Identification of potential diagnostic biomarkers for hypertension via integrated analysis of gene expression and DNA methylation.

OBJECTIVE: Hypertension refers to the elevated blood pressure (BP) in arteries, with a BP reading of 140/90 mm Hg or higher in adults. Over 40% of >25-year-old population have suffered from hypertension. Thus, this study aimed to find novel diagnostic biomarkers for hypertension. METHODS: All hypertension-related mRNA and methylation datasets were downloaded from the GEO database. Liner model method was used to identify differentially expressed genes (DEGs) between hypertension and control groups. Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes enrichment analysis was employed to obtain functional information. CpG sites and the corresponding genes associated with hypertension were screened using epigenome-wide association study (EWAS) analysis. RESULTS: There were 37 DEGs between the hypertension group and control group, which were significantly enriched in 84 Biological Process terms, 31 Cellular Component terms, 18 Molecular Function terms and 9 signalling pathways. EWAS results indicated that 1072 CpG sites were associated with hypertension occurrence, corresponding to 1029 genes. After cross-analysis, complement factor D (CFD) and OTU deubiquitinase, ubiquitin aldehyde binding 2 (OTUB2) with methylation modification were identified as diagnostic markers for hypertension. CONCLUSION: In conclusion, CFD and OTUB2 were potential biomarkers of hypertension occurrence. Our results will provide more information for hypertension diagnosis and would be more reliable combined with multiple biomarkers.

In the GSE24752 dataset, there were 37 differentially expressed genes between the hypertension group and the normal group.In the GSE42774 dataset, there were 1072 CpG sites, corresponding to 1029 genes, associated with hypertension occurrence.CFD and OTUB2 were potential biomarkers that were associated with hypertension occurrence.

Internet + wearable device training effects on limb function recovery and serum neurocytokine content in stroke patients.

BACKGROUND: The traditional method of post-hospital intervention and guidance of stroke patients has some limitations. OBJECTIVE: To investigate the effects of Internet + wearable device training on limb function recovery and the levels of serum neurocytokines (BDNF, NT-3, and NGF) in stroke patients. METHODS: 80 stroke patients with hemiplegia were randomly selected from the Department of Neurorehabilitation, Affiliated Rehabilitation Hospital of Chongqing Medical University. They were divided into a control group and an observation group, with 40 patients in each group. The control group received routine post-hospital follow-up guidance, while the observation group received Internet remote home rehabilitation guidance combined with wearable device training. The interventions were compared between the two groups. RESULTS: At 4 weeks and 12 weeks after discharge, the observation group showed higher scores on the Fugl-Meyer scale (FMA), Berg Balance Scale (BBS), modified Barthel Index (MBI), stride length, gait speed, gait frequency, and higher levels of BDNF, NT-3, and NGF. Additionally, the observation group had lower scores on the Hamilton Anxiety and Depression Scale (HADS) (P < 0.05). CONCLUSIONS: The application of Internet remote home rehabilitation guidance combined with wearable device training in stroke patients with hemiplegia can improve limb function recovery. It effectively increases the levels of BDNF, NT-3, and NGF, promoting the nutritional repair of damaged nerves. These findings hold clinical significance.

Microinvasive intrascleral double continuous suture repair surgery for cyclodialysis clefts.

BACKGROUND: The traditional suturing method for cyclodialysis cleft usually requires an incision in the sclera for direct suturing, resulting in greater damage and a high risk of postoperative complications. The purpose of this work is to propose a newly intrascleral double continuous suture repair technique for the treatment of cyclodialysis clefts. METHODS: Seven patients with cyclodialysis cleft underwent microinvasive intrascleral double continuous suture repair surgery to restore the attachment of the detached ciliary body to the sclera without scleral incision. All operations were performed by the same surgeon. Preoperative and postoperative visual acuity (VA), intraocular pressure (IOP), slit lamp and corneal examination results, ultrasound biomicroscopy (UBM) and optical coherence tomography (OCT) results were recorded. RESULTS: Closure of the cyclodialysis cleft was achieved in 7 eyes and no obvious complications occurred after the operation. Intraocular pressure increased from preoperatively 6.8 ± 1.35 mmHg (range: 4.8-8.0 mmHg) to postoperatively 12.5 ± 4.0 mmHg (range: 8.0-20.0 mmHg) (paired sample T test, P < 0.01). Best-corrected Snellen visual acuity improved from preoperatively range 20/2000-20/63 to range 20/200-20/25 at final follow-up. CONCLUSION: In short, intrascleral double continuous suture repair surgical is safe and effective in treating cyclodialysis cleft, with minimal surgical trauma.

