Accurate prediction of drug-target interactions (DTIs) plays a pivotal role in drug discovery, facilitating optimization of lead compounds, drug repurposing and elucidation of drug side effects. However, traditional DTI prediction methods are often limited by incomplete biological data and insufficient representation of protein features. In this study, we proposed KG-CNNDTI, a novel knowledge graph-enhanced framework for DTI prediction, which integrates heterogeneous biological information to improve model generalizability and predictive performance. The proposed model utilized protein embeddings derived from a biomedical knowledge graph via the Node2Vec algorithm, which were further enriched with contextualized sequence representations obtained from ProteinBERT. For compound representation, multiple molecular fingerprint schemes alongside the Uni-Mol pre-trained model were evaluated. The fused representations served as inputs to both classical machine learning models and a convolutional neural network-based predictor. Experimental evaluations across benchmark datasets demonstrated that KG-CNNDTI achieved superior performance compared to state-of-the-art methods, particularly in terms of Precision, Recall, F1-Score and area under the precision-recall curve (AUPR). Ablation analysis highlighted the substantial contribution of knowledge graph-derived features. Moreover, KG-CNNDTI was employed for virtual screening of natural products against Alzheimer's disease, resulting in 40 candidate compounds. 5 were supported by literature evidence, among which 3 were further validated in vitro assays.
Alzheimer Disease/drug therapy* ; Biological Products/therapeutic use* ; Humans ; Neural Networks, Computer ; Machine Learning ; Drug Discovery/methods* ; Algorithms ; Drug Evaluation, Preclinical/methods*

Objective To analyze the feasibility and efficacy of a deep convolutional neural network(DCNN)model based on chest CT images to evaluate bone mineral density(BMD).Methods A total of 1 048 health check subjects'2 096 central level images of lumbar 1 and 2 vertebral bodies were used for experiments and analysis in this retrospective study.According to the results of quanti-tative computed tomography(QCT)BMD measurement,the subjects were divided into three categories:normal,osteopenia,osteopo-rosis(OP).Herein,a DCNN segmentation model was constructed based on chest CT images[training set(n=1 096),tuning set(n=200),and test set(n=800)],the segmentation performance was evaluated using the Dice similarity coefficient(DSC)to com-pare the consistency with the manually sketched region of vertebral body.Then,the DCNN classification models 1(fusion feature construction of lumbar 1 and 2 vertebral bodies)and model 2(image feature construction of lumbar 1 alone)was developed based on the training set(n=530).Model performance was compared in a test set(n=418)by the receiver operating characteristic(ROC)curve analysis.Results When the number of images in the training set(n=300)was adopted,the DSC value was 0.950 in the test set.The results showed that the sensitivity,specificity and area under the curve(AUC)of model 1 and model 2 in diagno-sing osteopenia and OP were 0.716,0.960,0.952;0.941,0.948,0.980;0.638,0.954,0.940;0.843,0.959,0.978,respectively.The AUC value of normal model 1 was higher than that of model 2(0.990 vs 0.983,P=0.033),while there was no significant difference in AUC values between osteopenia and OP(P=0.210,0.546).Conclusion A DCNN may have the potential to evaluate bone mass based on chest CT images,which is expected to become an effective tool for OP screening.

Aim To investigate the pharmacological effects of paeonol as a formyl peptide receptor activator on rheumatoid arthritis (HA).Methods The target rlataset was obtained from the high throughput Gene Expression Database ( GEO) , and multiple data sets were combined by USING R language to explore three groups of macrophage differentially expressed genes ( DEGs) in untreated,lipopolysaccharide (LPS) treat¬ment and paeonol and LPS treatment, and their enrich-ment pathway was analyzed.Protein-protein interaction (PPI) networks were constructed in the STRING data¬base anrl visualized in Cytoscape software.The inhibi¬tor}' effect of Hub gene formyl peptide receptor ( FPR) on RA inflammation was validated by TNF-cx stimula¬tion of fibroblast synovial cells ( FLS).Results Through bioinformatics analysis, 169 differential genes ( DEGs) related to inflammation and 275 DEGs related to the mechanism of paeonol action were obtained.Combined analysis of the two groups of DEGs showed that FPR played a key role in the anti-inflammatory mechanism of paeonol.Further studies on the mecha¬nism of paeonol showed that paeonol activated FPR, and the inhibitory effect of paeonol on FLS inflamma¬tion was rescued by TRP-ARg-TRP-TRP-TRP-TRP- TRP-TRP-NH2 (WRW4).Conclusion Paeonol can inhibit the inflammatory development of RA through the FPR pathway.

