In situ measurement of the three-dimensional distribution of labile copper in sediment pore water using a microneedle sensor with nanoporous structure.

Conventional ex situ analytical methods for sediment pore water are susceptible to disruptions in the speciation equilibrium of metals due to changes in external conditions. This study introduced an innovative in situ method for detecting the three-dimensional distribution of labile copper (CuLabile) in sediment pore water with high spatial resolution using a highly stable microneedle electrochemical sensor. The sensor featured a nanoporous tip structure and embedded gold nanomaterials with excellent electrocatalytic performance. The nanoporous structure could prevent the nanomaterials from falling off because of friction during the in situ detection process in sediments. The sensor exhibited good detection performance under different salinity conditions with a detection limit of 0.2 nM. Vertical and three-dimensional distributions of CuLabile in sediment pore water were successfully obtained using the in situ microneedle sensor. The results showed that the concentration of CuLabile was in the range of 5.2-43.5 nM, with a maximum value at a depth of approximately 4 cm, while there was almost no difference in the horizontal direction of a specific sediment sample column. Furthermore, this functional sensor could be extended to the in situ detection of other labile metals in sediment pore water.

The association between ambient air pollution and colorectal cancer: a Mendelian randomization study.

Mounting epidemiology studies have reported the potential associations between ambient air pollution exposure and colorectal cancer (CRC). However, the genetic association between ambient air pollution and CRC remains unclear. Using the Genome-wide association study (GWAS) data from UK biobank, we explored the genetic association of CRC (5,657 cases and 372,016 controls) with four ambient air pollutants (PM2.5, PM10, NO2, NOx; n = 423,796 to 456,380) under the framework of Mendelian randomization (MR). Our results revealed a significant association between long-term NO2 exposure (per 10 µg/m3) and increased CRC risk, with an odds ratio (OR) of 1.02 (95% confidence interval [CI]: 1.00-1.03), while no statistical association was found between CRC risk and the other air pollutants. Sensitivity analysis confirmed the robustness of the results. It is imperative to consider the impact of air pollution, particularly NO2, in mitigating the risk of CRC.

Effective binning of metagenomic contigs using contrastive multi-view representation learning.

Contig binning plays a crucial role in metagenomic data analysis by grouping contigs from the same or closely related genomes. However, existing binning methods face challenges in practical applications due to the diversity of data types and the difficulties in efficiently integrating heterogeneous information. Here, we introduce COMEBin, a binning method based on contrastive multi-view representation learning. COMEBin utilizes data augmentation to generate multiple fragments (views) of each contig and obtains high-quality embeddings of heterogeneous features (sequence coverage and k-mer distribution) through contrastive learning. Experimental results on multiple simulated and real datasets demonstrate that COMEBin outperforms state-of-the-art binning methods, particularly in recovering near-complete genomes from real environmental samples. COMEBin outperforms other binning methods remarkably when integrated into metagenomic analysis pipelines, including the recovery of potentially pathogenic antibiotic-resistant bacteria (PARB) and moderate or higher quality bins containing potential biosynthetic gene clusters (BGCs).

Field determination and ecological health risk assessment of trace metals in typical mariculture area of China.

Field determination of dissolved trace metals (Cu, Pb and Cd) by using automated electrochemical system had been done in three typical mariculture areas of Yellow Sea (YS), East China Sea (ECS) and South China Sea (SCS) in China. Higher concentrations of Cu and Pb were found in ECS while the Cd concentration showed a decreasing trend from north to south of China. The metal distribution and ecological health risk assessments were also conducted. Cu and Pb in the YS and Cu in SCS were moderately contaminated. ECS had considerable Cu contamination and very high Pb contamination. Compared with other coastal areas, mariculture affected the concentration and spatial distribution of trace metals, but it was not a necessarily dominant factor. Overall, the results contribute to the further development of field and on-board metal detection technology and lay a foundation for the realization of field ecological health risk assessments of mariculture waters.

Viologen Guest-Mediated Luminescence Emission Tuning and Photochromic Behavior by a Series of Viologen@Zn-MOF Materials.

