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Gravimetric resonant-inspired biosensors have attracted increasing attention in industrial and point-of-care applications, enabling label-free detection of biomarkers such as DNA and antibodies. Capacitive micromachined ultrasonic transducers (CMUTs) are promising tools for developing miniaturized high-performance biosensing complementary metal–oxide–silicon (CMOS) platforms. However, their operability is limited by inefficient functionalization, aggregation, crosstalk in the buffer, and the requirement for an external high-voltage (HV) power supply. In this study, we aimed to propose a CMUTs-based resonant biosensor integrated with a CMOS front–end interface coupled with ethylene–glycol alkanethiols to detect single-stranded DNA oligonucleotides with large specificity. The topography of the functionalized surface was characterized by energy-dispersive X-ray microanalysis. Improved selectivity for on-chip hybridization was demonstrated by comparing complementary and non-complementary single-stranded DNA oligonucleotides using fluorescence imaging technology. The sensor array was further characterized using a five-element lumped equivalent model. The 4 mm2 application-specific integrated circuit chip was designed and developed through 0.18 μm HV bipolar-CMOS-double diffused metal–oxide–silicon (DMOS) technology (BCD) to generate on-chip 20 V HV boosting and to track feedback frequency under a standard 1.8 V supply, with a total power consumption of 3.8 mW in a continuous mode. The measured results indicated a detection sensitivity of 7.943 × 10−3 μmol∙L−1∙Hz−1 over a concentration range of 1 to 100 μmol∙L−1. In conclusion, the label-free biosensing of DNA under dry conditions was successfully demonstrated using a microfabricated CMUT array with a 2 MHz frequency on CMOS electronics with an internal HV supplier. Moreover, ethylene–glycol alkanethiols successfully deposited self-assembled monolayers on aluminum electrodes, which has never been attempted thus far on CMUTs, to enhance the selectivity of bio-functionalization. The findings of this study indicate the possibility of full-on-chip DNA biosensing with CMUTs.

Abstract Due to the excellent mechanical, chemical, and electrical properties of third-generation semiconductor silicon carbide (SiC), pressure sensors utilizing this material might be able to operate in extreme environments with temperatures exceeding 300 °C. However, the significant output drift at elevated temperatures challenges the precision and stability of measurements. Real-time in situ temperature monitoring of the pressure sensor chip is highly important for the accurate compensation of the pressure sensor. In this study, we fabricate platinum (Pt) thin-film resistance temperature detectors (RTDs) on a SiC substrate by incorporating aluminum oxide (Al2O3) as the transition layer and utilizing aluminum nitride (AlN) grooves for alignment through microfabrication techniques. The composite layers strongly adhere to the substrate at temperatures reaching 950 °C, and the interface of the Al2O3/Pt bilayer remains stable at elevated temperatures of approximately 950 °C. This stability contributes to the excellent high-temperature electrical performance of the Pt RTD, enabling it to endure temperatures exceeding 850 °C with good linearity. These characteristics establish a basis for the future integration of Pt RTD in SiC pressure sensors. Furthermore, tests and analyses are conducted on the interfacial diffusion, surface morphological, microstructural, and electrical properties of the Pt films at various annealing temperatures. It can be inferred that the tensile stress and self-diffusion of Pt films lead to the formation of hillocks, ultimately reducing the electrical performance of the Pt thin-film RTD. To increase the upper temperature threshold, steps should be taken to prevent the agglomeration of Pt films.

Abstract The chip-scale hybrid optical pumping spin-exchange relaxation-free (SERF) atomic magnetometer with a single-beam arrangement has prominent applications in biomagnetic measurements because of its outstanding features, including ultrahigh sensitivity, an enhanced signal-to-noise ratio, homogeneous spin polarization and a much simpler optical configuration than other devices. In this work, a miniaturized single-beam hybrid optical pumping SERF atomic magnetometer based on a microfabricated atomic vapor cell is demonstrated. Although the optically thin Cs atoms are spin-polarized, the dense Rb atoms determine the experimental results. The enhanced signal strength and narrowed resonance linewidth are experimentally proven, which shows the superiority of the proposed magnetometer scheme. By using a differential detection scheme, we effectively suppress optical noise with an approximate five-fold improvement. Moreover, the cell temperature markedly affects the performance of the magnetometer. We systematically investigate the effects of temperature on the magnetometer parameters. The theoretical basis for these effects is explained in detail. The developed miniaturized magnetometer has an optimal magnetic sensitivity of 20 fT/Hz1/2. The presented work provides a foundation for the chip-scale integration of ultrahighly sensitive quantum magnetometers that can be used for forward-looking magnetocardiography (MCG) and magnetoencephalography (MEG) applications.

Abstract Pipe contaminant detection holds considerable importance within various industries, such as the aviation, maritime, medicine, and other pertinent fields. This capability is beneficial for forecasting equipment potential failures, ascertaining operational situations, timely maintenance, and lifespan prediction. However, the majority of existing methods operate offline, and the detectable parameters online are relatively singular. This constraint hampers real-time on-site detection and comprehensive assessments of equipment status. To address these challenges, this paper proposes a sensing method that integrates an ultrasonic unit and an electromagnetic inductive unit for the real-time detection of diverse contaminants and flow rates within a pipeline. The ultrasonic unit comprises a flexible transducer patch fabricated through micromachining technology, which can not only make installation easier but also focus the sound field. Moreover, the sensing unit incorporates three symmetrical solenoid coils. Through a comprehensive analysis of ultrasonic and induction signals, the proposed method can be used to effectively discriminate magnetic metal particles (e.g., iron), nonmagnetic metal particles (e.g., copper), nonmetallic particles (e.g., ceramics), and bubbles. This inclusive categorization encompasses nearly all types of contaminants that may be present in a pipeline. Furthermore, the fluid velocity can be determined through the ultrasonic Doppler frequency shift. The efficacy of the proposed detection principle has been validated by mathematical models and finite element simulations. Various contaminants with diverse velocities were systematically tested within a 14 mm diameter pipe. The experimental results demonstrate that the proposed sensor can effectively detect contaminants within the 0.5−3 mm range, accurately distinguish contaminant types, and measure flow velocity.

Abstract With the increasing development of intelligent robots and wearable electronics, the demand for high-performance flexible energy storage devices is drastically increasing. In this study, flexible symmetric microsupercapacitors (MSCs) that could operate in a wide working voltage window were developed by combining laser-direct-writing graphene (LG) electrodes with a phosphoric acid-nonionic surfactant liquid crystal (PA-NI LC) gel electrolyte. To increase the flexibility and enhance the conformal ability of the MSC devices to anisotropic surfaces, after the interdigitated LG formed on the polyimide (PI) film surface, the devices were further transferred onto a flexible, stretchable and transparent polydimethylsiloxane (PDMS) substrate; this substrate displayed favorable flexibility and mechanical characteristics in the bending test. Furthermore, the electrochemical performances of the symmetric MSCs with various electrode widths (300, 400, 500 and 600 μm) were evaluated. The findings revealed that symmetric MSC devices could operate in a large voltage range (0–1.5 V); additionally, the device with a 300 μm electrode width (MSC-300) exhibited the largest areal capacitance of 2.3 mF cm−2 at 0.07 mA cm−2 and an areal (volumetric) energy density of 0.72 μWh cm− 2 (0.36 mWh cm− 3) at 55.07 μW cm−2 (27.54 mW cm−3), along with favorable mechanical and cycling stability. After charging for ~20 s, two MSC-300 devices connected in series could supply energy to a calculator to operate for ~130 s, showing its practical application potential as an energy storage device. Moreover, the device displayed favorable reversibility, stability and durability. After 12 months of aging in air at room temperature, its electrochemical performance was not altered, and after charging-discharging measurements for 5000 cycles at 0.07 mA cm−2, ~93.6% of the areal capacitance was still retained; these results demonstrated its practical long-term application potential as an energy storage device.

