Objective To investigate the role of Toll-like receptor 4(TLR4)in the regulation of homocys-teine(Hcy)-induced ferroptosis in macrophages.Methods Mouse macrophage cells RAW264.7 were cultured and divided into control group,Hcy intervention group(Hcy group),and Hcy plus ferroptosis inhibitor group(Hcy+Fer-1 group).After transfection with interference fragments,macrophages were treated with Hcy,and then divided into control group,Hcy intervention group(Hcy group),TLR4 interference negative control plus Hcy intervention group(si-NC+Hcy group),and TLR4 interference plus Hcy intervention group(si-TLR4+Hcy group).Macrophages were transfected with overexpression lentivirus and treated with Hcy,then were divided into control group,Hcy intervention group(Hcy group),a TLR4 overexpression negative control plus Hcy intervention group(OE-NC+Hcy group),and a TLR4 overexpression plus Hcy intervention group(OE-TLR4+Hcy group).After 48 hours of intervention,real-time fluorescent quantitative PCR and western blot were used to detect the expression levels of TLR4 in macrophages treated with Hcy;western blot was used to detect the expression levels of ferroptosis-related proteins ACSL4,GPX4,and FTH1 in macrophages,and ferrous ion assay kit to detect the concentration of Fe2+in macrophages;reactive oxygen species(ROS)assay kit and laser confocal microscopy were used to detect the content of intracellular reactive oxygen species.Results Compared with those in the control group,the expression level of the pro-ferroptosis protein ACSL4 was increased in the Hcy group(P<0.05),while the expression levels of anti-ferroptosis proteins GPX4 and FTH1 were decreased(P<0.05);the concentration of Fe2+was increased(P<0.05),and the content of ROS was increased.Meanwhile,the protein and mRNA expres-sion levels of TLR4 were both increased in the Hcy group(P<0.05).After macrophages were transfected with TLR4 interference fragments,compared with those in the si-NC+Hcy group,the expression levels of GPX4 and FTH1 were increased(P<0.05);the expression level of ACSL4 was decreased(P<0.05);the concentration of Fe2+was decreased(P<0.05),and the content of ROS was reduced in the si-TLR4+Hcy group.After macro-phages were transfected with TLR4 overexpression lentivirus,compared with those in the OE-NC+Hcy group,the expression levels of GPX4 and FTH1 were decreased(P<0.05),and the expression level of ACSL4 was increased(P<0.05)in the OE-TLR4+Hcy group.Conclusion Hcy induces the occurrence of ferroptosis in macrophages,and Toll-like receptor 4 has a positive feedback regulatory effect on ferroptosis in macrophages.

Objective To investigate the role of Toll-like receptor 4(TLR4)in the regulation of homocys-teine(Hcy)-induced ferroptosis in macrophages.Methods Mouse macrophage cells RAW264.7 were cultured and divided into control group,Hcy intervention group(Hcy group),and Hcy plus ferroptosis inhibitor group(Hcy+Fer-1 group).After transfection with interference fragments,macrophages were treated with Hcy,and then divided into control group,Hcy intervention group(Hcy group),TLR4 interference negative control plus Hcy intervention group(si-NC+Hcy group),and TLR4 interference plus Hcy intervention group(si-TLR4+Hcy group).Macrophages were transfected with overexpression lentivirus and treated with Hcy,then were divided into control group,Hcy intervention group(Hcy group),a TLR4 overexpression negative control plus Hcy intervention group(OE-NC+Hcy group),and a TLR4 overexpression plus Hcy intervention group(OE-TLR4+Hcy group).After 48 hours of intervention,real-time fluorescent quantitative PCR and western blot were used to detect the expression levels of TLR4 in macrophages treated with Hcy;western blot was used to detect the expression levels of ferroptosis-related proteins ACSL4,GPX4,and FTH1 in macrophages,and ferrous ion assay kit to detect the concentration of Fe2+in macrophages;reactive oxygen species(ROS)assay kit and laser confocal microscopy were used to detect the content of intracellular reactive oxygen species.Results Compared with those in the control group,the expression level of the pro-ferroptosis protein ACSL4 was increased in the Hcy group(P<0.05),while the expression levels of anti-ferroptosis proteins GPX4 and FTH1 were decreased(P<0.05);the concentration of Fe2+was increased(P<0.05),and the content of ROS was increased.Meanwhile,the protein and mRNA expres-sion levels of TLR4 were both increased in the Hcy group(P<0.05).After macrophages were transfected with TLR4 interference fragments,compared with those in the si-NC+Hcy group,the expression levels of GPX4 and FTH1 were increased(P<0.05);the expression level of ACSL4 was decreased(P<0.05);the concentration of Fe2+was decreased(P<0.05),and the content of ROS was reduced in the si-TLR4+Hcy group.After macro-phages were transfected with TLR4 overexpression lentivirus,compared with those in the OE-NC+Hcy group,the expression levels of GPX4 and FTH1 were decreased(P<0.05),and the expression level of ACSL4 was increased(P<0.05)in the OE-TLR4+Hcy group.Conclusion Hcy induces the occurrence of ferroptosis in macrophages,and Toll-like receptor 4 has a positive feedback regulatory effect on ferroptosis in macrophages.

