Rutaecarpine ameliorates imiquimod-induced psoriasis-like dermatitis in mice associated with alterations in the gut microbiota.

Psoriasis is accepted as a chronic, inflammatory, immune-mediated skin disease triggered by complex environmental and genetic factors. For a long time, disease recurrence, drug rejection, and high treatment costs have remained enormous challenges and burdens to patients and clinicians. Natural products with effective immunomodulatory and anti-inflammatory activities from medicinal plants have the potential to combat psoriasis and complications. Herein, an imiquimod (IMQ)-induced psoriasis-like dermatitis model is established in mice. The model mice are treated with 1% rutaecarpine (RUT) (external use) or the oral administration of RUT at different concentrations. Furthermore, high-throughput 16S rRNA gene sequencing is applied to analyze the changes in the diversity and composition of the gut microbiota. Based on the observation of mouse dorsal skin changes, RUT can protect against inflammation to improve psoriasis-like skin damage in mice. Additionally, RUT could suppress the expression levels of proinflammatory cytokines (IL-23, IL-17A, IL-22, IL-6, and IFN-α) within skin tissue samples. Concerning gut microbiota, we find obvious variations within the composition of gut microflora between IMQ-induced psoriasis mice and RUT-treated psoriasis mice. RUT effectively mediates the recovery of gut microbiota in mice induced by IMQ application. Psoriasis is linked to the production of several inflammatory cytokines and gut microbiome alterations. This research shows that RUT might restore gut microbiota homeostasis, reduce inflammatory cytokine production, and ameliorate psoriasis symptoms. In conclusion, the gut microbiota might be a therapeutic target or biomarker for psoriasis that aids in clinical diagnosis and therapy.

The effect of ultrasound-assisted thrombolysis studied in blood-on-a-chip.

BACKGROUND: Thromboembolism, which leads to pulmonary embolism and ischemic stroke, remains one of the main causes of death. Ultrasound-assisted thrombolysis (UAT) is an effective thrombolytic method. However, further studies are required to elucidate the mechanism of ultrasound on arterial and venous thrombi. METHODS: We employed the blood-on-a-chip technology to simulate thrombus formation in coronary stenosis and deep vein valves. Subsequently, UAT was conducted on the chip to assess the impact of ultrasound on thrombolysis under varying flow conditions. Real-time fluorescence was used to assess thrombolysis and drug penetration. Finally, scanning electron microscopy and immunofluorescence were used to determine the effect of ultrasound on fibrinolysis. RESULTS: The study revealed that UAT enhanced the thrombolytic rate by 40% in the coronary stenosis chip and by 10% in the deep venous valves chip. This enhancement is attributed to the disruption of crosslinked fibrin fibers by ultrasound, leading to increased urokinase diffusion within the thrombus and accumulation of plasminogen on the fibrinogen α chain. Moreover, the acceleration of the dissolution rate of thrombi in the venous valve chip by ultrasound was not as significant as that in the coronary stenosis chip. CONCLUSION: These findings highlight the differential impact of ultrasound on thrombolysis under various flow conditions and emphasize the valuable role of the blood-on-a-chip technology in exploring thrombolysis mechanisms.

Enabling High-Performance Layered Li-Rich Oxide Cathodes by Regulating the Formation of Integrated Cation-Disordered Domains.

Layered Li-rich oxide cathode materials are capable of offering high energy density due to their cumulative cationic and anionic redox mechanism during (de)lithiation process. However, the structural instability of the layered Li-rich oxide cathode materials, especially in the deeply delitiated state, results in severe capacity and voltage degradation. Considering the minimal isotropic structural evolution of disordered rock salt oxide cathode during cycling, cation-disordered nano-domains have been controllably introduced into layered Li-rich oxides by co-doping of d0-TM and alkali ions. Combining electrochemical and synchrotron-based advanced characterizations, the incorporation of the phase-compatible cation-disordered domains can not only hinder the oxygen framework collapse along the c axis of layered Li-rich cathode under high operation voltage but also promote the Mn and anionic activities as well as Li+ (de)intercalation kinetics, leading to remarkable improvement in rate capability and mitigation of capacity and voltage decay. With this unique layered/rocksalt intergrown structure, the intergrown cathode yields an ultrahigh capacity of 288.4 mAh g-1 at 0.1 C, and outstanding capacity retention of ≈90.0% with obviously suppressed voltage decay after 100 cycles at 0.5, 1, and 2 C rate. This work provides a new direction toward advanced cathode materials for next-generation Li-ion batteries.

