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Abstract Background Myasthenia gravis (MG) is an autoimmune disease characterized by pathogenic antibodies that target structures of the neuromuscular junction. The evidence suggests that the regulation of long noncoding RNAs (lncRNAs) that is mediated by transcription factors (TFs) plays a key role in the pathophysiology of MG. Nevertheless, the detailed molecular mechanisms of lncRNAs in MG remain largely undetermined. Methods Using microarray analysis, we analyzed the lncRNA levels in MG. By bioinformatics analysis, LINC01566 was found to potentially play an important role in MG. First, qRT‒PCR was performed to verify the LINC1566 expressions in MG patients. Then, fluorescence in situ hybridization was conducted to determine the localization of LINC01566 in CD4 + T cells. Finally, the impact of LINC01566 knockdown or overexpression on CD4 + T-cell function was also analyzed using flow cytometry and CCK-8 assay. A dual-luciferase reporter assay was used to validate the binding of the TF FOSL1 to the LINC01566 promoter. Results Based on the lncRNA microarray and differential expression analyses, we identified 563 differentially expressed (DE) lncRNAs, 450 DE mRNAs and 19 DE TFs in MG. We then constructed a lncRNA-TF-mRNA network. Through network analysis, we found that LINC01566 may play a crucial role in MG by regulating T-cell-related pathways. Further experiments indicated that LINC01566 is expressed at low levels in MG patients. Functionally, LINC01566 is primarily distributed in the nucleus and can facilitate CD4 + T-cell apoptosis and inhibit cell proliferation. Mechanistically, we hypothesized that LINC01566 may negatively regulate the expressions of DUSP3, CCR2, FADD, SIRPB1, LGALS3 and SIRPB1, which are involved in the T-cell activation pathway, to further influence the cellular proliferation and apoptosis in MG. Moreover, we found that the effect of LINC01566 on CD4 + T cells in MG was mediated by the TF FOSL1, and in vitro experiments indicated that FOSL1 can bind to the promoter region of LINC01566. Conclusions In summary, our research revealed the protective roles of LINC01566 in clinical samples and cellular experiments, illustrating the potential roles and mechanism by which FOSL1/LINC01566 negatively regulates CD4 + T-cell activation in MG.

Summary: Electroporation temporarily enhances cell membrane permeability and promotes the absorption of external molecules. We have developed a device termed the rolling microneedle electrode array (RoMEA) that combines a densely arranged microneedle array of electrodes with rolling structures. Use RoMEA to create uniform skin micropores for efficient, low-damage transfection of nucleic acids over extended areas of the body. We describe in detail the design, fabrication, and assembly of the device and the application of in vivo electroporation of nucleic acids.For complete details on the use and execution of this protocol, please refer to Tongren Yang et al. 1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

The anomaly detection in data links aims to identify the state of the link during data transmission, which is a critical task for ensuring information transmission security. Most anomaly detection methods focus solely on individual link characteristics, disregarding the inter-link structural information, thus hindering effective generalization to graph-structured data. In this study, we introduce a Graph Learning-based Data Link Anomaly Detection model (GLDAE) that considers both the link features and the communication network structure. Specifically, GLDAE comprises a graph enhancement module, a link feature autoencoder, a structure autoencoder, and a discriminator, enabling simultaneous learning of edge features and the latent representation of the graph structure. Moreover, to enhance the model’s generalization capability, we employ contrastive learning between the original graph and its enhanced version. Additionally, to achieve joint learning of edge features and graph structure, we integrate edge feature embeddings and structure embeddings as inputs to the decoder. Finally, utilizing the well-trained encoder to encode link features and derive a new feature representation, we feed it into an MLP classifier to determine the link’s status. Experimental evaluations were conducted on four authentic datasets (NF-UNSW-NB15, NF-UNSW-NB15-v2, NF-ToN-IoT, NF-ToN-IoT-v2), comparing our model against state-of-the-art baseline models, showcasing the substantial potential of our approach.