Abstract With the rapid development of various fields, including aerospace, industrial measurement and control, and medical monitoring, the need to quantify flow velocity measurements is increasing. It is difficult for traditional flow velocity sensors to fulfill accuracy requirements for velocity measurements due to their small ranges, susceptibility to environmental impacts, and instability. Herein, to optimize sensor performance, a flexible microelectromechanical system (MEMS) thermal flow sensor is proposed that combines the working principles of thermal loss and thermal temperature difference and utilizes a flexible cavity substrate made of a low-thermal-conductivity polyimide/SiO2 (PI/SiO2) composite porous film to broaden the measurement range and improve the sensitivity. The measurement results show that the maximum measurable flow velocity can reach 30 m/s with a resolution of 5.4 mm/s. The average sensitivities of the sensor are 59.49 mV/(m s−1) in the medium-to-low wind velocity range of 0–2 m/s and 467.31 mV/(m s−1) in the wind velocity range of 2–30 m/s. The sensor proposed in this work can enable new applications of flexible flow sensors and wearable devices.

Abstract Hydraulic technology with smaller sizes and higher reliability trends, including fault prediction and intelligent control, requires high-performance temperature and pressure-integrated sensors. Current designs rely on planar wafer- or chip-level integration, which is limited by pressure range, chip size, and low reliability. We propose a small-size temperature/high-pressure integrated sensor via the flip-chip technique. The pressure and temperature units are arranged vertically, and the sensing signals of the two units are integrated into one plane through silicon vias and gold–gold bonding, reducing the lateral size and improving the efficiency of signal transmission. The flip-chip technique ensures a reliable electrical connection. A square diaphragm with rounded corners is designed and optimised with simulation to sense high pressure based on the piezoresistive effect. The temperature sensing unit with a thin-film platinum resistor measures temperature and provides back-end high-precision compensation, which will improve the precision of the pressure unit. The integrated chip is fabricated by MEMS technology and packaged to fabricate the extremely small integrated sensor. The integrated sensor is characterised, and the pressure sensor exhibits a sensitivity and sensitivity drift of 7.97 mV/MPa and −0.19% FS in the range of 0–20 MPa and −40 to 120 °C. The linearity, hysteresis, repeatability, accuracy, basic error, and zero-time drift are 0.16% FS, 0.04% FS, 0.06% FS, 0.18% FS, ±0.23% FS and 0.04% FS, respectively. The measurement error of the temperature sensor and temperature coefficient of resistance is less than ±1 °C and 3142.997 ppm/°C, respectively. The integrated sensor has broad applicability in fault diagnosis and safety monitoring of high-end equipment such as automobile detection, industrial equipment, and oil drilling platforms.

Abstract Purpose It is reported that insomnia and obstructive sleep apnea (OSA) increase the incidence of adverse cardiovascular events. The aim of this study was to analyze the risk of cardiovascular disease and mortality in elderly patients with comorbid insomnia and obstructive sleep apnea (COMISA). Methods We included 868 elderly patients with OSA who underwent sleep monitoring at a multicenter sleep room from January 2015 to October 2017. We collected demographic data, clinical features, medical history, sleep parameters, and laboratory findings. Cox proportional hazards analysis was used to identify the relationship between COMISA and adverse cardiovascular events and all-cause mortality. Results There were 181 elderly patients with COMISA. The median follow-up was 43 months, during which we observed major adverse cardiac events (MACE) in 90 patients. The Kaplan-Meier survival curve indicated a significant relationship between COMISA and MACE (P log Rank < 0.001). Multivariate Cox regression analysis showed that COMISA increased the incidence of MACE (HR = 2.328, 95% CI: 1.349–4.018, P = 0.002), hospitalization for unstable angina (HR = 2.915, 95% CI: 1.397–6.081, P = 0.004), and the combination of all events (HR = 2.301, 95% CI: 1.393–3.803, P = 0.001). However, there were no significant differences in cardiovascular death, all-cause mortality, myocardial infarction, or hospitalized heart failure in patients with COMISA (P > 0.05). Subgroup analyses showed that among COMISA patients, male sex (HR = 2.800, 95% CI: 1.458-5.377, P = 0.002), age

Existing microfabricated atomic vapor cells have only one optical channel, which is insufficient for supporting the multiple orthogonal beams required by atomic devices. In this study, we present a novel wafer-level manufacturing process for fabricating multi-optical-channel atomic vapor cells and an innovative method for batch processing the inner sidewalls of millimeter glass holes to meet optical channel requirements. Surface characterization and transmittance tests demonstrate that the processed inner sidewalls satisfy the criteria for an optical channel. In addition, the construction of an integrated processing platform enables multilayer non-isothermal anode bonding, the filling of inert gases, and the recovery and recycling of noble gases. Measurements of the absorption spectra and free-induction decay signals of xenon-129 (129Xe) and xenon-131 (131Xe) under different pump-probe schemes demonstrate the suitability of our vapor cell for use in atomic devices including atomic gyroscopes, dual-beam atomic magnetometers, and other optical/atomic devices. The proposed micromolding technology has broad application prospects in the field of optical-device processing.

Abstract In order to fulfill the complex cognitive behaviors in neuromorphic systems with reduced peripheral circuits, the reliable electronic synapses mimicked by single device that achieves diverse long‐term and short‐term plasticity are essential. Phase change random access memory (PCRAM) is of great potential for artificial synapses, which faces, however, difficulty to realize short‐term plasticity due to the long‐lasting resistance drift. This work reports the ruthenium‐doped Ge2Sb2Te5 (RuGST) based PCRAM, demonstrating a series of synaptic behaviors of short‐term potentiation, pair‐pulse facilitation, long‐term depression, and short‐term plasticity in the same single device. The optimized RuGST electronic synapse with the high transformation temperature of hexagonal phase >380°C, the outstanding endurance >108 cycles, the low resistance drift factor of 0.092, as well as the extremely high linearity with correlation coefficients of 0.999 and 0.976 in parts of potentiation and depression. Further investigations also go insight to mechanisms of Ru doping according to thorough microstructure characterization, revealing that Ru dopant is able to enter GST lattices thus changing and stabilizing atomic arrangement of GST. This leads to the short‐term plasticity realized by RuGST PCRAM. Eventually, the proposed RuGST electronic synapses performs a high accuracy of ~94.1% in a task of image recognition of CIFAR‐100 database using ResNet 101. This work promotes the development of PCRAM platforms for large‐scale neuromorphic systems.

It takes more than 20 years for normal colorectal mucosa to develop into metastatic carcinoma. The long time window provides a golden opportunity for early detection to terminate the malignant progression. Here, we aim to enable liquid biopsy of T1a stage colorectal cancer (CRC) and precancerous advanced adenoma (AA) by profiling circulating small extracellular vesicle (sEV)-derived RNAs. We exhibited a full RNA landscape for the circulating sEVs isolated from 60 participants. A total of 58,333 annotated RNAs were detected from plasma sEVs, among which 1,615 and 888 sEV-RNAs were found differentially expressed in plasma from T1a stage CRC and AA compared to normal controls (NC). Then we further categorized these sEV-RNAs into six modules by a weighted gene coexpression network analysis and constructed a 60-gene t-SNE model consisting of the top 10 RNAs of each module that could well distinguish T1a stage CRC/AA from NC samples. Some sEV-RNAs were also identified as indicators of specific endoscopic and morphological features of different colorectal lesions. The top-ranked biomarkers were further verified by RT-qPCR, proving that these candidate sEV-RNAs successfully identified T1a stage CRC/AA from NC in another cohort of 124 participants. Finally, we adopted different algorithms to improve the performance of RT-qPCR-based models and successfully constructed an optimized classifier with 79.3% specificity and 99.0% sensitivity. In conclusion, circulating sEVs of T1a stage CRC and AA patients have distinct RNA profiles, which successfully enable the detection of both T1a stage CRC and AA via liquid biopsy.

