Metabolomics and molecular docking-directed anti-obesity study of the ethanol extract from Gynostemma pentaphyllum (Thunb.) Makino.

ETHNOPHARMACOLOGICAL RELEVANCE: Gynostemma pentaphyllum (Thunb.) Makino (G. pentaphyllum) is an oriental herb documented to treat many diseases, including obesity, hyperlipidemia, metabolic syndromes and aging. However, the anti-obesity mechanism of G. pentaphyllum remains poorly understood. AIM OF THE STUDY: To reveal the anti-obesity mechanism of G. pentaphyllum Extract (GPE) in High-Fat Diet (HFD)-induced obese mice through untargeted metabolomics, Real-Time Quantitative PCR (RT-qPCR), and immunohistochemical experiments. Additionally, to tentatively identify the active constituents through LC-MS/MS and molecular docking approaches. MATERIALS AND METHODS: GPE was prepared using ethanol reflux and purified by HP-20 macroporous resins. The components of GPE were identified by Liquid Chromatography- Mass Spectrometry (LC-MS) system. Forty-two C57BL/6 J mice were randomly and evenly divided into six groups, with seven mice in each group: the control group, obese model group, Beinaglutide group (positive control), and GPE low, medium, and high-dose groups (50 mg/kg, 100 mg/kg, and 200 mg/kg of 80% ethanol extract). Body weight, liver weight, blood glucose, blood lipids, and liver histopathological changes were assessed. Untargeted metabolomics was employed to characterize metabolic changes in obese mice after GPE treatment. The expression of genes related to differential metabolites was verified using Real-Time Quantitative PCR (RT-qPCR) and immunohistochemical experiments. The constituents with anti-obesity effects from GPE were tentatively identified through molecular docking approaches. RESULTS: A total of 17 compounds were identified in GPE. GPE significantly lowered body weight, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in obese mice and reduced liver weight and hepatic steatosis. Serum metabolomics identified 20 potential biomarkers associated with GPE treatment in obese mice, primarily related to tryptophan metabolism. GPE treatment downregulated the expression of Slc6a19 and Tph1 and upregulated Ucp1 expression. Molecular docking illustrated that compounds such as 20(R)-ginsenoside Rg3, Araliasaponin I, Damulin B, Gypenoside L, Oleifolioside B, and Tricin7-neohesperidoside identified in GPE exhibited favorable interaction with Tph1. CONCLUSION: The extract of G. pentaphyllum can inhibit the absorption of tryptophan and its conversion to 5-HT through the Slc6a19/Tph1 pathway, upregulating the expression of Ucp1, thereby promoting thermogenesis in brown adipose tissue, facilitating weight loss, and mitigating symptoms of fatty liver. Triterpenoids such as Araliasaponin I, identified in GPE, could be the potential inhibitor of Tph1 and responsible for the anti-obesity activities.

Dihydroartemisinin inhibits tumor progress via blocking ROR1-induced STAT3-activation in non-small cell lung cancer.

In non-small cell lung cancer (NSCLC), identifying a component with certain molecular targets can aid research on cancer treatment. Dihydroartemisinin (DHA) is a semisynthetic derivative of artemisinin which induced the anti-cancer effects via the STAT3 signaling pathway, but the underlying molecular mechanism is still elusive. In this study, we first proved that DHA prohibits the growth of tumors both in vitro and in vivo. Data from transcriptomics showed that DHA reduced the expression level of the genes involved in cell cycle-promoting and anti-apoptosis, and most importantly, DHA restricted the expression level of receptor tyrosine kinase-like orphan receptor 1 (ROR1) which has been reported to have abnormal expression on tumor cells and had close interaction with STAT3 signaling. Then, we performed comprehensive experiments and found that DHA remarkably decreased the expression of ROR1 at both mRNA and protein levels and it also diminished the phosphorylation level of STAT3 in NSCLC cell lines. In addition, our data showed that exogenously introduced ROR1 could significantly enhance the phosphorylation of STAT3 while blocking ROR1 had the opposite effects indicating that ROR1 plays a critical role in promoting the activity of STAT3 signaling. Finally, we found that ROR1 overexpression could partially reverse the decreased activity of STAT3 induced by DHA which indicates that DHA-induced anti-growth signaling is conferred, at least in part, through blocking ROR1-mediated STAT3 activation. In summary, our study indicates that in NSCLC, ROR1 could be one of the critical molecular targets mediating DHA-induced STAT3 retardation.