Abstract Facial palsy (FP) profoundly influences interpersonal communication and emotional expression, necessitating precise diagnostic and monitoring tools for optimal care. However, current electromyography (EMG) systems are limited by their bulky nature, complex setups, and dependence on skilled technicians. Here we report an innovative biosensing approach that utilizes a PEDOT:PSS-modified flexible microneedle electrode array (P-FMNEA) to overcome the limitations of existing EMG devices. Supple system-level mechanics ensure excellent conformality to the facial curvilinear regions, enabling the detection of targeted muscular ensemble movements for facial paralysis assessment. Moreover, our apparatus adeptly captures each electrical impulse in response to real-time direct nerve stimulation during neurosurgical procedures. The wireless conveyance of EMG signals to medical facilities via a server augments access to patient follow-up evaluation data, fostering prompt treatment suggestions and enabling the access of multiple facial EMG datasets during typical 6-month follow-ups. Furthermore, the device’s soft mechanics alleviate issues of spatial intricacy, diminish pain, and minimize soft tissue hematomas associated with traditional needle electrode positioning. This groundbreaking biosensing strategy has the potential to transform FP management by providing an efficient, user-friendly, and less invasive alternative to the prevailing EMG devices. This pioneering technology enables more informed decision-making in FP-management and therapeutic intervention.

LiDAR-unmanned aerial system (LiDAR-UAS) technology can accurately and efficiently obtain detailed and accurate three-dimensional spatial information of objects. The classification of objects in estuarine areas is highly important for management, planning, and ecosystem protection. Owing to the presence of slopes in estuarine areas, distinguishing between dense vegetation (lawns and trees) on slopes and the ground at the tops of slopes is difficult. In addition, the imbalance in the number of point clouds also poses a challenge for accurate classification directly from point cloud data. A multifeature-assisted and multilayer fused neural network (MLF-PointNet++) is proposed for LiDAR-UAS point cloud classification in estuarine areas. First, the 3D shape features that characterize the geometric characteristics of targets and the visible-band difference vegetation index (VDVI) that can characterize vegetation distribution are used as auxiliary features to enhance the distinguishability of dense vegetation (lawns and trees) on slopes and the ground at the tops of slopes. Second, to enhance the extraction of target spatial information and contextual relationships, the feature vectors output by different layers of set abstraction in the PointNet++ model are fused to form a combined feature vector that integrates low and high-level information. Finally, the focal loss function is adopted as the loss function in the MLF-PointNet++ model to reduce the effect of imbalance in the number of point clouds in each category on the classification accuracy. A classification evaluation was conducted using LiDAR-UAS data from the Moshui River estuarine area in Qingdao, China. The experimental results revealed that MLF-PointNet++ had an overall accuracy (OA), mean intersection over union (mIOU), kappa coefficient, precision, recall, and F1-score of 0.976, 0.913, 0.960, 0.953, 0.953, and 0.953, respectively, for object classification in the three representative areas, which were better than the corresponding values for the classification methods of random forest, BP neural network, Naive Bayes, PointNet, PointNet++, and RandLA-Net. The study results provide effective methodological support for the classification of objects in estuarine areas and offer a scientific basis for the sustainable development of these areas.

Abstract Microneedles, especially hollow microneedles (HMNs), play an important role in drug delivery, but most of the current HMNs are manufactured based on silicon microfabrication (lithography, etching, etc.), which are slightly conservative due to the lack of low‐cost, batch‐scale and customized preparation approach, especially for the HMNs with flexible substrate. For the first time, we propose the use of a high‐precision 3D printed master mold followed by a dual‐molding process for the preparation of HMNs with different shapes, heights, and inner and outer diameters to satisfy different drug delivery needs. The 3D printed master mold and negative mold can be reused, thereby significantly reducing the cost. HMNs are based on biocompatible materials, such as heat‐curing polymers or light‐curing resins. The thickness and rigidity/flexibility characteristics of the substrate can be customized for different applications. The drug delivery efficiency of the fabricated HMNs was verified by the in situ treatment of psoriasis on the backs of mice, which required only a 0.1‐fold oral dose to achieve similar efficacy, and the associated side effects and drug toxicity were reduced. Thus, this dual‐molding process can reinvigorate HMNs development.

