ATSE: a peptide toxicity predictor by exploiting structural and evolutionary information based on graph neural network and attention mechanism.

MOTIVATION: Peptides have recently emerged as promising therapeutic agents against various diseases. For both research and safety regulation purposes, it is of high importance to develop computational methods to accurately predict the potential toxicity of peptides within the vast number of candidate peptides. RESULTS: In this study, we proposed ATSE, a peptide toxicity predictor by exploiting structural and evolutionary information based on graph neural networks and attention mechanism. More specifically, it consists of four modules: (i) a sequence processing module for converting peptide sequences to molecular graphs and evolutionary profiles, (ii) a feature extraction module designed to learn discriminative features from graph structural information and evolutionary information, (iii) an attention module employed to optimize the features and (iv) an output module determining a peptide as toxic or non-toxic, using optimized features from the attention module. CONCLUSION: Comparative studies demonstrate that the proposed ATSE significantly outperforms all other competing methods. We found that structural information is complementary to the evolutionary information, effectively improving the predictive performance. Importantly, the data-driven features learned by ATSE can be interpreted and visualized, providing additional information for further analysis. Moreover, we present a user-friendly online computational platform that implements the proposed ATSE, which is now available at http://server.malab.cn/ATSE. We expect that it can be a powerful and useful tool for researchers of interest.

Two-Stage Calibration Scheme for Magnetic Measurement System on Guided Munition.

In order to calibrate the magnetic measurement system used in guided munition on site, a two-stage calibration (TSC) scheme without reference is proposed in this paper. Analyzing the interfering magnetic field in the projectile and misalignment angles between the projectile coordinate system and measurement coordinate system establishes a proper mathematical equivalent model and derives a calibration method. The first stage is ellipsoid fitting to obtain the equivalent zero-offset, equivalent sensitivity and equivalent non-orthogonal angles of the sensor; the second stage is to calibrate the misalignment angles between the projectile coordinate system and the measurement coordinate system with the three-position calibration (TPC) method. Complete calibration is convenient to operate and does not need an additional reference, which has wide applicability. The simulation results show that the deviation in the measured value after compensation is within 100 nT. The experiment proves that the error of compensated magnetic value is about 150 nT, which meets the accuracy of requirements in guided munitions.

[Effects of Yangjing capsule on the ultrastructure of seminal vesicles in aged rats].

OBJECTIVE: To observe the effects of Yangjing Capsule (YJC) on the ultrastructure of seminal vesicles in aged male rats, and explore its mechanism of improving the secretion of seminal vesicles. METHODS: Fifty male SD rats aged 18 -20 months were randomly and equally divided into a control group, a testosterone undecanoate group, and a high-dose, a medium-dose and a low-dose YJC group, all fed intragastrically for 30 days. Then the seminal vesicles of the rats were removed and the seminal fluid squeezed into the test tube to be weighed and measured for the concentration of seminal vesicle fluid fructose, and the bilateral seminal vesicles were placed in formaldehyde and glutaraldehyde fixatives for histological observation. RESULTS: The seminal vesicle gland viscera coefficient, seminal vesicle fluid weight and fructose concentration of the rats were (1164.5 +/- 212.6) g/g x 10(6), (0.83 +/- 0.30) g and (4.35 +/- 0.31) mg/ml in the control group, (1510.5 +/- 313.1) g/g x 10(6), (0.82 +/- 0.25) g and (5.35 +/- 0.71) mg/ml in the testosterone undecanoate group, (1484.3 +/- 262.7) g/g x 10(6), (1.14 +/- 0.18) g and (5.30 +/- 0.45) mg/ml in the high-dose YJC group, (1396.6 +/- 268.9) g/g x 10(6), (0.83 +/- 0.24) g and (4.71 +/- 0.41) mg/ml in the medium-dose YJC group, and (1475.0 +/- 305.2) g/g x 10(6), (0.74 +/- 0.28) g and (4.50 +/- 0.23) mg/ml in the low-dose YJC group. Compared with the control, high-dose YJC significantly improved seminal vesicle secretion (P < 0.05), while medium- and low-dose only achieved a trend of improvement. After HE staining, the YJC groups showed more active epithelial hyperplasia, increased cellular layers, rich and transparent cytoplasm with abundant secretory granules, fat droplets and lipofuscin, blurred glandular cavity edge, and eosinophilic intraluminal secretions, as compared with the control group. The structural change was most significant in the high-dose group. Statistically significant differences were observed in the numerical density and bulk density of the secretory granules between the YJC and control groups (P < 0.05). CONCLUSION: Yangjing Capsule can improve the secretion of seminal vesicles by increasing the secretory granules of the main