RHOF activation of AKT/ß-catenin signaling pathway drives acute myeloid leukemia progression and chemotherapy resistance.

Acute myeloid leukemia (AML) is a clonal malignancy originating from leukemia stem cells, characterized by a poor prognosis, underscoring the necessity for novel therapeutic targets and treatment methodologies. This study focuses on Ras homolog family member F, filopodia associated (RHOF), a Rho guanosine triphosphatase (GTPase) family member. We found that RHOF is overexpressed in AML, correlating with an adverse prognosis. Our gain- and loss-of-function experiments revealed that RHOF overexpression enhances proliferation and impedes apoptosis in AML cells in vitro. Conversely, genetic suppression of RHOF markedly reduced the leukemia burden in a human AML xenograft mouse model. Furthermore, we investigated the synergistic effect of RHOF downregulation and chemotherapy, demonstrating significant therapeutic efficacy in vivo. Mechanistically, RHOF activates the AKT/ß-catenin signaling pathway, thereby accelerating the progression of AML. Our findings elucidate the pivotal role of RHOF in AML pathogenesis and propose RHOF inhibition as a promising therapeutic approach for AML management.

Early-Stage Protein Adsorption Sequence on Blood-Contacting Surfaces: Answer to Vroman's Question.

Plasma protein adsorption on blood-contacting surfaces is the initiating significant event and modulates the subsequent coagulation response. Despite decades of research in this area, Vroman's questions in 1986 "Who gets there first?" and "When does the next protein arrive?" remain unanswered due to the lack of detection techniques with sufficient temporal resolution. In this work, we develop a droplet microfluidic technology to detect protein adsorption sequences on six typical blood-contacting surfaces in milliseconds. Apolipoproteins (Apo) are found to be the first proteins to adsorb onto the surfaces in a plasma droplet, and the specific type of apolipoprotein depends on the surface. Apo CI is the first protein adsorbed on gold, platinum, graphene, stainless steel, and polyvinyl chloride with the adsorption time varying from 0.01 to 1 s, while Apo CIII preferentially reaches the titanium alloy surface within 1 s. Subsequent to the initial adsorption, Apo AI, AII, and other proteins continue to adsorb until albumin arrives. Thus, the adsorption sequence is revealed, and Vroman's questions are answered. Moreover, this finding demonstrates the influence of the initial protein adsorption on subsequent coagulation at the surface, and it offers new insights into the development of anticoagulant surfaces.

Interventional Removal of Travelling Microthrombi Using Targeted Magnetic Microbubble.

Microthrombus is one of the major causes of the sequelae of Corona Virus Disease 2019 (COVID-19 and leads to subsequent embolism and necrosis. Due to their small size and irregular movements, the early detection and efficient removal of microthrombi in vivo remain a great challenge. In this work, an interventional method is developed to identify and remove the traveling microthrombi using targeted-magnetic-microbubbles (TMMBs) and an interventional magnetic catheter. The thrombus-targeted drugs are coated on the TMMBs and magnetic nanoparticles are shelled inside, which allow not only targeted adhesion onto the traveling microthrombi, but also the effective capture by the magnetic catheter in the vessel. In the proof-of-concept experiments in the rat models, the concentration of microthrombus is reduced by more than 60% in 3 min, without damaging the organs. It is a promising method for treating microthrombus issues.

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.

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.

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.

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.

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.