An Ultrathin Flexible Programmable Spin Logic Device Based on Spin-Orbit Torque.

Flexible electronic devices have shown increasingly promising value facilitating our daily lives. However, flexible spintronic devices remain in their infancy. Here, this research demonstrates a type of nonvolatile, low power dissipation, and programmable flexible spin logic device, which is based on the spin-orbit torque in polyimide (PI)/Ta/Pt/Co/Pt heterostructures fabricated via capillary-assisted electrochemical delamination. The magnetization switching ratio is shown to be about 50% for the flexible device and does not change after 100 cycles of bending, indicating the device has stable performance. By designing the path of pulse current, five Boolean logic gates AND, NAND, NOT, NOR, and OR can be realized in an integrated two-element device. Moreover, such peeling-off devices can be successfully transferred to almost any substrate, such as paper and human skin, and maintain high performance. The flexible PI/Ta/Pt/Co/Pt spin logic device serves as logic-in-memory architecture and can be used in wearable electronics.

Technology Roadmap for Flexible Sensors.

Humans rely increasingly on sensors to address grand challenges and to improve quality of life in the era of digitalization and big data. For ubiquitous sensing, flexible sensors are developed to overcome the limitations of conventional rigid counterparts. Despite rapid advancement in bench-side research over the last decade, the market adoption of flexible sensors remains limited. To ease and to expedite their deployment, here, we identify bottlenecks hindering the maturation of flexible sensors and propose promising solutions. We first analyze challenges in achieving satisfactory sensing performance for real-world applications and then summarize issues in compatible sensor-biology interfaces, followed by brief discussions on powering and connecting sensor networks. Issues en route to commercialization and for sustainable growth of the sector are also analyzed, highlighting environmental concerns and emphasizing nontechnical issues such as business, regulatory, and ethical considerations. Additionally, we look at future intelligent flexible sensors. In proposing a comprehensive roadmap, we hope to steer research efforts towards common goals and to guide coordinated development strategies from disparate communities. Through such collaborative efforts, scientific breakthroughs can be made sooner and capitalized for the betterment of humanity.

Efficacy and safety of repeated transcranial magnetic stimulation combined with escitalopram in the treatment of major depressive disorder: a meta-analysis.

Objective: This study was designed to systematically review the efficacy and safety of repeated transcranial magnetic stimulation (rTMS) combined with escitalopram in treating major depressive disorder (MDD). Methods: Databases including PubMed, Embase, Cochrane, Web of Science, CNKI, Wanfang, VIP Journal, and China Biomedical Literature databases were electronically searched for randomized controlled trials of rTMS combined with escitalopram intervention for MDD treatment from the inception of these databases to 27 May 2023. Two reviewers independently screened the studies, extracted the data, and assessed the quality of the included studies. R 4.2.2 was then used for a meta-analysis. Results: In total, 19 articles involving 1,032 patients were included. The results of the meta-analysis showed that Hamilton Depression Rating Scale (HAMD) scores were significantly lower in the group receiving rTMS combined with escitalopram (experimental group) than that in the control group [weighted mean difference (WMD) = -5.30, 95% confidence interval (95% CI): -6.44 to -4.17, p < 0.01]. The response rate of the experimental group was significantly higher than that of the control group [odds ratio (OR): 5.48; 95% CI: 3.72 to 8.07; p < 0.01]. No significant difference in the adverse reaction rate was observed between the two groups (OR: 1.04, 95% CI: 0.71 to 1.52, p = 0.82). Conclusion: Our findings suggest that rTMS combined with escitalopram can benefit patients with MDD in a safe manner, which may help in guiding clinical practice. Systematic review registration: DOI number: 10.37766/inplasy2023.11.0114, INPLASY2023110114.

Carbon nanotube-based flexible high-speed circuits with sub-nanosecond stage delays.