The interaction between the gut microbiota and mercaptopurine (6-MP), a crucial drug used in pediatric acute lymphoblastic leukemia (ALL) treatment, has not been extensively studied. Here we reveal the significant perturbation of gut microbiota after 2-week 6-MP treatment in beagles and mice followed by the functional prediction that showed impairment of SCFAs production and altered amino acid synthesis. And the targeted metabolomics in plasma also showed changes in amino acids. Additionally, targeted metabolomics analysis of feces showed changes in amino acids and SCFAs. Furthermore, ablating the intestinal microbiota by broad-spectrum antibiotics exacerbated the imbalance of amino acids, particularly leading to a significant decrease in the concentration of S-adenosylmethionine (SAM). Importantly, the depletion of gut microbiota worsened the damage of small intestine caused by 6-MP, resulting in increased intestinal permeability. Considering the relationship between toxicity and 6-MP metabolites, we conducted a pharmacokinetic study in pseudo germ-free rats to confirm that gut microbiota depletion altered the methylation metabolites of 6-MP. Specifically, the concentration of MeTINs, a secondary methylation metabolite, showed a negative correlation with SAM, the pivotal methyl donor. Additionally, we observed a strong correlation between Alistipes and SAM levels in both feces and plasma. In conclusion, our study demonstrates that 6-MP disrupts the gut microbiota, and depleting the gut microbiota exacerbates 6-MP-induced intestinal toxicity. Moreover, SAM derived from microbiota plays a crucial role in influencing plasma SAM and the methylation of 6-MP. These findings underscore the importance of comprehending the role of the gut microbiota in 6-MP metabolism and toxicity.

Abstract Extracellular vesicles (EVs) have emerged as promising biomaterials for the treatment of different disease. However, only handful types of EVs with clinical transformation potential have been reported to date, and their preparation on a large scale under biosafety‐controlled conditions is limited. In this study, we characterize a novel type of EV with promising clinical application potential: dehydration‐induced extracellular vesicles (DIMVs). DIMV is a type of micron‐diameter cell vesicle that contains more bioactive molecules, such as proteins and RNA, but not DNA, than previously reported cell vesicles. The preparation of DIMV is extraordinarily straightforward, which possesses a high level of biosafety, and the protein utilization ratio is roughly 600 times greater than that of naturally secreted EVs. Additional experiments demonstrate the viability of pre‐ or post‐isolation DIMV modification, including gene editing, nucleic acid encapsulation or surface anchoring, size adjustment. Finally, on animal models, we directly show the biosafety and immunogenicity of DIMV, and investigate its potential application as tumour vaccine or drug carrier in cancer treatment.

BackgroundTargeted agents are widely utilized in the treatment of ulcerative colitis (UC). Hence, a comprehensive understanding of comparative drug efficacy in UC is of great importance for drug development and clinical practice. Our objective was the quantitative evaluation of the comparative efficacy of targeted agents for UC.MethodsThree mathematical models were developed based on data from randomized controlled trials in patients with moderate-to-severe UC to describe the time-course and dose-response of efficacy defined as clinical remission, clinical response, and endoscopic improvement, as well as the placebo effect. The covariate effects were further evaluated. Model simulation was performed in a hypothetical population to compare the efficacies across different drugs.ResultsThe analysis dataset was composed of data from 35 trials of 12 drugs in UC. Time–response relationships were evaluated that indicated a gradual onset of drug efficacy in adalimumab, ozanimod, and Janus kinase (JAK) inhibitors. The dose-response relationships were estimated for each drug respectively. Patient age, disease duration, baseline weight, prior tumor necrosis factor (TNF) inhibitor exposure, and current treatment with corticosteroid showed an impact on efficacy, suggesting that younger patients with shorter UC duration without prior anti-TNF treatment and current corticosteroids therapy tend to display greater treatment effects.ConclusionThis study developed three longitudinal models for UC to quantitatively describe the efficacy of targeted agents, as well as the influencing factors of efficacy. Infliximab and upadacitinib were determined to be the most effective biological and small targeted molecules, respectively. These findings may provide valuable implications for guiding future decision-making in clinical practice and drug development for UC.

Abstract Pressure sensors play a vital role in aerospace, automotive, medical, and consumer electronics. Although microelectromechanical system (MEMS)-based pressure sensors have been widely used for decades, new trends in pressure sensors, including higher sensitivity, higher accuracy, better multifunctionality, smaller chip size, and smaller package size, have recently emerged. The demand for performance upgradation has led to breakthroughs in sensor materials, design, fabrication, and packaging methods, which have emerged frequently in recent decades. This paper reviews common new trends in MEMS pressure sensors, including minute differential pressure sensors (MDPSs), resonant pressure sensors (RPSs), integrated pressure sensors, miniaturized pressure chips, and leadless pressure sensors. To realize an extremely sensitive MDPS with broad application potential, including in medical ventilators and fire residual pressure monitors, the “beam-membrane-island” sensor design exhibits the best performance of 66 μV/V/kPa with a natural frequency of 11.3 kHz. In high-accuracy applications, silicon and quartz RPS are analyzed, and both materials show ±0.01%FS accuracy with respect to varying temperature coefficient of frequency (TCF) control methods. To improve MEMS sensor integration, different integrated “pressure + x” sensor designs and fabrication methods are compared. In this realm, the intercoupling effect still requires further investigation. Typical fabrication methods for microsized pressure sensor chips are also reviewed. To date, the chip thickness size can be controlled to be

Abstract Investigating the influencing factors of new‐onset hypertension in the elderly with obstructive sleep apnea (OSA). 450 Chinese older patients with OSA who were non‐hypertensive at baseline were enrolled. All patients had undergone polysomnography monitoring in the multicenter study. The primary endpoint was incident hypertension. Kaplan–Meier survival analysis was performed, and multivariate Cox proportional hazards models were generated to determine the factors influencing new‐onset hypertension. A total of 176 (39.1%) patients developed hypertension. The hypertension group had older age, higher hemoglobin (Hb) level and apnea‐hypopnea index (AHI) values than the non‐hypertension group (all p

PurposeIdentifying the etiology of acute ischemic stroke (AIS) before endovascular treatment (EVT) is important but challenging. In CT perfusion imaging processed by perfusion software, we observed a phenomenon called patchy profile sign (PPS), that is, the hypoperfusion morphology in RAPID software is a discontinuous sheet pattern. This phenomenon is predominantly observed in patients diagnosed with intracranial atherosclerotic stenosis (ICAS). The study intends to assess whether the PPS can be used to differentiate ICAS from intracranial embolism.MethodPatients with AIS due to M1 segment occlusion of the MCA who underwent mechanical thrombectomy were retrospectively enrolled. The receiver operating characteristic (ROC) curve analysis was performed to assess the value of PPS in predicting ICAS. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the PPS for prediction of ICAS were calculated.ResultsA total of 51 patients were included in the study. The PPS was observed in 10 of 19 (52.6%) patients with ICAS, and in 2 of 32 (6.3%) patients with intracranial embolism (p

Microfabricated alkali metal vapor cells are the core components for miniaturizing quantum devices, such as atomic clocks, atomic gyroscopes, and atomic magnetometers. Alkali metals are prone to thermal migration at the bonding interface during the sealing of the vapor cell, which leads to bonding failure. In this study, a non-isothermal anodic bonding process based on plasma activation was developed to achieve high-strength bonding at low temperatures using the temperature gradient to keep the alkali metal away from the bonding interface. This procedure eliminates interference from the alkali metal and significantly increases the success rate of anodic bonding of vapor cells. Simulation results for the temperature field and the residual stresses during anodic bonding demonstrate that the procedure is theoretically feasible. The effect of plasma treatment on the contact angle and roughness of the bonding surface revealed a mechanism for improving the bond strength. In addition, the construction of an integrated processing platform made it possible to perform non-isothermal anode bonding, injection of alkali metal, filling of inert gases, and recovery and recycling of noble gases. The high strength and good hermeticity of the bonding interface were demonstrated by the bond strength, cross-sectional high-resolution transmission electron microscopy observations, and leakage rate tests. Finally, the absorption spectrum and free-induction decay signal of the fabricated vapor cell were measured.

