absolute amplitudes of the traps changed after irradiation, which indicated trap densities decreased near the drain and those increased near the gate. The observed changes in the trapping behaviors are consistent with the changes in the electrical properties. To identify the activation energies and locations of traps, the current-transient response was measured at various temperatures before and after electron irradiation. The possible reason for the increased activation energies is that electron irradiation turned the Ga vacancies that decorated the dislocations into pure dislocations and increased the barrier height.

Microplastics (MPs), recognized as significant emerging contaminants, are prevalent in both terrestrial and aquatic ecosystems. This study investigates the potential of biochar derived from Polygonum amphibiumL. (PAL) sourced from Taihu Lake and processed through a low-temperature carbonization method, for in the removal of MPs. This approach addresses the escalating presence of MPs in aqueous environment, especially during the COVID-19 pandemic, simultaneously tackles the issue of waste biomass contributing to eutrophication. The study focused on the impact of carbonization temperatures (450℃-550℃) on physicochemical properties of biochar. Additionally, the effect of contact time, initial concentration of MPs, and environmental factors at various carbonization temperatures were also examined. The results reveal that the biochar yield and adsorption performance of biochar are significantly influenced by carbonization temperature. The adsorption capacity of biochar for MPs removal increases with the carbonization temperature up to 500 ℃, attributed to enhanced diffusion, surface adsorption, interactions, and cation-π electron interactions between the biochar and MPs. However, at a pyrolysis temperature of 550 ℃, the increase in adsorption capacity of biochar-550 is marginal due to increased competitive binging and destabilization of biochar under basic conditions. Overall, the optimum carbonization temperature is identified as 500 ℃, yielding a char rate is 32.23% and an adsorption capacity for MPs of 80.3 mg/g, thereby offering a promising solution for MP removal and water eutrophication management.

• The macroscopic and microscopic features of long-term stress relaxation aging (SRA) under multivariable aging conditions were systematically investigated. • The comprehensive underlying mechanisms of SRA were unraveled considering the interplay between stress relaxation behavior and age-hardening response. • The stress reduction rate rises sharply and the interplaying mechanisms changed greatly when the initial stress or the temperature exceeds a certain threshold. • The strength is enhanced primarily by precipitation strengthening and supplementarily by dislocation strengthening, while SOE degenerates strengthening effect. • There is a strong competition process of enthalpy reduction and entropy increase in the internal energy system composed of the material elastic strain during SRA. Large 2219 Al–Cu alloy aerospace integral components suffer from long-term stress relaxation aging (SRA) due to complex temperature and stress loads during aging treatment/forming and service process, which makes it difficult to ensure their appropriate residual stress and excellent mechanical and service properties. However, the research is limited to a thorough understanding of macroscopic and microscopic features and underlying mechanisms of the long-term SRA under multivariable aging conditions. Therefore, this study investigated macroscopic and microscopic features of long-term SRA under different temperatures (120 °C to 190 °C), initial stress levels (100 MPa to 250 MPa) and durations (0 h to 50 h) through stress relaxation curves, metallographic traits, Vickers hardness, tensile performance, dislocations and phases of precipitation. On the basis of experimental outcomes, the comprehensive mechanisms beneath SRA were unraveled through dislocation theory, multiphase strengthening mechanisms and thermodynamics, where the interplays of stress relaxation behavior with age-hardening response were taken into consideration. The results showed elevations in the rate of stress reduction as the temperature and initial stress rose. At an initial stress greater than the yield stress of alloy, a marked increase in stress relaxation was found, and the mechanisms transform from the intragranular motion of dislocations and diffusion of grain boundaries to the intragranular and intergranular motion of dislocations and migration of grain boundaries. The stress reduction rate rose sharply when the temperature exceeded 175 °C, and the dislocation movement mechanisms transform from gliding to climbing of dislocations. Stress relaxation is in nature progressive transformation of strain from elastic into a permanently inelastic state via the motion of dislocations, leading to the decrease of movable dislocations and the increase of immovable dislocations with more stable configurations. The age hardening is mainly determined by precipitation strengthening, supplementarily by dislocation strengthening, and obvious stress orientation effect (SOE) of G.P. zones and θ" phases degenerates strengthening effect. The interplay between stress relaxation behavior and age-hardening response influences the thermal–mechanical coupling SRA of 2219 Al–Cu alloy, which depends fundamentally on the motion of dislocations and their interplay with precipitated phases. This is a thermal activation process concerning the interplay between internal (age-hardening resistance) stress and external (initial) stress. The initial energy of elastic strain offers Gibbs free energy as the SRA driver, and a steady state of stress relaxation is attained with the lowest energy of elastic strain. These findings provide valuable insights into exploring innovative aging treatment/forming for optimizing residual stress, mechanical performance and service property in a synergistic manner. [Display omitted] [ABSTRACT FROM AUTHOR]

