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*

To investigate the effects of zearalenone(ZEA)on the proliferation and apoptosis of sika deer antler chondrocytes,the chondrocytes were isolated and cultured in vitro and treated with 50μmol/L ZEA for 24 h.Flow cytometry was used to assess cell proliferation,cell cycle,apoptosis,mitochondrial membrane potential,and intracellular levels of reactive oxygen species(ROS).The expression changes of hypertrophic cartilage cell marker genes Col X,Runx2,Alpl,and apoptosis-related genes Casp-3,Bax,Bcl-2 were measured using quantitative PCR.Additionally,glutathione reductase(GR)activity and the levels of the oxidative stress marker malondialdehyde(MDA)were determined.The results showed that after 24 h of ZEA treatment,cell proliferation was sig-nificantly inhibited,with an increase in the number of cells in the G0/G1 phase and a decrease in the S phase.The expression levels of hypertrophic chondrocyte marker genes Col X,Runx2 and Al-pl were significantly increased.Apoptosis rate was significantly increased,with elevated expression of pro-apoptotic genes Casp-3,Bax and reduced expression of the anti-apoptotic gene Bcl-2.The content of MDA in the antler chondrocytes increased,ROS levels rose,and GR activity decreased.The mitochondrial membrane potential reduced.The results suggested that ZEA could inhibit the proliferation of antler chondrocytes and promote the apoptosis by regulating cellular oxidative stress responses and the expression of apoptosis-related genes.

To construct a recombinant fowl adenovirus 4(FAdV-4)expressing the Cap protein of goose astrovirus genotype 2(GoAstV-2),the expression cassette of Cap gene was inserted into the natural 1 966 bp deletion region of the FAdV-4 genome in the infectious clone p15A-cm-FAdV4-HNJZ.The resulted recombinant plasmid p15A-cm-FAdV4-HNJZ-Cap/GoAstV-2 was linearized with restriction enzyme and transfected into chicken hepatoma cell line(LMH)to rescue the recombinant FAdV-4 expressing the Cap protein of GoAstV-2,rF Ad V4-Cap/GoAstV-2.After 15 passages in LMH cells,the recombinant rFAdV4-Cap/GoAstV-2 was identified by PCR using primers flanking the insertion site of the Cap gene expression cassette and using viral genome DNA extracted from rFAdV4-Cap/GoAstV-2 infected LMH cells as template.LMH cells were in-fected with 15th passage rFAdV4-Cap/GoAstV-2 and indirect immunofluorescence was performed with a polyclonal antibody against Cap protein as the primary antibody.Western blot was carried out with lysates of rFAdV4-Cap/GoAstV-2 infected LMH cells.The in vitro replication dynamic of the 15th passage of the rFAdV4-Cap/GoAstV-2 was also investigated in LMH cells.The results demonstrated that the Cap gene of GoAstV-2 was presented in the genome of the recombinant vi-rus rF AdV4-Cap/Go Ast V-2,and could be expressed stably.The prepared recombinant virus in this study will lay a foundation for developing inactivated bivalent vaccine candidate against co-in-fection of FAdV-4 and GoAstV-2 in goose.

Objective:To investigate the characteristics of brain network reorganization in migraine patients and its relationship with the grading of right-to-left shunt (RLS) in patent foramen ovale(PFO) by integrated 3.0T structural magnetic resonance imaging (MRI),resting-state functional MRI(fMRI),and contrast-enhanced transthoracic echocardiography, thereby toexplore the mechanism underlying cognitive impairment in migraine.Methods:A total of 49 migraine patients (migraine group)and 16 demographically matched healthy subjects (healthy control group) who received diagnosis and treatment at China-Japan Union Hospital of Jilin University from September 2020 to September 2023 were selected as the study participants. Structural images (T1-weighted) and resting-state functional images were obtained from brain imaging (MRI and fMRI) data. The amplitude of low-frequency fluctuation (ALFF) algorithm was used to quantify the intensity of spontaneous neural activity in brain regions, while the Fazekas scale and the Age-Related White Matter Changes (ARWMC) scale were employed to assess white matter lesions. Participants were evaluated using the Mini-Mental State Examination (MMSE). Based on the results of contrast-enhanced transthoracic echocardiography (cTTE),the migraine group was further subdivided into A1 group (18 cases, no PFO), A2 group (17 cases, PFO with small-to-moderate RLS) and A3 group (14 case, PFO with large RLS) group, the differences in brain functional activity and cognitive function were compared among these groups.Results:By Fazekas scale scores and ARWMC scale scores, the incidence of hyperintense foci in the deep white matter regions in the migraine group were higher than those in the healthy control group: 67.3%(33/49) vs. 6/16, 61.2%(30/49) vs. 5/16, there were statistical differences ( P<0.05). Compared with the healthy control group, the migraine group exhibited higher spontaneous neural activity intensity in the brainstem,bilateral posterior cingulate cortex,left medial frontal gyrus,and left middle frontal gyrus,while showing reduced brain activity in the right angular gyrus region. The short-term delayed recall scores and total MMSE scores in the migraine group were lower than thosein the healthy control group: (1.61 ± 1.06) scores vs. (2.44 ± 0.81) scores, (25.06 ± 2.31) scores vs. (27.94 ± 1.44) scores, there were statistical differences ( P<0.05). The short-term delayed recall scores mong the A1 group, A2 group and A3 group had statistical difference( P<0.05). Conclusions:Migraine patients exhibit specific brain functional network reorganization and cognitive dysfunction, which are closely related to the degree of RLS.