The encapsulation of various guest molecules into the pores of metal-organic frameworks (MOFs) to form hybrid materials has attracted significant attention due to their unique spatial distribution and certain preferential geometry of the guests inside the MOFs. This arrangement often results in the guests exhibiting unique physical and chemical properties due to their intramolecular interactions with the host. In this article, five viologen derivatives were introduced as guests in a Zn-MOF with different benzene ring lengths, resulting in the formation of host-guest three-dimensional (3D) MOFs. The five compounds exhibited guest-dependent emission wavelength, color, and excellent photochromic behavior upon ultraviolet (UV) light radiation due to the distinct electronic transfer and π···π stacking interactions between the viologen guests and the host framework. This study provides a host-guest strategy for designing color-tunable luminescent and highly sensitive photochromic materials.

A Reliable Low-Latency Multipath Routing Algorithm for Urban Rail Transit Ad Hoc Networks.

With the advancement of urban rail transit towards intelligence, the demand for urban rail transit communication has increased significantly, but the traditional urban rail transit vehicle-ground communication system has been unable to meet the future vehicle-ground communication requirements. To improve the performance of vehicle-ground communication, the paper proposes a reliable low-latency multipath routing (RLLMR) algorithm for urban rail transit ad hoc networks. First, RLLMR combines the characteristics of urban rail transit ad hoc networks and uses node location information to configure a proactive multipath to reduce route discovery delay. Second, the number of transmission paths is adaptively adjusted according to the quality of service (QoS) requirements for vehicle-ground communication, and then the optimal path is selected based on the link cost function to improve transmission quality. Third, in order to enhance the reliability of communication, a routing maintenance scheme has been added, and the static node-based local repair scheme is used in routing maintenance to reduce the maintenance cost and time. The simulation results show that compared with traditional AODV and AOMDV protocols, the proposed RLLMR algorithm has good performance in improving latency and is slightly inferior to the AOMDV protocol in improving reliability. However, overall, the throughput of the RLLMR algorithm is better than that of the AOMDV.

Deep Vein Thrombosis Is Facilitated by Endothelial-Derived Extracellular Vesicles via the PDI-GRP94-GPIIb/IIIa Pathway in Mice.

AIMS: Deep vein thrombosis (DVT) is a prevalent cardiovascular condition. Endothelial-derived extracellular vesicles (EVs) may play a crucial role in platelet-dependent DVT development via platelet activation, but the mechanism is not clear yet. This research aims to understand how platelets and endothelial-derived EVs work in DVT. METHODS: The interaction between protein disulfide isomerase (PDI) and glucose-regulated protein 94 (GRP94) was founded by molecular docking. Inferior vena cava stasis-induced mice received PDI and GRP94 inhibitor treatments. Platelet activation, endothelial-derived EVs, and PDI were measured using flow cytometry. The expression of PDI and dimetric GRP94 in platelets co-cultured with hypoxic endothelial cells was confirmed by Western blot or native PAGE. The fluorescence resonance energy transfer assay shows conformational changes in GPIIb/IIIa on platelet surfaces. A tracking experiment was performed using PKH26, which labelled endothelial-derived EVs, and the endocytosis of EVs by platelets was tracked by confocal microscope. RESULTS: In a DVT mouse model, platelets enhance venous thrombus formation in a coagulation-independent manner, instead, platelet activation and the length of the thrombus are related to PDI and GRP94 activity. Next, we found that the expression level of endothelial-derived EVs carrying PDI is significantly increased in plasma. Endothelial-derived EVs carrying PDI are endocytosed by platelets, in which the content of GRP94 dimer is elevated, and consequently increases the expression of surface GPIIb/IIIa. In addition, PDI allosterically interacts with GPIIb/IIIa, which is re-configurated into an activated form. CONCLUSION: Endothelial-derived EVs carrying PDI induce DVT via interplay with GRP94 and GPIIb/IIIa in platelets. These findings emphasize the significance of platelets in DVT formation, and PDI may be a suitable target in DVT prevention.

Stimulation of soluble guanylate cyclase by vericiguat reduces skeletal muscle atrophy of mice following chemotherapy.