The synthesis of photocatalysts with both broad light absorption and efficient charge separation is significant for a high solar energy conversion, which still remains to be a challenge. Herein, a narrow-bandgap Y2Ti2O5S2(YTOS) oxysulfide nanosheet coexposed with defined {101} and {001} facets synthesized by a flux-assisted solid-state reaction was revealed to display the character of an anisotropic charge migration. The selective photodeposition of cocatalysts demonstrated that the {101} and {001} surfaces of YTOS nanosheets were the reduction and oxidation regions during photocatalysis, respectively. Density functional theory (DFT) calculations indicated a band energy level difference between the {101} and {001} facets of YTOS, which contributes to the anisotropic charge migration between them. The exposed Ti atoms on the {101} surface and S atoms on the {001} surface were identified, respectively, as reducing and oxidizing centers of YTOS nanosheets. This anisotropic charge migration generated a built-in electric field between these two facets, quantified by spatially resolved surface photovoltage microscopy, the intensity of which was found to be highly correlated with photocatalytic H2production activity of YTOS, especially exhibiting a high apparent quantum yield of 18.2% (420 nm) after on-site modification of a Pt@Au cocatalyst assisted by Na2S–Na2SO3hole scavengers. In conjunction with an oxygen-production photocatalyst and a [Co(bpy)3]2+/3+redox shuttle, the YTOS nanosheets achieved a solar-to-hydrogen conversion efficiency of 0.15% via a Z-scheme overall water splitting. Our work is the first to confirm anisotropic charge migration in a perovskite oxysulfide photocatalyst, which is crucial for enhancing charge separation and surface catalytic efficiency in this material.

Strong metal-support interaction (SMSI) has been widely discussed for activity promotion of heterogeneous catalysis, but the effect of SMSI on photocatalysis remains unclear. Here, we employ bismuth vanadate (BiVO4)-supported iridium (denoted as Ir/BVO) as a model photocatalyst to observe highly dispersed iridium overlayers as well as moderate SMSI effect between Ir and BiVO4. It is revealed that charge separation on the Ir/BVO can be remarkably promoted by the SMSI effect. Together with the right distribution of dual cocatalysts (Ir and IrO2) achieved by a simple photoinduction, the water oxidation activity on optimal Ir/BVO is about 75 times higher than that on pristine BVO. Finally, we construct an effective redox-driven Z-scheme overall water splitting system with a benchmark apparent quantum efficiency of 16.9% under visible light irradiation of 420 ± 10 nm at room temperature. Our work extends the application of SMSI to photocatalysis to provide an alternative way of promoting photocatalytic activity.

Vacancies, as well as their derivatives, usually play a crucial role in many essential properties of materials. However, they always behave erratically, especially under universal thermal vibration, and are therefore difficult to accurately locate. Until now, the lack of an accurate and flexible method for locating and identifying vacancies has hampered the development of relative fields. In this paper, we present a new method to solve this problem. The strategy is to target the atomic cage enwrapping vacancies instead of the vacancies themselves. The core of the method is a time-averaged atomic volume spectrum (TAVS). The key to this method is to identify atoms using time-averaged rather than transient atomic volume, thereby simultaneously denoising intrinsic thermal vibration and avoiding vacancy migration jump. Using this method, we have succeeded for the first time in obtaining the panoramic maps of spontaneously trapped defects in quenched and annealed face-centered cubic aluminum and even the instantaneous images of a steady trapping process. All characteristics of each trapped vacancy, including location, dimension, volume and morphology, as well as aggregate statistical data such as vacancy amount and concentration, can be completely and accurately obtained. Furthermore, these first maps of defects (vacancies) revealed some surprising and interesting phenomena for future exploration. In conclusion, this method provides not only a means of locating and catching vacancies, but also a strategy for identifying and characterizing vacancies. On the basis of its successful application in FCC Al, the TAVS method can be easily extended to other systems as well.