Raffinose Ameliorates DSS-Induced Colitis in Mice by Modulating Gut Microbiota and Targeting the Inflammatory TLR4-MyD88-NF-κB Signaling Pathway.

This study aimed to explore the protective effects of raffinose (Raf) against inflammatory bowel disease in mice with colitis. Mice were administered 100, 200, or 400 mg/kg Raf for 21 d, followed by drinking-water containing 3% dextran sulfate sodium salt (DSS) for 3 d. Thereafter, the phenotype, pathological lesions in the colon, cytokines levels, and gut microbiota were evaluated. Treatment with Raf reduced the severity of the pathological changes in the colon, mitigating the reduction in colon length. Following Raf intervention, serum levels of inflammatory cytokines (IL-2, IL-6, IL-1ß, and TNF-α) tended to return to normal. These results suggest that the anti-inflammatory effects of Raf are associated with a reduction in TLR4-MyD88-NF-κB pathway expression in mouse colonic tissues. Analysis of gut microbiota abundance and its correlation with colitis parameters revealed that DSS-induced dysbiosis was partially mitigated by Raf. In conclusion, Raf exerts a protective effect in colitis by modulating the gut microbiota and TLR4-MyD88-NF-κB pathway.

Effect of the supplementation of exogenous complex non-starch polysaccharidases on the growth performance, rumen fermentation and microflora of fattening sheep.

The objective of this study was to evaluate the effects of exogenous non-starch polysaccharidases (a mixture of cellulase, xylanase, ß-glucanase and mannanase) on the growth performance and nutrient digestibility, rumen fermentation, and rumen microflora of sheep. The animal trial was conducted using 36 5-month-old female fattening hybrid sheep (Duolang♂ × Hu♀) who were randomly assigned into four groups comprising nine sheep per treatment: CON, T1, T2, and T3, with 0, 0.1, 0.3, and 0.5% NSPases/kg DM of TMR, respectively. This complex enzyme product was screened for optimal ratios based on previous in vitro tests and responded positively to the in vitro fermentation of the TMR. When treated with NSPases, there was a non-linear effect of average daily gain and feed conversion rate, with the greatest improvement observed in the T2 group. There were no significant differences (p > 0.05) in nutrient intake or apparent digestibility among the NSPase-supplemented groups. In addition, T2 group had a significantly higher acetate to propionate ratio and pH (p < 0.05) than the other groups, and NH3-N and microbial protein concentrations showed a quadratic curve. The results revealed that both immunoglobulins and serum hormones increased linearly with addition (p < 0.05). As the T2 group showed the best growth performance, the CON and T2 groups were subjected to rumen metagenomic analysis. The results showed higher abundance of bacteria and lower abundance of Viruses in the rumen microbiota of the T2 group compared to the CON group. In addition, Uroviricota and Proteobacteria abundance was significantly lower in the T2 group than in the CON group at the phylum level (p < 0.05). These results suggest that the supplementation of high-concentrate rations with NSPases enhance immunity, reduces virus abundance in the rumen, improves rumen health, and promotes rumen fermentation. Our findings provide novel insights for improving growth performance and alleviating inflammatory responses arising from high concentrate feeding patterns in ruminants. However, the biological mechanisms cannot be elucidated by exploring the composition of rumen microbe alone, and further studies are required.