Elimination of Random Mixed Noise in ECG Using Convolutional Denoising Autoencoder With Transformer Encoder.

Electrocardiogram (ECG) signals frequently encounter diverse types of noise, such as baseline wander (BW), electrode motion (EM) artifacts, muscle artifact (MA), and others. These noises often occur in combination during the actual data acquisition process, resulting in erroneous or perplexing interpretations for cardiologists. To suppress random mixed noise (RMN) in ECG with less distortion, we propose a Transformer-based Convolutional Denoising AutoEncoder model (TCDAE) in this study. The encoder of TCDAE is composed of three stacked gated convolutional layers and a Transformer encoder block with a point-wise multi-head self-attention module. To obtain minimal distortion in both time and frequency domains, we also propose a frequency weighted Huber loss function in training phase to better approximate the original signals. The TCDAE model is trained and tested on the QT Database (QTDB) and MIT-BIH Noise Stress Test Database (NSTDB), with the training data and testing data coming from different records. All the metrics perform the most robust in overall noise and separate noise intervals for RMN removal compared with the baseline methods. We also conduct generalization tests on the Icentia11k database where the TCDAE outperforms the state-of-the-art models, with a 55% reduction of the false positives in R peak detection after denoising. The TCDAE model approximates the short-term and long-term characteristics of ECG signals and has higher stability even under extreme RMN corruption. The memory consumption and inference speed of TCDAE are also feasible for its deployment in clinical applications.

How Society Anxiety Influences Attention Control in College Students: The Moderated Mediation Effect of Cognitive Flexibility and Resting-state Electroencephalography Activity.

Social anxiety is a prevalent issue among college students, adversely affecting their overall well-being. Drawing from the cognitive model of social anxiety and attention control theory, heightened levels of social anxiety may correspond to poorer attention control ability. However, little is known about the underlying cognitive mechanisms of the relationship between social anxiety and attention control. To address this research gap, the current study recruited a sample of 156 college students (56 women) who underwent self-report measures of social anxiety, cognitive flexibility, and attention control, followed by a resting-state EEG recording. The results revealed a significant negative predictive effect of social anxiety on attention control, with cognitive flexibility partially mediating this relationship. Furthermore, resting-state theta power emerged as a significant moderator, accentuating the negative impact of social anxiety on cognitive flexibility among individuals with lower theta power. In addition, frontal alpha asymmetry (FAA) demonstrated a moderating effect, with lower FAA intensifying the predictive influence of cognitive flexibility on attention control. Taken together, these results suggested that social anxiety can predict attention control either directly or indirectly via the mediating role of cognitive flexibility, and lower theta power and FAA has a risk amplification effect, which provide novel insights into the treatment and prevention of social anxiety and its negative impact on college students.

Dual-Frequency Ultrasound Assisted Thrombolysis in Interventional Therapy of Deep Vein Thrombosis.

Deep vein thrombosis (DVT) is one of the main causes of disability and death worldwide. Currently, the treatment of DVT still needs a long time and faces a high risk of major bleeding. It is necessary to find a rapid and safe method for the therapy of DVT. Here, a dual-frequency ultrasound assisted thrombolysis (DF-UAT) is reported for the interventional treatment of DVT. A series of piezoelectric elements are placed in an interventional catheter to emit ultrasound waves with two independent frequencies in turn. The low-frequency ultrasound drives the drug-loaded droplets into the thrombus, while the high-frequency ultrasound causes the cavitation of the droplets in the thrombus. With the joint effect of the enhanced drug diffusion and the cavitation under the dual-frequency ultrasound, the thrombolytic efficacy can be improved. In a proof-of-concept experiment performed with living sheep, the recanalization of the iliac vein is realized in 15 min using the DF-UAT technology. Therefore, the DF-UAT can be one of the most promising methods in the interventional treatment of DVT.

Reusable Zwitterionic Porous Organic Polymers for Bilirubin Removal in Serum.

