Aptamer-Loop DNA Nanoflower Recognition and Multicolor Fluorescent Carbon Quantum Dots Labeling System for Multitarget Living Cell Imaging.

Visualization of multiple targets in living cells is important for understanding complex biological processes, but it still faces difficulties, such as complex operation, difficulty in multiplexing, and expensive equipment. Here, we developed a nanoplatform integrating a nucleic acid aptamer and DNA nanotechnology for living cell imaging. Aptamer-based recognition probes (RPs) were synthesized through rolling circle amplification, which were further self-assembled into DNA nanoflowers encapsulated by an aptamer loop. The signal probes (SPs) were obtained by conjugation of multicolor emission carbon quantum dots with oligonucleotides complementary to RPs. Through base pairing, RPs and SPs were hybridized to generate aptamer sgc8-, AS1411-, and Apt-based imaging systems. They were used for individual/simultaneous imaging of cellular membrane protein PTK7, nucleolin, and adenosine triphosphate (ATP) molecules. Fluorescence imaging and intensity analysis showed that the living cell imaging system can not only specifically recognize and efficiently bind their respective targets but also provide a 5-10-fold signal amplification. Cell-cycle-dependent distribution of nucleolin and concentration-dependent fluorescence intensity of ATP demonstrated the utility of the system for tracking changes in cellular status. Overall, this system shows the potential to be a simple, low-cost, highly selective, and sensitive living cell imaging platform.

A Microfluidic 3D-Tumor-Spheroid Model for the Evaluation of Targeted Therapies from Angiogenesis-Related Cytokines at the Single Spheroid Level.

Angiogenesis is a key player in drug resistance to targeted therapies for breast cancer. The average expression of angiogenesis-related cytokines is widely associated with the treatments of target therapies for a population of cells or spheroids, overlooking the distinct responses for individuals. In this work, a highly integrated microfluidic platform is developed for the generation of monodisperse multicellular tumor spheroids (MTSs), drug treatments, and the measurement of cytokines for individual MTSs in a single chip. The platform allows the correlation evaluation between cytokine secretion and drug treatment at the level of individual spheroids. For validation, quantities of six representative proangiogenic cytokines are tested against treatments with four model drugs at varying times and concentrations. By applying a linear regression model, significant correlations are established between cytokine secretion and the treated drug concentration for individual spheroids. The proposed platform provides a high-throughput method for the investigation of the molecular mechanism of the cytokine response to targeted therapies and paves the way for future drug screening using predictive regression models at the single-spheroid level.

Performance Limits and Advancements in Single 2D Transition Metal Dichalcogenide Transistor.

Two-dimensional (2D) transition metal dichalcogenides (TMDs) allow for atomic-scale manipulation, challenging the conventional limitations of semiconductor materials. This capability may overcome the short-channel effect, sparking significant advancements in electronic devices that utilize 2D TMDs. Exploring the dimension and performance limits of transistors based on 2D TMDs has gained substantial importance. This review provides a comprehensive investigation into these limits of the single 2D-TMD transistor. It delves into the impacts of miniaturization, including the reduction of channel length, gate length, source/drain contact length, and dielectric thickness on transistor operation and performance. In addition, this review provides a detailed analysis of performance parameters such as source/drain contact resistance, subthreshold swing, hysteresis loop, carrier mobility, on/off ratio, and the development of p-type and single logic transistors. This review details the two logical expressions of the single 2D-TMD logic transistor, including current and voltage. It also emphasizes the role of 2D TMD-based transistors as memory devices, focusing on enhancing memory operation speed, endurance, data retention, and extinction ratio, as well as reducing energy consumption in memory devices functioning as artificial synapses. This review demonstrates the two calculating methods for dynamic energy consumption of 2D synaptic devices. This review not only summarizes the current state of the art in this field but also highlights potential future research directions and applications. It underscores the anticipated challenges, opportunities, and potential solutions in navigating the dimension and performance boundaries of 2D transistors.