A blind image super-resolution network guided by kernel estimation and structural prior knowledge.

The goal of blind image super-resolution (BISR) is to recover the corresponding high-resolution image from a given low-resolution image with unknown degradation. Prior related research has primarily focused effectively on utilizing the kernel as prior knowledge to recover the high-frequency components of image. However, they overlooked the function of structural prior information within the same image, which resulted in unsatisfactory recovery performance for textures with strong self-similarity. To address this issue, we propose a two stage blind super-resolution network that is based on kernel estimation strategy and is capable of integrating structural texture as prior knowledge. In the first stage, we utilize a dynamic kernel estimator to achieve degradation presentation embedding. Then, we propose a triple path attention groups consists of triple path attention blocks and a global feature fusion block to extract structural prior information to assist the recovery of details within images. The quantitative and qualitative results on standard benchmarks with various degradation settings, including Gaussian8 and DIV2KRK, validate that our proposed method outperforms the state-of-the-art methods in terms of fidelity and recovery of clear details. The relevant code is made available on this link as open source.

[Regulatory effect of Yangjing Capsule on the expressions of phosphor-Erk1 and phosphor-Akt1 in the corpus cavernosum of aged rats].

OBJECTIVE: To observe the effect of Yangjing Capsule on the expressions of P-Erk1 and P-Akt1 in the corpus cavernosum of aged rats and to explore its action mechanism. METHODS: Forty 24-month-old SD rats were equally randomized into an experimental and a control group, 10 selected from each group for detection of the eNOS expression before medication. The rats in the experimental group (n = 10) were treated intragastrically with Yangjing Capsule, while those in the control with physiological saline, both at 0.5 g per kg body weight per day for 4 weeks. Then all the rats were killed, and the corpus cavernosum tissues harvested for determination of the expressions of eNOS, P-Erk1 and P-Akt1 by HE staining, RT-PCR and immunohistochemistry. RESULTS: Obvious distension was observed in the experimental group, but not in the control. The expression of eNOS in the rat corpus cavernosum was significantly higher after treatment than before treatment in the experimental group (24.10 +/- 2.40 vs 18.80 +/- 2.04, P < 0.05), but presented no obvious difference in the control (18.15 +/- 1.98 vs 19.35 +/- 1.50, P > 0.05), and it was remarkably higher in the former than in the latter (P < 0.05). The expression of P-Erk1 was markedly lower in the experimental than in the control rats (0.71 +/- 0.13 vs 0.83 +/- 0.17, P < 0.01), but that of P-Akt1 exhibited no remarkable difference in the same condition of GAPDH between the two groups (0.58 +/- 0.17 vs 0.48 + 0.13, P > 0.01). CONCLUSION: Both P-Erk1 and P-Akt were expressed in the corpus cavernosum of the aged rats. Yangjing Capsule could improve the sexual function of aged rats, which might be associated with the lowered expression of P-Erk1.

Mechanical thrombectomy for symptomatic stent thrombosis after carotid artery stenting.

Background: As there is still no consensus on the treatment of carotid stent thrombosis (CST), we would like to describe our experience with the revascularization of CST by mechanical thrombectomy. Methods: We retrospectively studied patients who underwent mechanical thrombectomy after CST at Xuzhou Municipal First People's Hospital and Xuzhou Central Hospital between January 2020 and November 2022. The results of the procedures, complications, and clinical and imaging follow-up were recorded. Results: A total of six patients were included in this study. The stenosis grade before stent implantation was ≥85% in all patients, and the stenosis length ranged from 7 to 20 mm. Patients experienced CST within 6 days to 45 months after carotid artery stenting (CAS); the median admission on the National Institutes of Health Stroke Scale (NIHSS) at CST was 12 (range 8-25). Mechanical thrombectomy was successfully performed in all patients. There was no periprocedural death, and the modified Rankin Scale (mRS) at the 3-month follow-up was 0-2. All patients showed recovery from their neurological deficits. Conclusion: The treatment of symptomatic CST with mechanical thrombectomy resulted in satisfactory clinical outcomes. This regimen could be effective and safe, and future prospective and randomized studies are warranted.