Abstract With the growing demand for thermal management of electronic devices, cooling of high-precision instruments, and biological cryopreservation, heat flux measurement of complex surfaces and at ultralow temperatures has become highly imperative. However, current heat flux sensors (HFSs) are commonly used in high-temperature scenarios and have problems when applied in low-temperature conditions, such as low sensitivity and embrittlement. In this study, we developed a flexible and highly sensitive HFS that can operate at ultralow to high temperatures, ranging from −196 °C to 273 °C. The sensitivities of HFSs with thicknesses of 0.2 mm and 0.3 mm, which are efficiently manufactured by the screen-printing method, reach 11.21 μV/(W/m2) and 13.43 μV/(W/m2), respectively. The experimental results show that there is a less than 3% resistance change from bending to stretching. Additionally, the HFS can measure heat flux in both exothermic and absorptive cases and can measure heat flux up to 25 kW/m2. Additionally, we demonstrate the application of the HFS to the measurement of minuscule heat flux, such as heat dissipation of human skin and cold water. This technology is expected to be used in heat flux measurements at ultralow temperatures or on complex surfaces, which has great importance in the superconductor and cryobiology field.

Abstract Background Time-restricted eating (TRE), a feasible form of intermittent fasting, has been proven to benefit metabolic health in animal models and humans. To our knowledge, specific guidance on the appropriate period for eating during TRE has not yet been promoted. Therefore, to compare and assess the relative effectiveness estimates and rankings of TRE with different eating windows on human metabolic health, we conducted a systematic review and network meta-analysis (NMA). Method PubMed, EMBASE and the Cochrane Library were searched for randomized controlled trials that compared different eating windows on human metabolic health for adults. A Bayesian NMA was used to compare direct and indirect effects to determine the best different eating windows, and scientific evidence using GRADE. Results Twenty-seven RCTs comparing TRE with different eating windows on human metabolic health were reviewed, and all were included in the NMA. Compared with the normal diet group (non-TRE), the TRE group has certain benefits in reducing weight and fasting insulin. In terms of reducing fasting insulin, the 18:6 group (eating time = 6 h) was better than the 14:10 group (eating time = 10 h) and 16:8 group (eating time = 8 h) (P 0.05). Conclusions Our research showed that no particular metabolic advantages of various eating windows were found. Therefore, our results suggested that different eating windows could promote similar benefits for metabolic parameters.

Abstract Flexible electronics have demonstrated various strategies to enhance the sensory ability for tactile perception and wearable physiological monitoring. Fibrous microstructures have attracted much interest because of their excellent mechanical properties and fabricability. Herein, a structurally robust fibrous mat was first fabricated by electrospinning, followed by a sequential process of functionalization utilizing ultrasonication treatment and in situ polymerization growth. Electrospun polyurethane (PU) microfibers were anchored with multi-walled carbon nanotubes (MWCNTs) to form conductive paths along each fiber by a scalable ultrasonic cavitation treatment in an MWCNT suspension. After, a layer of poly(3,4-ethylene dioxythiophene) (PEDOT) was grown on the surface of PU fibers decorated with MWCNTs to enhance the conductive conjunctions of MWCNTs. Due to the superior electromechanical behaviors and mechanical reinforcement of PEDOT, the PEDOT/MWCNT@PU mat-based device exhibits a wide working range (0–70 kPa), high sensitivity (1.6 kPa−1), and good mechanical robustness (over 18,000 cycles). The PEDOT/MWCNT@PU mat-based sensor also demonstrates a good linear response to different temperature variations because of the thermoelectricity of the PEDOT/MWCNT composite. This novel strategy for the fabrication of multifunctional fibrous mats provides a promising opportunity for future applications for high-performance wearable devices.

Neuroblastoma (NB) is a common solid tumor in children and infants, the formation and regression of which is closely linked to the tumor-host immune relationship. Stimulator of interferon genes (STING) agonists, particularly cyclic dinucleotide (CDN), have promising potential in NB therapy by generating innate and adaptive immune stimulation, thus leading to tumor control. CDN delivery in vivo is challenging due to the negative charge, hydrophilicity, and susceptibility to degradation by phosphodiesterase, which hinders the effectiveness of CDN. Thus, our study proposed four methods to load CDN into liposomes, using 2′,3′-cGAMP as the model drug. Lipid nanoparticles were prepared, followed by physicochemical characterization. Subsequently, cellular inhibition and immune stimulation were investigated. As a result, lipid calcium phosphate nanoparticles (LCP-NPs) possessed the highest encapsulation efficiency among the four preparation methods, with a diameter of 82.57±3.72 nm. LCP-NPs maintained size stability under refrigeration conditions at 4°C within 48 h. The surface of the liposome was positively charged. Compared to free cGAMP, LCP-NPs resulted in a slower release, enhanced cytotoxicity against tumor cells, greater activation of the cGAS-STING pathway, and increased expression of the immune factors. Taken together, these findings clearly demonstrated the effectiveness of the liposomal delivery system for cGAMP and provided a promising strategy for the treatment of NB.

SiC, as a representative of the third generation semiconductors, is widely investigated in power devices and sensors. However, ohmic contacts, an important component for signal output of various SiC chips, have always faced challenges with unclear formation mechanism and difficulty to withstand high temperature. To solve such problems, two sets of NPN-type SiC ohmic contact were prepared, including Ti/TaSi2/Pt and Ni/W. Experimental results show that whether ohmic contact can be formed mainly depends on the contact metal. The alloy phase with lower work function is formed after high temperature annealing, which reduces the height and width of the Schottky barrier. For the prepared SiC ohmic contacts, It was demonstrated that the invasion of oxygen atoms cause contacts failure, and incorporation of barrier layer (Ta-based layer) and effective protective layer (Pt layer) determine whether high temperatures can be tolerated. Finally, piezoresistive 4H–SiC pressure sensor chips with dimensions of 3000 μm × 3000 μm × 200 μm were fabricated using the obtained ohmic contacts. Sensor chips output resistance were monitored up to 600 °C in air to show stability of the ohmic contact. The highly stable and high temperature ohmic contact can be applied in a variety of SiC devices.

Abstract Microelectromechanical system (MEMS) pressure sensors based on silicon are widely used and offer the benefits of miniaturization and high precision. However, they cannot easily withstand high temperatures exceeding 150 °C because of intrinsic material limits. Herein, we proposed and executed a systematic and full-process study of SiC-based MEMS pressure sensors that operate stably from −50 to 300 °C. First, to explore the nonlinear piezoresistive effect, the temperature coefficient of resistance (TCR) values of 4H-SiC piezoresistors were obtained from −50 to 500 °C. A conductivity variation model based on scattering theory was established to reveal the nonlinear variation mechanism. Then, a piezoresistive pressure sensor based on 4H-SiC was designed and fabricated. The sensor shows good output sensitivity (3.38 mV/V/MPa), accuracy (0.56% FS) and low temperature coefficient of sensitivity (TCS) (−0.067% FS/°C) in the range of −50 to 300 °C. In addition, the survivability of the sensor chip in extreme environments was demonstrated by its anti-corrosion capability in H2SO4 and NaOH solutions and its radiation tolerance under 5 W X-rays. Accordingly, the sensor developed in this work has high potential to measure pressure in high-temperature and extreme environments such as are faced in geothermal energy extraction, deep well drilling, aeroengines and gas turbines.