A transient 3D numerical model was established to investigate the multi-coupling transport phenomena in the Al-alloy GMAW bead-on-plate welding process. An integrated self-adaptive distribution mode of “arc current density-arc pressure-electromagnetic force-arc heat” was proposed to adapt to the evolution of the surface morphology of the molten pool. The heat and force state of the molten pool was analyzed to investigate its influence on the bead formation. The results showed that the arc pressure and droplet impingement promoted the backward flow of the liquid metal, thus forming the gouging region. It decreased the concentration of the arc current density, thereby reducing the superheat of the liquid metal and facilitating the filling of the weld toe. Based on the characteristics of the temperature and velocity fields, the characteristics of weld formation in the three stages of arc preheating, melting, and solidification were analyzed. This study revealed the relationship between molten pool behavior and bead formation, promoting the implementation of Al-alloy GMAW in welding and additive manufacturing.

The complicated formation flight for multi-unmanned aerial vehicles is a challenge, especially when multi-mission requirements are taken into account. This paper studies the adaptive differential evolution-based distributed model predictive control approach to deal with the multi-unmanned aerial vehicle flight achieving obstacle/collision avoidance and formation keeping simultaneously in the complex environment. Specifically, the distributed model predictive controller is designed to achieve stable flight for each unmanned aerial vehicle as well as taking the state and input saturation into account, where the local optimization problem is solved by the adaptive differential evolution algorithm. Besides, the adaptive adjustment to the prediction horizon for the model predictive controller is introduced, while the asymptotic convergence of the rolling optimization is analyzed as well. Finally, simulation examples are provided to illustrate the validity of the proposed control structure.

In a wireless power transfer (WPT) system based on coupled magnetic resonance, 2-D planar coils are commonly used as coupling structures. As the spatial position between the coupling structures changes, the system transmission efficiency decreases dramatically, seriously reducing the flexibility of power transfer. To solve this problem and achieve a power transfer with a high degree of freedom in a 3-D space, a novel 3-D coil based on a 26-faced polyhedron is proposed as the transmitting coil winding structure, which is wound using the regular monolithic winding method without overlapping. By means of this coil, it is ensured that the winding direction of each planar coil is different from those of the adjacent planes so that the magnetic fields between adjacent coils are mutually reinforced, thus enhancing the spatial magnetic field density of the system and enabling a stable and efficient transmission of power at any position. The transmitting coil can be enlarged by changing the coil structure, thereby enabling omnidirectional WPT in a larger space. Through experimental research, the system can achieve omnidirectional WPT with an efficiency of 60%, and its transmission efficiency can remain stable within a defined range as the receiver moves.

This article proposes a distributed fixed-time fault-tolerant control methodology for networked six-degree-of-freedom fixed-wing unmanned aerial vehicles (UAVs) whose models are subjected to actuator faults and saturation. Two fixed-time antisaturation control strategies are developed for velocity and attitude channels. Notably, the adverse effects of actuator faults (e.g., lock-in-place and loss of effectiveness) and actuator saturation can be effectively compensated for by means of a new adaptive-gain-based design. This feature differs significantly from most of the existing fault-tolerant control schemes. A fixed-time-based sliding-mode surface is delicately embedded in the control design in order to provide the attitude channel with the fixed-time tracking property. Model uncertainties and external disturbances can be effectively handled by using a bound estimation method and smooth functions. On the basis of Lyapunov stability theory, the closed-loop system is shown to be stable in the sense of the fixed-time concept. Actuator saturations are rigorously enforced, and the tracking errors of velocity and attitude converge to a residual set around the origin within a fixed time in spite of model uncertainties, external disturbances, and actuator faults. Numerical examples are carried out to validate the effectiveness of the theoretical findings.

Surface topography plays an important role in mixed lubrication. However, the influence of the surface topography's morphological characteristics on lubrication performance is still not fully understood. In this article, we employ digital filtering and the Johnson transformation system, and we use a mixed plasto-elastohydrodynamic lubrication model to simulate the lubricated contact between rough spherical surfaces with different morphological characteristic parameters. The influence of skewness, kurtosis, and the wavelength factor, that is, the ratio between the autocorrelation lengths in the transversal and longitudinal directions, on contact pressure, film thickness, and von Mises (subsurface) stress, is examined with the mixed plasto-elastohydrodynamic lubrication model. The results confirm that plastic deformation leads to lower pressure distribution, distributed over a larger contact area than the pure elastohydrodynamic lubrication solution. Moreover, it is found that an increase in the kurtosis may improve the lubrication performance, while the opposite is true for the skewness and the wavelength factor. We believe that the insights obtained by means of the numerical simulations presented herein, would facilitate the design and manufacturing processes of the surfaces used for machine elements operating in the mixed plasto-elastohydrodynamic lubrication regime.

