NMDA receptor internalization down-regulates NMDA receptor-mediated synaptic responses through the inhibition of remaining (non-internalized) surface NMDA receptors

Cell-surface protein endocytosis is critically involved in the regulation of organismal homeostasis, immune responses, development and neurotransmission [1,2,3,4]. Mechanisms underlying the endocytosis of cell surface proteins have been extensively investigated. However, until very recently no study has reported how non-internalized cell surface proteins may behave following endocytosis of same type of proteins. Here, we highlight findings that regulated NMDA receptor (NMDAR) internalization not only reduces the amount of NMDARs expressed on neuronal surface but also through activating PKD1 pathway phosphorylates and down-regulates remaining (non-internalized) surface NMDARs. This down-regulation of remaining surface NMDARs plays a critical role in the modulation of NMDAR-mediated synaptic responses by NMDAR internalization

Experimental Study on Performance of Two-phase Ejector Refrigeration Cycle System with Two-throat Nozzle

The two-phase ejector refrigeration cycle (TPERC) system with a two-throat nozzle ejector was investigated experimentally, and the entrainment ratio of the ejector and the COP of the system were compared with those of the ejector with Laval nozzle and the TPERC system respectively. The experimental results indicate that the entrainment ratios of the two-throat nozzle ejectors with different geometric size are greater than those of the Laval nozzle ejectors under the working condition of the evaporating/condensing temperatures 1?/45?, the maximum increment of the entrainment ratio is about 18%, and the COP of the TPERC system with two-throat nozzle ejector is greater than that of the TPERC system with Laval nozzle ejector, the maximum increment of the COP is about 12%. Under the condition of the fixed evaporating temperature 1?, the entrainment ratios of both the two-throat nozzle ejector and the Laval nozzle ejector achieve the maximum values as the condensing temperature is about 45?. Under the condition of the fixed condensing temperature 50?, the entrainment ratios of the two types of ejectors achieve the maximum values as the evaporating temperature is about 3?

Methological quality of systematic reviews and meta-analyses on acupuncture for stroke: a review of review

Objective: To assess the methodological quality of systematic reviews and meta-analyses regarding acupuncture intervention for stroke and the primary studies within them. Methods: Two researchers searched PubMed, Cumulative index to Nursing and Allied Health Literature, Embase, ISI Web of Knowledge, Cochrane, Allied and Complementary Medicine, Ovid Medline, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Wanfang and Traditional Chinese Medical Database to identify systematic reviews and meta-analyses about acupuncture for stroke published from the inception to December 2016. Review characteristics and the criteria for assessing the primary studies within reviews were extracted. The methodological quality of the reviews was assessed using adapted Oxman and Guyatt Scale. The methodological quality of primary studies was also assessed. Results: Thirty-two eligible reviews were identified, 15 in English and 17 in Chinese. The English reviews were scored higher than the Chinese reviews (P=0.025), especially in criteria for avoiding bias and the scope of search. All reviews used the quality criteria to evaluate the methodological quality of primary studies, but some criteria were not comprehensive. The primary studies, in particular the Chinese reviews, had problems with randomization, allocation concealment, blinding, dropouts and withdrawals, intent-to-treat analysis and adverse events. Conclusions: Important methodological flaws were found in Chinese systematic reviews and primary studies. It was necessary to improve the methodological quality and reporting quality of both the systematic reviews published in China and primary studies on acupuncture for stroke

Conspicuity of breast lesions at different b values on diffusion-weighted imaging

BACKGROUND: Diffusion-weighted (DW) imaging has shown potential to differentiate between malignant and benign breast lesions. However, different b values have been used with varied sensitivity and specificity. This study aims to prospectively evaluate the influence of b value on the detection and assessment of breast lesions. METHODS: Institutional review board approval and informed patient consent were obtained. Between February 2010 and September 2010, sixty women suspected of having breast cancer by clinical examination and mammography underwent bilateral breast MRI and DW imaging (with maximum b values of 600, 800, and 1000 s/mm(2)). Conspicuity grades of lesions at different b values on DW images were performed. Signal intensity and apparent diffusion coefficient (ADC) values were recorded and compared among different b values by the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and receiver operating characteristic (ROC) curve. RESULTS: Fifty-seven lesions from 52 recruited patients including 39/57 (68%) malignant and 18/57 (32%) benign were confirmed with pathology. DCE MRI accurately detected 53 lesions with the sensitivity of 93.0% and specificity of 66.7%, and DW imaging accurately detected 51 lesions with the sensitivity of 89.5% and specificity of 100%. There were no significant differences in conspicuity grades compared among the three b values (P = 0.072), although the SNR and CNR of breast lesions decreased significantly with higher b values. Mean ADCs of malignant lesions (b = 600 s/mm(2), 1.07 ± 0.26 × 10(-3) mm(2)/s; b = 800 s/mm(2), 0.96 ± 0.22 × 10(-3) mm(2)/s; b = 1000 s/mm(2), 0.92 ± 0.26 × 10(-3) mm(2)/s) were significantly lower than those of benign lesions (b = 600 s/mm(2), 1.55 ± 0.40 × 10(-3) mm(2)/s; b = 800 s/mm(2), 1.43 ± 0.38 × 10(-3) mm(2)/s; b = 1000 s/mm(2), 1.49 ± 0.38 × 10(-3) mm(2)/s) with all P values <0.001, but there were no significant differences among the three b values (P = 0.303 and 0.840 for malignant and benign lesions, respectively). According to the area under the ROC curves, which were derived from ADC and differentiate malignant from benign lesions, no significant differences were found among the three b values (P = 0.743). CONCLUSIONS: DW imaging is a potential adjunct to conventional MRI in the differentiation between malignant and benign breast lesions. Varying the maximum b value from 600 to 1000 s/mm(2) does not influence the conspicuity of breast lesions on DW imaging at 1.5 T