High-speed flexible circuits are required in flexible systems to realize real-time information analysis or to construct wireless communication modules for emerging applications. Here, we present scaled carbon nanotube-based thin film transistors (CNT-TFTs) with channel lengths down to 450 nm on 2-µm-thick parylene substrates, achieving state-of-the-art performances of high on-state current (187.6 µA µm-1) and large transconductance (123.3 µS µm-1). Scaling behavior analyses reveal that the enhanced performance introduced by scaling is attributed to channel resistance reduction while the contact resistance (180 ± 50 kΩ per tube) remains unchanged, which is comparable to that achieved in devices on rigid substrates, indicating great potential in ultimate scaled flexible CNT-TFTs with high performance comparable to their counterparts on rigid substrates where contact resistance dominates the performance. Five-stage flexible ring oscillators are built to benchmark the speed of scaled devices, demonstrating a 281 ps stage delay at a low supply voltage of 2.6 V.

An epidermal electronic system for physiological information acquisition, processing, and storage with an integrated flash memory array.

Epidermal electronic systems that simultaneously provide physiological information acquisition, processing, and storage are in high demand for health care/clinical applications. However, these system-level demonstrations using flexible devices are still challenging because of obstacles in device performance, functional module construction, or integration scale. Here, on the basis of carbon nanotubes, we present an epidermal system that incorporates flexible sensors, sensor interface circuits, and an integrated flash memory array to collect physiological information from the human body surface; amplify weak biosignals by high-performance differential amplifiers (voltage gain of 27 decibels, common-mode rejection ratio of >43 decibels, and gain bandwidth product of >22 kilohertz); and store the processed information in the memory array with performance on par with industrial standards (retention time of 108 seconds, program/erase voltages of ±2 volts, and endurance of 106 cycles). The results shed light on the great application potential of epidermal electronic systems in personalized diagnostic and physiological monitoring.

Carbon Nanotube-Based Flexible Ferroelectric Synaptic Transistors for Neuromorphic Computing.

Biological nervous systems evolved in nature have marvelous information processing capacities, which have great reference value for modern information technologies. To expand the function of electronic devices with applications in smart health monitoring and treatment, wearable energy-efficient computing, neuroprosthetics, etc., flexible artificial synapses for neuromorphic computing will play a crucial role. Here, carbon nanotube-based ferroelectric synaptic transistors are realized on ultrathin flexible substrates via a low-temperature approach not exceeding 90 °C to grow ferroelectric dielectrics in which the single-pulse, paired-pulse, and repetitive-pulse responses testify to well-mimicked plasticity in artificial synapses. The long-term potentiation and long-term depression processes in the device demonstrate a dynamic range as large as 2000×, and 360 distinguishable conductance states are achieved with a weight increase/decrease nonlinearity of no more than 1 by applying stepped identical pulses. The stability of the device is verified by the almost unchanged performance after the device is kept in ambient conditions without additional passivation for 240 days. An artificial neural network-based simulation is conducted to benchmark the hardware performance of the neuromorphic devices in which a pattern recognition accuracy of 95.24% is achieved.

High-Performance Carbon Nanotube-Based Transient Complementary Electronics.

Transient electronics is an emerging class of electronic devices that can physically degrade or disintegrate after a stable period of service, showing a vast prospect in applications of "green" consumer electronics, hardware-secure devices, medical implants, etc. Complementary metal-oxide-semiconductor (CMOS) technology is dominant in integrated circuit design for its advantages of low static power consumption, high noise immunity, and simple design layout, which also work and are highly preferred for transient electronics. However, the performance of complementary transient electronics is severely restricted by the confined selection of transient materials and compatible fabrication strategies. Here, we report the realization of high-performance transient complementary electronics based on carbon nanotube thin films via a reliable electrostatic doping method. Under a low operating voltage of 2 V, on a 1.5 µm-thick water-soluble substrate made of poly(vinyl alcohol), the width-normalized on-state currents of the p-type and n-type transient thin-film transistors (TFTs) reach 4.5 and 4.7 µA/µm, and the width-normalized transconductances reach 2.8 and 3.7 µS/µm, respectively. Meanwhile, these TFTs show small subthreshold swings no more than 108 mV/dec and current on/off ratios above 106 with good uniformity. Transient CMOS inverters, as basic circuit components, are demonstrated with a voltage gain of 24 and a high noise immunity of 67.4%. Finally, both the degradation of the active components and the disintegration of the functional system are continuously monitored with nontraceable remains after 10 and 5 h, respectively.

A Flexible Integrated Bending Strain and Pressure Sensor System for Motion Monitoring.

