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BackgroundInternet addiction (IA) among students, worsened by Coronavirus disease 2019 (COVID-19) pandemic, has become a social problem with the digitalization of school learning and many aspects of daily life. However, few studies on IA have been conducted among students after the lifting of COVID-19 restrictions in China.MethodThis large-sample, cross-sectional, online survey was conducted to explore the characteristics of IA and the association among IA, academic satisfaction, and mental health problems from December 14, 2022 to February 28, 2023 in Sichuan, China. All participants (N = 22,605) were students in colleges and universities, recruited via their teachers and professors.ResultsOf all the participants, 14,921 (66.0%) participants had IA. Participants with IA were more likely to have depression symptom, anxiety symptom, insomnia, and lifetime suicidal ideation. In addition, participants with severe IA had significantly higher rates of mental health problems (e.g., depression, anxiety, insomnia, and suicidal ideation) than those with mild IA. A significant IA-by-academic satisfactory-interaction on mental health was identified: participants with higher level of IA showed particularly severe symptom of depression, anxiety and insomnia when affected by low satisfactory of academy (p

BackgroundAlthough the COVID-19 pandemic has greatly changed the way students studied, it is still unknown about the impact of the COVID-19 pandemic on students’ academic performance and mental health.ObjectiveTo explore the academic performance and mental health status of middle and high school students after the lifting of COVID-19 restrictions in China.MethodsAn online survey was conducted in Sichuan province, China from Dec 14, 2022 to Feb 28, 2023. All participants were students in middle and high schools, recruited via their teachers. The general information, COVID-19-related information, and academic performance were collected. The Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Internet Addiction Test (IAT) were used to assess the mental health problems.ResultsOf 60,268 participants, 36,247 (60.2%) middle and high school students reported that their studies were affected by the COVID-19 pandemic, and 24,864 (41.2%) reported that their academic performance had worsened. The prevalence of depression and anxiety symptoms was 38.4 and 32.7%, respectively. There was a significant association between academic performance change and mental health problems. The logistic regression analysis showed that improved academic performance was a protective factor for depression, and declined academic performance was a risk factor for depression and anxiety. Being COVID-19 infected, family members being infected, with quarantine experience, and with COVID-19-related stigma were risk factors for depression and anxiety.ConclusionAcademic studies and mental health status of middle and high school students in Sichuan, China have been negatively impacted by the COVID-19 pandemic, even after the lifting of COVID-19 restrictions. Students’ academic performance, academic concerns, and mental health status should be considered for educational policymakers and institutions to improve students’ academic studies and mental well-being.

PurposeEndothelial dysfunction, which was associated with chronic hypothyroidism, was an early event in atherosclerosis. Whether short-term hypothyroidism following thyroxine withdrawal during radioiodine (RAI) therapy was associated with endothelial dysfunction in patients with differentiated thyroid cancer (DTC) was unclear. Aim of the study was to assess whether short-term hypothyroidism could impair endothelial function and the accompanied metabolic changes in the whole process of RAI therapy.MethodsWe recruited fifty-one patients who underwent total thyroidectomy surgery and would accept RAI therapy for DTC. We analyzed thyroid function, endothelial function and serum lipids levels of the patients at three time points: the day before thyroxine withdrawal(P1), the day before 131I administration(P2) and 4-6 weeks after RAI therapy(P3). A high-resolution ultrasound named flow-mediated dilation (FMD) was used to measure endothelial function of the patients.ResultsWe analyzed the changes of FMD, thyroid function and lipids at three time points. FMD(P2) decreased significantly compared to FMD(P1) (P1vsP2, 8.05 ± 1.55vs 7.26 ± 1.50, p

Objective. Antithyroglobulin antibodies (TgAbs) could be used as a surrogate tumor marker of TgAb-positive-differentiated thyroid carcinoma. This study aims to determine whether the change in TgAb levels over time could be used as a predictor of responses to therapy in pediatric papillary thyroid carcinoma (PTC) patients. Methods. We retrospectively analyzed the records of 48 pediatric PTC patients with TgAb levels ≥50 IU/ml 6 months after initial 131I treatment. Suppressed thyroglobulin (Tg) levels 6 months after initial 131I treatment were used to divide the patients into positive Tg (P-Tg, Tg ≥ 0.2 ng/ml) and negative Tg (N-Tg, Tg

