分类： 生物学 >> 生物物理学 >> 细胞生物学 提交时间： 2016-05-12
Wei, Yan
Han, Chanshuai
Wang, Yujing
Wu, Beibei
Su, Tao
Liu, Ying
He, Rongqiao
Wang, Yujing
Wu, Beibei
Liu, Ying
He, Rongqiao
摘要： Type 2 diabetes mellitus (T2DM) is regarded as one of the serious risk factors for age-related cognitive impairment; however, a causal link between these two diseases has so far not been established. It was recently discovered that, apart from high D-glucose levels, T2DM patients also display abnormally high concentrations of uric D-ribose. Here, we show for the first time that the administration of D-ribose, the most active glycator among monosaccharides, produces high levels of advanced glycation end products (AGEs) and, importantly, triggers hyperphosphorylation of Tau in the brain of C57BL/6 mouse and neuroblastoma N2a cells. However, the administration of D-glucose showed no significant changes in Tau phosphorylation under the same experimental conditions. Crucially, suppression of AGE formation using an AGEs inhibitor (aminoguanidine) effectively prevents hyperphosphorylation of Tau protein. Further study shows AGEs resulted from ribosylation activate calcium-/calmodulin-dependent protein kinase type II (CaMKII), a key kinase responsible for Tau hyperphosphorylation. These data suggest that there is indeed a mechanistic link between ribosylation and Tau hyperphosphorylation. Targeting ribosylation by inhibiting AGE formation may be a promising therapeutic strategy to prevent Alzheimer's disease-like Tau hyperphosphorylation and diabetic encephalopathies.
分类： 生物学 >> 生物物理学 >> 肿瘤学 提交时间： 2016-05-11
Wu, Beibei
Wei, Yan
Wang, Yujing
Su, Tao
Liu, Ying
He, Rongqiao
He, Rongqiao
He, Rongqiao
Wu, Beibei
Wang, Yujing
Zhou, Lei
摘要： In addition to D-Glucose, D-Ribose is also abnormally elevated in the urine of type 2 diabetic patients, establishing a positive correlation between the concentration of uric D-Ribose and the severity of diabetes. Intraperitoneal injection of D-Ribose causes memory loss and brain inflammation in mice. To simulate a chronic progression of age-related cognitive impairment, we orally administered D-Ribose by gavage at both a low and high dose to 8 week-old male C57BL/6J mice daily for a total of 6 months, followed by behavioral, histological and biochemical analysis. We found that long-term oral administration of D-Ribose impairs spatial learning and memory, accompanied by anxiety-like behavior. Tau was hyperphosphorylated at AT8, S396, S214 and T181 in the brain. A beta-like deposition was also found in the hippocampus for the high dose group. D-Glucose-gavaged mice did not show significant memory loss and anxiety-like behavior under the same experimental conditions. These results demonstrate that a long-term oral administration of D-Ribose not only induces memory loss with anxiety-like behavior, but also elevates A beta-like deposition and Tau hyperphosphorylation, presenting D-Ribose-gavaged mouse as a model for agerelated cognitive impairment and diabetic encephalopathy.