ObjectiveThis retrospective analysis aims to assess the efficacy of transesophageal ultrasound-guided patent foramen ovale (PFO) closure in treating migraine in adolescents and compare the therapeutic outcomes of PFO closure for migraine with and without aura.MethodsWe conducted a retrospective analysis of 86 cases of adolescents (12–20 years old) who underwent PFO closure for migraine at our institution over the past 3 years. The efficacy was evaluated using the visual analogue scale (VAS), headache impact test (HIT)-6, and pediatric migraine disability assessment (PedMIDAS) scores, as well as by assessing the monthly frequency of migraine attacks, duration of each attack, and overall migraine burden. The patients were divided into two groups: an aura group (55 cases) and a non-aura group (31 cases) to investigate difference in therapeutic efficacy between the groups. The effect of residual shunt on migraine burden was assessed.ResultsAmong the 86 patients, 46 (54%) experienced complete remission of migraine, while 71 (83%) achieved a >50% reduction in migraine burden during the one-year follow-up period. Patients in the aura group showed more significant improvements in VAS, HIT-6, and PedMIDAS scores, as well as in monthly migraine attack frequency, duration of each attack, and overall migraine burden, than patients in the non-aura group. Moreover, patients with residual shunt did not exhibit statistically significant differences in therapeutic efficacy compared to patients with complete closure.ConclusionPFO closure can effectively alleviate migraine symptoms in adolescents with migraine with concomitant PFO. The therapeutic efficacy is particularly pronounced for migraine with aura. Furthermore, minor levels of residual shunt have no effect on the improvement in migraine symptoms.

Abstract MicroRNAs (miRNAs) are relatively stable in blood, emerging as one of the most promising biomarkers in tumor liquid biopsy. Both total and extracellular vesicles (EVs) encapsulated miRNA have been studied for prognostic potential in a variety of cancers. Here, we systematically compared and verified the total and vesicle‐derived miRNA expression profiles from plasma samples in healthy controls and patients with esophageal squamous cell carcinoma (ESCC). In the present study, four miRNA species miR‐636, miR‐7641, miR‐28‐3p, and miR‐1246 that were differentially expressed in ESCC patients were chosen for further study. We first elucidated their essential function in ESCC progression and further explored their preliminary mechanism by identifying target proteins and involving signal pathways. Subsequently, the prognostic miRNA panels including miR‐636, miR‐7641, miR‐1246, and miR‐28‐3p for ESCC diagnosis were constructed and validated using different cohort. Our results showed that the panel including the above four miRNAs derived from plasma EVs was most effective in distinguishing tumor patients from normal subjects, while integrated plasma EVs‐derived miR‐1246, miR‐28‐3p and total plasma miRNAs miR‐636, miR‐7641 showed the best capability in predicting lymph node metastasis. In summary, our studies revealed that plasma EVs‐derived miRNAs could be emerged as promising biomarkers for ESCC diagnosis.

This paper presents the development of a novel micro force sensor based on a laterally movable gate field-effect transistor (LMGFET). A precise electrical model is proposed for the performance evaluation of small-scale LMGFET devices and exhibits improved accuracy in comparison with previous models. A novel sandwich structure consisting of a gold cross-axis decoupling gate array layer and two soft photoresistive SU-8 layers is utilized. With the proposed dual-differential sensing configuration, the output current of the LMGFET lateral operation under vertical interference is largely eliminated, and the relative output error of the proposed sensor decreases from 4.53% (traditional differential configuration) to 0.01%. A practicable fabrication process is also developed and simulated for the proposed sensor. The proposed LMGFET-based force sensor exhibits a sensitivity of 4.65 µA·nN−1, which is comparable with vertically movable gate field-effect transistor (VMGFET) devices, but has an improved nonlinearity of 0.78% and a larger measurement range of ±5.10 µN. These analyses provide a comprehensive design optimization of the electrical and structural parameters of LMGFET devices and demonstrate the proposed sensor’s excellent force-sensing potential for biomedical micromanipulation applications.

Abstract Ultrasonic fluid bubble detection is important in industrial controls, aerospace systems and clinical medicine because it can prevent fatal mechanical failures and threats to life. However, current ultrasonic technologies for bubble detection are based on conventional bulk PZT-based transducers, which suffer from large size, high power consumption and poor integration with ICs and thus are unable to implement real-time and long-term monitoring in tight physical spaces, such as in extracorporeal membrane oxygenation (ECMO) systems and dialysis machines or hydraulic systems in aircraft. This work highlights the prospect of capacitive micromachined ultrasonic transducers (CMUTs) in the aforementioned application situations based on the mechanism of received voltage variation caused by bubble-induced acoustic energy attenuation. The corresponding theories are established and well validated using finite element simulations. The fluid bubbles inside a pipe with a diameter as small as 8 mm are successfully measured using our fabricated CMUT chips with a resonant frequency of 1.1 MHz. The received voltage variation increases significantly with increasing bubble radii in the range of 0.5–2.5 mm. Further studies show that other factors, such as bubble positions, flow velocities, fluid medium types, pipe thicknesses and diameters, have negligible effects on fluid bubble measurement, demonstrating the feasibility and robustness of the CMUT-based ultrasonic bubble detection technique.

Abstract With the increasing demand for multidirectional vibration measurements, traditional triaxial accelerometers cannot achieve vibration measurements with high sensitivity, high natural frequency, and low cross-sensitivity simultaneously. Moreover, for piezoresistive accelerometers, achieving pure axial deformation of the piezoresistive beam can greatly improve performance, but it requires the piezoresistive beam to be located in a specific position, which inevitably makes the design more complex and limits the performance improvement. Here, a monolithically integrated triaxial high-performance accelerometer with pure axial stress piezoresistive beams was designed, fabricated, and tested. By controlling synchronous displacements at both piezoresistive beam ends, the pure axial stress states of the piezoresistive beams could be easily achieved with position independence without tedious calculations. The measurement unit for the z-axis acceleration was innovatively designed as an interlocking proof mass structure to ensure a full Wheatstone bridge for sensitivity improvement. The pure axial stress state of the piezoresistive beams and low cross-sensitivity of all three units were verified by the finite element method (FEM). The triaxial accelerometer was fabricated and tested. Results showing extremely high sensitivities (x axis: 2.43 mV/g/5 V; y axis: 2.44 mv/g/5 V; z axis: 2.41 mV/g/5 V (without amplification by signal conditioning circuit)) and high natural frequencies (x/y axes: 11.4 kHz; z-axis: 13.2 kHz) were obtained. The approach of this paper makes it simple to design and obtain high-performance piezoresistive accelerometers.

Objective:. The effectiveness of statins in reducing atherosclerotic calcification remains controversial. The aim of this study was to confirm that simvastatin reduces atherosclerotic calcification and stabilizes plaque by restricting endoplasmic reticulum stress (ERS)-mediated apoptosis. Methods:. Twenty-four 8-week-old male apolipoprotein E (ApoE)-/- mice (C57BL/6J genetic background) were selected and randomly divided into model (n = 12) and simvastatin (n = 12) groups. Twelve male C57BL/6J mice were selected as control group (n = 12). The mice were adaptively fed for 2 weeks and were put on a high-fat diet thereafter. After 9 weeks, they were treated with simvastatin (20 mg/kg) or phosphate-buffered saline daily for 8 weeks. Aortic sinus samples were obtained from ApoE-/- and C57BL/6J mice for hematoxylin and eosin, von Kossa, alizarin Red S, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, and immunohistochemical staining after in vivo treatment with simvastatin. In addition, mouse vascular smooth muscle cells were analyzed after exposure to simvastatin in vitro. Results:. Administration of simvastatin in vivo drastically attenuated the atherosclerosis, calcification, and apoptosis, and decreased the serum levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. The expression levels of glucose-regulated protein, 78 kDa (GRP78), C/EBP homologous protein (CHOP), and caspase 12 (CASP12) in the aortic sinus decreased in the simvastatin group compared with the model group. In vitro, simvastatin or simvastatin plus ERS inhibitor (taurine) attenuated calcification and apoptosis, and reduced the expression of ERS-related proteins GRP78, CHOP, and CASP12. Conclusion:. Treatment with simvastatin suppressed atherosclerotic calcification. This effect may be mediated through the inhibition of ERS-related apoptosis.