ObjectiveThe objective of this study was to investigate the clinicopathological characteristics, long-term outcomes, and prognostic factors of elderly patients with distant metastases at initial diagnosis from well-differentiated thyroid cancer (WDTC) during radioactive iodine (131I) treatment and follow-up.MethodsA retrospective review of medical records identified 183 elderly patients with DTC who underwent 131I treatment at our institution between 2006 and 2019.ResultsIn total, 57 elderly WDTC patients with distant metastases were enrolled in this study. After 131I treatment, 32 (56.14%) patients had 131I avidity and 25 (43.86%) had non-131I avidity; 35 (61.40%) cases were classified as radioiodine refractory (RR)-WDTC and 22 (38.60%) as non-RR-WDTC. At the end of follow-up, 25 (43.86%) patients had died and 32 (56.14%) were alive. The 5- and 10-year overall survival (OS) rates were 71.50% and 30.49%, respectively, while the 5- and 10-year disease-specific survival (DSS) rates were 76.89% and 48.71%, respectively. Multivariate analyses showed that gross extrathyroidal extension and RR-DTC were independent prognostic factors for poor OS (P=0.04 and P=0.03, respectively), while gross extrathyroidal extension, extrapulmonary distant metastases, and RR-WDTC were independent prognostic factors for poor DSS at the end of follow-up (P=0.02, P=0.03, and P=0.02, respectively).ConclusionsWDTC with distant metastases at initial diagnosis accounted for 31.15% of all elderly patients with DTC. Gross extrathyroidal extension and RR-DTC were the major factors associated with poor OS; gross extrathyroidal extension, extrapulmonary distant metastases, and RR-DTC were independent prognostic factors for poor DSS in elderly DTC patients with distant metastases.

Inflammation is crucial to tumorigenesis and progression of many cancers. Inflammatory molecules in tumor microenvironment exert pro- or anti-tumor effects. Among them, interleukin, mainly produced by CD3+ and CD4+ T lymphocytes, is a class of small molecule proteins which play an important role in intercellular communication. Numerous studies have confirmed that interleukins are closely related to thyroid cancer. Interleukins regulate the proliferation and migration of thyroid cancer cells and they have prospects in discriminating benign and malignant thyroid diseases, predicting the risk of tumorigenesis, evaluating the prognosis and monitoring the recurrence of thyroid cancer. Besides, the effective application of interleukins in treatment of thyroid cancer has been confirmed by some cell and animal researches. The present review will introduce the potential mechanisms of interleukins in thyroid cancer and focus on the applications of interleukins in clinical practice of thyroid cancer, which will help update understanding of the progress of interleukins researches in thyroid cancer.

Background: The lung is the most frequent site of distant metastasis from differentiated thyroid cancer (DTC). However, lung metastasis from papillary thyroid cancer (PTC) with persistently negative thyroglobulin (Tg) and elevated Tg antibody (TgAb) levels is an extremely rare entity, and the prognosis is therefore elusive. We investigated the clinical characteristics, long-term outcomes, and prognostic factors of lung metastases in PTC patients with persistently negative thyroglobulin (Tg) and elevated Tg antibody (TgAb) levels during radioactive iodine (131I) treatment and follow-up.Methods: We retrospectively reviewed 10,482 patients with DTC who underwent postoperative 131I treatment from 2007 to 2017 at Shanghai Sixth's People's Hospital. The relationships between progression-free survival (PFS) and several variables were assessed by univariate and multivariate analyses using the Kaplan–Meier method and a Cox proportional hazards model, respectively.Results: Forty-seven patients with PTC were enrolled in this study (4.48‰ of all patients with DTC). The median age at the initial diagnosis of lung metastasis was 39.6 ± 15.4 years, and the patients comprised 14 male and 33 female patients (male: female ratio = 1.00:2.36). Twenty-five patients had 131I avidity and 22 had non-131I avidity. At the end of the 5-years follow-up, 12 patients exhibited progressive disease (PD), and 2 patients had died. At the end of the 10-years follow-up, 21 patients showed PD and five patients had died. The 5- and 10-year PFS rates were 74.47 and 53.32%, respectively; the 5- and 10-years overall survival (OS) rates were 95.74 and 89.36%, respectively. The timing of diagnosis of lung metastases, maximal size of lung metastases, and 131I avidity were significantly associated with the 5-years PFS rate (P = 0.035, P = 0.030, and P