RNA extraction-free reduced graphene oxide-based RT-LAMP fluorescence assay for highly sensitive SARS-CoV-2 detection.

Infectious diseases have always been a seriously endanger for human life and health. A rapid, accurate and ultra-sensitive virus nucleic acid detection is still a challenge to deal with infectious diseases. Here, a RNA extraction-free reduced graphene oxide-based reverse transcription-loop-mediated isothermal amplification (EF-G-RT-LAMP) fluorescence assay was developed to achieve high-throughput, rapid and ultra-sensitive SARS-CoV-2 RNA detection. The whole detection process only took ∼36 min. The EF-G-RT-LAMP assay achieves a detection limit of 0.6 copies µL-1 with a wide dynamic range of aM-pM. A large number (up to 384) of samples can be detected simultaneously. Simulated detection of the COVID-19 pseudovirus and clinical samples in nasopharyngeal swabs demonstrated a high-throughput, rapid and ultra-sensitive practical detection capability of the EF-G-RT-LAMP assay. The results proved that the assay would be used as a rapid, easy-to-implement approach for epidemiologic diagnosis and could be extended to other nucleic acid detections.

Ivosidenib in Chinese patients with relapsed or refractory isocitrate dehydrogenase 1 mutated acute myeloid leukemia: a registry study.

Ivosidenib, an isocitrate dehydrogenase 1 (IDH1) inhibitor, has demonstrated clinical benefits in a pivotal study (AG120-C-001) in patients with IDH1-mutated (mIDH1) acute myeloid leukemia (AML). A registry study (CS3010-101: NCT04176393) was conducted to assess the pharmacokinetic (PK) characteristics, safety, and efficacy of ivosidenib in Chinese patients with relapsed or refractory (R/R) mIDH1 AML. Patients received ivosidenib 500 mg once daily for 28-day cycles until disease progression. Ten subjects underwent intensive PK/progressive disease (PD) assessments. All subjects had the clinical response assessed at screening, every 28 days through month 12, and then every 56 days. Between November 12, 2019, and April 2, 2021, 30 patients were enrolled; 26 (86.7%) had de novo AML and 18 (60.0%) were transfusion-dependent at baseline. Following single and repeated doses of ivosidenib, median time to maximum plasma concentration (T max) was 4.0 and 2.0 hours, respectively. The inter-individual variability of pharmacokinetic exposure was moderate to high (coefficient of variation [CV], 25%-53%). No obvious accumulation was observed after repeated doses at cycle 2 day 1. Regarding the clinical response, the CR + CRh rate was 36.7% (95% confidence interval [CI]: 19.9%-56.1%), the median duration of CR + CRh was 19.7 months (95% CI: 2.9 months-not reached [NR]), and median duration of response (DoR) was 14.3 months (95% CI: 6.4 months-NR). Consistent clinical benefits and safety of ivosidenib were consistently observed at the final data cutoff with median follow-up time 26.0 months, as compared with primary data cutoff, and the data from Chinese R/R mIDH1 AML patients were also consistent with results from pivotal study.

Humidity-Responsive Liquid Metal Core-Shell Materials for Enduring Heat Retention and Insulation.

High humidity in extremely cold weather can undermine the insulation capability of the clothing, imposing serious life risks. Current clothing insulation technologies have inherent deficiencies in terms of insulation efficiency and humidity adaptability. Here, humidity-stimulated self-heating clothing using aluminum core-liquid metal shell microparticles (Al@LM-MPs) as the filler is reported. Al@LM-MPs exhibit a distinctive capability to react to water molecules in the air to generate heat, exhibiting remarkable sensitivity across a broad temperature range. This ability leads to the creation of intelligent clothing capable of autonomously responding to extreme cold and wet weather conditions, providing both enduring heat retention and insulation capabilities.

Rapid fractionation of corn stover by microwave-assisted protic ionic liquid [TEA][HSO4] for fermentative acetone-butanol-ethanol production.

