Deciphering the Pharmacological Mechanisms of Wen-Jing-Zhi-Tong Decoction in Treating Primary Dysmenorrhea by UPLC-Q-ExactiveOrbitrap-MS/MS with GC-MS and Network Pharmacology.

BACKGROUND: Primary dysmenorrhea (PDM) is a prevalent menstrual disorder among women, often underreported and undertreated. Wen-Jing-Zhi-Tong Decoction (WJZTD), a patented Traditional Chinese Medicine (TCM) herbal decoction, has shown efficacy in treating PDM. However, the underlying therapeutic mechanism of WJZTD in PDM treatment remains to be elucidated. OBJECTIVE: This study aimed to employ integrative pharmacology and experimental validation to investigate the potential therapeutic mechanisms of WJZTD in treating PDM. METHODS: The bioactive compounds of WJZTD were identified by UPLC-Q-Exactive-Orbitrap MS/MS and GC-MS. Putative targets of WJZTD were obtained from Swiss Target Prediction, STITCH, and BATMAN-TCM databases. Known targets of PDM were retrieved from Gene Cards and Drug Bank databases. Protein-to-protein interactions were constructed to screen key targets using the STRING database. Subsequently, GO and KEGG pathway enrichment analyses were performed based on Metascape. Finally, a PDM rat model was established to validate the potential therapeutic mechanisms of WJZTD using Western Blot, PCR, and ELISA. RESULTS: 390 bioactive compounds in WJZTD were identified through UPLC-Q-ExactiveOrbitrap MS/MS and GC-MS. Network pharmacology revealed 7 key compounds with 20 targets and pathways that are crucial for WJZTD in treating PDM. Behavioral tests confirmed that WJZTD can effectively ameliorate menstrual pain in PDM. WJZTD also inhibited prostaglandin production, thereby relieving uterine smooth muscle contraction. The downregulation of the BDNF/TrkB/ERK/CREB signaling pathway, identified as the key target and pathway through network pharmacology, may be crucial to the anti-nociceptive and anti-inflammatory effects of WJZTD in treating PDM. CONCLUSION: This study provides the first comprehensive analysis of the key compounds, targets, and pathways of WJZTD, laying a solid foundation for future pharmacological studies on PDM. The anti-nociceptive and anti-inflammatory effect may be attributed to the downregulation of the BDNF/TrkB/ERK/CREB signaling pathway.

High-density, highly sensitive sensor array of spiky carbon nanospheres for strain field mapping.

While accurate mapping of strain distribution is crucial for assessing stress concentration and estimating fatigue life in engineering applications, conventional strain sensor arrays face a great challenge in balancing sensitivity and sensing density for effective strain mapping. In this study, we present a Fowler-Nordheim tunneling effect of monodispersed spiky carbon nanosphere array on polydimethylsiloxane as strain sensor arrays to achieve a sensitivity up to 70,000, a sensing density of 100 pixel cm-2, and logarithmic linearity over 99% within a wide strain range of 0% to 60%. The highly ordered assembly of spiky carbon nanospheres in each unit also ensures high inter-unit consistency (standard deviation ≤3.82%). Furthermore, this sensor array can conformally cover diverse surfaces, enabling accurate acquisition of strain distributions. The sensing array offers a convenient approach for mapping strain fields in various applications such as flexible electronics, soft robotics, biomechanics, and structure health monitoring.

Skin-Integrated Electrodes Based on Room-Temperature Curable, Highly Conductive Silver/Polydimethylsiloxane Composites.

The quality of electrophysiological (EP) signals heavily relies on the electrode's contact with the skin. However, motion or exposure to water can easily destabilize this connection. In contrast to traditional methods of attaching electrodes to the skin surface, this study introduces a skin-integration strategy inspired by the skin's intergrown structure. A highly conductive and room-temperature curable composite composed of silver microflakes and polydimethylsiloxane (Ag/PDMS) is applied to the skin. Before curing, the PDMS oil partially diffuse into the stratum corneum (SC) layer of the skin. Upon curing, the composite solidifies into an electrode that seamlessly integrated with the skin, resembling a natural extension. This skin-integration strategy offers several advantages. It minimizes motion artifacts resulting from relative electrode-skin displacement, significantly reduces interface impedance (67% of commercial Ag/AgCl gel electrodes at 100 Hz) and withstands water flushes due to its hydrophobic nature. These advantages pave the way for promising advancements in EP signal recording, particularly during motion and underwater conditions.

Flexible EEG Electrodes with Embedded Pressure Sensors and Customized Interface Towards Comfortable Home EEG Monitoring.