Wide band gap semiconductors keep on pushing the limits of power electronic devices to higher switching speeds and higher operating temperatures, including diodes and transistors on low-cost Si substrates. Alternatively, erasable conducting walls created within ferroelectric single-crystal films integrated on the Si platform have emerged as a promising gateway to adaptive nanoelectronics in sufficient output power, where the repetitive creation of highly charged domain walls (DWs) is particularly important to increase the wall current density. Here, we observe large conduction of the head-to-head DW at an optimized inclination angle of 15° within a LiNbO3single crystal that is 3–4 orders of magnitude higher than that of the tail-to-tail DW. The wall conduction is diode-like with a linear current density of higher than 1 mA/μm and an on/off ratio of larger than 106under the application of a repetitive switching voltage pulse in time less than 10 ns and an endurance number of higher than 105. The high-power diodes can not only perform direct data processing in high-density nonvolatile DW memories in fast operation speeds and low-energy consumption but also function as sensors in compact electromechanical systems, selectors in phase-change memory and resistive random-access memory, and half-wave/full-wave rectifiers in modern nanocircuits in dimensions approaching the thickness of the depletion layer below which the tradition p–n junction malfunctions.

AbstractAs a natural medication and food plant resource, Liquidambar formosanaHance (L.) leaves are growing popularity in the fields of medicine and health care. The essential oil of L.leaves was extracted by continuous flow microreactor, and the extraction rate is 53.2%. 26 compounds from essential oil were identified by gas chromatography/mass spectrometry (GC/MS). The main components of these compounds are α-pinene, β-pinene and limonene. Ten of them are reported for the first time. The antibacterial activity of essential oil was investigated by the inhibition zone method, minimum inhibitory concentration and inhibition growth curve experiment. The results show that the essential oil had inhibitory effects on both Escherichia coli(E. coli) and Bacillus subtilis (B.subtilis), and the minimum inhibitory concentrations are 1.0 μg/mL and 1.2 μg/mL. The inhibition effect on gram-negative bacteria E.coliis stronger. The results of this study show that the essential oil contains rich medicinal value components and have great potential for exploitation. This research provided a scientific foundation for understanding essential oil while also providing a theoretical foundation for their full and rational utilization. Simultaneously, research into the antibacterial properties of essential oil provides a scientific basis for the further development of the anti-bacterial agents that exists in plants.

Suction cups are widely used in press lines to handle and transfer sheet metal. The release time, which directly affects production efficiency and safety, refers to the dropping off period in which the product completely separates from the suction cups. As of now, no release time data is currently available for use in evaluating press line. To provide such data, an experimental setup has been developed. The setup includes vacuum and non-vacuum system designed to simulate the release process of the press line and an electronic triggering system calculating the release time based on controlling the load. The four most commonly used suction cups, namely the large (110 mm diameter) double and single layer suction cups and small (60 mm diameter) double and single layer suction cups, were tested using the setup. The results show that the measurement system is practical and will provide important information for press line optimisation.

With the development of computing and communication technologies, an extremely large amount of data has been collected, stored, utilized, and shared, while new security and privacy challenges arise. Existing access control mechanisms provided by big data platforms have limitations in granularity and expressiveness. In this article, we present SparkAC, a novel access control mechanism for secure data sharing and analysis in Spark. In particular, we first propose a purpose-aware access control (PAAC) model, which introduces new concepts of data processing purpose and data operation purposeand an automatic purpose analysis algorithm that identifies purposes from data analytics operations and queries. Moreover, we develop a unified access control mechanism that implements PAAC model in two modules. GuardSpark++ supports structured data access control in Spark Catalyst and GuardDAG supports unstructured data access control in Spark core. Finally, we evaluate GuardSpark++ and GuardDAG with multiple data sources, applications, and data analytics engines. Experimental results show that SparkAC provides effective access control functionalities with very small (GuardSpark++) or medium (GuardDAG) performance overhead.

