GaN integrated optical devices for glycerol viscosity measurement.

This Letter presents the fabrication and characterization of a chip-scale GaN optical device for measuring glycerol viscosity. The monolithically integrated GaN chip with a size of 1 × 1 mm2 comprises a light-emitting diode (LED) and a photodiode (PD) on a transparent sapphire substrate. The glycerol droplet applied to the device acts as a medium for coupling light from the LED to the PD. When a mechanical impulse is applied, the droplet undergoes a damped vibration that depends on its viscosity, causing a change in its shape and altering the path of light propagation. The viscosity of the glycerol sample can be determined by obtaining the rate of attenuation of the measured photocurrent signals. The proposed unit offers a fast time response in microseconds and requires only a small sample volume of 5 µl. The developed device is highly suitable for the practical measurement of glycerol viscosity due to its miniaturization, low cost, and ease of operation without the need for external optical components.

Influence of Interface Type on Dynamic Deformation Behavior of 3D-Printed Heterogeneous Titanium Alloy Materials.

Using the Split Hopkinson Pressure Bar technique, strain-limited dynamic compressive loading experiments were performed on TA1/TA15 heterostructure (HS) materials. The plastic deformation mechanisms, fracture forms, and energy absorption properties of an HS material with a metallurgical bonding interface (MB) and an HS material without a metallurgical bonding interface (NMB) are compared and analyzed. The results show that there is no significant difference between the two deformation mechanisms. The fracture forms are all "V-shaped" fractures within the TA1 part. The NMB was carried for 57 µs before failure and absorbed 441 J/cm3 of energy. The MB was carried for 72 µs before failure and absorbed 495 J/cm3 of energy. Microstructure observations show that there is a coordinated deformation effect near the MB interface compared to the NMB, with both TA1 and TA15 near the interface carrying stresses. This causes an enhancement of the MB load-bearing time and a 12% increase in energy absorption.

Protopine ameliorates OVA-induced asthma through modulatingTLR4/MyD88/NF-κB pathway and NLRP3 inflammasome-mediated pyroptosis.

BACKGROUND: Chronic airway inflammation and hyperresponsiveness are characteristics of asthma. The isoquinoline alkaloid protopine (PRO) has been shown to exert anti-inflammatory effects, but its mechanism of action in asthma is not known. PURPOSE: Investigate the protective properties of PRO upon asthma and elucidate its mechanism. STUDY DESIGN AND METHODS: The effects of PRO in asthma treatment were assessed by histology, biochemical analysis, and real-time reverse transcription-quantitative polymerase chain reaction. Then, we integrated molecular docking, western blotting, cellular experiments, immunohistochemistry, immunofluorescence analysis, flow cytometry, and metabolomics analysis to reveal its mechanism. RESULTS: In vivo, PRO therapy reduced the number of inflammatory cells (eosinophils, leukocytes, monocytes) in bronchoalveolar lavage fluid (BALF), ameliorated pathologic alterations in lung tissues, and inhibited secretion of IgG and histamine. Molecular docking showed that PRO could dock with the proteins of TLR4, MyD88, TRAF6, TAK1, IKKα, and TNF-α. Western blotting displayed that PRO inhibited the TLR4/NF-κB signaling pathway. PRO regulated expression of the pyroptosis-related proteins NLR family pyrin domain containing 3 (NLRP3) inflammasome, gasdermin D, caspase-1, and drove caspase-1 inactivation to affect inflammatory responses by inhibiting the NLRP3 inflammasome. In vitro, 24 h after treatment with PRO, cell activity, as well as levels of reactive oxygen species (ROS) and interleukin (IL)-1ß and IL-18, decreased significantly. Immunofluorescence staining showed that PRO decreased expression of TLR4 and MyD88 in vitro. PRO decreased nuclear translocation of NF-κB p65. Twenty-one potential biomarkers in serum were identified using metabolomics analysis, and they predominantly controlled the metabolism of phenylalanine, tryptophan, glucose, and sphingolipids. CONCLUSION: PRO reduced OVA-induced asthma. The underlying mechanism was associated with the TLR4/MyD88/NF-κB pathway and NLRP3 inflammasome-mediated pyroptosis.

Genesis of a functional astrocyte syncytium in the developing mouse hippocampus.