Objective: To investigate the impact of obstructive sleep apnea (OSA) on long-term cardiovascular outcomes in patients with acute coronary syndrome (ACS). Methods: This is a single-center, prospective cohort study. Between June 2015 to January 2020, consecutive ACS patients hospitalized at Beijing Anzhen Hospital, Capital Medical University were enrolled. All patients underwent portable sleep breathing monitoring, and they were then divided into moderate/severe OSA group (apnea-hypopnea index (AHI)≥15 events/hour) and no/mild OSA group (AHI<15 events/hour). The primary endpoint was major adverse cardiac and cerebrovascular event (MACCE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, ischemia-driven revascularization and hospital admission for unstable angina or heart failure. MACCE were compared yearly by the log-rank test. Multivariable Cox regression analyses were performed to determine the independent predictors of MACCE. Results: A total of 1 927 patients with ACS were enrolled, including 1 629 males (84.5%), aged (56.4±10.5) years. Moderate/severe OSA was present in 1 014 (52.6%) patients. Compared with no/mild OSA group, moderate/severe OSA group exhibited a higher body mass index (P<0.05). Hypertension, prior PCI were more prevalent in moderate/severe OSA group (both P<0.05). The difference of ACS category between the two groups was statistically significant (P=0.021). The rate of patients who underwent PCI and the number of stents were higher in the moderate/severe OSA group. During a 5-year follow-up (median 2.9 years (IQR 1.5-3.6 years)), the cumulative incidence of MACCE was significantly higher in the moderate/severe OSA group than in the no/mild OSA group (34.0% vs. 24.0%, HR=1.346, 95%CI 1.100-1.646, log-rank P=0.004). The cumulative incidence of MACCE remained statistically higher at 4 and 5 year in the moderate/severe OSA group as compared to the no/mild OSA group (33.3% vs. 22.9%, HR=1.397, 95%CI 1.141-1.710, log-rank P=0.001; 34.0% vs. 24.0%, HR=1.341, 95%CI 1.096-1.640, log-rank P=0.004, respectively). Multivariate analysis showed that moderate/severe OSA (HR=1.312, 95%CI 1.054-1.631, P=0.015) was an independent predictor of long-term MACCE in ACS patients. Conclusions: Moderate/severe OSA is observed in more than 52% ACS patients. Moderate/severe OSA is an independent predictor of long-term MACCE.

Objective: To study the formation regularity and kinetic parameters of advanced glycation end-products during the processing of boiled Cervi Cornu Pantotrichum (CCP). Methods: UV-visible spectrophotometry and UPLC-MS/MS method were used to determine the change of browning index and content of typical advanced glycation end-products, Nε-(carboxymethyl) lysine and Nε-(carboxyethyl) lysine, of the processing system of simulated boiled CCP. The formation regularity and kinetic parameters of advanced glycation end-products during the processing of boiled CCP were discussed by constructing glucose and lysine to simulate the Maillard reaction system of CCP processing. Results: The activation energy of browning reaction, Nε-(carboxymethyl) lysine and Nε-(carboxyethyl) lysine reaction during processing of boiled CCP were 5.07, 40.44 and 78.47 kJ/mol, respectively, and all of them were zero-order kinetics. The activation energies of the above reactions in the baking process were 6.72, 89.34 and 164.77 kJ/mol, respectively, and all of them were zero-order kinetics. Compared to the formation of Nε-(carboxymethyl) lysine, the formation of Nε-(carboxyethyl) lysine required higher activation energy and was more difficult to occur. Conclusion: The temperature changed in the baking process has a significantly higher effect on the kinetic parameters of the advanced glycation end-products than in the boiling process. Long-term higher baking temperature resulted in more advanced glycation end-products produced in the boiled CCP. This study provides a solid theoretical basis for the blocking and inhibition strategies of advanced glycation end-products in the processing of CCP, which is also a great significance for the production of green safety CCP and strengthening the safety of traditional Chinese medicine.

To investigate the effect of ginseng neutral polysaccharide on gut microbiota composition and diversity as well as the therapeutic effect for antibiotic associated diarrhea( AAD) in mice. The water-soluble ginseng neutral polysaccharide( WGPN) was purified from water-soluble ginseng polysaccharides( WGP) by DEAE-sepharose fast flow column,which was obtained from the roots of Panax ginseng. AAD mice were induced by gastric gavage with lincomycin hydrochloride,followed by administration of normal saline( natural recovery group,NR) or WGPN( WGPN group) for one week. Body weight changes,psychosis and diarrhea status were observed and assessed. 12 h after the last administration,histological observation of ileum and 16 S rRNA high throughput sequencing analysis of intestinal contents were conducted to identify the effects of WGPN on AAD mice. The results showed that WGPN could alleviate the symptoms of diarrhea in mice,decrease the inflammation and edema of ileum,and increase the length of intestinal villi. As compared to NR mice,WGPN could increase the relative abundance of Lactobacillus,and significantly decrease the relative abundance of Bacteroides,Streptococcus,Ochrobactrum and Pseudomonas at the genus level. In conclusion,WGPN could improve the gut microecology by recovering the ileum structure and improving the diversity and composition of the gut microbiota in AAD mice.
Animals ; Anti-Bacterial Agents ; Diarrhea ; Gastrointestinal Microbiome ; Mice ; Panax ; Polysaccharides