Background: The chemotherapeutic doxorubicin (DOX) promotes severe skeletal muscle atrophy, which induces skeletal muscle weakness and fatigue. Soluble guanylate cyclase (sGC) contributes to a variety of pathophysiological processes, but whether it is involved in DOX-induced skeletal muscle atrophy is unclear. The present study aimed to stimulate sGC by vericiguat, a new oral sGC stimulator, to test its role in this process. Methods: Mice were randomly divided into four groups: control group, vericiguat group, DOX group, and DOX + vericiguat group. Exercise capacity was evaluated before the mice were sacrificed. Skeletal muscle atrophy was assessed by histopathological and molecular biological methods. Protein synthesis and degradation were monitored in mice and C2C12 cells. Results: In this study, a significant decrease in exercise capacity and cross-sectional area (CSA) of skeletal muscle fibers was found in mice following DOX treatment. Furthermore, DOX decreased sGC activity in mice and C2C12 cells, and a positive correlation was found between sGC activity and CSA of skeletal muscle fibers in skeletal muscle. DOX treatment also impaired protein synthesis, shown by puromycin detection, and activated ubiquitin-proteasome pathway. Following sGC stimulation, the CSA of muscle fibers was elevated, and exercise capacity was enhanced. Stimulation of sGC also increased protein synthesis and decreased ubiquitin-proteasome pathway. In terms of the underlying mechanisms, AKT/mTOR and FoxO1 pathways were impaired following DOX treatment, and stimulation of sGC restored the blunted pathways. Conclusion: These results unravel sGC stimulation can improve skeletal muscle atrophy and increase the exercise capacity of mice in response to DOX treatment by enhancing protein synthesis and inhibiting protein degradation. Stimulation of sGC may be a potential treatment of DOX-induced skeletal muscle dysfunction.

Progression of bilateral morning glory syndrome associated with unilateral persistent fetal vasculture: A case report of long term follow-up in an infant.

PURPOSE: To describe a case of Bilateral Morning Glory Syndrome (MGS) associated with Unilateral Persistent Fetal Vasculature (PFV) in a 3-day old neonate. OBSERVATIONS: A 3-day-old neonate was found bilateral retinal abnormalities due to neonatal eye screening. Dilated fundus exam showed bilateral optic disc dysplasia with the persistent hyaloid vessels in right eye at first. With the progress of the disease, optic disc was enlarged with central umbilication which with a similar anomalous radiating peripapillary vascular appearance, the persistent hyaloid vessels in vitreous cavity of right eye gradually disappear, a large amount of exudation can be seen in the posterior pole retina with macular movement in both eyes. Bilateral vitrectomy was performed in this case, then the condition of the neonate's both eyes is stable until 1 year old. CONCLUSIONS AND IMPORTANCE: This is a rare case that showing the development of MGS and PFV and the relationship between these two diseases. In addition, we completely observed the whole process of the change of the persistent hyaloid vessels in the vitreous cavity of a case of MGS associated with PFV.

Circulating miR-143 and miR-145 as promising biomarkers for evaluating severity of coronary artery stenosis in patients with acute coronary syndrome.

BACKGROUND: Multiple studies have provided evidence that miR-143 and miR-145 play a crucial role in the pathogenesis and progression of atherosclerosis. In the present study, we aim to investigate the expression of plasma miR-143 and miR-145 in patients with acute coronary syndrome (ACS) and their association with the severity of coronary artery stenosis. METHODS: The study enrolled 279 patients with ACS, including 201 patients with unstable angina (UA) and 78 patients with acute myocardial infarction (AMI), and 65 matched subjects as the control group. The plasma levels of miR-143 and miR-145 were detected by quantitative real-time PCR (qRT-PCR). Gensini score was applied to evaluate the severity of coronary artery stenosis. RESULTS: Plasma levels of miR-143 and miR-145 in patients with ACS were both decreased compared with the control group (p < 0.001). Plasma levels of miR-143 and miR-145 were negatively correlated with Gensini score (miR-143: r = -0.246, p < 0.001; miR-145: r = -0.222, p < 0.001). Logistic regression analysis showed that miR-143 and miR-145 were protective factors for the onset of ACS, UA, or AMI separately. MiR-143 (AUC: 0.786, p < 0.001) and miR-145 (AUC: 0.793, p < 0.001) were able to predict the degree of coronary artery stenosis greater than 50 %. CONCLUSION: The plasma levels of miR-143 and miR-145 were significantly decreased in ACS patients and were negatively correlated with coronary stenosis. In conclusion, plasma miR-143 and miR-145 levels can be used as noninvasive biomarkers for evaluating coronary artery stenosis.

An antifouling gel-protected iridium needle sensor: Long-term, on-site monitoring of copper in seawater.