Astrocytes are increasingly shown to operate as an isopotential syncytium in brain function. Protoplasmic astrocytes acquire this ability to functionally go beyond the single-cell level by evolving into a spongiform morphology, cytoplasmically connecting into a syncytium, and expressing a high density of K+ conductance. However, none of these cellular/functional features exist in neonatal newborn astrocytes, which imposes a basic question of when a functional syncytium evolves in the developing brain. Our results show that the spongiform morphology of individual astrocytes and their spatial organization all reach stationary levels by postnatal day (P) 15 in the hippocampal CA1 region. Functionally, astrocytes begin to uniformly express a mature level of passive K+ conductance by P11. We next used syncytial isopotentiality measurement to monitor the maturation of the astrocyte syncytium. In uncoupled P1 astrocytes, the substitution of endogenous K+ by a Na+ -electrode solution ([Na+ ]p ) resulted in the total elimination of the physiological membrane potential (VM ), and outward K+ conductance as predicted by the Goldman-Hodgkin-Katz (GHK) equation. As more astrocytes are coupled to each other through gap junctions during development, the [Na+ ]p -induced loss of physiological VM and the outward K+ conductance is progressively compensated by the neighboring astrocytes. By P15, a stably established syncytial isopotentiality (-73 mV), and a fully compensated outward K+ conductance appeared in all [Na+ ]p -recorded astrocytes. Thus, in view of the developmental timeframe wherein a singular syncytium is anatomically and functionally established for intra-syncytium K+ equilibration, an astrocyte syncytium becomes fully operational at P15 in the mouse hippocampus.

Interface Engineering in Chip-Scale GaN Optical Devices for Near-Hysteresis-Free Hydraulic Pressure Sensing.

In this work, a compact, near-hysteresis-free hydraulic pressure sensor is presented through interface engineering in a GaN chip-scale optical device. The sensor consists of a monolithic GaN-on-sapphire device responsible for light emission and detection and a multilevel microstructured polydimethylsiloxane (PDMS) film prepared through a low-cost molding process using sandpaper as a template. The micro-patterned PDMS film functions as a pressure-sensing medium to effectively modulate the reflectance properties at the sapphire interface during pressure loading and unloading. The interface engineering endows the GaN optical device with near-hysteresis-free performance over a wide pressure range of up to 0-800 kPa. Verified by a series of experimental measurements on its dynamic responses, the tiny hydraulic sensor exhibits superior performance in hysteresis, stability, repeatability, and response time, indicating its considerable potential for a broad range of practical applications.

Cattle Bile Arisaema Aqueous Extracts Protect Against Febrile Seizures in Rats Through Regulating Neurotransmitters and Suppressing Neuroinflammation.

Cattle bile Arisaema (CBA) is a traditional medicine used for the treatment of febrile seizures (FS) for thousands of years in China. However, its application is greatly limited due to cost reasons, and pig bile Arisaema (PBA) is the main commercial product instead. Additionally, the underlying mechanism of CBA for the treatment of FS still remains unknown. In this study, we investigated the anti-convulsant effect and potential mechanism of the CBA aqueous extract for the first time through a hot-water bath-induced FS rat model. Our results showed that pre-treatment with CBA dramatically lowered the incidence rate and generation times and prolonged the latency of FS. In addition, CBA effectively ameliorated neuronal damage and regulated neurotransmitter disorder induced by FS in the rat hippocampus. The enzyme-linked immunosorbent assay, western blotting, immunohistochemical, and qRT-PCR results exhibited that CBA suppressed the expression of GFAP, TLR4, NF-κB, HMGB1, NLRP3, TNF-α, IL-1ß, and IL-6 and consequently inhibited the neuroinflammation induced by FS. Interestingly, although the CBA and PBA aqueous extracts possessed the same trend on the changes caused by FS, the improvement of FS by CBA is markedly better than that by PBA. These findings indicate that CBA exerts a protective effect on febrile seizures through regulating neurotransmitter disorder and suppressing neuroinflammation.

A Versatile, Incubator-Compatible, Monolithic GaN Photonic Chipscope for Label-Free Monitoring of Live Cell Activities.

The ability to quantitatively monitor various cellular activities is critical for understanding their biological functions and the therapeutic response of cells to drugs. Unfortunately, existing approaches such as fluorescent staining and impedance-based methods are often hindered by their multiple time-consuming preparation steps, sophisticated labeling procedures, and complicated apparatus. The cost-effective, monolithic gallium nitride (GaN) photonic chip has been demonstrated as an ultrasensitive and ultracompact optical refractometer in a previous work, but it has never been applied to cell studies. Here, for the first time, the so-called GaN chipscope is proposed to quantitatively monitor the progression of different intracellular processes in a label-free manner. Specifically, the GaN-based monolithic chip enables not only a photoelectric readout of cellular/subcellular refractive index changes but also the direct imaging of cellular/subcellular ultrastructural features using a customized differential interference contrast (DIC) microscope. The miniaturized chipscope adopts an ultracompact design, which can be readily mounted with conventional cell culture dishes and placed inside standard cell incubators for real-time observation of cell activities. As a proof-of-concept demonstration, its applications are explored in 1) cell adhesion dynamics monitoring, 2) drug screening, and 3) cell differentiation studies, highlighting its potential in broad fundamental cell biology studies as well as in clinical applications.