This article presents a four-level pulse-amplitude modulation (PAM-4) transceiver targeting very-short-reach and medium-reach (MR) electrical links. The receiver (RX) employs a sample-based four-tap feed-forward equalizer (FFE) for pre- and post-cursor inter-symbol interference (ISI) compensation. The two-stage 16-way interleaving provides sufficient operation time for FFE summation, which relaxes the bandwidth (BW) requirement and improves power efficiency. The non-uniform segmented three-tap FFE reduces the parasitic capacitance in the transmitter (TX). The one-unit interval (UI)-pulse generator in the 4:1 multiplexer uses a pre-charge phase to achieve a fast edge with single-stage logic. Fabricated in 28-nm CMOS technology, the transceiver achieves a bit error rate (BER) of < 1 $e-11$ at 112-Gb/s transmission with a channel loss of 20.8 dB and an energy efficiency of 2.29 pJ/b.

Coherent detection with polarization multiplexing is widely used because of its high spectral efficiency. However, it utilizes analog-to-digital converters (ADCs) and digital signal processing (DSP), which consume a large amount of power and thereby hinder its application in power-sensitive short-reach links. In this article, we present a 200-Gb/s analog $C$ -band dual-polarization quadrature phase shift keying (DP-QPSK) coherent optical receiver (RX), which uses four-way time-interleaved sampling to relax the internal bandwidth limit. The RX utilizes a chromatic dispersion (CD) equalizer, a polarization demultiplexer (Pol. DEMUX), and carrier recovery (CR) to eliminate the intersymbol interferences induced by fiber impairments and the carrier frequency offset. A subsampling scheme is adopted for low-power adaptation. The decrease in the frequency offset detection range caused by subsampling is prevented using a consecutive slice sampling technique. Measurement results show that our RX supports equalization for impairments equivalent to a 10-km fiber and CR for a residual carrier frequency offset of 12 MHz. A bit error rate (BER) of less than $1e-10$ is achieved with an energy efficiency of 4.6 pJ/b.

The surface states of a semiconductor photocatalyst are essential for interfacial charge transfer in heterogeneous photocatalytic reactions. Here, we report that the light-driven hydrogen evolution reaction (HER) activity of 0.5 mol % Rh-doped rutile increases by more than 30 times compared with that of rutile when ascorbic acid is used as a sacrificial agent. Intensity-modulated photocurrent spectroscopy and surface photovoltage spectroscopy are employed to reveal the impact of surface states on the photo-oxidation reactions. It is found that the adsorption of ascorbic acid molecules dramatically reduces the activity of rutile due to coverage of the HER-active Ti sites. Nevertheless, for Rh-doped rutile, ascorbic acid neutralizes the Rh(IV) sites that would otherwise cause severe recombination of electron–hole pairs and resurrects its photocatalytic performance. This work demonstrates the key role of interfacial chemistry in photocatalytic reactions and provides a strategy for excavating the potential of various photocatalysts.

Graphene oxide (GO) has been widely used to enhance the tensile/compressive strength of cement-based materials, whereas its shear reinforcing effect is still unknown. To verify the feasibility of GO as a shear reinforcement material, the shear reinforcing effect of GO on cement was experimentally investigated. The nanoscale Young’s modulus (E) of the GO-enhanced cement was measured with the peak force quantitative nanomechanical mapping method to clarify the enhancing mechanism. Results show that the addition of 0.02 and 0.04 wt% GO in cement could improve the shear strength by about 12 and 40%, respectively, which is mainly due to the enhanced cohesion, and at the nanoscale, the average Eof the low-density hydration product increased by 1.6 and 13.2%, whereas that of high-density hydration product remains almost unchanged. There exist fewer nanoholes/cracks and unhydrated cement grains but more the high-density hydration product in GO-enhanced cement, implying a denser microstructure and higher hydration degree. GO can enhance the shear strength of cement because of its enhancing effects on the microstructure, nanoscale Young’s modulus of hydration products, as well as the hydration degree.