To realize stable and comfortable dry electroencephalography (EEG) recording for home healthcare, a flexible pressure-sensitive electrode (PSE) is proposed, and a dedicated multi-channel pressure sensor interface is developed. The PSE monitors the pressure on the electrode during continuous EEG recording. With the PSE, stable but comfortable electrode-skin contact can be achieved. The analog front-end of the sensor interface is fabricated in 180-nm CMOS, occupying an active area of 0.25 mm2. The flexible sensor exhibited a -2.5 kΩ/kPa sensitivity. The sensor interface enjoyed a large stimulus range of up to 2.65 mApp and showed a resolution of 0.047 - 8.0 mΩ/√Hz. It is digital-compatible, reconfigurable, and area-efficient, which can be migrated into various EEG acquisition integrated circuits and systems.

A Five-Channel Weighted Real-Time Algorithm for High-Density Electrodes Spike Sorting.

With the application of high-density neural probes, a neuron can be detected by multiple adjacent probes, and the traditional single-channel spike sorting is no longer suitable. In this paper, we propose a five-channel weighted real-time spike sorting algorithm based on template-matching to process neural signals recorded by high-density probes. This work uses the signals of the center channel and the adjacent four channels to form a five-channel template by weighting, and employs a modified OSort algorithm with unsupervised learning to update the template. We implemented automatic online spike sorting, and tested it with both ground truth recordings and simulated datasets. The experiments show that our algorithm utilizing the information of adjacent channels has a higher sorting accuracy than traditional single-channel spike sorting. The average sorting accuracy reaches 89%, compared to 78% for single-channel.

A 1.5 mm2 4-Channel EEG/BIOZ Acquisition ASIC With 15.2-Bit 3-Step ADC Based on a Signal-Dependent Low-Power Strategy.

This article presents a multichannel EEG/BIOZ acquisition application specific integrated circuit (ASIC) with 4 EEG channels and a BIOZ channel, a switch resistor low-pass filter (SR-LPF). Each EEG channel includes a frontend, and a 4-channel multiplexed analog-to-digital converter (ADC), while the BIOZ channel features a pseudo sine current generator and a pair of readout paths with multiplexed SR-LPF and ADC. The ASIC is designed for size and power minimization, utilizing a 3-step ADC with a novel signal-dependent low power strategy. The proposed ADC operates at a sampling rate of 1600 S/s with a resolution of 15.2 bits, occupying only 0.093 mm2. With the help of the proposed signal-dependent low-power strategy, the ADC's power dissipation drops from 32.2 µW to 26.4 µW, resulting in an 18% efficiency improvement without performance degradation. Moreover, the EEG channels deliver excellent noise performance with a NEF of 7.56 and 27.8 nV/√Hz at the expense of 0.16 mm2 per channel. In BIOZ measurement, a 5-bit programmable current source is used to generate pseudo sine injection current ranging from 0 to 22 µApp, and the detection sensitivity reaches 2.4 mΩ/√Hz. Finally, the presented multichannel EEG/BIOZ acquisition ASIC has a compact active area of 1.5 mm2 in an 180nm CMOS technology.

An Energy-Efficient Flexible Multi-Modal Wireless Sweat Sensing System Based on Laser Induced Graphene.

Real-time sweat monitoring is vital for athletes in order to reflect their physical conditions, quantify their exercise loads, and evaluate their training results. Therefore, a multi-modal sweat sensing system with a patch-relay-host topology was developed, which consisted of a wireless sensor patch, a wireless data relay, and a host controller. The wireless sensor patch can monitor the lactate, glucose, K+, and Na+ concentrations in real-time. The data is forwarded via a wireless data relay through Near Field Communication (NFC) and Bluetooth Low Energy (BLE) technology and it is finally available on the host controller. Meanwhile, existing enzyme sensors in sweat-based wearable sports monitoring systems have limited sensitivities. To improve their sensitivities, this paper proposes a dual enzyme sensing optimization strategy and demonstrates Laser-Induced Graphene (LIG)-based sweat sensors decorated with Single-Walled Carbon Nanotubes (SWCNT). Manufacturing an entire LIG array takes less than one minute and costs about 0.11 yuan in materials, making it suitable for mass production. The in vitro test result showed sensitivities of 0.53 µA/mM and 3.9 µA/mM for lactate and glucose sensing, and 32.5 mV/decade and 33.2 mV/decade for K+ and Na+ sensing, respectively. To demonstrate the ability to characterize personal physical fitness, an ex vivo sweat analysis test was also performed. Overall, the high-sensitivity lactate enzyme sensor based on SWCNT/LIG can meet the requirements of sweat-based wearable sports monitoring systems.