Copper (Cu), a natural micronutrient with ecotoxicological significance, is involved in the carbon and nitrogen cycles occurring in marine ecosystems. Here, we developed a novel, antifouling gel-protected iridium (Ir) needle electrode modified with gold nanoparticles (G-IrNS) for long-term continuous and steady Cu monitoring. The gel formed an efficient membrane that effectively prevented the fouling of the sensing surface and displayed anti-convective properties, ensuring that mass transport toward the sensor surface was wholly controlled via diffusion. The repeatability, reproducibility, and stability of G-IrNS showed that it was suitable for long-term and on-site monitoring of Cu in seawater. Cu concentrations were successfully measured via fixed-point continuous monitoring for >2 weeks and onboard continuous monitoring in Bohai Sea using one sensor. Moreover, the relationship between Cu concentrations measured on-site via G-IrNS and its dissolved concentration in Bohai Sea was evaluated. G-IrNS can be applied to other metal ions as well, especially for long-term automatic on-site monitoring, thereby providing a basis for further research.

Tip-porous microneedle: A highly stable sensing platform for direct determination of labile metals in natural seawater.

Nanomaterial-functionalized voltammetric microsensors are promising tools for detecting trace metals at low concentrations in the complex environment of natural seawater. However, the sensitivity reduction caused by the loss of modified nanomaterials in the detection process has always been a major problem. Herein, to fabricate a highly stable sensing platform, a microneedle electrode with a hierarchical porous tip was prepared through electrochemical etching technology to firmly embed nanoparticles. Using copper (Cu) as a model trace metal, a micro-cluster needle sensor based on a gold nanoparticle (AuNP)-embedded tip-porous microneedle electrode (P-MNE) was fabricated for the direct voltammetric determination of labile Cu in natural seawater. The porous structure of P-MNE not only provided a larger specific surface area and active sites for AuNPs which had excellent electrocatalytic performance for Cu2+ determination, but also protected from their loss during the detection process in seawater. Therefore, this novel micro-cluster needle sensor exhibited significantly improved stability with a relative standard deviation (RSD) of 1.5% for 30 detections. The linear range of Cu2+ on this micro-cluster needle sensor was from 0.1 to 1000 nM with a detection limit of 0.03 nM. More importantly, this micro-cluster needle sensor was successfully used for directly detecting labile Cu in natural seawater samples without any preaccumulation treatment or reagent addition to obtain the contribution proportions of the labile fraction in total dissolved Cu. Furthermore, this sensing platform might also be extended to the reliable determination of other labile metals in seawater by changing the functional nanoparticles embedded in the nanopores.

Observation and Analysis of Clinical Efficacy of Zhuang Medicine Lotus Acupuncture Cupping Stasis Therapy on Patients with Postherpetic Neuralgia.

OBJECTIVE: To explore the clinical efficacy of Zhuang Medicine Lotus Acupuncture Cupping Stasis Therapy on patients with postherpetic neuralgia (PHN) and its action mechanism. METHODS: 36 patients are randomly divided into Lotus Acupuncture Cupping Stasis Therapy group, pure cupping group and gabapentin group, with a total of five observation points for the first, fifth, tenth, fifteenth, and twentieth sessions of therapy (one session every three days). At each observation point, the venous blood of the patients is taken, and the contents of and changes in WNT3a, Frizzled8, ß-catenin, IL-18, TNF-α, NR2B, NK-1 and SP are tested by ELISA, RT-PCR and WesternBlot, respectively. The VAS scores and safety of the patients in the three groups are compared. RESULTS: With increased time spent in therapy, the VAS scores of patients in each group decreased gradually and there was a significant reduction in pain in patients in the Lotus Acupuncture Cupping Stasis Therapy group compared to the gabapentin and pure cupping groups (P<0.05). The levels of IL-18, TNF-α, NK-1, SP, WNT3a, Frizzled 8 and ß-catenin in the serum of all patients experienced a constant decline over time (P<0.05); the levels of the aforesaid factors in the serum of patients in the Lotus Acupuncture Cupping Stasis Therapy group dropped remarkably after the tenth session of therapy compared to those in gabapentin and pure cupping groups (P<0.05). CONCLUSIONS: Zhuang Medicine Lotus Acupuncture Cupping Stasis Therapy can significantly reduce the pain of PHN patients, with a good therapeutic effect, and it is worthy of clinical use.