With the intensification of aging in China, geriatric health issues have become increasingly prominent.Geriatric medicine, as a pivotal discipline for enhancing the health of the elderly, is confronted with challenges such as an incomplete disciplinary system and a shortage of talents.This paper emphasizes the interdisciplinary, comprehensive, and social characteristics of geriatric medicine, and proposes strategies such as enhancing the level of disease diagnosis and treatment, advocating multidisciplinary team-based diagnosis and treatment, and improving rehabilitation and long-term care systems.Simultaneously, it calls for attention to disciplinary management and innovation, refining talent cultivation and incentive mechanisms, establishing quality control systems, and advancing information technology construction.Furthermore, it is necessary to perfect the educational system, strengthen scientific research exploration, and foster international cooperation to construct a new developmental paradigm for geriatric medicine with systematic thinking, thereby achieving the goal of healthy aging.

To construct a recombinant fowl adenovirus 4(FAdV-4)expressing the Cap protein of goose astrovirus genotype 2(GoAstV-2),the expression cassette of Cap gene was inserted into the natural 1 966 bp deletion region of the FAdV-4 genome in the infectious clone p15A-cm-FAdV4-HNJZ.The resulted recombinant plasmid p15A-cm-FAdV4-HNJZ-Cap/GoAstV-2 was linearized with restriction enzyme and transfected into chicken hepatoma cell line(LMH)to rescue the recombinant FAdV-4 expressing the Cap protein of GoAstV-2,rF Ad V4-Cap/GoAstV-2.After 15 passages in LMH cells,the recombinant rFAdV4-Cap/GoAstV-2 was identified by PCR using primers flanking the insertion site of the Cap gene expression cassette and using viral genome DNA extracted from rFAdV4-Cap/GoAstV-2 infected LMH cells as template.LMH cells were in-fected with 15th passage rFAdV4-Cap/GoAstV-2 and indirect immunofluorescence was performed with a polyclonal antibody against Cap protein as the primary antibody.Western blot was carried out with lysates of rFAdV4-Cap/GoAstV-2 infected LMH cells.The in vitro replication dynamic of the 15th passage of the rFAdV4-Cap/GoAstV-2 was also investigated in LMH cells.The results demonstrated that the Cap gene of GoAstV-2 was presented in the genome of the recombinant vi-rus rF AdV4-Cap/Go Ast V-2,and could be expressed stably.The prepared recombinant virus in this study will lay a foundation for developing inactivated bivalent vaccine candidate against co-in-fection of FAdV-4 and GoAstV-2 in goose.

With the intensification of aging in China, geriatric health issues have become increasingly prominent.Geriatric medicine, as a pivotal discipline for enhancing the health of the elderly, is confronted with challenges such as an incomplete disciplinary system and a shortage of talents.This paper emphasizes the interdisciplinary, comprehensive, and social characteristics of geriatric medicine, and proposes strategies such as enhancing the level of disease diagnosis and treatment, advocating multidisciplinary team-based diagnosis and treatment, and improving rehabilitation and long-term care systems.Simultaneously, it calls for attention to disciplinary management and innovation, refining talent cultivation and incentive mechanisms, establishing quality control systems, and advancing information technology construction.Furthermore, it is necessary to perfect the educational system, strengthen scientific research exploration, and foster international cooperation to construct a new developmental paradigm for geriatric medicine with systematic thinking, thereby achieving the goal of healthy aging.

To investigate the effects of zearalenone(ZEA)on the proliferation and apoptosis of sika deer antler chondrocytes,the chondrocytes were isolated and cultured in vitro and treated with 50μmol/L ZEA for 24 h.Flow cytometry was used to assess cell proliferation,cell cycle,apoptosis,mitochondrial membrane potential,and intracellular levels of reactive oxygen species(ROS).The expression changes of hypertrophic cartilage cell marker genes Col X,Runx2,Alpl,and apoptosis-related genes Casp-3,Bax,Bcl-2 were measured using quantitative PCR.Additionally,glutathione reductase(GR)activity and the levels of the oxidative stress marker malondialdehyde(MDA)were determined.The results showed that after 24 h of ZEA treatment,cell proliferation was sig-nificantly inhibited,with an increase in the number of cells in the G0/G1 phase and a decrease in the S phase.The expression levels of hypertrophic chondrocyte marker genes Col X,Runx2 and Al-pl were significantly increased.Apoptosis rate was significantly increased,with elevated expression of pro-apoptotic genes Casp-3,Bax and reduced expression of the anti-apoptotic gene Bcl-2.The content of MDA in the antler chondrocytes increased,ROS levels rose,and GR activity decreased.The mitochondrial membrane potential reduced.The results suggested that ZEA could inhibit the proliferation of antler chondrocytes and promote the apoptosis by regulating cellular oxidative stress responses and the expression of apoptosis-related genes.