Objective·To analyze the differences and classify hypertrophic cardiomyopathy(HCM)patients and healthy controls(HC)using short-axis cine cardiac magnetic resonance(CMR)images-derived radiomics features.Methods·One hundred HCM subjects were included,and fifty HC were randomly selected at 2∶1 ratio during January 2018 to December 2021 in the Department of Cardiology,Renji Hospital,Shanghai Jiao Tong University School of Medicine.The CMR examinations were performed by experienced radiologists on these subjects.CVI 42 post-processing software was used to obtain left ventricular morphology and function measurements,including left ventricular ejection fraction(LVEF),left ventricular end-diastolic volume(LVEDV)and left ventricular end-diastolic mass(LVEDM).The 3D radiomic features of the end-diastolic myocardial region were extracted from short-axis images CMR cine.The distribution of the radiomic features in the two groups was analysed and machine learning models were constructed to classify the two groups.Results·One hundred and seven 3D radiomic features were selected and extracted.After exclusion of highly correlated features,least absolute shrinkage and selection operator(LASSO)was used,and a 5-fold cross-validation was performed.There were still 11 characteristics with non-zero coefficients.The K-best method was used to decide the top 8 features for subsequent analysis.Among them,four features were significantly different between the two groups(all P<0.05).Support vector machine(SVM)and random forest(RF)models were constructed to discriminate the two groups.The results showed that the maximum area under the curve(AUC)for the single-feature model(first order grayscale:entropy)was 0.833(95%CI 0.685?0.968)and the maximum accuracy for the multi-feature model was 83.3%with an AUC of 0.882(95%CI 0.705?0.980).Conclusion·There are significant differences in both left ventricular function and left ventricular morphology between HCM and HC.The 3D myocardial radiomic features of the two groups are also significantly different.Although single feature is able to distinguish the two groups,the combination of multi-features show better classification performance.

Purpose/Significance To grasp the technological advantages of digitization empowerment,and to explore the effective path of digitization enabling medical education.Method/Process From the three aspects of experience enhancement,content enrichment and process coordination,the function mode of digitization enabling medical education is clarified.Result/Conclusion To achieve digitization enabling medical education,it's necessary to deepen digital sharing,promote the reconstruction of digital scenes of medical education,op-timize the presentation of digital content of medical education,and coordinate the operation of digital process of medical education.

Magnetic ferrite nanoparticles (MFNPs) have great application potential in biomedical fields such as magnetic resonance imaging, targeted drugs, magnetothermal therapy and gene delivery. MFNPs can migrate under the action of a magnetic field and target specific cells or tissues. However, to apply MFNPs to organisms, further modifications on the surface of MFNPs are required. In this paper, the common modification methods of MFNPs are reviewed, their applications in medical fields such as bioimaging, medical detection, and biotherapy are summarized, and the future application directions of MFNPs are further prospected.
Ferric Compounds ; Magnetic Resonance Imaging/methods* ; Magnetics ; Magnetite Nanoparticles/therapeutic use* ; Nanoparticles

OBJECTIVE: To compare the performance of serum cancer antigen 125 (CA125), human epididymis protein 4 (HE4), Risk of Ovarian Malignancy Algorithm (ROMA) and Copenhagen index (CPH-I) for differential diagnosis of benign and malignant diseases in patients with ovarian mass. METHODS: We retrospectively analyzed the data of 719 women with pelvic mass, and the performance of preoperative serum levels of CA125 and HE4, ROMA and CPH-I for differential diagnosis of the masses was compared. RESULTS: Of the 710 women analyzed, 531 were diagnosed with benign ovarian lesions, 44 with borderline ovarian tumors (BOTs), 119 with epithelial ovarian cancers (EOCs), and 25 with non-EOCs. In differentiating ovarian cancer (OC) and BOT from benign lesions, the area under the receiver-operator characteristic (ROC) curve (AUC) was 0.854 for HE4, 0.856 for ROMA, 0.854 for CPH-I, and 0.792 for CA125, demonstrating better diagnostic performance of HE4, ROMA, and CPH-I than CA125 alone; the diagnostic sensitivity was 56.9% for HE4, 70.2% for CA125, 69.1% for ROMA, and 63.8% for CPH-I; the specificity was the best with HE4 (94.4%) and CPH-I (94.7%). In sub-analysis of EOC benign lesions, the AUCs of HE4, ROMA, and CPH-I increased to 0.946, 0.947, and 0.943, respectively, all greater than that of CA125 (0.888). In other sub-analyses, HE4, ROMA, and CPH-I all showed greater AUCs than CA125 alone. CONCLUSIONS This study confirms the accuracy of HE4, ROMA, and CPH-I for differentiating malignant from benign ovarian mass, and all these 3 tests show better performance than CA125. Furthermore, HE4 and CPH-I is superior to ROMA and CA125 in terms of specificity, while CA125 and ROMA have better diagnostic sensitivities.
Algorithms ; Biomarkers, Tumor ; CA-125 Antigen ; Carcinoma, Ovarian Epithelial ; Female ; Humans ; Neoplasms, Glandular and Epithelial ; Ovarian Neoplasms ; Proteins ; Retrospective Studies ; WAP Four-Disulfide Core Domain Protein 2