Compact GaN-based optical inclinometer.

In this Letter, a compact optical inclinometer in sub-centimeter size is proposed and demonstrated. A 1×1 mm2 GaN-on-sapphire chip composed of a light-emitting diode and photodetector is fabricated through wafer-scale processes and integrated with a spherical glass cavity with a diameter of 5 mm, which contains ethanol as a liquid pendulum. When applying inclinations relative to the horizon, the extent to which the chip is immersed in ethanol changes, thereby altering the amount of light received by the on-chip detector. The underlying mechanisms of angle-dependent reflectance characteristics at the sapphire boundary are identified, and the measured photocurrent signal can be used as quantitative readouts for determining the angle of inclination from -60 to +60°. A linear response with a sensitivity of 19.4 nA/° and an estimated resolution of 0.003° is obtained over a wide linear range from -40 to +40°. Verified by a series of dynamic experiments, the developed inclinometer exhibits a high degree of repeatability and stability, which paves the way for its widespread usage and applications.

Chip-Scale In Situ Salinity Sensing Based on a Monolithic Optoelectronic Chip.

Salinity is an indispensable parameter for various applications such as biomedical diagnostics, environmental chemical analysis, marine monitoring, etc. Miniaturized salinity sensors have significant potential in portable applications in various scenarios and designs with highly desirable features of convenience, reliability, economy, and high sensitivity and also the capability of real-time measurements. Herein, we demonstrate a highly refractive index-sensitive sensor based on a microscale III-nitride chip that consists of a light emitter and a photodetector. This highly monolithically integrated chip shows an excellent sensitivity of salinity of 2606 nA/(mol/L) (or 446 nA/%) and a response time of 0.243 s. In addition, wireless communication technologies can be easily integrated with the sensing device, which enables automatic remote control for data collection and postprocessing. Remarkably, a polymer-based antifouling coating on the surface of the sensing chip has been established to significantly improve its long-term stability in mimicked marine water. The demonstrated ultrasensitive, ultracompact, cost-effective, fast response, wireless-compatible, and easy-to-use features endow the current device with a huge potential for in situ salinity sensing under varying environmental conditions.

Chip-scale optical airflow sensor.

Airflow sensors are an essential component in a wide range of industrial, biomedical, and environmental applications. The development of compact devices with a fast response and wide measurement range capable of in situ airflow monitoring is highly desirable. Herein, we report a miniaturized optical airflow sensor based on a GaN chip with a flexible PDMS membrane. The compact GaN chip is responsible for light emission and photodetection. The PDMS membrane fabricated using a droplet-based molding process can effectively transform the airflow stimuli into optical reflectance changes that can be monitored by an on-chip photodetector. Without the use of external components for light coupling, the proposed sensor adopting the novel integration scheme is capable of detecting airflow rates of up to 53.5 ms-1 and exhibits a fast response time of 12 ms, holding great promise for diverse practical applications. The potential use in monitoring human breathing is also demonstrated.

A comprehensive review of research progress on the genus Arisaema: Botany, uses, phytochemistry, pharmacology, toxicity and pharmacokinetics.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Arisaema belongs to the family Araceae, which includes Chinese herbal medicines with wide-ranging pharmacological functions, including those useful for the treatment of stubborn phlegm, cough, epilepsy, tetanus, snakebite, rheumatoid arthritis, and other ailments. AIM OF THE STUDY: The current study aimed to comprehensively review the botany, uses, phytochemistry, pharmacology, toxicity, quality control and pharmacokinetics of plants in the genus Arisaema and to provide novel insights to develop future research in this field. MATERIALS AND METHODS: Relevant information on the genus Arisaema was obtained from published scientific materials (including materials from PubMed, Elsevier, Web of Science, Google Scholar, Baidu Scholar, CNKI, and Wiley) and other literature sources (e.g., the Chinese Pharmacopoeia, 2020 edition; Chinese herbal books and PhD and MSc thesis). RESULTS: The application information complied with this review and included processing techniques, traditional uses, clinical applications and classic prescriptions. Approximately 260 compounds, including flavonoids, alkaloids, saccharides, steroids, fatty acids, amino acids and volatile oils, have been separated and identified from the genus Arisaema. The isolated compounds exhibit wide-ranging pharmacological activities such as antitumor activity, analgesic and sedative activity, antioxidant activity and anti-inflammatory activity. The toxicity and irritant impacts, quality control, and pharmacokinetics are also discussed in this review. CONCLUSIONS: Plants in the genus Arisaema are valuable resources with therapeutic potential for a broad spectrum of ailments. Based on the limited literature, this review comprehensively and systematically summarizes current knowledge regarding the genus Arisaema for the first time. However, there have been insufficient studies on the active ingredients and germplasm and insufficient in-depth mechanistic studies. Therefore, isolation and identification of additional effective components and through research on the germplasm, pharmacodynamic mechanisms, and toxicology should be conducted to assess effectiveness and safety and to ensure the quality of the related drugs.