Herein, we report a straightforward strategy to construct reusable, hemocompatible, and highly efficient bilirubin adsorbents by installing zwitterionic modules into a porous organic polymer (POP) for hemoperfusion application. Three types of zwitterions with different amounts are used to evaluate their impacts on the characteristics of POPs, including carboxybetaine methacrylate (CB), sulfobetaine methacrylate (SB), and 2-methacryloyloxyethyl phosphorylcholine (MPC). Results show that zwitterions can improve hemocompatibility, hydrophilicity, and bilirubin uptake of the POP. Among all zwitterionic POPs, POP-CB-40% exhibits the best bilirubin uptake, ∼46.5 times enhancement compared with the non-zwitterionic POP in 100% serum. This enhancement can be attributed to the improved hydrophilicity and protein resistance ability in biological solutions. More importantly, the reusability test shows that POP-CB-40% maintains ∼99% of bilirubin uptake capacity at fifth recycling in 100% serum. Findings in this work provide a guideline for the design of biocompatible and efficient POP-based bilirubin adsorbents for hemoperfusion therapy.

Enhanced Anticoagulation of Hierarchy Liquid Infused Surfaces in Blood Flow.

Liquid infused surfaces (LIS) hold remarkable potential in anticoagulation. However, liquid loss of LIS in the bloodstream remains a challenge toward its clinical application. Here, micronano hierarchy structures are obtained on the titanium alloy substrate by regulating the microspheres' distribution. When the gap between the microspheres is smaller than the diameter of the red blood cell (RBC), the LIS is more stable under the blood wash and presents a better anticoagulation performance. The proper interval is found to prevent the RBCs from entering the gap and remove the liquid on the surface. The retained thickness of the liquid film is measured by the atomic force microscopy (AFM) technique. The LIS is applied on the front guide vane of an artificial heart pump and exhibits significant improvement on anticoagulation in the blood circulation in vitro for 25 h. The techniques and findings can be used to optimize the anticoagulation performance of LIS-related biomedical implant devices.

Fucosyltransferase 5 Promotes the Proliferative and Migratory Properties of Intrahepatic Cholangiocarcinoma Cells via Regulating Protein Glycosylation Profiles.

Background: The incidence of intrahepatic cholangiocarcinoma (ICC) is increasing globally, and its prognosis has not improved substantially in recent years. Understanding the pathogenesis of ICC may provide a theoretical basis for its treatment. In this study, we investigated the effects and underlying mechanisms of fucosyltransferase 5 (FUT5) on the malignant progression of ICC. Methods: FUT5 expression in ICC samples and adjacent nontumor tissues was compared using quantitative real-time polymerase chain reaction and immunohistochemical assays. We performed cell counting kit-8, colony formation, and migration assays to determine whether FUT5 influenced the proliferation and mobility of ICC cells. Finally, mass spectrometry was performed to identify the glycoproteins regulated by FUT5. Results: FUT5 mRNA was significantly upregulated in most ICC samples compared with corresponding adjacent nontumor tissues. The ectopic expression of FUT5 promoted the proliferation and migration of ICC cells, whereas FUT5 knockdown significantly suppressed these cellular properties. Mechanistically, we demonstrated that FUT5 is essential for the synthesis and glycosylation of several proteins, including versican, ß3 integrin, and cystatin 7, which may serve key roles in the precancer effects of FUT5. Conclusions: FUT5 is upregulated in ICC and promotes ICC development by promoting glycosylation of several proteins. Therefore, FUT5 may serve as a therapeutic target for the treatment of ICC.

Performance improvement of GaN-based microdisk lasers by using a PEALD-SiO2 passivation layer.

Dry-etching is often utilized to shape GaN-based materials. However, it inevitably causes plenty of sidewall defects as non-radiative recombination centers and charge traps that deteriorate GaN-based device performance. In this study, the effects of dielectric films deposited by plasma-enhanced atomic layer deposition (PEALD) and plasma-enhanced chemical vapor deposition (PECVD) on GaN-based microdisk laser performance were both investigated. The results demonstrated that the PEALD-SiO2 passivation layer largely reduced the trap-state density and increased the non-radiative recombination lifetime, thus leading to the significantly decreased threshold current, notably enhanced luminescence efficiency and smaller size dependence of GaN-based microdisk lasers as compared with the PECVD-Si3N4 passivation layer.