BACKGROUND: The use of ionic liquids (ILs) to fractionate lignocelluloses for various bio-based chemicals productions is in the ascendant. On this basis, the protic ILs consisting of triethylammonium hydrogen sulfate ([TEA][HSO4]) possessed great promise due to the low price, low pollution, and high efficiency. In this study, the microwave-assistant [TEA][HSO4] fractionation process was established for corn stover fractionation, so as to facilitate the monomeric sugars production and supported the downstream acetone-butanol-ethanol (ABE) fermentation. RESULTS: The assistance of microwave irradiation could obviously shorten the fractionation period of corn stover. Under the optimized condition (190 W for 3 min), high xylan removal (93.17 ± 0.63%) and delignification rate (72.90 ± 0.81%) were realized. The mechanisms for the promotion effect of the microwave to the protic ILs fractionation process were ascribed to the synergistic effect of the IL and microwaves to the depolymerization of lignocellulose through the ionic conduction, which can be clarified by the characterization of the pulps and the isolated lignin specimens. Downstream valorization of the fractionated pulps into ABE productions was also investigated. The [TEA][HSO4] free corn stover hydrolysate was capable of producing 12.58 g L-1 of ABE from overall 38.20 g L-1 of monomeric sugars without detoxification and additional nutrients supplementation. CONCLUSIONS: The assistance of microwave irradiation could significantly promote the corn stover fractionation by [TEA][HSO4]. Mass balance indicated that 8.1 g of ABE and 16.61 g of technical lignin can be generated from 100 g of raw corn stover based on the novel fractionation strategy.

Elementary cellular automata realized by stateful three-memristor logic operations.

Cellular automata (CA) are computational systems that exhibit complex global behavior arising from simple local rules, making them a fascinating candidate for various research areas. However, challenges such as limited flexibility and efficiency on conventional hardware platforms still exist. In this study, we propose a memristor-based circuit for implementing elementary cellular automata (ECA) by extending the stateful three-memristor logic operations derived from material implication (IMP) logic gates. By leveraging the inherent physical properties of memristors, this approach offers simplicity, minimal operational steps, and high flexibility in implementing ECA rules by adjusting the circuit parameters. The mathematical principles governing circuit parameters are analyzed, and the evolution of multiple ECA rules is successfully demonstrated, showcasing the robustness in handling the stochastic nature of memristors. This approach provides a hardware solution for ECA implementation and opens up new research opportunities in the hardware implementation of CA.

Strongly Interacting Bose-Fermi Mixtures: Mediated Interaction, Phase Diagram, and Sound Propagation.

Motivated by recent surprising experimental findings, we develop a strong-coupling theory for Bose-Fermi mixtures capable of treating resonant interspecies interactions while satisfying the compressibility sum rule. We show that the mixture can be stable at large interaction strengths close to resonance, in agreement with the experiment, but at odds with the widely used perturbation theory. We also calculate the sound velocity of the Bose gas in the ^{133}Cs-^{6}Li mixture, again finding good agreement with the experimental observations both at weak and strong interactions. A central ingredient of our theory is the generalization of a fermion mediated interaction to strong Bose-Fermi scatterings and to finite frequencies. This further leads to a predicted hybridization of the sound modes of the Bose and Fermi gases, which can be directly observed using Bragg spectroscopy.

Polarized Tunneling Transistor for Ultralow-Energy-Consumption Artificial Synapse toward Neuromorphic Computing.