Improving myopia awareness via school-based myopia prevention health education among Chinese students

AIM: To investigate the myopia awareness level, knowledge, attitude, and skills at baseline and to implement and evaluate the efficacy of myopia prevention health education among Chinese students. METHODS: A total of 1000 middle school students from 2 middle schools were invited to participate in the study, and myopia prevention health education was conducted. The students were assessed at baseline, followed by a survey. The efficacy of health education was evaluated using the self-comparison method pre- and post-health education. RESULTS: The study included 957 and 850 pre- and post-health education participants, respectively. The baseline knowledge of all respondents on myopic symptoms (87.5%), myopia is a risk of eyes (72.9%), myopia prevention (91.3%), myopia increases with age (86.7%), performing periodic eye examinations (92.8%), and one first, one foot, and one inch (84.8%) significantly increased after health education (P&#x003C;0.001 for all). However, the percentage of students who still did not think it necessary to take breaks after 30-40min of continuous near work was 27.0%. The opinion that “myopia can be cured” was still present in 38.3%. CONCLUSION: Implementing school-based myopia prevention health education improves knowledge, attitudes, and skills regarding myopia among Chinese middle school students

Towards a global One Health index: a potential assessment tool for One Health performance

BACKGROUND: A One Health approach has been increasingly mainstreamed by the international community, as it provides for holistic thinking in recognizing the close links and inter-dependence of the health of humans, animals and the environment. However, the dearth of real-world evidence has hampered application of a One Health approach in shaping policies and practice. This study proposes the development of a potential evaluation tool for One Health performance, in order to contribute to the scientific measurement of One Health approach and the identification of gaps where One Health capacity building is most urgently needed. METHODS: We describe five steps towards a global One Health index (GOHI), including (i) framework formulation; (ii) indicator selection; (iii) database building; (iv) weight determination; and (v) GOHI scores calculation. A cell-like framework for GOHI is proposed, which comprises an external drivers index (EDI), an intrinsic drivers index (IDI) and a core drivers index (CDI). We construct the indicator scheme for GOHI based on this framework after multiple rounds of panel discussions with our expert advisory committee. A fuzzy analytical hierarchy process is adopted to determine the weights for each of the indicators. RESULTS: The weighted indicator scheme of GOHI comprises three first-level indicators, 13 second-level indicators, and 57 third-level indicators. According to the pilot analysis based on the data from more than 200 countries/territories the GOHI scores overall are far from ideal (the highest score of 65.0 out of a maximum score of 100), and we found considerable variations among different countries/territories (31.8–65.0). The results from the pilot analysis are consistent with the results from a literature review, which suggests that a GOHI as a potential tool for the assessment of One Health performance might be feasible. CONCLUSIONS: GOHI—subject to rigorous validation—would represent the world’s first evaluation tool that constructs the conceptual framework from a holistic perspective of One Health. Future application of GOHI might promote a common understanding of a strong One Health approach and provide reference for promoting effective measures to strengthen One Health capacity building. With further adaptations under various scenarios, GOHI, along with its technical protocols and databases, will be updated regularly to address current technical limitations, and capture new knowledge. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40249-022-00979-9

S1PR1 regulates ovarian cancer cell senescence through the PDK1-LATS1/2-YAP pathway

Cell senescence deters the activation of various oncogenes. Induction of senescence is, therefore, a potentially effective strategy to interfere with vital processes in tumor cells. Sphingosine-1-phosphate receptor 1 (S1PR1) has been implicated in various cancer types, including ovarian cancer. The mechanism by which S1PR1 regulates ovarian cancer cell senescence is currently elusive. In this study, we demonstrate that S1PR1 was highly expressed in human ovarian cancer tissues and cell lines. S1PR1 deletion inhibited the proliferation and migration of ovarian cancer cells. S1PR1 deletion promoted ovarian cancer cell senescence and sensitized ovarian cancer cells to cisplatin chemotherapy. Exposure of ovarian cancer cells to sphingosine-1-phosphate (S1P) increased the expression of 3-phosphatidylinositol-dependent protein kinase 1 (PDK1), decreased the expression of large tumor suppressor 1/2 (LATS1/2), and induced phosphorylation of Yes-associated protein (p-YAP). Opposite results were obtained in S1PR1 knockout cells following pharmacological inhibition. After silencing LATS1/2 in S1PR1-deficient ovarian cancer cells, senescence was suppressed and S1PR1 expression was increased concomitantly with YAP expression. Transcriptional regulation of S1PR1 by YAP was confirmed by chromatin immunoprecipitation. Accordingly, the S1PR1-PDK1-LATS1/2-YAP pathway regulates ovarian cancer cell senescence and does so through a YAP-mediated feedback loop. S1PR1 constitutes a druggable target for the induction of senescence in ovarian cancer cells. Pharmacological intervention in the S1PR1-PDK1-LATS1/2-YAP signaling axis may augment the efficacy of standard chemotherapy.</p