This study aims to understand the connectivity characteristics of construction land during the spatial evolution of historic urban areas. The complex network analysis method is employed to examine the evolution of the spatial structure of construction land in the four periods of the Changsha historic urban area. The results indicate that the spatial network morphology of construction land follows a repeated development pattern resembling a cluster–mother–child relationship. Additionally, the vulnerability in the evolution of land use spatial relationships is very low, while the overall stability of the land use network structure decreases. The spatial equilibrium of land use shows a downwards trend, the accessibility of land where existing cultural relics and historic sites are located is generally moderate to low, and some plots require improvement. In the evolution of connectivity in the construction land of historic urban areas, the main development challenges are the uneven growth caused by imbalanced land value influenced by capital and the need to balance the preservation of land use patterns with improved accessibility to cultural relics and historic sites. Therefore, it is highly important to dynamically detect and optimize the network structure of construction land to protect and develop historic urban areas.

In this letter, we introduce a decentralized, nonlinear, discontinuous, and computationally simple control law for large scale multiagent navigation systems. The control is based on extending Gauss's principle of least constraint with a dynamic incorporation of inequality constraints, actuator saturation, and actuator dynamics. With no individual path planner, each agent executes its motion and generates its control actions by reacting solely to the evolution of its constrained dynamics, which is equivalent to solving a linear matrix equation with a dimension up to around 20 without iteration at each time instant. Numerical experiments are conducted on hundreds of two-dimensional (2-D) double integrators subjected to path and collision constraints, demonstrating the promise of the proposed method.

PD-1 blockade unleashes CD8 T cells1, including those specific for mutation-associated neoantigens (MANA), but factors in the tumour microenvironment can inhibit these T cell responses. Single-cell transcriptomics have revealed global T cell dysfunction programs in tumour-infiltrating lymphocytes (TIL). However, the majority of TIL do not recognize tumour antigens2, and little is known about transcriptional programs of MANA-specific TIL. Here, we identify MANA-specific T cell clones using the MANA functional expansion of specific T cells assay3in neoadjuvant anti-PD-1-treated non-small cell lung cancers (NSCLC). We use their T cell receptors as a ‘barcode’ to track and analyse their transcriptional programs in the tumour microenvironment using coupled single-cell RNA sequencing and T cell receptor sequencing. We find both MANA- and virus-specific clones in TIL, regardless of response, and MANA-, influenza- and Epstein–Barr virus-specific TIL each have unique transcriptional programs. Despite exposure to cognate antigen, MANA-specific TIL express an incompletely activated cytolytic program. MANA-specific CD8 T cells have hallmark transcriptional programs of tissue-resident memory (TRM) cells, but low levels of interleukin-7 receptor (IL-7R) and are functionally less responsive to interleukin-7 (IL-7) compared with influenza-specific TRM cells. Compared with those from responding tumours, MANA-specific clones from non-responding tumours express T cell receptors with markedly lower ligand-dependent signalling, are largely confined to HOBIThighTRM subsets, and coordinately upregulate checkpoints, killer inhibitory receptors and inhibitors of T cell activation. These findings provide important insights for overcoming resistance to PD-1 blockade.

Vasculature is a key component of many biological tissues and helps to regulate a wide range of biological processes. Modeling vascular networks or the vascular interface in organ-on-a-chip systems is an essential aspect of this technology. In many organ-on-a-chip devices, however, the engineered vasculatures are usually designed to be encapsulated inside closed microfluidic channels, making it difficult to physically access or extract the tissues for downstream applications and analysis. One unexploited benefit of tissue extraction is the potential of vascularizing, perfusing, and maturing the tissue in well-controlled, organ-on-a-chip microenvironments and then subsequently extracting that product for in vivo therapeutic implantation. Moreover, for both modeling and therapeutic applications, the scalability of the tissue production process is important. Here we demonstrate the scalable production of perfusable and extractable vascularized tissues in an “open-top“ 384-well plate (referred to as IFlowPlate), showing that this system could be used to examine nanoparticle delivery to targeted tissues through the microvascular network and to model vascular angiogenesis. Furthermore, tissue spheroids, such as hepatic spheroids, can be vascularized in a scalable manner and then subsequently extracted for in vivo implantation. This simple multiple-well plate platform could not only improve the experimental throughputs of organ-on-a-chip systems but could potentially help expand the application of model systems to regenerative therapy.