An ASIC for Gripper Finger Haptic Force Feedback in Minimally Invasive Surgery.

In this article, we present an application specific integrated circuit (ASIC) for gripper finger haptic force feedback in minimally invasive surgery (MIS). It consists of a driving current source, a sensing channel, a digital to analog converter (DAC), a power management unit (PMU), a clock generator and a digital control unit (DCU). The driving current source features a 6-bit DAC to provide a temperature-insensitive current from 0.27 mA to 1.15 mA for the sensor array. The sensing channel contains a programmable instrumentation amplifier (PIA), a low-pass filter (LPF), an incremental analog-to-digital converter (ADC) with its input buffer (BUF). The gain of the sensing channel ranges from 2.76 to 140. The DAC generates a tunable reference voltage to compensate possible sensor array offset. The input referred noise of the sensing channel is around 3.6 µVrms at a sampling rate of 850S/s. A custom 2-wire communication protocol is implemented to support two chips on gripper fingers operating in parallel with low latency, ensuring real-time surgical condition estimation for surgeons. Manufactured in the TSMC 180nm CMOS technology, this chip occupies only 1.37 mm2 core area, and the entire system requires only 4 wires (including power / ground) to operate. Combined with its high accuracy, low latency, and high integration level, this work allows real-time, high-performance haptic force feedback with compact system size, particularly suitable for MIS applications.

Highly Efficient and Stable Self-Powered Mixed Tin-Lead Perovskite Photodetector Used in Remote Wearable Health Monitoring Technology.

Realization of remote wearable health monitoring (RWHM) technology for the flexible photodiodes is highly desirable in remote-sensing healthcare systems used in space stations, oceans, and forecasting warning, which demands high external quantum efficiency (EQE) and detectivity in NIR region. Traditional inorganic photodetectors (PDs) are mechanically rigid and expensive while the widely reported solution-processed mixed tin-lead (MSP) perovskite photodetectors (PPDs) exhibit a trade-off between EQE and detectivity in the NIR region. Herein, a novel functional passivating antioxidant (FPA) strategy has been introduced for the first time to simultaneously improve crystallization, restrain Sn2+ oxidization, and reduce defects in MSP perovskite films by multiple interactions between thiophene-2-carbohydrazide (TAH) molecules and cations/anions in MSP perovskite. The resultant solution-processed rigid mixed Sn-Pb PPD simultaneously achieves high EQE (75.4% at 840 nm), detectivity (1.8 × 1012 Jones at 840 nm), ultrafast response time (trise /tfall = 94 ns/97 ns), and improved stability. This work also highlights the demonstration of the first flexible photodiode using MSP perovskite and FPA strategy with remarkably high EQE (75% at 840 nm), and operational stability. Most importantly, the RWHM is implemented for the first time in the PIN MSP perovskite photodiodes to remotely monitor the heart rate of humans at rest and after-run conditions.

Strain Release and Defect Passivation in Formamidinium-Dominated Perovskite via a Novel in-Plane Thermal Gradient Assisted Crystallization Strategy.

It is essential to release annealing induced strain during the crystallization process to realize efficient and stable perovskite solar cells (PSCs), which does not seem achievable using the conventional annealing process. Here we report a novel and facile thermal gradient assisted crystallization strategy by simply introducing a slant angle between the preheated hot plate and the substrate. A distinct crystallization sequence resulted along the in-plane direction pointing from the hot side to the cool side, which effectively reduced the crystallization rate, controlled the perovskite grain growth, and released the in-plane tensile strain. Moreover, this strategy enabled uniform strain distribution in the vertical direction and assisted in reducing the defects and aligning the energy bands. The corresponding device demonstrated champion power conversion efficiencies (PCEs) of 23.70% and 21.04% on the rigid and flexible substrates, respectively. These highly stable rigid devices retained 97% of the initial PCE after 1097 h of storage and more than 80% of the initial PCE after 1000 h of continuous operation at the maximum power point. This novel strategy opens a simple and effective avenue to improve the quality of perovskite films and photovoltaic devices via strain modulation and defect passivation.

A 17.7µW CDS-CTIA for Wireless-powered Wearable Electrochemical Sweat Sensors.