Harmonic and DC Bias Hysteresis Characteristics Simulation Based on an Improved Preisach Model.

Transformers, reactors and other electrical equipment often work under harmonics and DC-bias working conditions. It is necessary to quickly and accurately simulate the hysteresis characteristics of soft magnetic materials under various excitation conditions in order to achieve accurate calculations of core loss and the optimal design of electrical equipment. Based on Preisach hysteresis model, a parameter identification method for asymmetric hysteresis loop simulation is designed and applied to the simulation of hysteresis characteristics under bias conditions of oriented silicon steel sheets. In this paper, the limiting hysteresis loops of oriented silicon steel sheets are obtained through experiments under different working conditions. The first-order reversal curves(FORCs) with asymmetric characteristics is generated numerically, and then the Everett function is established under different DC bias conditions. The hysteresis characteristics of the oriented silicon steel sheets under harmonics and DC bias are simulated by improving FORCs identification method of the Preisach model. By comparing the results of simulation and experiment, the effectiveness of the proposed method is verified, so as to provide an important reference for material production and application.

Wall shear gradient dependent thrombosis studied in blood-on-a-chip with stenotic, branched, and valvular constructions.

Thrombosis is the leading cause of death, while the effect of the shear flow on the formation of thrombus in vascular constructions has not been thoroughly understood, and one of the challenges is to observe the origination of thrombus with a controlled flow field. In this work, we use blood-on-a-chip technology to mimic the flow conditions in coronary artery stenosis, neonatal aortic arch, and deep venous valve. The flow field is measured by the microparticle image velocimeter (µPIV). In the experiment, we find that the thrombus often originates at the constructions of stenosis, bifurcation, and the entrance of valve, where the flow stream lines change suddenly, and the maximum wall shear rate gradient appears. Using the blood-on-a-chip technology, the effect of the wall shear rate gradients on the formation of the thrombus has been illustrated, and the blood-on-a-chip is demonstrated to be a perspective tool for further studies on the flow-induced formation of thrombosis.

Diagnosis of atrial fibrillation using self-complementary attentional convolutional neural network.

BACKGROUND AND OBJECTIVE: Automatic recognition of wearable dynamic electrocardiographic (ECG) signals is a difficult problem in biomedical signal processing. However, with the widespread use of long-range ambulatory ECG, a large number of real-time ECG signals are generated in the clinic, and it is very difficult for clinicians to perform timely atrial fibrillation (AF) diagnosis. Therefore, developing a new AF diagnosis algorithm can relieve the pressure on the healthcare system and improve the efficiency of AF screening. METHODS: In this study, a self-complementary attentional convolutional neural network (SCCNN) was designed to accurately identify AF in wearable dynamic ECG signals. First, a 1D ECG signal was converted into a 2D ECG matrix using the proposed Z-shaped signal reconstruction method. Then, a 2D convolutional network was used to extract shallow information from adjacent sampling points at close distances and interval sampling points at distant distances in the ECG signal. The self-complementary attention mechanism (SCNet) was used to focus and fuse channel information with spatial information. Finally, fused feature sequences were used to detect AF. RESULTS: The accuracies of the proposed method on the three public databases were 99.79%, 95.51%, and 98.80%. The AUC values were 99.79%, 95.51%, and 98.77%, respectively. The sensitivity on the clinical database was as high as 99.62%. CONCLUSIONS: These results show that the proposed method can accurately identify AF and has good generalization.

Measurement and Simulation of Magnetic Properties of Nanocrystalline Alloys under High-Frequency Pulse Excitation.

In order to broaden the application of nanocrystalline soft magnetic materials in electrical engineering under extreme conditions, nanocrystalline alloys must also have good characteristics under high-frequency and nonsinusoidal excitation. In this paper, the magnetic properties of Fe-based nanocrystalline alloys excited by high repetition frequency pulses were measured. Excitation frequency and duty cycles are two important factors in the study of magnetic properties under pulse excitation. With the amplitude of the pulse remaining constant, different local hysteresis curves were obtained by changing the frequency and duty cycle. The experimental results proved that the higher the frequency is and the smaller the duty cycle is, the narrower the local hysteresis loop is. Finally, the finite element method (FEM) was used to model the magnetic core coupling with an impulse circuit based on the measured magnetic properties. Compared with the experimental results, the simulation results showed that the field-circuit coupling analysis model can effectively reflect the influence law of the frequency and duty cycle on magnetic properties.