Tissue building does not occur exclusively during development. Even after a whole body is built from a single cell, tissue building can occur to repair and regenerate tissues of the adult body. This confers resilience and enhanced survival to multicellular organisms. However, this resiliency comes at a cost, as the potential for misdirected tissue building creates vulnerability to organ deformation and dysfunction–the hallmarks of disease. Pathological tissue morphogenesis is associated with fibrosis and cancer, which are the leading causes of morbidity and mortality worldwide. Despite being the priority of research for decades, scientific understanding of these diseases is limited and existing therapies underdeliver the desired benefits to patient outcomes. This can largely be attributed to the use of two-dimensional cell culture and animal models that insufficiently recapitulate human disease. Through the synergistic union of biological principles and engineering technology, organ-on-a-chip systems represent a powerful new approach to modeling pathological tissue morphogenesis, one with the potential to yield better insights into disease mechanisms and improved therapies that offer better patient outcomes. This Review will discuss organ-on-a-chip systems that model pathological tissue morphogenesis associated with (1) fibrosis in the context of injury-induced tissue repair and aging and (2) cancer.

The study of flow behaviour of water-sand mixtures in fractured rocks is of great necessity to understand the producing mechanism and prevention of water inrush and sand gushing accidents. A self-developed seepage test system is used in this paper to conduct laboratory experiments in order to study the influence of the particle size distribution, the void ratio, and the initial mass of Aeolian sand on the flow behavior. It is concluded that the water flow velocity is insensitive to the initial mass of the Aeolian sand but increases with the power exponent in the Talbot formula and the specimen height. The outflow of the Aeolian sand increases with the power exponent in the Talbot formula, the specimen height, and the initial mass of the Aeolian sand. Besides, the outflow of the Aeolian sand changes exponentially with the water flow velocity. Finally, it is found that the fractured specimen has a maximum sand filtration capacity beyond which the outflow of the Aeolian sand significantly increases with the initial mass of the Aeolian sand.

Diabetic kidney disease (DKD) is the main cause of chronic kidney disease (CKD) and progresses faster in males than in females. We identify sex-based differences in kidney metabolism and in the blood metabolome of male and female individuals with diabetes. Primary human proximal tubular epithelial cells (PTECs) from healthy males displayed increased mitochondrial respiration, oxidative stress, apoptosis, and greater injury when exposed to high glucose compared with PTECs from healthy females. Male human PTECs showed increased glucose and glutamine fluxes to the TCA cycle, whereas female human PTECs showed increased pyruvate content. The male human PTEC phenotype was enhanced by dihydrotestosterone and mediated by the transcription factor HNF4A and histone demethylase KDM6A. In mice where sex chromosomes either matched or did not match gonadal sex, male gonadal sex contributed to the kidney metabolism differences between males and females. A blood metabolomics analysis in a cohort of adolescents with or without diabetes showed increased TCA cycle metabolites in males. In a second cohort of adults with diabetes, females without DKD had higher serum pyruvate concentrations than did males with or without DKD. Serum pyruvate concentrations positively correlated with the estimated glomerular filtration rate, a measure of kidney function, and negatively correlated with all-cause mortality in this cohort. In a third cohort of adults with CKD, male sex and diabetes were associated with increased plasma TCA cycle metabolites, which correlated with all-cause mortality. These findings suggest that differences in male and female kidney metabolism may contribute to sex-dependent outcomes in DKD.

Cardiovascular diseases (CVD) are the leading cause of death around the world, being responsible for 31.8% of all deaths in 2017 (Roth, G. A. et al. The Lancet2018, 392, 1736−1788). The leading cause of CVD is ischemic heart disease (IHD), which caused 8.1 million deaths in 2013 (Benjamin, E. J. et al. Circulation2017, 135, e146−e603). IHD occurs when coronary arteries in the heart are narrowed or blocked, preventing the flow of oxygen and blood into the cardiac muscle, which could provoke acute myocardial infarction (AMI) and ultimately lead to heart failure and death. Cardiac regenerative therapy aims to repair and refunctionalize damaged heart tissue through the application of (1) intramyocardial cell delivery, (2) epicardial cardiac patch, and (3) acellular biomaterials. In this review, we aim to examine these current approaches and challenges in the cardiac regenerative therapy field.

Naive human pluripotent stem cells (hPSCs) can be used to generate mature human cells of all three germ layers in mouse–human chimeric embryos. Here, we describe a protocol for generating mouse–human chimeric embryos by injecting naive hPSCs converted from the primed state. Primed hPSCs are treated with a mammalian target of rapamycin inhibitor (Torin1) for 3 h and dissociated to single cells, which are plated on mouse embryonic fibroblasts in 2iLI medium, a condition essentially the same for culturing mouse embryonic stem cells. After 3–4 d, bright, dome-shaped colonies with mouse embryonic stem cell morphology are passaged in 2iLI medium. Established naive hPSCs are injected into mouse blastocysts, which produce E17.5 mouse embryos containing 0.1–4.0% human cells as quantified by next-generation sequencing of 18S ribosomal DNA amplicons. The protocol is suitable for studying the development of hPSCs in mouse embryos and may facilitate the generation of human cells, tissues and organs in animals.