French error type annotation for dictation: A platform with automatic error type annotation for French dictation exercises.

Dictation is considered an efficient exercise for testing the language proficiency of learners of French as a Foreign Language (FFL). However, the traditional teaching approach to dictation reduces the instructional feedback efficiency. To remedy this, this study adopts a design-based research approach and builds an automatic error type annotation platform for dictation practice named FRETA-D (French error type annotation for dictation) to pursue intelligent pedagogical feedback for both FFL teachers and students. FRETA-D can automatically identify error boundaries as well as classify the errors into fine-grained error types in learners' dictation texts. FRETA-D features a dataset-independent classifier based on a framework with 25 main error types, which is generalized from French grammar rules and characteristics of frequent learner dictation errors. Five French teachers are invited to evaluate the appropriateness of automatically predicted error types of 147 randomly selected samples, and the acceptance rate reaches more than 85%. Automatic evaluation on 1,009 sentences by comparing with manually labeled references also shows promising results, reaching more than 85% consistency with human judgments. The accessibility of FRETA-D has also been confirmed by 50 Chinese undergraduate FFL learners with different professional backgrounds. FRETA-D facilitates conducting dynamic statistical analysis of learners'error types. And we share the same findings with previous studies that there exist causal links between the dictation errors and learners' mastery of French phoneme and grapheme.

Biomarkers for the Clinical Diagnosis of Alzheimer's Disease: Metabolomics Analysis of Brain Tissue and Blood.

With an increase in aging populations worldwide, age-related diseases such as Alzheimer's disease (AD) have become a global concern. At present, a cure for neurodegenerative disease is lacking. There is an urgent need for a biomarker that can facilitate the diagnosis, classification, prognosis, and treatment response of AD. The recent emergence of highly sensitive mass-spectrometry platforms and high-throughput technology can be employed to discover and catalog vast datasets of small metabolites, which respond to changed status in the body. Metabolomics analysis provides hope for a better understanding of AD as well as the subsequent identification and analysis of metabolites. Here, we review the state-of-the-art emerging candidate biomarkers for AD.

Neopterin as a Predictor of Functional Outcome and Mortality in Chinese Patients with Acute Ischemic Stroke.

Immune responses and inflammation play an important role in the pathogenesis of ischemic stroke. We therefore evaluated the 6-month prognostic value of early measurement of serum neopterin levels, a marker of inflammation and immune system activation, in Chinese patients with acute ischemic stroke (AIS). Consecutive AIS patients admitted to the emergency department were identified. Clinical information was collected. Serum concentration of neopterin and NIH stroke scale (NIHSS) were measured at the time of admission. Functional outcome was measured by modified Rankin scale (mRS) 6 months after admission. Multivariate analyses were performed using logistic regression models. During the inclusion period, 312 patients with first-ever AIS were included and 290 completed follow-up. The results indicated that the serum neopterin levels were significantly (P < 0.0001) higher in acutely ischemic stroke patients as compared to normal controls. Neopterin was an independent prognostic marker of 6-month functional outcome and death [odds ratio (OR) 4.33 (1.83-10.32) and 6.68 (2.44-12.13), respectively, P < 0.0001 for both, adjusted for NIHSS, other predictors and vascular risk factors] in patients with AIS. Neopterin improved the area under the receiver operating characteristic curve of the NHISS score for functional outcome from 0.75 (95 % CI 0.69-0.83) to 0.85 (95 % CI 0.79-0.91; P < 0.001) and for mortality from 0.76 (95 % CI 0.68-0.85) to 0.87 (95 % CI 0.81-0.94; P < 0.001). Serum neopterin is a useful, independent tool to predict functional outcome and mortality 6 months after stroke.