Contextual Relevance of Sustainable Supply Chain: Recycling, Philanthropy, or Both?

Many firms have already been actively or passively involved in sustainable supply chain management with the objective of improving the triple bottom line (TBL). But whether the limited funds should be allocated to both community responsibility activities (e.g., corporate philanthropy) and environmental protection activities (e.g., recycling) is a confusing question. This paper provides deep insights into the combination strategy of two corporate social responsibility (CSR) types in a two-tier sustainable supply chain by modeling analysis. The decision models in eight scenarios with different combinations of CSR types are proposed and applied for the determination of equilibrium scenarios. The paper's findings highlight: under certain conditions, (1) the supply chain with two types of CSR is the equilibrium scenario and improves the TBL; (2) counter-intuitively, balancing short- and long-term benefits, firms are more willing to cooperate with partners with relatively low consumers sensitivity of CSR activities; (3) it is wise for the manufacturer to allocate more funding to environmental responsibility than to community responsibility. In addition, considering both short- and long-term benefits, comparing with the manufacturer, the retailer has a stronger incentive to improve recycling efficiency.

Cybervictimization and nonsuicidal self-injury: The mediating role of depressive symptoms and the moderating role of emotional reactivity.

BACKGROUND: Nonsuicidal self-injury (NSSI) has garnered growing attention in recent years, and cybervictimization (CV) has been identified as a risk factor for NSSI among adolescents. However, little is known about this association's longitudinal mediating and moderating mechanisms. Guided by the experiential avoidance model, the present study used a short longitudinal design to examine the mediating role of depressive symptoms and the moderating role of emotional reactivity between CV and NSSI. METHODS: A total of 577 Chinese middle school students (Mage = 14.38, SD = 0.67) completed the measures of CV, NSSI, depressive symptoms, and emotional reactivity. They provided data in two waves (T1 and T2, 6 months apart). RESULTS: The results found a longitudinal association between CV and NSSI as well as the mediating role of depressive symptoms. Moreover, emotional reactivity amplified the relationship between CV and NSSI via depressive symptoms; specifically, the relationship between depressive symptoms and NSSI was only significant for adolescents with high emotional reactivity. CONCLUSION: The current study has found that emotional reactivity moderated the indirect effect of depressive symptoms on the relationship between CV and NSSI. These findings have implications for the identification and intervention of NSSI in early adolescents.

Cybervictimization and non-suicidal self-injury among Chinese adolescents: A longitudinal moderated mediation model.

BACKGROUND: Cybervictimization is a risk factor for nonsuicidal self-injury (NSSI). However, there is a lack of evidence on how and under what conditions cybervictimization may influence NSSI. The present study investigated the mediating effect of self-esteem and the moderating effect of peer attachment on the relationship between cybervictimization and NSSI among Chinese adolescents. METHODS: Using three-wave longitudinal data for one year, a total of 1368 Chinese adolescents (60 % boys; Mage at Wave 1 = 15.05 years, SD = 0.85) completed the measurement using a self-report method. RESULTS: The longitudinal moderated mediation model revealed that cybervictimization is associated with NSSI via restraining the protective effect of self-esteem. Moreover, high peer attachment could buffer the negative effects of cybervictimization, and protect their self-esteem from being hurt, consequently reducing the likelihood of NSSI. LIMITATIONS: All variables in this study were self-reported, and the results should be cautiously generalized to other cultures, according to a sample of Chinese adolescents. CONCLUSIONS: Results highlight the relation between cybervictimization and NSSI. Recommended intervention and prevention strategies include enhancing the self-esteem of adolescents, breaking the cycle of cybervictimization to NSSI, and providing adolescents with more opportunities to build positive friendships with their peers to buffer the negative effects of cybervictimization.

Artificial Intelligence-Based Psoriasis Severity Assessment: Real-world Study and Application.