分类： 医学、药学 >> 临床医学 提交时间： 2023-10-09 合作期刊: 《中国全科医学》
摘要： Background Breast cancer has become the most common malignant tumor threatening the health of Chinese women in recent years. The use of tamoxifen（TAM）has successfully reduced the recurrence and progression of estrogen receptor-positive breast cancer, however, it also increases the risk of endometrial lesions. Objective To explore the risk factors for endometrial lesions in breast cancer patients taking TAM, determine the optimal threshold value of endometrial thickness, and improve the positive detection rate of hysteroscopy. Methods Breast cancer patients taking TAM（20 mg/d）who underwent hysteroscopic endometrial biopsy admitted to theDepartment of Gynecology of the First Affiliated Hospital with Nanjing Medical University from January 2015 to January 2022 were retrospectively selected as the study objects and divided into the negative hysteroscopicendometrial biopsy group（normal endometrium）and positive hysteroscopic endometrial biopsy group（endometrial lesions including endometrial polyps, endometrial hyperplasia without atypia, endometrial atypical hyperplasia and endometrial carcinoma）. Clinical data of the patients were collected, including age, BMI, history of hypertension and diabetes, delivery times, presence of menopause and abnormal uterine bleeding/postmenopausal bleeding（AUB/PMB）, receiving of chemotherapy, duration of TAM treatment, use of gonadotropin-releasing hormone agonists（GnRH-a）, endometrial thickness, echo features of intrauterine lesions. Multivariate Logistic regression analysis was used to explore the risk factors for endometrial lesions in breast cancer patients taking TAM. The receiver operating characteristic（ROC）curve of endometrial thickness for predicting endometrial lesions detected by hysteroscopy was plotted, and the area under the ROC curve（AUC）and its 95%CI were calculated to determine the optimal cut-off value of endometrial thickness for receiving hysteroscopic surgery. Results The proportion of patients with AUB/PMB, duration of TAM treatment 24 months, intrauterine hyperechoic lesions and endometrial thickness in the positive hysteroscopic endometrial biopsy group were higher than those in the negative hysteroscopic endometrial biopsy group（P<0.05）. Multivariate Logistic regression analysis showed that AUB/PMB〔OR=7.731, 95%CI（1.949, 30.699）, P=0.004〕, endometrial thickening〔OR=1.223, 95%CI（1.091, 1.371）, P=0.001〕 and intrauterine hyperechoic lesions〔OR=13.383, 95%CI（2.751, 65.103）, P=0.001〕were independent risk factors for endometrial lesions detected by hysteroscopy in breast cancer patients taking TAM. The AUC of endometrial thickness for predicting endometrial lesions detected by hysteroscopy in breast cancer patients taking TAM was 0.753〔95%CI（0.638, 0.868）, P<0.001〕, with the Youden index of 0.54, optimal cut-off value of 9.15 mm, sensitivity and specificity of 0.755 and 0.786, respectively. Conclusion The risk of endometrial lesions is increased in breast cancer patients taking TAM with AUB/PMB, endometrial thickness 9.15 mm suggested by ultrasound and intrauterine hyperechoic lesions, when the hysteroscopy and endometrial biopsy should be actively considered.
分类： 计算机科学 >> 计算机科学的集成理论 提交时间： 2022-11-27 合作期刊: 《数据智能（英文）》
摘要： Knowlege is important for text-related applications. In this paper, we introduce Microsoft Concept Graph, a knowledge graph engine that provides concept tagging APIs to facilitate the understanding of human languages. Microsoft Concept Graph is built upon Probase, a universal probabilistic taxonomy consisting of instances and concepts mined from the Web. We start by introducing the construction of the knowledge graph through iterative semantic extraction and taxonomy construction procedures, which extract 2.7 million concepts from 1.68 billion Web pages. We then use conceptualization models to represent text in the concept space to empower text-related applications, such as topic search, query recommendation, Web table understanding and advertisements relevance. Since the release in 2016, Microsoft Concept Graph has received more than 100,000 page views, 2 million API calls and 3,000 registered downloads from 50,000 visitors over 64 countries.
分类： 物理学 >> 普通物理:统计和量子力学,量子信息等 提交时间： 2017-05-02
Bi, YJ [Bi, Yujing][ 1 ]
Yang, WC [Yang, Wenchao][ 1 ]
Du, R [Du, Rui][ 1 ]
Zhou, JJ [Zhou, Jingjing][ 1 ]
Liu, M [Liu, Meng][ 1 ]
Liu, Y [Liu, Yang][ 1 ]
Wang, DY [Wang, Deyu][ 1 ]
摘要： In this work, we investigate the influence of oxygen non-stoichiometry on the characteristics of LiNi0.8Co0.1Mn0.1O2 cathode material. Among the investigated samples, the level of Ni/Li disorder in the bulk and the thickness of auto-generated layer on the surface share the same trend as the amount of oxygen loss in LiNi0.8Co0.1Mn0.1O2 materials. It indicates that the aforementioned key structural in- stabilities should be tightly related to the oxygen defects and the induced structural relaxation. As a consequence of structural entirety, the sample with the least defects presents the highest discharge capacity (192.9 mAhg 1 at 0.1C), the best rate capability (160.1 mAhg 1 at 5C), and the most stable cyclibility (89.9% at 200th). Our results demonstrate that oxygen deficiency plays a key role to determine the electrochemical performance of high-nickel cathode materials.
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