Six new compounds, (7R,8S,8′R)-balanophorone (1), (7′S,8′R,8R)-yunnanensin A (2), (3S)-thunberginol C (3), (8R,8′R)-maninsigin B (4), (7S,8R)-4,7,8-dihydroxy-9,9-dimethyl-chroman (5), and 4-hydroxy-1-(4-hydroxy-3-methoxyphenyl)butan-1-one (6), along with eight known compounds (7–14), were isolated from the herbaceous stems of Ephedra intermedia Schrenket C. A. Meyer. Their structures were elucidated based on their spectroscopic (MS, NMR, IR, and UV) data, and their absolute configurations were determined by comparing their calculated and experimental electronic circular dichroic (ECD) spectra. Moreover, compounds 1 and 3–6 were evaluated for their ability to protect human pulmonary epithelial cells (BEAS-2B) from injury induced by lipopolysaccharide (LPS) in vitro. The results showed that compound 6 exhibited a significant protective effect against LPS-induced injury in BEAS-2B, and compound 5 exhibited a slightly protective effect at the concentration of 10 μM.

Highlights Polyimide-based flexible microneedle array (PI-MNA) electrodes realize high electrical/mechanical performance and are compatible with wearable wireless recording systems. The normalized electrode–skin interface impedance (EII) of the PI-MNA electrodes reaches 0.98 kΩ cm2 at 1 kHz and 1.50 kΩ cm2 at 10 Hz, approximately 1/250 of clinical standard electrodes. This is the first report on the clinical study of microneedle electrodes. The PI-MNA electrodes are applied to clinical long-term continuous monitoring for polysomnography. Abstract Microneedle array (MNA) electrodes are an effective solution to achieve high-quality surface biopotential recording without the coordination of conductive gel and are thus very suitable for long-term wearable applications. Existing schemes are limited by flexibility, biosafety, and manufacturing costs, which create large barriers for wider applications. Here, we present a novel flexible MNA electrode that can simultaneously achieve flexibility of the substrate to fit a curved body surface, robustness of microneedles to penetrate the skin without fracture, and a simplified process to allow mass production. The compatibility with wearable wireless systems and the short preparation time of the electrodes significantly improves the comfort and convenience of electrophysiological recording. The normalized electrode–skin contact impedance reaches 0.98 kΩ cm2 at 1 kHz and 1.50 kΩ cm2 at 10 Hz, a record low value compared to previous reports and approximately 1/250 of the standard electrodes. The morphology, biosafety, and electrical/mechanical properties are fully characterized, and wearable recordings with a high signal-to-noise ratio and low motion artifacts are realized. The first reported clinical study of microneedle electrodes for surface electrophysiological monitoring was conducted in tens of healthy and sleep-disordered subjects with 44 nights of recording (over 8 h per night), providing substantial evidence that the electrodes can be leveraged to substitute for clinical standard electrodes.

Acute lung injury (ALI) is a common critical disease with a high mortality rate. Natural products have marked efficacy in the prevention and treatment of ALI, in addition, estrogen and its receptors are involved in the pathogenesis and development of lung injury. Our previous research shows that sesquiterpenes isolated from the stems and leaves of Dioscorea opposita Thunb. have anti-inflammatory and estrogenic-like activity. In the present study, sesquiterpene (A1) is a natural extract from the stems and leaves of Dioscorea opposita Thunb. with a view to determining whether A1 can improve lung function in a mouse model of LPS-induced ALI and exploring the involvement of the estrogen receptor β (ERβ) pathway. A1 (20 or 40 mg/kg, i. g., 2 times/day) was administered for 3 d, followed by the induction of ALI via an intratracheal LPS drip (5 mg/kg/2 h). The lung function and levels of inflammation, immune cells, apoptosis, and ERβ expression were examined. The antagonistic activity of specific ERβ blocker (THC, 1 μM) against A1 (20 μM) in co-cultured BEAS-2B cells and splenic lymphocytes induced with LPS (1 μg/mL, 24 h) was also investigated to assess whether the observed effects of A1 were mediated by ERβ. A1 improved lung function, regulated the immune system, and decreased inflammation and apoptosis. Moreover, A1 increased the expression of ERβ in LPS-induced mice, and antagonism of ERβ decreased the protective effects of A1 in a co-culture system. A1 had anti-ALI effects that might partially mediated through ERβ signaling. Our data provide molecular justification for the use of A1 in the treatment of ALI.