Objective To explore the effect of the treadmill exercise intervention on the behavior function and the concentration of dopamine in the striatum of the rat model of Parkinson's disease (PD).Methods Healthy male Sprague-Dawley rats were randomly divided into a sham operation quiet (Control) group,sham-operation+Exercise (Control + Ex) group,6-hydroxydopamine (6-OHDA) quiet (PD) group,and 6-OHDA+Exercise (PD + Ex) group.PD and PD + Ex groups were injected 6-OH-DA into the right medial forebrain bundle to establish the unilateral PD rat model,while the sham operation groups were injected the same amount of physiological saline at the same site.On the 7th days after modeling,the rats were subcutaneously injected Apo morphine for rotational behavior test to exclude those not meeting the requirements for the PD model.One week after the operation,the exercise group started treadmill training at the speed of 11 m/min,30 min/day and 5 days/week,for a total of four weeks.The locomotor activity of PD rats was evaluated using the open field test.The DA concentration in striatum was detected using micro dialysis high performance liquid chromatography and electrochemistry.The expression of tyrosine hydroxylase positive fiber in the striatum was assessed using the immunohistochemistry.Results Compared with the Control group,significant decrease was observed in the moving distance of PD and PD + Ex groups (P＜0.01),while significant increase was found of PD + Ex group compared with PD group after 3 and 4weeks of training (P＜0.01).Compared with the Control group,DA concentration in the striatal decreased significantly in PD and PD + Ex groups,but that of PD + Ex group increased significantly after 3 and 4weeks' training compared with the PD group (P＜0.01).Conclusion There is a highly positive correlation between the total moving distance and the DA concentration in the striatum of PD rats.The moving distance and the DA concentration both have changed "sequentially" with the prolongation of 6-OHDA and exercise intervention.The exercise intervention can reduce the DA loss of the striatum and improve the locomotor function of PD rats.It is presumed that the mechanism may be related to the neuroprotective effect of exercise,which can reduce the damage of 6-OHDA neurotoxin to DA neurons and promote their survival.

NESCA, a newly discovered signaling adapter protein in the NGF-pathway, contains a RUN domain at its N-terminus. Here we report the crystal structure of the NESCA RUN domain determined at 2.0-Å resolution. The overall fold of the NESCA RUN domain comprises nine helices, resembling the RUN domain of RPIPx and the RUN1 domain of Rab6IP1. However, compared to the other RUN domains, the RUN domain of NESCA has significantly different surface electrostatic distributions at the putative GTPase-interacting interface. We demonstrate that the RUN domain of NESCA can bind H-Ras, a downstream signaling molecule of TrkA, with high affinity. Moreover, NESCA RUN can directly interact with TrkA. These results provide new insights into how NESCA participates in the NGF-TrkA signaling pathway.
Adaptor Proteins, Signal Transducing ; chemistry ; genetics ; metabolism ; Amino Acid Sequence ; Binding Sites ; Crystallography, X-Ray ; Gene Expression ; Humans ; Models, Molecular ; Molecular Sequence Data ; Nerve Growth Factor ; chemistry ; genetics ; metabolism ; Oncogene Protein p21(ras) ; chemistry ; genetics ; metabolism ; Protein Binding ; Protein Structure, Tertiary ; Receptor, trkA ; chemistry ; genetics ; metabolism ; Recombinant Proteins ; chemistry ; genetics ; metabolism ; Sequence Homology, Amino Acid ; Signal Transduction ; rab GTP-Binding Proteins ; chemistry

1H-nuclear magnetic resonance spectroscopy ( 1H-NMRs ) analysis was performed on serum specimens obtained from 60 preoperative patients with esophageal squamous cell carcinoma ( ESCC )and 30 healthy controls, and supernatant from 2 ESCC cell lines Eca-109 and TE-13.The characteristic fingerprint was profiled with 1H-NMRs data in healthy controls.Serum 1H-NMRs from 60 preoperative patients with ESCC were measured and compared with the 1H-NMRs from 30 healthy controls.We found some specific peaks in 1H-NMRs profile of serum specimens from ESCC patients, especially at 1.0-1.2 mg/L and 3.4 - 3.6 mg/L.The results were verified by the 1H-NMRs measurement on the supernatant from 2 ESCC cell lines Eca-109 and TE-3.Our results suggest that this two absorption peaks may be characteristic for ESCC and 1H-NMRs analysis on serum specimens may provide information for early diagnosis of ESCC.