Abstract Flexible strain sensors are promising candidates for intelligent wearable devices. Among previous studies, although crack-based sensors have attracted a lot of attention due to their ultrahigh sensitivity, large strain usually causes fractures in the conductive paths. Because of the unstable crack structure, the tradeoff between sensitivity and workable strain range is still a challenge. As carbon nanotubes (CNTs) and silver nanowires (AgNWs) can form a strong interface with the thermoplastic substrate and strengthen the conductive network by capillary force during water evaporation, CNTs and AgNWs were deposited on electrospun TPU fiber mats via vacuum-assisted filtration in this work. The prestretching treatment constructed a microcrack structure that endowed the sensor with the combined characteristics of a wide working range (0~171% strain), ultrahigh sensitivity (a gauge factor of 691 within 0~102% strain, ~2 × 104 within 102~135% strain, and >11 × 104 within 135~171% strain), a fast response time (~65 ms), small hysteresis, and superior durability (>2000 cycles). Subsequently, the sensing mechanism of the sensor was studied. Distributed microcrack propagation based on the “island-bridge” structure was explained in detail, and its influence on the strain-sensing behavior of the sensor was analyzed. Finally, the sensor was assembled to monitor various vibration signals and human motions, demonstrating its potential applications in the fields of electronic skin and human health monitoring.

Summary: Flexible thin-film thermocouples (TFTCs) have been garnering interest as temperature sensors due to the advantages of being flexible, ultrathin, and ultralight. Additionally, they have fast response times and enable detection of temperature. These properties have made them suitable for applications such as wearable electronics, healthcare, portable personal devices, and smart detection systems. This review presents the progress in the development of flexible TFTCs. The mechanism, structural design, materials, fabrication methods, and related applications of flexible TFTCs are also elaborated. Finally, future development directions of flexible TFTCs are discussed such as wide-range temperature measurement, multiple sensor integration, and achieving reliable cold-end compensation systems.

IntroductionIn the present study, sympathetic skin response (SSR) characteristics were explored in children with Guillain–Barré syndrome (GBS) and the value of early diagnosis and prognostic evaluation in GBS complicated by autonomic dysfunction (AD) was evaluated.MethodsA total of 25 children with GBS and 30 healthy controls (HCs) were enrolled in this prospective study. SSR findings for the two groups were compared. SSR and nerve conduction study (NCS) results were compared among patients with GBS, and differences in clinical characteristics between the groups with abnormal and normal SSR were analyzed.ResultsWithin the GBS group, six patients (24%) required mechanical ventilation, 17 patients (66.7%) had AD, 18 patients (72%) had an abnormal SSR, and 13 patients (52%) had AD combined with SSR abnormalities. There was a statistically significant difference in SSR latency in the lower limbs between the GBS group and HCs (P < 0.05). There was no statistically significant difference between SSR and NCS results in the acute phase of GBS (P > 0.05), and there was no significant difference in the rate of AD or in Hughes functional grade at nadir between the groups with abnormal and normal SSR (P>0.05). However, there was a statistically significant difference between the results of SSR and NCS tests during the recovery phase (P = 0.003). Abnormal SSR mainly occurred in cases of the acute inflammatory demyelinating polyradiculoneuropathy (AIDP) subtype. In addition, SSR was abnormal in all pediatric GBS patients with poor prognosis 1 month after onset of symptoms.ConclusionTwo-thirds of the children with GBS have AD. SSR could be used for early diagnosis and follow-up of GBS and may also be helpful in evaluating disease severity and short-term prognosis.

IntroductionBiologics is used for treating moderate to severe plaque psoriasis (MSPP), which represent one of the foremost therapeutic advancements in disease of dermatology. Up to now, the relative efficacy and safety across approved andinvestigational biologics for MSPP is still unclear.MethodsThis study aimed to comparative effectiveness of various biological treatments for MSPP measured by PASI75, PASI90 and PASI100 (The ratio of patients whose Psoriasis Area and Severity Index score (PASI) decreased by ≥ 75%, 90% and 100% compared with baseline, respectively). In addition, random models were used together with a Bayesian method to compare direct and indirect Adverse Events (AEs) of biologics with placebo, to make probabilistic statements and predictions on their AEs. The analytic data set was made up of summarized data from 54 trials, including 27,808 patients, with treatment of 17 biologics. Three mathematic models with nonparametric placebo evaluations were established to characterize the longitudinal direction profile for the three efficacy measures as above mentioned.ResultsOur results showed significant differences among treatments. Bimekizumab, sonelokimab, and ixekizumab were found to be the most effective treatments among the biologics. The effects of covariate were further evaluated, patients’ age, body weight, duration of disease and percentage of patients previously treated with a biological therapy showed impact on the efficacy. In addition, we found that ixekizumab and risankizumab displayed relatively stable as for efficacy and safety.DiscussionOur findings provide valuable insights into the comparative effectiveness and safety of biologics for MSPP treatment. These results may aid in clinical decision-making and ultimately improve patient outcomes.

Summary: DNA origami-engineered nanostructures are widely used in biomedical applications involving transmembrane delivery. Here, we propose a method to enhance the transmembrane capability of DNA origami sheets by changing their configuration from two-dimensional to three-dimensional. Three DNA nanostructures are designed and constructed, including the two-dimensional rectangular DNA origami sheet, the DNA tube, and the DNA tetrahedron. The latter two are the variants of the DNA origami sheet with three-dimensional morphologies achieved through one-step folding and multi-step parallel folding separately. The design feasibility and structural stability of three DNA nanostructures are confirmed by molecular dynamics simulations. The fluorescence signals of the brain tumor models demonstrate that the tubular and the tetrahedral configurational changes could dramatically increase the penetration efficiency of the original DNA origami sheet by about three and five times, respectively. Our findings provide constructive insights for further rational designs of DNA nanostructures for transmembrane delivery.

The integration of epitaxial complex oxides on semiconductor and flexible substrates is required but challenging. Here, the authors report the highly heterogeneous epitaxy of transferrable BaTiO3-δ membrane with enhanced flexoelectricity on Ge (011).

Abstract Flexible sensors used to detect NO2 gas generally have problems such as poor repeatability, high operating temperature, poor selectivity, and small detection range. In this work, a new spraying platform with a simple structure, low cost, and good film-forming consistency was designed and built to make a sensitive film (rGO/SnO2) for NO2 gas sensors. The relationship between the solid content of rGO and SnO2 nanoparticles, annealing temperature, and sensor performance was studied. The results show that the interdigital electrode-sensitive film formed by spraying 0.25 ml of a 0.4 wt% rGO/SnO2 mixture and annealing at 250 °C exhibited the best comprehensive performance for NO2 detection. The sensor’s response value for 100 ppm NO2 gas was 0.2640 at room temperature (25 °C), and the response time and recovery time were 412.4 s and 587.3 s, respectively. In the range of 20–100 ppm, the relationship between the response and NO2 concentration was linear, and the correlation coefficient was 0.9851. In addition, a soft-monitoring node module with an overlimit warning function for NO2 gas was designed and manufactured based on flexible electronics. Finally, the flexible sensor and node module were embedded into woven fabric that could be used to make a mask or a watch that could detect NO2 gas, realizing the practical application of flexible NO2 gas sensors in the field of wearable electronics.