Kidney-on-a-chip devices may revolutionize the discovery of new therapies. However, fabricating a 3D glomerulus remains a challenge, due to a requirement for a microscale soft material with complex topography to support cell culture in a native configuration. Here, we describe the use of microfluidic spinning to recapitulate complex concave and convex topographies over multiple length scales, required for biofabrication of a biomimetic 3D glomerulus. We produced a microfluidic extruded topographic hollow fiber (h-FIBER), consisting of a vessel-like perfusable tubular channel for endothelial cell cultivation, and a glomerulus-like knot with microconvex topography on its surface for podocyte cultivation. Meter long h-FIBERs were produced in microfluidics within minutes, followed by chemically induced inflation for generation of topographical cues on the 3D scaffold surface. The h-FIBERs were assembled into a hot-embossed plastic 96-well plate. Long-term perfusion, podocyte barrier formation, endothelialization, and permeability tests were easily performed by a standard pipetting technique on the platform. Following long-term culture (1 month), a functional filtration barrier, measured by the transfer of albumin from the blood vessel side to the ultrafiltrate side, suggested the establishment of an engineered glomerulus.

ABSTRACTThe elongation closed-loop control mode is essential for the temper rolling of the ultra-thin tin plate. During an unsteady process, the interstand tension is used for the stabilization of the elongation. But due to the drastic changes of the rolling force and rolling speed, the elongation fluctuation is beyond the tension control, which leads to the flatness degradation. In order to stabilize the elongation and the flatness, the adaptive compensation control for rolling force during the unsteady process is discussed in this work. This gain compensation for rolling force is based on the theoretical results from the rolling force model and validated from experimental results. Industrial experiments and application show the fluctuation of the elongation reduces by 90.11% during the unsteady process. Meanwhile, the change range of interstand tension reduces from 14% to less than 5%, length of the flatness degradation period decreases from over 180 m to shorter than 60 m.

The elongation closed-loop control mode is essential for the temper rolling of the ultra-thin tin plate. During an unsteady process, the interstand tension is used for the stabilization of the elongation. But due to the drastic changes of the rolling force and rolling speed, the elongation fluctuation is beyond the tension control, which leads to the flatness degradation. In order to stabilize the elongation and the flatness, the adaptive compensation control for rolling force during the unsteady process is discussed in this work. This gain compensation for rolling force is based on the theoretical results from the rolling force model and validated from experimental results. Industrial experiments and application show the fluctuation of the elongation reduces by 90.11% during the unsteady process. Meanwhile, the change range of interstand tension reduces from 14% to less than 5%, length of the flatness degradation period decreases from over 180 m to shorter than 60 m.

ABSTRACTPrecision toxicology evaluates the toxicity of certain substances by isolating a small group of cells with a typical phenotype of interest followed by a single cell sequencing-based analysis. In this in vitroattempt, ochratoxin A (OTA), a typical mycotoxin and food contaminant, is found to induce G0/G1 phase cell cycle arrest in human renal proximal tubular HKC cells at a concentration of 20 μM after a 24h-treatment. A small number of G0/G1 phase HKC cells are evaluated in both the presence and absence of OTA. These cells are sorted with a flow cytometer and subjected to mRNA and DNA methylation sequencing using Smart-Seq2 and single-cell reduced-representation bisulfite sequencing (scRRBS) technology, respectively. Integrated analysis of the transcriptome and methylome profiles reveals that OTA causes abnormal expression of the essential genes that regulate G1/S phase transition, act as signal transductors in G1 DNA damage checkpoints, and associate with the anaphase-promoting complex/cyclosome. The alteration of their DNA methylation status is a significant underlying epigenetic mechanism. Furthermore, Notch signaling and Ras/MAPK/CREB pathways are found to be suppressed by OTA. This attempt at precision toxicology paves the way for a deeper understanding of OTA toxicity and provides an innovative strategy to researchers in the toxicology and pharmacology field.