Mg2SiO4 and MgSiO3 ceramics with superior microwave dielectric properties are considered to be promising candidates for 5G applications. However, a slight deviation from the stoichiometric Mg/Si ratio will significantly influence their microwave dielectric properties, which will hinder their practical applications. In this work, the xMgO-SiO2 (x = 1~2) ceramics were synthesized by a solid-state reaction method. The influence of the Mg/Si ratio x on the crystalline phase, microstructure, and microwave dielectric properties was investigated through X-ray diffraction (XRD), a scanning electron microscope (SEM), and the resonant cavity method. The XRD patterns revealed the coexistence of Mg2SiO4 and MgSiO3 within the x range of 1~2, which was further demonstrated by the energy-dispersive X-ray spectra. The SEM images show a typical polycrystalline morphology of ceramics with an inhomogeneous grain size distribution. It is found that the microwave dielectric properties fluctuate at both sides of the x range while those remain relatively stable with minor changes at the intermediate components, indicating an obvious low composition dependence helpful for practical applications. Further, a demonstrator of a microstrip patch antenna for 5G applications using the 1.5MgO-SiO2 ceramic was designed and fabricated, and a return loss of −16.2 dB was demonstrated, which demonstrated the potential applications.

In this study, dense composites of xNaCl-(1−x)Ni0.5Zn0.5Fe2O4 (referred to as NaCl-NZO) and xH3BO3-(0.8−x)Ni0.5Zn0.5Fe2O4-0.2NaCl (referred to as HB-NZO-NaCl) were prepared using the cold sintering process. The objective was to investigate the cold sintering procedure for fabricating ferrite composite ceramics with comparable permeability and dielectric constants suitable for radio-frequency electronic device applications. Optimal cold sintering conditions were determined as 200 °C/30 min/500 MPa with a relative density of 95% for NaCl-NZO and 120 °C/30 min/300 MPa with a relative density of 95.4% for HB-NZO-NaCl. X-ray diffraction and scanning electron microscope analyses confirmed the absence of secondary phases. The resulting composite ceramics showed promising characteristics, with the 0.5NaCl-0.5NZO composition exhibiting a dielectric constant of 6.2 @ 100 MHz, dielectric loss of 0.02 @ 100 MHz, permeability of 2.5 @ 100 MHz, and magnetic loss of 0.001 @ 100 MHz. Similarly, the 0.3HB-0.5NZO-0.2NaCl composition displayed a dielectric constant of 5.9 @ 100 MHz, dielectric loss of 0.02 @ 100 MHz, permeability of 5.1 @ 100 MHz, and magnetic loss of 5 × 10−4 @ 100 MHz. These findings indicate potential applications in wireless communication.

If not cured promptly, tissue ischemia and hypoxia can cause serious consequences or even threaten the life of the patient. Hemoglobin-based oxygen carrier-201 (HBOC-201), bovine hemoglobin polymerized by glutaraldehyde and stored in a modified Ringer's lactic acid solution, has been investigated as a blood substitute for clinical use. HBOC-201 was approved in South Africa in 2001 to treat patients with low hemoglobin (Hb) levels when red blood cells (RBCs) are contraindicated, rejected, or unavailable. By promoting oxygen diffusion and convective oxygen delivery, HBOC-201 may act as a direct oxygen donor and increase oxygen transfer between RBCs and between RBCs and tissues. Therefore, HBOC-201 is gradually finding applications in treating various ischemic and hypoxic diseases including traumatic hemorrhagic shock, hemolysis, myocardial infarction, cardiopulmonary bypass, perioperative period, organ transplantation, etc. However, side effects such as vasoconstriction and elevated methemoglobin caused by HBOC-201 are major concerns in clinical applications because Hbs are not encapsulated by cell membranes. This study summarizes preclinical and clinical studies of HBOC-201 applied in various clinical scenarios, outlines the relevant mechanisms, highlights potential side effects and solutions, and discusses the application prospects. Randomized trials with large samples need to be further studied to better validate the efficacy, safety, and tolerability of HBOC-201 to the extent where patient-specific treatment strategies would be developed for various clinical scenarios to improve clinical outcomes.