Using less annotation workload to establish a pathological auxiliary diagnosis system for gastric cancer.

Pathological diagnosis of gastric cancer requires pathologists to have extensive clinical experience. To help pathologists improve diagnostic accuracy and efficiency, we collected 1,514 cases of stomach H&E-stained specimens with complete diagnostic information to establish a pathological auxiliary diagnosis system based on deep learning. At the slide level, our system achieves a specificity of 0.8878 while maintaining a high sensitivity close to 1.0 on 269 biopsy specimens (147 malignancies) and 163 surgical specimens (80 malignancies). The classified accuracy of our system is 0.9034 at the slide level for 352 biopsy specimens (201 malignancies) from 50 medical centers. With the help of our system, the pathologists' average false-negative rate and average false-positive rate on 100 biopsy specimens (50 malignancies) are reduced to 1/5 and 1/2 of the original rates, respectively. At the same time, the average uncertainty rate and the average diagnosis time are reduced by approximately 22% and 20%, respectively.

CUSS-Net: A Cascaded Unsupervised-Based Strategy and Supervised Network for Biomedical Image Diagnosis and Segmentation.

Biomedical image segmentation and classification are critical components in a computer-aided diagnosis system. However, various deep convolutional neural networks are trained by a single task, ignoring the potential contribution of mutually performing multiple tasks. In this paper, we propose a cascaded unsupervised-based strategy to boost the supervised CNN framework for automated white blood cell (WBC) and skin lesion segmentation and classification, called CUSS-Net. Our proposed CUSS-Net consists of an unsupervised-based strategy (US) module, an enhanced segmentation network named E-SegNet, and a mask-guided classification network called MG-ClsNet. On the one hand, the proposed US module produces coarse masks that provide a prior localization map for the proposed E-SegNet to enhance it in locating and segmenting a target object accurately. On the other hand, the enhanced coarse masks predicted by the proposed E-SegNet are then fed into the proposed MG-ClsNet for accurate classification. Moreover, a novel cascaded dense inception module is presented to capture more high-level information. Meanwhile, we adopt a hybrid loss by combining a dice loss and a cross-entropy loss to alleviate the imbalance training problem. We evaluate our proposed CUSS-Net on three public medical image datasets. Experiments show that our proposed CUSS-Net outperforms representative state-of-the-art approaches.

[Effects of Yixin Kangtai capsule on spermatogenesis and the levels of superoxide dismutase and malondialdehyde in aged SD rats].

OBJECTIVE: To observe the effects of Yixin Kangtai Capsule (YKC) on sperm concentration and motility, superoxide dismutase (SOD) and malondialdehyde (MDA) in aged SD rats, and to explore its possible mechanisms of action. METHODS: We randomly assigned fifty 24-month-old male SD rats to five groups of equal number: blank control, testosterone undecanoate, high-dose YKC, medium-dose YKC and low-dose YKC, and treated them intragastrically with physiological saline at 10 ml/kg, testosterone un-decanoate suspension at 4 mg/kg, and YKC at 0.6 g/kg, 0.3 g/kg and 0.15 g/kg, respectively, once a day for 30 days. Then we harvested the epididymides, which were stripped of fat and envelope, cut into pieces and placed in the saline at 37 degrees C for 10 to 15 minutes. Then we detected the sperm parameters with the Weili CASA sperm analysis system, measured the levels of serum SOD and MDA, and, following HE staining, observed the histomorphological changes of the testicular tissue under the light microscope. RESULTS: Compared with the controls, the rats treated with high-, medium- and low-dose YKC exhibited significantly increased sperm concentration ([152.3 +/- 24.0] x 10(6)/ml vs [334.5 +/- 97.7], [302.7 +/- 158.9] and [221.4 +/- 75.6] x 10(6)/ml, P < 0.05) and markedly improved sperm motility ([26.5 +/- 2.0]% vs [35.5 +/- 5.9], [33.1 +/- 5.4] and [28.4 +/- 2.1]%, P < 0.01). High-dose YKC significantly increased the level of serum SOD ([22.0 +/- 5.3] U/ml, P < 0.01) and reduced the content of MDA ([13.6 +/- 4.6] nmol/ ml, P < 0.01). Testicular histology showed that YKC induced more active proliferation of cells, and increased the number of dividing cells and that of mature sperm in the lumen, with little interstitium, abundant blood vessels, and well-developed stromal cells. CONCLUSION: Yixin Kangtai Capsule can improve spermatogenesis in aged SD rats by regulating the levels of SOD and MDA.