Inequality constraint on the maximum genus for 3D structural compliance topology optimization.

Structural topology constraints in topology optimization are an important research topic. The structural topology is characterized by the topological invariance of the number of holes. The holes of a structure in 3D space can be classified as internally enclosed holes and external through-holes (or tunnels). The genus is the number of tunnels. This article proposes the quotient set design variable method (QSDV) to implement the inequality constraint on the maximum genus allowed in an optimized structure for 3D structural topology optimization. The principle of the QSDV is to classify the changing design variables according to the connectivity of the elements in a structure to obtain the quotient set and update the corresponding elements in the quotient set to meet the topological constraint. Based on the standard relaxation algorithm discrete variable topology optimization method (DVTOCRA), the effectiveness of the QSDV is illustrated in numerical examples of a 3D cantilever beam.

Integrated Bioinformatics Analysis Identifies microRNA-200a-5p as a New Plasma Marker in Patients with Venous Thromboembolism.

BACKGROUND: Venous thromboembolism (VTE) is a major global health problem with high incidence and mortality. Vein endothelial cell (VEC) dysfunction is the primary cause of VTE. MicroRNAs (miRNAs) assist in the regulation of VEC functional pathways. Our objective was to identify potential miRNA target genes associated with VTE. MATERIALS AND METHODS: To explore the association between mRNAs and miRNAs in VTE, we performed an mRNA or miRNA microarray analysis and experiments in vitro. In addition, five online bioinformatics tools identified the target genes of differentially expressed miRNAs, and a miRNA-gene network was constructed. As a result, hub miRNA and mRNA were confirmed. Finally, wound healing assay and transwell migration assay were performed to elucidate the effect of hub miRNA in VEC. Luciferase reporter assay and real-time quantitative polymerase chain reaction (RT-qPCR) were performed to decide the role of miRNA in the expression of hub mRNA. RESULTS: Screening identified eight overlapping dysregulated genes in patients with VTE, three of which demonstrated a significantly decreased expression of miR-200a-5p. Low expression miR-200a-5p in VTE patients is confirmed by a receiver operating characteristic analysis (AUC = 0.800, P = 0.023) and binary logistic regression (OR = 0.359, 95% confidence interval: 0.605-0.995). RT-qPCR results showed that the miR-200a-5p level was decreased in hypoxia VEC (P = 0.038). MiR-200a-5p significantly promoted the migration ability of VEC. The result of Dual-luciferase reporter assay showed that cytochrome coxidase Ⅶc (COX7C) directly inhibit the miR-200a-5p expression by binding 5'UTR of miR-200a-5p (P = 0.011). CONCLUSIONS: We anticipate that the miR-200a-5p-COX7C pair might be involved in the progression of VTE. Moreover, miR-200a-5p might be a therapeutic target for VTE.

Design and characteristic analysis of multi-degree-of-freedom ultrasonic motor based on spherical stator.

The multidimensional motion ultrasonic motor with a single spherical stator is studied in this paper. It has the characteristics of miniaturization and can be used in precision motion applications. By bonding six identical pieces of piezoelectric ceramic onto the stator and applying the voltage signal of high frequency, the deformation of the inverse piezoelectric effect is used to excite the stator yaw vibration mode. The orthogonal superposition of the modes of the spherical stator on the driving foot produces elliptical trajectory around X, Y, and Z directions by different excitation methods. According to the yaw vibration mode of the spherical stator, 12 driving feet are designed to drive the rotation of the spherical rotor. The structure and mechanical characteristics of the motor are simulated by using simulation software, and the transient response of the stator driving foot was obtained, which proved its feasibility. Finally, the output performance of the motor in actual operation is given through experiments, which provides a new reference scheme in the field of precise multi-degree-of-freedom motion. At a voltage of 100 V and a frequency of 26.7 kHz, the prototype has a no-load speed of 73, 70, and 114 rpm around X, Y, and Z axes, respectively.

Dynamics and temperature field analysis of piezoelectric driven three-stator multi-degree-of-freedom ultrasonic motor.