Background/Aims: As biomarkers, circulating tumor cells (CTCs) from solid tumors can predict metastases and prognoses, and help monitor treatment efficacy. However, conventional CellSearch methods have low sensitivity to differentiated thyroid cancer (DTC) CTCs. In this study, for the first time, we used negative enriching (NE) immunofluorescence–in situ hybridization (iFISH) of chromosome 8 to capture and identify CTCs in DTC patients; and investigated how CTCs correlate with clinicopathological factors and prognosis in DTC patients with distant metastases (DM). Methods: In this prospective study, we enrolled 72 patients with DTC before they underwent 131I treatment, and 30 healthy controls (HC). Their CTCs were measured in 7.5 ml peripheral blood using the NE–iFISH technique. CTC was defined by the aneuploidy. Results: We detected CTCs in 62 (86.1%) of the 72 subjects with DTC. The mean number of CTCs in patients with DTC with DM (DM+) was significantly higher than in the HC group (P< 0.001) and DTC patients without DM (DM-; P=0.0016). We found CTCs ≥ 5 was significantly associated with DM+ DTC (P=0.009; sensitivity: 64.3%; specificity: 83.8%); CTCs ≥ 7 was related to poor response to 131I treatment (sensitivity: 73.7 %; specificity: 69.6 %), and was also associated with worse prognosis in DM+ DTC (P< 0.001). Conclusion: We found CTCs ≥ 5 to be a potential predictive index for DM+ DTC; and CTCs ≥7 as a possible indicator of poor response to 131I treatment and worse prognosis in DM+ DTC.

Abstract Differentiated thyroid cancer (DTC) patients with negative serum thyroglobulin (Tg), negative 131I whole–body scintigraphy (131I-WBS) at first post-ablation and progressively increased TgAb level are a relatively rare entity in the follow-up after total thyroidectomy and radioactive iodine therapy. The value of 18F-FDG PET/CT in detecting the recurrence of disease in these patients has only been reported in a small case series. The goal of this study was to investigate the diagnostic accuracy of 18F-FDG PET/CT in detecting recurrent disease in these specific PTC patients and to identify risk factors for patients with positive 18F-FDG PET/CT results. Eighty-two PTC patients who had 18F-FDG PET/CT scans with negative Tg, negative 131I-WBS at first post-ablation and progressively increased TgAb levels were included. We found that the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 18F-FDG PET/CT in this patient group were determined as 84%, 72%, 92%, 57% and 82%, respectively. 18F-FDG PET/CT scan had a good diagnostic performance and should be performed routinely in PTC patients with negative Tg, negative 131I-WBS at first postablation and progressively increased TgAb level, especially when span for progressively increased TgAb level ≥ 3 years and/or progressively increased TgAb value up to 150 IU/mL.

Purpose: The aims of the current study were to explore plasma lncRNAs as a novel biomarker panel for the diagnosis of non-131I-avid lung metastases of PTC and to investigate the plasma lncRNA expression levels associated with survival in PTC patients with lung metastases. Methods: The expression of lncRNAs was examined using an lncRNA microarray chip. The lncRNAs with the most significant difference in expression between PTC patients with non-131I-avid lung metastases and PTC patients with 131I-avid lung metastases were verified by quantitative reverse-transcription polymerase chain reaction. The Kaplan-Meier method was used to determine whether the plasma lncRNA levels might be indicative of patient prognosis. Results: Compared with 131I-avid lung metastases, we discovered that two lncRNAs (ENST00000462717 andENST00000415582) were upregulated and two (TCONS_00024700 and NR_028494) were downregulated in the non-131I-avid lung metastases of PTC. Receiver operating characteristic curve (ROC) analyses indicated that the use of these four lncRNAs had high diagnostic sensitivity and specificity for predicting non-131I-avid lung metastases of PTC. The merged areas under the curve for ENST00000462717, ENST00000415582, TCONS_00024700,and NR_028494 in the training and validation sets were 0.890, 0.936, 0.975, and 0.918, respectively. Low (ENST00000462717 and ENST00000415582) and high plasma lncRNA levels(TCONS_00024700and NR_028494) were also found to be associated with better prognosis of PTC patients with lung metastases(PConclusions: ENST00000462717, ENST00000415582, TCONS_00024700, and NR_028494 may be used as novel and minimally invasive markers for the diagnosis and prognostic assessment of non-131I-avid lung metastases from PTC.