Flexible sensors have attracted increasing research interest due to their broad application potential in the fields of human-computer interaction, medical care, sports monitoring, etc. Constructing an integrated sensor system with high performance and being capable of discriminating different stimuli remains a challenge. Here, we proposed a flexible integrated sensor system for motion monitoring that can measure bending strain and pressure independently with a low-cost and simple fabrication process. The resistive bending strain sensor in the system is fabricated by sintering polyimide (PI), demonstrating a gauge factor of 9.54 and good mechanical stability, while the resistive pressure sensor is constructed based on a composite structure of silver nanowires (AgNWs) and polydimethylsiloxane (PDMS)-expandable microspheres with a tunable sensitivity and working range. Action recognition is demonstrated by attaching the flexible integrated sensor system on the wrist with independent strain and pressure information recorded from corresponding sensors. It shows a great application potential in motion monitoring and intelligent human-machine interfaces.

Sensation and Perception of a Bioinspired Flexible Smart Sensor System.

The somatosensory system helps the human body to become aware of various stimuli and to interact with its surroundings. Humans are able to identify and to process abundant sensory information quickly due to their unique perception characteristics. As the largest sensory organ, skin has a large number of discrete receptors to sense and to transform stimuli of touch, pressure, pain, temperature, etc. into electrical signals, which are preprocessed at various levels before reaching the brain, greatly reducing the computational burden on the central nervous system. In addition, the conduction speed varies for different stimulus information, which simplifies the parallel processing of a variety of information. In this Perspective, we discuss a bioinspired design for a flexible smart sensor system by simulating the human somatosensory system. In this design, sensors with selective responses, signals separated in time sequences, and hierarchical information processing are adopted to optimize the sensing and perceiving processes, to reduce power consumption, and to improve the speed of a flexible smart sensor system.

A Flexible Two-Sensor System for Temperature and Bending Angle Monitoring.

A wearable electronic system constructed with multiple sensors with different functions to obtain multidimensional information is essential for making accurate assessments of a person's condition, which is especially beneficial for applications in the areas of health monitoring, clinical diagnosis, and therapy. In this work, using polyimide films as substrates and Pt as the constituent material of serpentine structures, flexible temperature and angle sensors were designed that can be attached to the surface of an object or the human body for monitoring purposes. In these sensors, changes in temperature and bending angle are converted into variations in resistance through thermal resistance and strain effects with a sensitivity of 0.00204/°C for temperatures in the range of 25 to 100 °C and a sensitivity of 0.00015/° for bending angles in the range of 0° to 150°. With an appropriate layout design, two sensors were integrated to measure temperature and bending angles simultaneously in order to obtain decoupled, compensated, and more accurate information of temperature and angle. Finally, the system was tested by being attached to the surface of a knee joint, demonstrating its application potential in disease diagnosis, such as in arthritis assessment.

A Tubular Flexible Triboelectric Nanogenerator with a Superhydrophobic Surface for Human Motion Detecting.

The triboelectric nanogenerator (TENG) is a newly arisen technology for mechanical energy harvesting from the environment, such as raindrops, wind, tides, and so on. It has attracted widespread attention in flexible electronics to serve as self-powered sensors and energy-harvesting devices because of its flexibility, durability, adaptability, and multi-functionalities. In this work, we fabricated a tubular flexible triboelectric nanogenerator (TF-TENG) with energy harvesting and human motion monitoring capabilities by employing polydimethylsiloxane (PDMS) as construction material, and fluorinated ethylene propylene (FEP) films coated with Cu as the triboelectric layer and electrode, serving in a free-standing mode. The tube structure has excellent stretchability that can be stretched up to 400%. Modifying the FEP films to obtain a superhydrophobic surface, the output performance of TF-TENG was increased by at least 100% compared to an untreated one. Finally, as the output of TF-TENG is sensitive to swing angle and frequency, demonstration of real-time monitoring of human motion state was realized when a TF-TENG was worn on the wrist.

Carbon Nanotube Field-Effect Transistor-Based Chemical and Biological Sensors.

Chemical and biological sensors have attracted great interest due to their importance in applications of healthcare, food quality monitoring, environmental monitoring, etc. Carbon nanotube (CNT)-based field-effect transistors (FETs) are novel sensing device configurations and are very promising for their potential to drive many technological advancements in this field due to the extraordinary electrical properties of CNTs. This review focuses on the implementation of CNT-based FETs (CNTFETs) in chemical and biological sensors. It begins with the introduction of properties, and surface functionalization of CNTs for sensing. Then, configurations and sensing mechanisms for CNT FETs are introduced. Next, recent progresses of CNTFET-based chemical sensors, and biological sensors are summarized. Finally, we end the review with an overview about the current application status and the remaining challenges for the CNTFET-based chemical and biological sensors.