Better Performance with Transformer: CPPFormer in the Precise Prediction of Cell-penetrating Peptides.

Owing to its superior performance, the Transformer model, based on the 'Encoder- Decoder' paradigm, has become the mainstream model in natural language processing. However, bioinformatics has embraced machine learning and has led to remarkable progress in drug design and protein property prediction. Cell-penetrating peptides (CPPs) are a type of permeable protein that is a convenient 'postman' in drug penetration tasks. However, only a few CPPs have been discovered, limiting their practical applications in drug permeability. CPPs have led to a new approach that enables the uptake of only macromolecules into cells (i.e., without other potentially harmful materials found in the drug). Most previous studies have utilized trivial machine learning techniques and hand-crafted features to construct a simple classifier. CPPFormer was constructed by implementing the attention structure of the Transformer, rebuilding the network based on the characteristics of CPPs according to their short length, and using an automatic feature extractor with a few manually engineered features to co-direct the predicted results. Compared to all previous methods and other classic text classification models, the empirical results show that our proposed deep model-based method achieves the best performance, with an accuracy of 92.16% in the CPP924 dataset, and passes various index tests.

[Kidney-tonifying and dampness-expelling Chinese herbal medicine combined with doxazosin for the treatment of chronic epididymitis].

OBJECTIVE: To study the clinical effects of kidney-tonifying and dampness-expelling Chinese herbal medicine combined with doxazosin in the treatment of chronic epididymitis. METHODS: A total of 64 patients with chronic epididymitis were equally randomized into a treatment and a control group, the former treated with kidney-tonifying and dampness-expelling Chinese herbal decoction combined with doxazosin, and the latter given doxazosin only, both for 4 weeks. The clinical symptoms were measured by Chronic Epididymitis Symptom Index (CESI), Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) before and after the treatment, and the therapeutic effects were evaluated. RESULTS: After 4 weeks of medication, the total mean scores on CESI, pain, and quality of life (QOL) were significantly decreased in both the treatment and the control groups (P < 0.05), even more significantly in the former than in the latter (P < 0.05), and so were the scores on SAS and SDS (P < 0.05), but with no significant differences between the two groups (P > 0.05). CONCLUSION: Either doxazosin alone or kidney-tonifying and dampness-expelling Chinese herbal decoction combined with doxazosin is obviously effective on chronic epididymitis, but the combined medication produces an even better efficacy.

Downregulation of Frizzled-7 induces the apoptosis of hepatocellular carcinoma cells through inhibition of NF-κB.