The spaceborne wide-area surveillance mode, achieved by a modified TOPSAR mode, is proposed for maritime monitoring. In the proposed mode, the requirements of detecting targets from different aspect angles with a high revisit rate can be satisfied by modifying the TOPSAR mode which steers antenna in the azimuth direction. The feasibility as well as its application in maritime monitoring are validated by theoretical analysis and simulation experiments.

Radioiodine treatment is a fundamental therapy for patients with papillary thyroid cancer (PTC). Sodium/iodide symporter (NIS)-mediated iodine uptake is a prerequisite for the efficacy of radioiodine therapy. Interleukin-6 (IL-6) is a pro-tumor cytokine, but its regulation of NIS expression in PTC has not been elucidated. In this study, we found that IL-6 enhanced the proliferation ability of PTC cells. Moreover, the negative association between IL-6 and NIS expression in thyroid cancer tissues was demonstrated. IL-6 downregulated thyroid-specific genes such as NIS, thyroid peroxidase, and thyroidstimulating hormone receptor and thyroid-specific transcription factors including thyroid transcription factor-1 (TTF-1) and paired box protein-8 (PAX-8). The inhibitory effects of IL-6 on NIS expression were alleviated by mitogen-activated protein kinase and Janus kinase inhibitors. Depletion of c-Jun or STAT3 also rescued IL-6-induced NIS downregulation, with STAT3 depletion exerting a stronger effect. TTF-1 protein expression was also restored by depleting c-Jun or STAT3. STAT3 depletion, but not c-Jun depletion, alleviated the inhibitory effect of IL-6 on PAX-8 expression. Moreover, the downregulation of NIS by IL-6 was rescued by overexpressing TTF-1 and PAX-8. Tocilizumab, an IL-6 receptor blocker, did not have any cytostatic activity in PTC cells, and it also failed to induce redifferentiation in vitro. However, we found that the drug blocked the inhibitory effect of IL-6 on NIS expression. In summary, IL-6 inhibits NIS transcription in PTC cells by activating mitogen-activated protein kinase and Janus kinase signaling. [ABSTRACT FROM AUTHOR]

Context: Pregnancy-related hormones may stimulate thyroid cancer growth, but whether pregnancy affects the prognoses of patients with lung metastases from differentiated thyroid cancer (DTC-LM) after surgery and radioiodine therapy is unclear.Objective: To assess the impact of pregnancy on DTC-LM through the comparison of prognoses between female patients with DTC-LM who did and did not become pregnant after surgery and radioiodine therapy.Methods: We retrospectively analyzed the records of 124 female patients aged 16 to 35 years who underwent surgery and radioiodine therapy for DTC-LM. These patients were divided into pregnancy group (n = 37) and nonpregnancy group (n = 87) according to whether they became pregnant after surgery and radioiodine therapy, regardless of whether they had a pregnant history before treatment.Results: The 5- and 10-year progression-free survival rates were 94.52% and 63.22% in pregnancy group versus 89.82% and 58.13% in nonpregnancy group. The 5- and 10-year cumulative overall survival rates of pregnancy group were 97.30% and 85.77% versus 93.50% and 81.95% in nonpregnancy group (all P > 0.05). The median time of follow-up in the pregnancy and nonpregnancy groups was 82 months (25-136 months) and 68 months (13-133 months), respectively. Non-radioiodine-avid LM and primary tumors needing repeated resection were independent predictors of poor progression-free survival for patients in pregnancy group.Conclusion: Pregnancy does not affect the prognoses of patients with DTC-LM after surgery and radioiodine therapy. Non-radioiodine-avid LM and repeated primary tumor surgeries are independent risk factors for poor prognoses of pregnant patients. [ABSTRACT FROM AUTHOR]