Since the temperature has a great effect on the service behavior of the ultrasonic motor, high temperature will affect its mechanical characteristics and service life. This article is on a model of a piezoelectric driven three-stator multi-degree-of-freedom ultrasonic motor. Firstly, the motion mechanism is analyzed, and the main causes of temperature rise are determined to be friction heat generation and vibration heat generation. Then, the theoretical model of temperature rise is built, and the temperature rise characteristics of the ultrasonic motor are simulated and analyzed by establishing a three-dimensional transient temperature field model. Finally, it is verified by temperature test experiment. The results show that the simulation analyses are consistent with the experimental results, and this analysis can correctly reflect the temperature rise characteristics of the motor. It provides a reference for further seeking the effect of the body temperature rise on the service behavior of the ultrasonic motor and improving the operating characteristics of the ultrasonic motor.

Nanocomposite based on graphene and intercalated covalent organic frameworks with hydrosulphonyl groups for electrochemical determination of heavy metal ions.

An electrochemical sensor constructed by intercalated composites was developed for determination of heavy metal ions. The intercalated composites were composed of hydrosulphonyl functional covalent organic frameworks (COF-SH) and graphene (G). The presence of numerous adsorption sites, such as 18 sulfur atoms and 30 nitrogen atoms per big circle of COFs on COF-SH, was beneficial for the accumulation of heavy metals, while the graphene enhanced the electrical conductivity. The obtained sensor under the optimal conditions successfully detected the presence of heavy metal ions in coastal water samples at concentrations ranging from 1 to 1000 µg L-1. The detection limits of Cd (II), Pb (II), Cu (II), and Hg (II) were 0.3, 0.2, 0.2, and 1.1 µg L-1, respectively. Furthermore, the sensor still exhibited good stability after multiple uses less than 5%. When it is used in the analysis of actual samples, the recovery of standard addition is higher than 95%. In sum, the combination of hydrosulphonyl functional COFs with graphene looks very promising for the assembly of sensors with high sensitivity toward the determination of heavy metal ions for coastal environmental monitoring.

On-site electrochemical determination of phosphate with high sensitivity and anti-interference ability in turbid coastal waters.

Phosphate is considered to be an important biogenic element and responsible for eutrophication in aquatic ecosystems, existing in both dissolved and absorbed forms. Due to the complex matrix of coastal seawater, a high sensitivity and anti-interference method for phosphate detection is required for environmental protection. In this study, a novel electrochemical method was proposed based on reduced graphene oxide-ordered mesoporous carbon screen-printed electrode (rGO-OMC/SPE) analysis, allowing sensitivity and reliable determination of phosphate in turbid coastal waters. Combining the good absorption capacity of OMC with the excellent electroconductivity of rGO, the fabricated electrode exhibits improved signal responses, enhanced by up to 43-fold. The platform was evaluated using turbidity interference test with good recovery percentages comprised between 96% and 105% in different phosphate concentration, and salinity interference test between 92% and 105%, respectively. A linear range from 0.2 to 150 µM phosphate was achieved, with a detection limit of 0.05 µM (s/n = 3). The fabricated platform was successfully used for on-site analysis of phosphate in turbid coastal waters. This reliable and effective method for the analysis of phosphate in turbid coastal waters allows for sensitivity and anti-interference determination, while also representing a significant step towards comprehensive and convenient analysis of phosphorus species.

iT4SE-EP: Accurate Identification of Bacterial Type IV Secreted Effectors by Exploring Evolutionary Features from Two PSI-BLAST Profiles.

Many gram-negative bacteria use type IV secretion systems to deliver effector molecules to a wide range of target cells. These substrate proteins, which are called type IV secreted effectors (T4SE), manipulate host cell processes during infection, often resulting in severe diseases or even death of the host. Therefore, identification of putative T4SEs has become a very active research topic in bioinformatics due to its vital roles in understanding host-pathogen interactions. PSI-BLAST profiles have been experimentally validated to provide important and discriminatory evolutionary information for various protein classification tasks. In the present study, an accurate computational predictor termed iT4SE-EP was developed for identifying T4SEs by extracting evolutionary features from the position-specific scoring matrix and the position-specific frequency matrix profiles. First, four types of encoding strategies were designed to transform protein sequences into fixed-length feature vectors based on the two profiles. Then, the feature selection technique based on the random forest algorithm was utilized to reduce redundant or irrelevant features without much loss of information. Finally, the optimal features were input into a support vector machine classifier to carry out the prediction of T4SEs. Our experimental results demonstrated that iT4SE-EP outperformed most of existing methods based on the independent dataset test.