Recent Advances in Flexible and Stretchable Sensing Systems: From the Perspective of System Integration.

Biological signals generated during various biological processes are critically important for providing insight into the human physiological status. Recently, there have been many great efforts in developing flexible and stretchable sensing systems to provide biological signal monitoring platforms with intimate integration with biological surfaces. Here, this review summarizes the recent advances in flexible and stretchable sensing systems from the perspective of electronic system integration. A comprehensive general sensing system architecture is described, which consists of sensors, sensor interface circuits, memories, and digital processing units. The subsequent content focuses on the integration requirements and highlights some advanced progress for each component. Next, representative examples of flexible and stretchable sensing systems for electrophysiological, physical, and chemical information monitoring are introduced. This review concludes with an outlook on the remaining challenges and opportunities for future fully flexible or stretchable sensing systems.

Tunable, Ultrasensitive, and Flexible Pressure Sensors Based on Wrinkled Microstructures for Electronic Skins.

Flexible pressure sensors play an important role in electronic skins (E-Skins), which mimic the mechanical forces sensing properties of human skin. A rational design for a pressure sensor with adjustable characteristics is in high demand for different application scenarios. Here, we present tunable, ultrasensitive, and flexible pressure sensors based on compressible wrinkled microstructures. Modifying the morphology of polydimethylsiloxane (PDMS) microstructure enables the device to obtain different sensitivities and pressure ranges for different requirements. Furthermore, by intentionally introducing hollow structures in the PDMS wrinkles, our pressure sensor exhibits an ultrahigh sensitivity of 14.268 kPa-1. The elastic microstructure-based capacitive sensor also possesses a very low detectable pressure limit (1.5 Pa), a fast response time (<50 ms), a wide pressure range, and excellent cycling stability. Implementing respiratory monitoring and vocalization recognition is realized by attaching the flexible pressure sensor onto the chest and throat, respectively, showing its great application potential for disease diagnosis, monitoring, and other advanced clinical/biological wearable technologies.

Kirigami-Inspired Deformable 3D Structures Conformable to Curved Biological Surface.

By introducing stretchability and/or deformability to planar electronics, devices can conformably attach to 3D curved surfaces with minimal invasiveness, which is of great interest for next-generation wearables in clinical and biological applications. Here, a feasible route is demonstrated to generate deformable 3D structures as a robust platform to construct electronic systems by utilizing silver nanowires/parylene hybrid films in a way analogous to the art of kirigami. The hybrid films exhibit outstanding electrical conductivity along with decent optical transparency, flexibility, and long-term stability. These merits enable these films to work as electrodes for electrocardiogram recording with comparable accuracy to a commercial counterpart, and to fabricate a 7-GHz monopole antenna with good omni-directionality and a peak gain of 1.35 dBi. More importantly, a general scheme for constructing 3D deformable electronic systems is presented, including unique patterning procedures and rational cut designs inspired by kirigami. As an example, deformable transparent humidity sensors are fabricated to work on elbows and finger joints for sweating monitoring. The strategy demonstrated here for 3D deformable system construction is versatile and holds great promise for future advanced health monitoring at diverse and complex epidermal surfaces.

Configurable multifunctional integrated circuits based on carbon nanotube dual-material gate devices.

Nanoelectronic devices with specifically designed structures for performance promotion or function expansion are of great interest, aiming for diversified advanced nanoelectronic systems. In this work, we report a dual-material gate (DMG) carbon nanotube (CNT) device with multiple functions, which can be configured either as a high-performance p-type field-effect transistor (FET) or a diode by changing the input manners of the device. When operating as a FET, the device exhibits a large current on/off ratio of more than 108 and a drain-induced barrier lowering of 97.3 mV V-1. When configured as a diode, the rectification ratio of the device can be greater than 105. We then demonstrate configurable analog and digital integrated circuits that are enabled by utilizing these devices. The configurability enables the realization of transformable functions in a single device or circuits, which gives future electronic systems the flexibility to adapt to the diverse requirements of their applications and/or ever-changing operating environments.