The aim of the present study was to investigate the functional role of Frizzled-7 (FZD7) in the apoptosis of hepatoma cells. HepG2 and Huh-7 hepatocellular carcinoma (HCC) cell lines with FZD7 expression were selected for use in the present study. The small hairpin RNA (shRNA) eukaryotic expression vector specific to FZD7 was constructed using gene recombination, and was then transfected into HepG2 and Huh-7 hepatoma cell lines using Lipofectamine 2000 to assess whether the downregulation of FZD7 could affect the proliferative ability of these cells. The results demonstrated that the downregulation of FZD7 expression significantly inhibited the proliferative ability of both cell types through the induction of cell apoptosis, as evidenced using Cell Counting kit-8 assays and flow cytometry. Furthermore, the western blotting results demonstrated that silencing of FZD7 increased the activities of caspase-3 and caspase-9. These increases were also associated with the downregulation of the inhibitor of the apoptosis protein family. Additionally, it was revealed that silencing of FZD7 expression caused the downregulation of apoptosis regulator Bcl-2 and Bcl-XL in HepG2, and Huh-7 cells, as determined through western blot analysis and reverse transcription-quantitative polymerase chain reaction. In the following work, ELISA and western blot analysis revealed that the knockdown of FZD7 inhibited the expression and activities of nuclear factor-κB (NF-κB) p65. Furthermore, it was demonstrated that the expression levels of phosphylated-Smad2/3 were markedly upregulated in sh-FZD7-transfected HepG2 and Huh-7 cells. Then, shRNA eukaryotic expression vector specific to transforming growth factor (TGF)-ß receptor II was transfected into both cell lines to investigate the association between the TGF-ß/Smad signaling pathway and NF-κB p65. Notably, when the TGF-ß/Smad signaling pathway was inhibited, no significant differences in the cell apoptosis rate and NF-κB expression levels were identified in HCC cells. Overall, the results of the present study suggest that the shRNA-mediated knockdown of FZD7 induces apoptosis of hepatoma cell lines through the inhibition of NF-κB. In addition, the TGF-ß/Smad signaling pathway appeared to partially participate in the underlying molecular mechanism of FZD7 in HCC.

Short hairpin RNA silencing of TGF-ßRII and FZD-7 synergistically suppresses proliferation and metastasis of hepatocellular carcinoma cells.

Transforming growth factor-ß (TGF-ß) is a multifunctional regulator of cell growth, apoptosis, differentiation and migration. The Wnt/ß-catenin signaling pathway has been implicated in a wide spectrum of diseases, including numerous cancers and degenerative disease. The aim of the present study was to investigate if simultaneous blocking of TGF-ß and Wnt/ß-catenin signaling pathways exerts synergistic anti-tumor effects on hepatocellular carcinoma (HCC) cells. Short hairpin (sh) RNA eukaryotic expression vectors, specific to TGF-ß receptor II (RII) and Frizzled receptor (FZD)-7, were constructed by gene recombination. The expression vectors were transfected into human HCC HepG2 and Huh-7 cells using Lipofectamine 2000 to investigate the synergistic effects between TGF-ß and Wnt/ß-catenin signaling pathways on HCC cell proliferation, invasion and migration and the cell-cycle distribution. Western blot analysis was used to identify the expression of ß-catenin, c-Myc and cyclin D1 in transfected cells to investigate the underlying mechanisms that cause TGF-ß and Wnt/ß-catenin signaling in HCC cells. shTGF-ßRII-c and shFZD-7-2 were selected as the most efficient plasmids. A cell growth assay and colony-forming assay consistently demonstrated that the proliferative activity of the co-transfected group was significantly decreased compared to the single-transfected group. A wound healing invasion and migration assay demonstrated that co-transfection of shTGF-ßRII-c and shFZD-7-2 decreased the invasion and migration abilities of the cells compared with either single-transfected group. In addition, the present study demonstrated that the observed reduction in cell proliferation was due to the cells arresting at the G1 phase of the cell cycle, and the downregulation of ß-catenin, c-Myc and cyclin D1 impaired the proliferative and invasive abilities of the HCC cells. The present results demonstrate that simultaneous blocking of TGF-ß and Wnt/ß-catenin signaling by targeting TGF-ßRII and FZD-7 may inhibit the proliferation and metastasis of HCC cells more effectively compared with blocking either the TGF-ß or Wnt/ß-catenin pathway.