Abstract Highly precise micromanipulation tools that can manipulate and interrogate cell organelles and components must be developed to support the rapid development of new cell-based medical therapies, thereby facilitating in-depth understanding of cell dynamics, cell component functions, and disease mechanisms. This paper presents a literature review on micro/nanomanipulation tools and their control methods for single-cell surgery. Micromanipulation methods specifically based on laser, microneedle, and untethered micro/nanotools are presented in detail. The limitations of these techniques are also discussed. The biological significance and clinical applications of single-cell surgery are also addressed in this paper.

Abstract A micromachined resonator immersed in liquid provides valuable resonance parameters for determining the fluidic parameters. However, the liquid operating environment poses a challenge to maintaining a fine sensing performance, particularly through electrical characterization. This paper presents a piezoelectric micromachined cantilever with a stepped shape for liquid monitoring purposes. Multiple modes of the proposed cantilever are available with full electrical characterization for realizing self-actuated and self-sensing capabilities. The focus is on higher flexural resonances, which nonconventionally feature two-dimensional vibration modes. Modal analyses are conducted for the developed cantilever under flexural vibrations at different orders. Modeling explains not only the basic length-dominant mode but also higher modes that simultaneously depend on the length and width of the cantilever. This study determines that the analytical predictions for resonant frequency in liquid media exhibit good agreement with the experimental results. Furthermore, the experiments on cantilever resonators are performed in various test liquids, demonstrating that higher-order flexural modes allow for the decoupled measurements of density and viscosity. The measurement differences achieve 0.39% in density and 3.50% in viscosity, and the frequency instability is below 0.05‰. On the basis of these results, design guidelines for piezoelectric higher-mode resonators are proposed for liquid sensing.

Abstract Purpose This study sought to identify the prevalence and factors associated with atrial fibrillation (AF) in older patients with obstructive sleep apnea (OSA) in China. Methods This was an explorative cross-sectional study. Between January 2015 and October 2017, we continuously recruited 1285 older patients with OSA who underwent overnight polysomnography from sleep centers of multiple hospitals. They were assessed using 12-lead ECG or 24-h dynamic ECG, and their baseline demographics, clinical characteristics, sleep parameters, and medical history were determined. Multivariate binary logistic regression analysis was used to investigate the factors related to AF in these older patients with OSA. Results The clinician classified 122 (9.5%) patients as having AF. The prevalence of AF significantly increased with age (P

A K–Rb–83Kr-based atomic comagnetometer for performing movement-related Magnetoencephalography (MEG) is theoretically studied in this paper. Parameters such as the spin-exchange rates, the spin-dephasing rates and the polarization of the nuclear spins are studied to configure the comagnetometer. The results show that the nuclear spin can generate a magnetic field of around 700 nT, at which the nuclear spin can compensate for a wide range of magnetic fields. In this paper, we also show the fabrication process for hybrid optical-pumping vapor cells, whereby alkali metals are mixed in a glove box that is then connected to the alkali vapor-cell fabrication system.

The miniaturization of quantum sensors is a popular trend for the development of quantum technology. One of the key components of these sensors is a coil which is used for spin modulation and manipulation. The bi-planar coils have the advantage of producing three-dimensional magnetic fields with only two planes of current confinement, whereas the traditional Helmholtz coils require three-dimensional current distribution. Thus, the bi-planar coils are compatible with the current micro-fabrication process and are quite suitable for the compact design of the chip-scale atomic devices that require stable or modulated magnetic fields. This paper presents a design of a miniature bi-planar coil. Both the magnetic fields produced by the coils and their inhomogeneities were designed theoretically. The magnetic field gradient is a crucial parameter for the coils, especially for generating magnetic fields in very small areas. We used a NMR (Nuclear Magnetic Resonance) method based on the relaxation of 131Xe nuclear spins to measure the magnetic field gradient in situ. This is the first time that the field inhomogeneities of the field of such small bi-planar coils have been measured. Our results indicate that the designed gradient caused error is 0.08 for the By and the Bx coils, and the measured gradient caused error using the nuclear spin relaxation method is 0.09±0.02, suggesting that our method is suitable for measuring gradients. Due to the poor sensitivity of our magnetometer under a large Bz bias field, we could not measure the Bz magnetic field gradient. Our method also helps to improve the gradients of the miniature bi-planar coil design, which is critical for chip-scale atomic devices.

Abstract The emergence of the coronavirus disease 2019 pandemic has dramatically increased the global prevalence of depression. Unfortunately, antidepressant drugs benefit only a small minority of patients. Thus, there is an urgent need to develop new interventions. Accumulating evidence supports a causal relationship between gut microbiota dysbiosis and depression. To advance microbiota‐based diagnostics and therapeutics of depression, a comprehensive overview of microbial alterations in depression is presented to identify effector microbial biomarkers. This procedure generated 215 bacterial taxa from humans and 312 from animal models. Compared to controls, depression shows significant differences in β‐diversity, but no changes in microbial richness and diversity. Additionally, species‐specific microbial changes are identified like increased Eggerthella in humans and decreased Acetatifactor in rodent models. Moreover, a disrupted microbiome balance and functional changes, characterized by an enrichment of pro‐inflammatory bacteria (e.g., Desulfovibrio and Escherichia/Shigella) and depletion of anti‐inflammatory butyrate‐producing bacteria (e.g., Bifidobacterium and Faecalibacterium) are consistently shared across species. Confounding effects of geographical region, depression type, and intestinal segments are also investigated. Ultimately, a total of 178 species and subspecies probiotics are identified to alleviate the depressive phenotypes. Current findings provide a foundation for developing microbiota‐based diagnostics and therapeutics and advancing microbiota‐oriented precision medicine for depression.

Post-stroke depression (PSD) is the most common mood disorder caused by stroke. Stroke might bring about increased intestinal permeability accompanied by gut microbiota changes. According to the “gut-brain” axis hypothesis, increased intestinal permeability may contribute to PSD. Therefore, we investigated the association between increased intestinal permeability and the occurrence of PSD. Intestinal fatty acid binding protein (iFABP) is responsible for intestinal fatty acid absorption and transport and is often considered a biomarker of gut hyperpermeability, also known as leaky gut. We enrolled 48 healthy controls (HCs), 48 stroke patients without depression, and 48 PSD patients in this study. Plasma iFABP was measured in the three groups. CRP, LBP, and sCD14 were quantified for bacterial infection assessment. In addition, clinical laboratory indicators of lipid metabolism were assessed. The PSD patients exhibited higher iFABP levels compared with HCs and non-depressed stroke patients. Using OPLS discriminant analysis, four proteins (ApoA1, HDL-C, iFABP, and Lp(a)) were identified as potential biomarkers for distinguishing PSD patients from non-depression stroke patients. Our study discovered that elevated plasma iFABP levels in PSD patients correlated with the degree of depression, along with disturbed lipid metabolism. These findings also suggested the need to consider the role of a leaky gut in depression after stroke.