BACKGROUND: Psoriasis is one of the most frequent inflammatory skin conditions and could be treated via tele-dermatology, provided that the current lack of reliable tools for objective severity assessments is overcome. Psoriasis Area and Severity Index (PASI) has a prominent level of subjectivity and is rarely used in real practice, although it is the most widely accepted metric for measuring psoriasis severity currently. OBJECTIVE: This study aimed to develop an image-artificial intelligence (AI)-based validated system for severity assessment with the explicit intention of facilitating long-term management of patients with psoriasis. METHODS: A deep learning system was trained to estimate the PASI score by using 14,096 images from 2367 patients with psoriasis. We used 1962 patients from January 2015 to April 2021 to train the model and the other 405 patients from May 2021 to July 2021 to validate it. A multiview feature enhancement block was designed to combine vision features from different perspectives to better simulate the visual diagnostic method in clinical practice. A classification header along with a regression header was simultaneously applied to generate PASI scores, and an extra cross-teacher header after these 2 headers was designed to revise their output. The mean average error (MAE) was used as the metric to evaluate the accuracy of the predicted PASI score. By making the model minimize the MAE value, the model becomes closer to the target value. Then, the proposed model was compared with 43 experienced dermatologists. Finally, the proposed model was deployed into an app named SkinTeller on the WeChat platform. RESULTS: The proposed image-AI-based PASI-estimating model outperformed the average performance of 43 experienced dermatologists with a 33.2% performance gain in the overall PASI score. The model achieved the smallest MAE of 2.05 at 3 input images by the ablation experiment. In other words, for the task of psoriasis severity assessment, the severity score predicted by our model was close to the PASI score diagnosed by experienced dermatologists. The SkinTeller app has been used 3369 times for PASI scoring in 1497 patients from 18 hospitals, and its excellent performance was confirmed by a feedback survey of 43 dermatologist users. CONCLUSIONS: An image-AI-based psoriasis severity assessment model has been proposed to automatically calculate PASI scores in an efficient, objective, and accurate manner. The SkinTeller app may be a promising alternative for dermatologists' accurate assessment in the real world and chronic disease self-management in patients with psoriasis.

Nanodroplet-Coated Microbubbles Used in Sonothrombolysis with Two-Step Cavitation Strategy.

Thrombosis is a major cause of morbidity and mortality and sonothrombolysis is a promising method for its treatment. However, the slow diffusion of the thrombolytic agents into the thrombus results in slow recanalization. Here, nanodroplet-coated microbubbles (NCMBs) are designed and fabricated and a two-step cavitation strategy is used to accelerate the thrombolysis. The first cavitation of the NCMBs, cavitation and collapse of the microbubbles induced by low frequency ultrasound, drives the nanodroplets on the shell into the thrombus, while the second cavitation, the phase-change and volume expansion of drug-loaded nanodroplets triggered by high frequency ultrasound, loosens the thrombus by the sono-porosity effect. This two-step cavitation of the NCMBs is verified using a fibrin agarose model, where a rapid diffusion of the thrombolytic agents is observed. Furthermore, the NCMBs reach much higher thrombolysis efficiency in both in vitro and proof-of-concept experiments performed with living mice. The nanodroplet-coated microbubbles are a promising diffusion medicines carrier for efficient drug delivery.

Fatigue of red blood cells under periodic squeezes in ECMO.

Hemolysis usually happens instantly when red blood cells (RBCs) rupture under a high shear stress. However, it is also found to happen gradually in the extracorporeal membrane oxygenation (ECMO) under low but periodic squeezes. In particular, the gradual hemolysis is accompanied by a progressive change in morphology of RBCs. In this work, the gradual hemolysis is studied in a microfluidic device with arrays of narrow gaps the same as the constructions in ECMO. RBCs are seen to deform periodically when they flow through the narrow gaps, which causes the release of adenosine-triphosphate (ATP) from RBCs. The reduced ATP level in the cells leads to the fatigue of RBCs with the progressive changes in morphology and the gradual loss of deformability. An empirical model for the fatigue of RBCs is established under the periodic squeezes with controlled deformation, and it reveals a different way of the hemolysis that is dominated by the squeeze frequency. This finding brings a new insight into the mechanism of hemolysis, and it helps to improve the design of circulatory support devices.