Neural networks based on low-power artificial synapses can significantly reduce energy consumption, which is of great importance in today's era of artificial intelligence. Two-dimensional (2D) material-based floating-gate transistors (FGTs) have emerged as compelling candidates for simulating artificial synapses owing to their multilevel and nonvolatile data storage capabilities. However, the low erasing/programming speed of FGTs renders them unsuitable for low-energy-consumption artificial synapses, thereby limiting their potential in high-energy-efficient neuromorphic computing. Here, we introduce a FGT-inspired MoS2/Trap/PZT heterostructure-based polarized tunneling transistor (PTT) with a simple fabrication process and significantly enhanced erasing/programming speed. Distinct from the FGT, the PTT lacks a tunnel layer, leading to a marked improvement in its erasing/programming speed. The PTT's highest erasing/programming (operation) speed can reach ∼20 ns, which outperforms the performance of most FGTs based on 2D heterostructures. Furthermore, the PTT has been utilized as an artificial synapse, and its weight-update energy consumption can be as low as 0.0002 femtojoule (fJ), which benefits from the PTT's ultrahigh operation speed. Additionally, PTT-based artificial synapses have been employed in constructing artificial neural network simulations, achieving facial-recognition accuracy (95%). This groundbreaking work makes it possible for fabricating future high-energy-efficient neuromorphic transistors utilizing 2D materials.

PZT-Enabled MoS2 Floating Gate Transistors: Overcoming Boltzmann Tyranny and Achieving Ultralow Energy Consumption for High-Accuracy Neuromorphic Computing.

Low-power electronic devices play a pivotal role in the burgeoning artificial intelligence era. The study of such devices encompasses low-subthreshold swing (SS) transistors and neuromorphic devices. However, conventional field-effect transistors (FETs) face the inherent limitation of the "Boltzmann tyranny", which restricts SS to 60 mV decade-1 at room temperature. Additionally, FET-based neuromorphic devices lack sufficient conductance states for highly accurate neuromorphic computing due to a narrow memory window. In this study, we propose a pioneering PZT-enabled MoS2 floating gate transistor (PFGT) configuration, demonstrating a low SS of 46 mV decade-1 and a wide memory window of 7.2 V in the dual-sweeping gate voltage range from -7 to 7 V. The wide memory window provides 112 distinct conductance states for PFGT. Moreover, the PFGT-based artificial neural network achieves an outstanding facial-recognition accuracy of 97.3%. This study lays the groundwork for the development of low-SS transistors and highly energy efficient artificial synapses utilizing two-dimensional materials.

Safety and efficacy of zanubrutinib in relapsed/refractory marginal zone lymphoma: final analysis of the MAGNOLIA study.

The primary analysis of MAGNOLIA, an open-label, single-arm, multicenter, phase 2 study, demonstrated that the next-generation Bruton tyrosine kinase (BTK) inhibitor zanubrutinib provided a high overall response rate (ORR) in patients with relapsed/refractory marginal zone lymphoma (R/R MZL), with a favorable safety/tolerability profile. Presented here, is the final analysis of MAGNOLIA, performed to characterize the durability of response and longer-term safety and tolerability. Zanubrutinib (160 mg twice daily) was evaluated in 68 patients with R/R MZL who had received at least 1 anti-CD20-directed regimen. The primary end point was independent review committee (IRC)-assessed ORR. Secondary end points included investigator-assessed ORR, duration of response (DOR), progression-free survival (PFS), overall survival (OS), health-related quality of life, safety, and tolerability. With a median follow-up of 27.4 months, the IRC-assessed ORR was 68.2% (95% confidence interval [CI], 55.6-79.1), with a 24-month DOR event-free rate of 72.9% (95% CI, 54.4-84.9). PFS and OS at 24 months were 70.9% (95% CI, 57.2-81.0) and 85.9% (95% CI, 74.7-92.4), respectively. The zanubrutinib safety profile was consistent with the primary analysis, with no new safety signals observed. Atrial fibrillation/flutter (n = 2 [2.9%]) and hypertension (n = 3 [4.4%]) were uncommon. Neutropenia (n = 8 [11.8%]) was the most common grade ≥3 adverse event. In this final analysis of MAGNOLIA, zanubrutinib demonstrated sustained clinical responses beyond 2 years, with 73% of responders alive and progression free. Zanubrutinib continued to demonstrate a favorable safety/tolerability profile with the additional time on treatment. This trial was registered at www.clinicaltrials.gov as #NCT03846427.