Objective:To investigate the characteristics of brain network reorganization in migraine patients and its relationship with the grading of right-to-left shunt (RLS) in patent foramen ovale(PFO) by integrated 3.0T structural magnetic resonance imaging (MRI),resting-state functional MRI(fMRI),and contrast-enhanced transthoracic echocardiography, thereby toexplore the mechanism underlying cognitive impairment in migraine.Methods:A total of 49 migraine patients (migraine group)and 16 demographically matched healthy subjects (healthy control group) who received diagnosis and treatment at China-Japan Union Hospital of Jilin University from September 2020 to September 2023 were selected as the study participants. Structural images (T1-weighted) and resting-state functional images were obtained from brain imaging (MRI and fMRI) data. The amplitude of low-frequency fluctuation (ALFF) algorithm was used to quantify the intensity of spontaneous neural activity in brain regions, while the Fazekas scale and the Age-Related White Matter Changes (ARWMC) scale were employed to assess white matter lesions. Participants were evaluated using the Mini-Mental State Examination (MMSE). Based on the results of contrast-enhanced transthoracic echocardiography (cTTE),the migraine group was further subdivided into A1 group (18 cases, no PFO), A2 group (17 cases, PFO with small-to-moderate RLS) and A3 group (14 case, PFO with large RLS) group, the differences in brain functional activity and cognitive function were compared among these groups.Results:By Fazekas scale scores and ARWMC scale scores, the incidence of hyperintense foci in the deep white matter regions in the migraine group were higher than those in the healthy control group: 67.3%(33/49) vs. 6/16, 61.2%(30/49) vs. 5/16, there were statistical differences ( P<0.05). Compared with the healthy control group, the migraine group exhibited higher spontaneous neural activity intensity in the brainstem,bilateral posterior cingulate cortex,left medial frontal gyrus,and left middle frontal gyrus,while showing reduced brain activity in the right angular gyrus region. The short-term delayed recall scores and total MMSE scores in the migraine group were lower than thosein the healthy control group: (1.61 ± 1.06) scores vs. (2.44 ± 0.81) scores, (25.06 ± 2.31) scores vs. (27.94 ± 1.44) scores, there were statistical differences ( P<0.05). The short-term delayed recall scores mong the A1 group, A2 group and A3 group had statistical difference( P<0.05). Conclusions:Migraine patients exhibit specific brain functional network reorganization and cognitive dysfunction, which are closely related to the degree of RLS.

Objective:To compare and discuss the mid-to-long-term outcomes of mitral valve repair (MVP) versus biological mitral valve replacement (bMVR) in patients aged 60 years and above with rheumatic mitral valve disease.Methods:This is a retrospective cohort study. A total of 765 patients aged 60 years and older, diagnosed with rheumatic mitral valve disease and who underwent MVP or bMVR at Beijing Anzhen Hospital from January 2010 to January 2023, were retrospectively included. Among them, 186 were male and 579 were female, with an age of (66.1±4.5) years (range: 60 to 82 years). Patients were divided into two groups based on the surgical method: the mitral valve repair group (MVP group, n=256) and the bioprosthetic mitral valve replacement group (bMVR group, n=509). A 1∶1 propensity score matching was performed using a caliper value of 0.2 based on preoperative data. Paired sample t-tests, χ2 tests, or Fisher′s exact tests were used for intergroup comparisons. Kaplan-Meier method was employed to plot survival curves and valve-related reoperation rate curves for both groups before and after matching, and Log-rank tests were used to compare the mid-to long-term survival rates and valve-related reoperation rates between the two groups. Results:A total of 765 patients who completed follow-up were ultimately included, with a follow-up period ( M(IQR)) of 5.1(5.0) years (range: 1.0 to 12.9 years). After matching, each group consisted of 256 patients. The incidence of early postoperative atrial fibrillation (39.1% vs. 49.2%, χ2=4.95, P=0.026) and early mortality rates (2.0% vs. 6.2%, χ2=4.97, P=0.026) were lower in the MVP group. Unadjusted Kaplan-Meier analysis showed significantly higher 5-year and 10-year survival rates for the MVP group (92.54% vs. 83.02%, 86.22% vs. 70.19%, Log-rank: P=0.001). After adjustment with propensity scores, the Kaplan-Meier analysis still indicated higher 5-year and 10-year survival rates in the MVP group compared to the bMVR group (92.54% vs. 85.89%, 86.22% vs. 74.83%, Log-rank: P=0.024). There were no significant differences in the rates of valve-related reoperation between the two groups before and after matching (5-year and 10-year reoperation rates pre-matching: 1.75% vs. 0.57%, 5.39% vs. 7.54%, Log-rank: P=0.207; post-matching: 1.75% vs. 0, 5.39% vs. 9.27%, Log-rank: P=0.157). Conclusion:For patients aged 60 years and above with rheumatic mitral valve disease, mitral valve repair offers better mid-to-long-term survival compared to biological valve replacement.