The mechanical properties of materials deteriorate when hydrogen embrittlement (HE) occurs, seriously threatening the reliability and durability of the hydrogen system. Therefore, it is important to summarize the status and development trends of research on HE. This study reviewed 6676 publications concerned with HE from 1997 to 2022 based on the Web of Science Core Collection. VOSviewer was used to conduct the bibliometric analysis and produce visualizations of the publications. The results showed that the number of publications on HE increased after 2007, especially between 2017 and 2019. Japan was the country with the highest numbers of productive authors and citations of publications, and the total number of citations of Japanese publications was 24,589. Kyushu University was the most influential university, and the total number of citations of Kyushu University publications was 7999. Akiyama was the most prolific and influential author, publishing 88 publications with a total of 2565 citations. The USA, South Korea and some European countries are also leading in HE research; these countries have published more than 200 publications. It was also found that the HE publications generally covered five topics: “Hydrogen embrittlement in different materials”, “Effect of hydrogen on mechanical properties of materials”, “Effect of alloying elements or microstructure on hydrogen embrittlement”, “Hydrogen transport”, and “Characteristics and mechanisms of hydrogen related failures”. Research hotspots included “Fracture failure behavior and analysis”, “Microstructure”, “Hydrogen diffusion and transport”, “Mechanical properties”, “Hydrogen resistance”, and so on. These covered the basic methods and purposes of HE research. Finally, the distribution of the main subject categories of the publications was determined, and these categories covered various topics and disciplines. This study establishes valuable reference information for the application and development of HE research and provides a convenient resource to help researchers and scholars understand the development trends and research directions in this field.

Monitoring sleep conditions is of importance for sleep quality evaluation and sleep disease diagnosis. Accurate respiration detection provides key information about sleep conditions. Here, we propose a perforated temperature sensor that can be worn below the nasal cavity to monitor breath. The sensing system consists of two perforated temperature sensors, signal conditioning circuits, a transmission module, and a supporting analysis algorithm. The perforated structure effectively enhances the sensitivity of the system and shortens the response time. The sensor’s response time is 0.07 s in air and sensitivity is 1.4‰°C−1. The device can achieve a monitoring respiratory temperature range between normal room temperature and 40 °C. The simple and standard micromachining process ensures low cost and high reproducibility. We achieved the monitoring of different breathing patterns, such as normal breathing, panting, and apnea, which can be applied to sleep breath monitoring and exercise information recording.

A new flavonoid, saffloflavanside (1), a new sesquiterpene, safflomegastigside (2), and a new amide, saffloamide (3), together with twenty-two known compounds (4–25), were isolated from the flowers of Carthamus tinctorius L. Their structures were determined based on interpretation of their spectroscopic data and comparison with those reported in the literature. The protective effects against lipopolysaccharide (LPS)-stimulated damage on human normal lung epithelial (BEAS-2B) cells of the compounds were evaluated using MTT assay and cellular immunofluorescence assay. The results showed that compounds 2–3, 8–11, and 15–19 exhibited protective effects against LPS-induced damage to BEAS-2B cells. Moreover, compounds 2–3, 8–11, and 15–19 can significantly downregulate the level of nuclear translocation of NF-κB p-p65. In summary, this study revealed chemical constituents with lung protective activity from C. tinctorius, which may be developed as a drug for the treatment of lung injury.

Lung cancer is the most leading cause of cancer mortality throughout the world, of which about 85% cases comprise the non-small cell lung cancer (NSCLC). Estrogen and estrogen receptors are known to be involved in the pathogenesis and development of lung cancer. Dioscorea oppositifolia L. is a traditional Chinese medicine and a nutritious food, and can be an excellent candidate as an anti-cancer agent owing to its estrogen-like effects. However, the stems and leaves of D. oppositifolia L. are piled up in the field as a waste, causing environmental pollution and waste of resources. In the present study, a new diphenylethane (D1) was isolated from the stems and leaves of D. oppositifolia L. It was observed that D1 reduced the cell viability, migration, energy metabolism, and induced apoptosis in the A549 cells. Mechanistic studies showed that D1 reduced the STAT3 nuclear localization and downregulated the expression of the STAT3 target genes like Mcl-1, Bcl-xL and MMP-2 that are involved in the cell survival and mobility. Moreover, our results indicated that D1 exhibited estrogenic activities mediated by ERβ, and antagonising ERβ decreased the cytotoxic effect of D1 in A549 cells. In addition, inhibition of the nuclear translocation of STAT3 did not interfere with the binding of D1 and ERβ. However, after antagonizing ERβ, the nuclear translocation of STAT3 increased, thereby demonstrating that STAT3 was the downstream signaling molecule of ERβ. In conclusion, the D1 mediated anti-NSCLC in vitro effects or at least in part can be attributed to the ERβ-STAT3 signaling. Our findings suggest the role of D1 in treating NSCLC on a molecular level, and can help to improve the comprehensive utilization rate of D. oppositifolia L.