Wireless Electrical Signals Induce Functional Neuronal Differentiation of BMSCs on 3D Graphene Framework Driven by Magnetic Field.

Bone marrow mesenchymal stem cells (BMSCs) are suggested as candidates for neurodegeneration therapy by autologous stem cells to overcome the lack of neural stem cells in adults. However, the differentiation of BMSCs into functional neurons is a major challenge for neurotherapy. Herein, a methodology has been proposed to induce functional neuronal differentiation of BMSCs on a conductive three-dimensional graphene framework (GFs) combined with a rotating magnetic field. A wireless electrical signal of about 10 µA can be generated on the surface of GFs by cutting the magnetic field lines based on the well-known electromagnetic induction effect, which has been proven to be suitable for inducing neuronal differentiation of BMSCs. The enhanced expressions of the specific genes/proteins and apparent Ca2+ intracellular flow indicate that BMSCs cultured on GFs with 15 min/day rotating magnetic field stimulation for 15 days can differentiate functional neurons without any neural inducing factor. The animal experiments confirm the neural differentiation of BMSCs on GFs after transplantation in vivo, accompanied by stimulation of an external rotating magnetic field. This study overcomes the lack of autologous neural stem cells for adult neurodegeneration patients and provides a facile and safe strategy to induce the neural differentiation of BMSCs, which has potential for clinical applications of neural tissue engineering.

Research and Application of Shallow Geothermal Energy Development and Utilization in Shandong Province.

Shallow geothermal energy reserves are abundant and widely distributed in Shandong Province. Vigorously developing and utilizing shallow geothermal energy will play a significant role in improving energy pressure in Shandong Province. The energy efficiency of ground source heat pumps is closely related to geological and other conditions. However, few studies on geothermal exploitation and utilization have been affected by economic policies. This article will investigate the operation of shallow geothermal engineering in Shandong Province, summarize the current number of operating projects, calculate the engineering annual comprehensive performance coefficient (ACOP), analyze the size characteristics of different cities, and analyze their correlation with economy and policy. Through research, it is found that the number of shallow geothermal energy development and utilization is significantly positively correlated with socioeconomic level and policy orientation, and has a relatively small relationship with ACOP. The research results provide a basis and suggestions for improving and optimizing the energy efficiency coefficient of geothermal heat pumps and promoting the development and utilization of shallow geothermal.

Dual functional states of working memory realized by memristor-based neural network.

Working memory refers to the brain's ability to store and manipulate information for a short period. It is disputably considered to rely on two mechanisms: sustained neuronal firing, and "activity-silent" working memory. To develop a highly biologically plausible neuromorphic computing system, it is anticipated to physically realize working memory that corresponds to both of these mechanisms. In this study, we propose a memristor-based neural network to realize the sustained neural firing and activity-silent working memory, which are reflected as dual functional states within memory. Memristor-based synapses and two types of artificial neurons are designed for the Winner-Takes-All learning rule. During the cognitive task, state transformation between the "focused" state and the "unfocused" state of working memory is demonstrated. This work paves the way for further emulating the complex working memory functions with distinct neural activities in our brains.

Raman Characterization of the In-Plane Stress Tensor of Gallium Nitride.

Experimental characterization of the in-plane stress tensor is a basic requirement for the development of GaN strain engineering. In this work, a theoretical model of stress characterization for GaN using polarized micro-Raman spectroscopy was developed based on elasticity theory and lattice dynamics. Compared with other works, the presented model can give the quantitative relationship between all components of the in-plane stress tensor and the measured Raman shift. The model was verified by a calibration experiment under step-by-step uniaxial compression. By combining the stress characterization model with the expanding cavity model, the in-plane residual stress component field around Berkovich indentation on the (0001) plane GaN was achieved. The experimental results show that the distributions of the stress components, which significantly differed from the distribution of the Raman shift, were closely related to the GaN crystal structure and exhibited a gradient along each crystal direction.

Pharmacokinetics of single- and multiple-dose flumatinib in patients with chronic phase chronic myeloid leukemia.