A capacitor transimpedance amplifier (CTIA) for wireless-powered wearable electrochemical sweat sensors is designed and tested. Correlative double sampling (CDS) technology is utilized to suppress offset voltage and noise. Dedicated low-power and low-voltage designs meet the requirements of wireless-powered wearable applications where the power supply is limited, and voltage is unstable. The proposed CDS-CTIA is fabricated in 0.18-µm complementary metal oxide semiconductor (CMOS) process, occupying an active area of 0.0285mm2. The measured low-frequency gain is 33.2MΩ/150.4dBΩ under a 1.8V supply voltage, with a total power consumption of 17.694µW (including 14.882µW static power and 2.812µW dynamic power). The input current ranges from -24nA to +19nA, and the input referred noise current is 7.76pArms in the 0.1-100 Hz frequency band. The proposed CDS-CTIA is capable of operating under a wide power supply ranging from 0.9V to 2.0V. In addition, its practicality is verified by measuring glucose concentration with an enzyme electrode.

A Hardware-based Lightweight ANN for Real-time Wearable Blood Pressure Estimation.

Blood pressure (BP) is an important indicator of the state of cardiovascular health. BP estimation is an essential method to prevent the occurrence of hypertension. Currently, there is a strong focus on low power design for a wearable BP estimation device. This paper proposes a lightweight artificial neural network (ANN) for BP estimation and implements it on an ultra-low-power application-specific integrated circuit (ASIC). On the test set, the mean absolute error (MAE) and standard deviation (SD) of the estimated systolic BP and diastolic BP are 2.47 ± 3.48 mmHg and 1.45 ± 1.88 mmHg. Besides, in the case of 8-bit quantization, the MAE ± SD of the estimated systolic BP and diastolic BP are 12.41 ± 5.32 mmHg and 6.29 ± 3.03 mmHg respectively. The regression result R2 of overall SBP and DBP is 0.9702. This ASIC whose power is 19.72 µW is validated via the 0.18 µm CMOS process, occupying an area of 730 µmx 730 µm.

A Flexible and Miniaturized Chest Patch for Real-time PPG/ECG/Bio-Z Monitoring.

We proposed a lightweight and wearable chest patch for real-time monitoring of three vital signals, photoplethysmography (PPG), electrocardiography (ECG), and bioimpedance (Bio-Z). It comprises a flexible electrode patch and a miniaturized wireless signal acquisition module. Heart rate (HR), heart rate variability (HRV), and blood pressure (BP) can be extracted from the raw signals. The flexible electrode patch is comfortable for the user while maintaining stable contact with human skin, guaranteeing the wearability. Size of the signal acquisition module is only 17.3mm×14.5mm×9mm, and it weighs only 3.2g, including an 80mAh lithium polymer battery, which keeps the entire patch working for more than 4 hours. A host controller, involving a graphic user interface (GUI) is developed to receive and visualize the data from the chest patch. The proposed device successfully collected three vital signals with high signal quality and showed its potential in healthcare applications.

Bifunctional flexible fabrics with excellent Joule heating and electromagnetic interference shielding performance based on copper sulfide/glass fiber composites.

Flexible and wearable electronic technology is in great demand with the rise of smart electronic systems. Among these, multifunctional systems with high performance at low cost have attracted extensive attention of scholars from the practical application perspective. However, the fabrication of devices with multifunctionality without sacrificing their connatural flexibility advantages remains a huge challenge. In this study, a CuS-modified glass fiber first acts as a bifunctional wearable electronic device for superior thermal management and electromagnetic interference (EMI) shielding. Specifically, the inherent glass fiber was initially modified with a silane coupling agent for the amino group (-NH2) functionalization followed by further CuS deposition via a facile electroless plating technology. Interestingly, due to the strong interaction between CuS and the glass fiber through the coordinate -NH2 and Cu2+, the prepared copper sulfide/glass fibers (CuS/GFs) not only keep the inherent flexibility and lightness of the fiber substrate, but also have excellent electrothermal conversion performance accompanied by a wide temperature range (38 °C-209 °C), low working voltage (0.3 V-1.5 V), and rapid response time (reaching 209 °C within 10 s at 1.5 V). Moreover, the prepared CuS/GF textile also exhibits interesting electromagnetic interference shielding efficiency (EMI SE) of 61 dB as well as a high specific shielding effectiveness up to 6130.65 dB cm2 g-1 with a CuS mass loading of 9.95 mg cm-2. These features confirm the potential of CuS/GFs as a flexible, wearable, and efficient electrical heater and EMI shielding material for the new type of intelligent electronic devices.

Quantum effect-based flexible and transparent pressure sensors with ultrahigh sensitivity and sensing density.