Maillard reaction is a non-enzymatic browning reaction which is ubiquitous in the food industry and processing of Chinese materia medica (CMM). Maillard reaction can not only change the color and aroma of CMM, extend the shelf life of CMM, but also produce new active substances in CMM. In addition, a small amount of toxic and harmful substances such as 5-hydroxymethylfurfural and advanced glycation end-products produced by Maillard reaction have been given increasingly attention. It is of great significance to control the quality of CMM by changing the reaction temperature, time, potential of hydrogen, adding inhibitors, and anti-oxidants to regulate Maillard reaction. This paper reviews the general situation of Maillard reaction research and its research progress on the quality and regulation of CMM, and provides a reference for further research on the regulation of Maillard reaction for the quality control of CMM.

Heat shock protein 90 (HSP90) is a member of genetically conserved heat shock protein family. As an important molecular chaperone in eukaryotic cells, HSP90 plays a key regulatory role in maintaining cellular protein homeostasis. HSP90 clients encompass a wide range of proteins, thus HSP90 is involved in diverse biological process. With the deeper study, it is found that HSP90 takes an important part in the development and metastasis of cancer,and has become a promising target for the study of anticancer biology. We review the progress of HSP90 as molecular chaperone and its relationship with cancer.

The differences and the variations of chondroitin sulfate content in different parts of Cervi Cornu Pantotrichum(CCP) with different processing methods were investigated. The chondroitin sulfate from velvet was extracted by dilute alkali-concentrated salt method. Next， the chondroitin sulfate was digested by chondroitinase ABC.The contents of total chondroitin sulfate and chondroitin sulfate A， B and C in the samples were determined by high performance liquid chromatography(HPLC).The content of chondroitin sulfate in wax，powder，gauze，bone slices of CCP with freeze-drying processing is 14.13，11.99，1.74，0.32 g·kg⁻¹， respectively. The content of chondroitin sulfate in wax，powder，gauze，bone slices of CCP with boiling processing is 10.71，8.97，2.21，1.40 g·kg⁻¹， respectively. The content of chondroitin sulfate in wax，powder，gauze，bone slices of CCP without blood is 12.47，9.47，2.64，0.07 g·kg⁻¹， respectively. And the content of chondroitin sulfate in wax，powder，gauze，bone slices of CCP with blood is 8.22，4.39，0.87，0.28 g·kg⁻¹ respectively. The results indicated that the chondroitin sulfate content in different processing methods was significantly different.The content of chondroitin sulfate in CCP with freeze-drying is higher than that in CCP with boiling processing.The content of chondroitin sulfate in CCP without blood is higher than that in CCP with blood. The chondroitin sulfate content in differerent paris of the velvet with the same processing methods was arranged from high to low as： wax slices， powder， gauze slices， bone slices.
Animals ; Chondroitin Sulfates ; analysis ; Deer ; Horns ; chemistry

To investigate the chemical compositions of "antler powder" and "antler slice", two types of processed products of Cervi Cornu Pantotrichum (CCP) documented in Chinese Pharmacopoeia. With polysaccharides, crude protein, amino acids, fatty acids, mineral elements, biogenic amines, nucleosides and nucleobases as the evaluating indicators, the antler powder and antler slice processed with methods documented in Chinese Pharmacopoeia were compared in this study. The results showed that as compared with the antler powder by directly "chopping into pieces, and grinding into fine powder", the crude protein, amino acids, biogenic amines, nucleosides and nucleobases contents were reduced by 5.01%, 4.35%, 5.90%, 27.62% respectively in antler slices processed with 40% ethanol; the polysaccharides and nucleosides contents were reduced by 24.53% and 21.07% respectively in antler slices processed with 50% ethanol; and the crude protein and nucleosides contents were reduced by 1.65% and 20.52% in antler slices processed with 60% ethanol. While the contents of fatty acids and mineral elements were not decreased in these three methods. Polysaccharide, crude protein, amino acids, and nucleosides contents in "antler slices" were less than those in "antler powder", most notably in polysaccharides and nucleosides. According to the comprehensive scores of principal component analysis (PCA), the decrease of active ingredient determined in this study was lowest in antler slice processed with 50% ethanol.