Introduction: Flumatinib is a novel, oral breakpoint cluster region-abelson (BCR-ABL) tyrosine kinase inhibitor that has demonstrated manageable safety and promising efficacy in patients with newly diagnosed chronic phase (CP) chronic myeloid leukemia (CML). Methods: This study evaluated the pharmacokinetic (PK) profiles of flumatinib mesylate tablets at a dose of 400 mg and 600 mg in patients with CML-CP. The study was registered at chictr.org Identifier (ChiCTR2100044700). In this open-label, pharmacokinetic study, eligible patients were administered a single-dose of flumatinib 400 mg or 600 mg on day 1, followed by 2-day washout and 8 consecutive days of once-daily administration. Serial plasma samples were assayed for flumatinib and its metabolites (N-demethylate metabolite M1 and amide-bond hydrolytic metabolite M3). Results: Twenty-nine patients were assigned to flumatinib 400 mg (n=14) or 600 mg (n=15). Serum concentrations of flumatinib reached maximum measured plasma concentration (Cmax) at a median time of 2 hours after each single dose, and then eliminated slowly with a mean apparent terminal disposition half-life (t1/2) from 16.0 to 16.9 hours. Following single- and multiple-dose administration, flumatinib exposure (Cmax, area under the concentration-time curve from 0 to t hours (AUC0-t), area under the concentration-time curve from 0 hours to infinity (AUC0-∞)) increased in an approximately dose-proportional manner. There was approximately 4.1- and 3.4- fold drug accumulation at steady-state after multiple-dose administration at 400 mg and 600 mg, respectively. The drug-related AEs associated with both treatments were primarily low-grade and tolerable events. Conclusion: Analysis of PK parameters indicated that flumatinib exposure increased in an approximately dose-proportional manner. Further research needs to be conducted in a large sample-size study.

3D actuation of foam-core liquid metal droplets.

Precise manipulation of liquid metal (LM) droplets possesses the potential to enable a wide range of applications in reconfigurable electronics, robotics, and microelectromechanical systems. Although a variety of methods have been explored to actuate LM droplets on a 2D plane, versatile 3D manipulation remains a challenge due to the difficulty in overcoming their heavy weight. Here, foam-core liquid metal (FCLM) droplets that can maintain the surface properties of LM while significantly reducing the density are developed, enabling 3D manipulation in an electrolyte. The FCLM droplet is fabricated by coating LM on the surface of a copper-grafted foam sphere. The actuation of the FCLM droplet is realized by electrically inducing Marangoni flow on the LM surface. Two motion modes of the FCLM droplet are observed and studied and the actuation performance is characterized. Multiple FCLM droplets can be readily controlled to form 3D structures, demonstrating their potential to be further developed to form collaborative robots for enabling wider applications.

A Sensitive and Portable Double-Layer Microfluidic Biochip for Harmful Algae Detection.

Harmful algal blooms (HABs) are common disastrous ecological anomalies in coastal waters. An effective algae monitoring approach is important for natural disaster warning and environmental governance. However, conducting rapid and sensitive detection of multiple algae is still challenging. Here, we designed an ultrasensitive, rapid and portable double-layer microfluidic biochip for the simultaneous quantitative detection of six species of algae. Specific DNA probes based on the 18S ribosomal DNA (18S rDNA) gene fragments of HABs were designed and labeled with the fluorescent molecule cyanine-3 (Cy3). The biochip had multiple graphene oxide (GO) nanosheets-based reaction units, in which GO nanosheets were applied to transfer target DNA to the fluorescence signal through a photoluminescence detection system. The entire detection process of multiple algae was completed within 45 min with the linear range of fluorescence recovery of 0.1 fM-100 nM, and the detection limit reached 108 aM. The proposed approach has a simple detection process and high detection performance and is feasible to conduct accurate detection with matched portable detection equipment. It will have promising applications in marine natural disaster monitoring and environmental care.