Although high-performance flexible pressure sensors have been extensively investigated in recent years owing to their diverse applications in biomedical and information technologies, fabricating ultrasensitive sensors with high pixel density based on current transduction mechanisms still remains great challenging. Herein, we demonstrate a design idea based on Fowler-Nordheim tunnelling effect for fabrication of pressure sensors with ultrahigh sensitivity and sensing density by spin-coating extremely low urchin-like hollow carbon spheres (less than 1.5 wt.%) dispersed in polydimethylsiloxane, which is distinct from the current transduction mechanisms. This sensor exhibits an ultrahigh sensitivity of 260.3 kPa-1 at 1 Pa, a proof-of-concept demonstration of a high sensing density of 400 cm-2, high transparency and temperature noninterference. In addition, it can be fabricated by an industrially viable and scalable spin-coating method, providing an efficient avenue for realizing large-scale production and application of ultrahigh sensitivity flexible pressure sensors on various surfaces and in in vivo environments.

A Low Power Cardiovascular Healthcare System With Cross-Layer Optimization From Sensing Patch to Cloud Platform.

Nowadays, cardiovascular disease is still one of the primary diseases that limit life expectation of humans. To address this challenge, this work reports an Internet of Medical Things (IoMT)-based cardiovascular healthcare system with cross-layer optimization from sensing patch to cloud platform. A wearable ECG patch with a custom System-on-Chip (SoC) features a miniaturized footprint, low power consumption, and embedded signal processing capability. The patch also integrates wireless connectivity with mobile devices and cloud platform for optimizing the complete system. On the big picture, a "wearable patch-mobile-cloud" hybrid computing framework is proposed with cross-layer optimization for performance-power trade-off in embedded-computing. The measurement results demonstrate that the on-patch compression ratio of the raw ECG signal can reach 12.07 yielding a percentage root mean square variation of 2.29%. In the test with the MIT-BIH database, the average improvement of signal to noise ratio and mean square error are 12.63 dB and 94.47%, respectively. The average accuracy of disease prediction operation executed in cloud platform is 97%.

The Optimization of Analog Front-End for Fully Integrated Wearable Sweat Sensor.

The research area of the wearable electrochemical sensors is increasingly growing which are valuable for healthcare and fitness applications owing to their simplicity of operation, low-cost, and compact size. In this work, optimizing of programmable analog front-end for fully integrated wearable sweat sensor is proposed. The proposed system can detect glucose, lactate, sodium, potassium at the same time with low-power consumption which is suitable for continuous real-time sweat sensing system. The average power consumption of analog front-end in the proposed system is less than 2 mW at 3.3 V supply voltage.

[Design of the Mobile ECG Monitoring System Based on Android 4.3].

To monitor and record Electrocardiograph (ECG) signals for 24 hours, a mobile ECG monitoring system is designed based on Android 4.3. In this system, domestic indigenous E9622A is used to acquire ECG signals and TI CC2541 is adopted to communicate with mobile phones. The program is implemented on the Android platform to display and process ECG signals. The whole system is integrated on a 2 cm x 2 cm PCB. From experiments, it is shown that ECG signals can be obtained effectively when this system is worn, and clear ECG waveforms and parameters can be shown on the phones. With this system, arrhythmia can be diagnosed preliminarily. It is also shown that the system is low-power, low-cost, flexible and portable.

The application of EMD in activity recognition based on a single triaxial accelerometer.

Activities recognition using a wearable device is a very popular research field. Among all wearable sensors, the accelerometer is one of the most common sensors due to its versatility and relative ease of use. This paper proposes a novel method for activity recognition based on a single accelerometer. To process the activity information from accelerometer data, two kinds of signal features are extracted. Firstly, five features including the mean, the standard deviation, the entropy, the energy and the correlation are calculated. Then a method called empirical mode decomposition (EMD) is used for the feature extraction since accelerometer data are non-linear and non-stationary. Several time series named intrinsic mode functions (IMFs) can be obtained after the EMD. Additional features will be added by computing the mean and standard deviation of first three IMFs. A classifier called Adaboost is adopted for the final activities recognition. In the experiments, a single sensor is separately positioned in the waist, left thigh, right ankle and right arm. Results show that the classification accuracy is 94.69%, 86.53%, 91.84% and 92.65%, respectively. These relatively high performances demonstrate that activities can be detected irrespective of the position by reducing problems such as the movement constrain and discomfort.

[Design of portable 12-lead digital ECG with low power consumption].

The design of portable and low power consumption 12-lead ECG is based on the digital signal processor TMS320C5515 and the analog front end ADS1298. The ADS1298 collects the ECG signals and deliver them to TMS320C5515. The preprocessed ECG signals are displayed real-time on a LCD and can be stored without compression for a long time. The ECG signals can also be sent to an up computer by a USB connector so that ECG data can be analyzed offline. The system has small volume, high precision and low power consumption.