ObjectivesThis study aimed to develop a score including novel putative predictors for predicting the risk of sICH and outcomes after thrombolytic therapy with intravenous (IV) recombinant tissue-type plasminogen activator (r-tPA) in acute ischemic stroke patients.MethodsAll patients with acute ischemic stroke treated with IV r-tPA at three university-based hospitals in Chongqing, China, from 2014 to 2019 were retrospectively studied. Potential risk factors associated with sICH (NINDS criteria) were determined with multivariate logistic regression, and we developed our score according to the magnitude of logistic regression coefficients. The score was validated in another independent cohort. Area under the receiver operating characteristic curve (AUC-ROC) was used to assess the performance of the score. Calibration was evaluated using the Hosmer–Lemeshow goodness-of-fit method.ResultsThe SON2A2 score (0 to 8 points) consisted of history of smoking (no = 1, yes = 0, β = 0.81), onset-to-needle time (≥3.5 = 1,10 = 2, ≤10 = 0, β = 1.22), neutrophil percentage (≥80.0% = 1, 11 = 0, β = 1.30), and age (>65 years = 1, ≤65 years = 0, β = 0.89). The SON2A2 score was strongly associated with sICH (OR 1.98; 95%CI 1.675–2.34) and poor outcomes (OR 1.89; 95%CI 1.68–2.13). AUC-ROC in the derivation cohort was 0.82 (95%CI 0.77–0.86). Similar results were obtained in the validation cohort. The Hosmer–Lemeshow test revealed that predicted and observed event rates in derivation and validation cohorts were very close.ConclusionThe SON2A2 score is a simple, efficient, quick, and easy-to-perform scale for predicting the risk of sICH and outcome after intravenous r-tPA thrombolysis within 4.5 h in patients with ischemic stroke, and risk assessment using this test has the potential for early and personalized management of this disease in high-risk patients.

In the intelligent optimization process of aerospace thin-walled parts, there are issues such as solidification of core knowledge base, high system coupling degree, and real-time evaluation and optimization feedback required for the knowledge base. These problems make it difficult to expand the functions of the digital twin system and meet the growing processing needs, ultimately hindering the application of digital twin technology. To address these issues, a digital twin system for controlling processing errors in thin-walled parts was built using a microservices architecture. In addition, a method for building a digital twin system at the processing unit level with the best coupling degree was proposed, mainly targeting the dynamic characteristics analysis knowledge base of thin-walled parts. Furthermore, to meet the requirements for backward compatibility of the processing unit level digital twin system, a comprehensive solution including the construction, operation, evaluation, optimization, and visualization of a knowledge base for the dynamic characteristics of the processing unit was proposed, providing guidance for the digital transformation and upgrading of CNC machine tools and the optimization of processing technology based on digital twin technology.

Abstract Accurate temperature measurements can efficiently solve numerous critical problems and provide key information. Herein, a flexible micro-three-dimensional sensor, with a combination of platinum and indium oxide to form thermocouples, is designed and fabricated by a microfabrication process to achieve in situ real-time temperature measurements. The stability and reliability of the sensor are greatly improved by optimizing the process parameters, structural design, and preparation methods. A novel micro-three-dimensional structure with better malleability is designed, which also takes advantage of the fast response of a two-dimensional thin film. The as-obtained flexible temperature sensor with excellent stability and reliability is expected to greatly contribute to the development of essential components in various emerging research fields, including bio-robot and healthcare systems. The model of the application sensor in a mask is further proposed and designed to realize the collection of health information, reducing the number of deaths caused by the lack of timely detection and treatment of patients.

IntroductionTo study cerebrospinal fluid neurofilament light chain (CSF-NfL) levels as a prognostic biomarker in pediatric Guillain-Barré syndrome (GBS).MethodsProspective study enrolling 26 pediatric GBS patients and 48 healthy controls (HCs) from neurology units between 2017 to 2021. The CSF-NfL levels were measured by enzyme-linked immunosorbent assay. The children's disability levels were evaluated using Hughes Functional Score (HFS) at nadir, 1 month, and 6 months after onset. The receiver operating characteristic (ROC) curve derived from logistic regression (with age as a covariate) was used to assess the prognostic value of CSF-NfL on the possibility of walking aided at 1 month after symptom onset.ResultsThe mean CSF-NfL levels were significantly increased in GBS patients (111.76 pg/mL) as compared to that in HCs (76.82 pg/mL) (t = 6.754, p < 0.001). At follow- up, the mean CSF-NfL levels after treatment (65.69 pg/mL) declined significantly (t = 6.693, p < 0.001). CSF-NfL levels upon admission were significantly associated with the HFS at nadir (rs = 0.461, p = 0.018). Moreover, the mean CSF-NfL levels in GBS patients with poor prognosis (130.47pg/mL) were significantly higher than that in patients with good prognosis (104.87pg/mL) (t = 2.399, p = 0.025). ROC curve analysis of the predictive value of CSF-NfL levels with respect to the inability to walk unaided within 1 month showed a significant difference (area under the curve: 0.857,95% confidence interval 0.702-1.000; p = 0.006).ConclusionCSF-NfL levels were increased in pediatric GBS patients. High CSF-NfL level predicted worse motor function, and was strongly associated with poor short-term prognosis of pediatric GBS. We propose a biomarker for early prediction of outcome in pediatric GBS, which would be applicable for clinical practice and efficacy of treatment in the future.

ObjectivesTo analyze the characteristics of oral microbiota in plateau and plain youth and the possible function of the microbiome.Materials and methodsA total of 120 healthy young males (80 on the plateau, 40 on the plain) completed this cross-sectional study. Oral microflora samples were collected from all participants. The bacterial 16S rDNA was amplified using PCR and sequenced using Illumina MiSeq high-throughput sequencing. The data were analyzed to determine the microbial distribution and community structure of the oral microflora from the two groups. Metastats was used to test differences in relative species abundance between the groups. The correlation between the abundance of specific bacteria and blood indicators was also analyzed.ResultsAs demonstrated by alpha and beta diversity, the plateau group had lower microbial richness and a less even distribution of oral microbiota than the plain group. All predominant phyla and genera were qualitatively similar between the two groups, but their relative abundances differed. The relative abundance of bacteria in the phylum Firmicutes was significantly higher in the plateau group than in the plain group. At the genus level, Streptococcus spp. and Gemella spp. were also more abundant in the plateau group. The functional prediction indicated vigorous microbial metabolism in the oral bacterial community. We also found that the relative abundance of Streptococcus spp., the dominant genus, was positively correlated with triglyceride levels in the plateau group.ConclusionsWith increasing altitude, the diversity of oral microbiota and the relative proportion of predominant bacteria were altered. The distribution and related function of Streptococcus spp. were prominent in plateau samples. This comprehensive study of the relationship between oral microecology and elevation provides a point of reference for studying the human body’s adaptability or inadaptability to high altitude.

Introduction: Major depressive disorder is caused by gene–environment interactions, and the host microbiome has been recognized as an important environmental factor. However, the underlying mechanisms of the host–microbiota interactions that lead to depression are complex and remain poorly understood. Objectives: The present study aimed to explore the possible mechanisms underlying gut microbiota dysbiosis-induced depressive-like behaviors. Methods: We used high-performance liquid chromatography-tandem mass spectrometry to analyze alterations in the hippocampal lysine acetylome and succinylome in male mice that had received gut microbiota from fecal samples of either patients with major depressive disorder or healthy controls. This was followed by bioinformatic analyses. Results: A total of 315 acetylation sites on 223 proteins and 624 succinylation sites on 494 proteins were differentially expressed in the gut microbiota-dysbiosis mice. The significantly acetylated proteins were primarily associated with carbon metabolism disruption and gene transcription suppression, while the synaptic vesicle cycle and protein translation were the most significantly altered functions for succinylated proteins. Additionally, our findings suggest that gut microbiota dysbiosis disturbs mitochondria-mediated biological processes and the MAPK signaling pathway through crosstalk between acetylation and succinylation on relevant proteins. Conclusions: This is the first study to demonstrate modifications in acetylation and succinylation in gut microbiota-dysbiosis mice. Our findings provide new avenues for exploring the pathogenesis of gut microbiota dysbiosis-related depression, and highlight potential targets for depression treatment.