Purpose: The aims of the current study were to explore plasma lncRNAs as a novel biomarker panel for the diagnosis of non-131I-avid lung metastases of PTC and to investigate the plasma lncRNA expression levels associated with survival in PTC patients with lung metastases. Methods: The expression of lncRNAs was examined using an lncRNA microarray chip. The lncRNAs with the most significant difference in expression between PTC patients with non-131I-avid lung metastases and PTC patients with 131I-avid lung metastases were verified by quantitative reverse-transcription polymerase chain reaction. The Kaplan-Meier method was used to determine whether the plasma lncRNA levels might be indicative of patient prognosis. Results: Compared with 131I-avid lung metastases, we discovered that two lncRNAs (ENST00000462717 andENST00000415582) were upregulated and two (TCONS_00024700 and NR_028494) were downregulated in the non-131I-avid lung metastases of PTC. Receiver operating characteristic curve (ROC) analyses indicated that the use of these four lncRNAs had high diagnostic sensitivity and specificity for predicting non-131I-avid lung metastases of PTC. The merged areas under the curve for ENST00000462717, ENST00000415582, TCONS_00024700,and NR_028494 in the training and validation sets were 0.890, 0.936, 0.975, and 0.918, respectively. Low (ENST00000462717 and ENST00000415582) and high plasma lncRNA levels(TCONS_00024700and NR_028494) were also found to be associated with better prognosis of PTC patients with lung metastases(P<0.001). Conclusions: ENST00000462717, ENST00000415582, TCONS_00024700, and NR_028494 may be used as novel and minimally invasive markers for the diagnosis and prognostic assessment of non-131I-avid lung metastases from PTC. [ABSTRACT FROM AUTHOR]

Background: Serum miRNAs profiles between papillary thyroid carcinoma (PTC) patients with non-131I and 131I-avid lung metastases are differentially expressed. These miRNAs have to be further validated and the role of these miRNAs in the molecular function level of thyroid cancer cell lines has not been investigated. Methods: Expression levels of six identified miRNAs were assessed via quantitative real-time PCR (qRT-PCR) in the serum of eligible patients. Dual-luciferase reporter assay was used to determine the potential target of miR-106a. Cell viability and apoptosis were evaluated by MTT assay and flow cytometry analysis, respectively. The change of gene expression was detected by qRT-PCR and western blotting analysis. In vitro iodine uptake assay was conducted by a λ-counter. Results: Compared to PTC patients with 131I-avid lung metastases, miR-106a was up-regulated in the serum of patients with non-131I-avid lung metastases. The results of dual-luciferase reporter assay demonstrated that miR-106a directly targeted retinoic acid receptor beta (RARB) 3'-UTR. miR-106a-RARB promoted viability of thyroid cancer cells by regulating MEKK2-ERK1/2 and MEKK2-ERK5 pathway. miR-106a-RARB inhibited apoptosis of thyroid cancer cells by regulating ASK1-p38 pathway. Moreover, miR-106a-RARB could regulate the expression of sodium iodide symporter, TSH receptor and alter the iodine uptake function of thyroid cancer cells. Conclusions: miRNA-106a, directly targeting RARB, associates with the viability, apoptosis, differentiation and the iodine uptake function of thyroid cancer cell lines by regulating MAPK signaling pathway in vitro. These findings in the present study may provide new strategies for the diagnosis and treatment in radioiodine-refractory differentiated thyroid carcinoma. [ABSTRACT FROM AUTHOR]

Context: Data from a large cohort of patients with pulmonary metastases from differentiated thyroid cancer (DTC) were retrospectively analyzed. Objective: To assess the effect of radioiodine therapy and investigate the prognostic factors of survival for patients with pulmonary metastasis secondary to DTC. Methods: A total of 372 patients with pulmonary metastasis from DTC treated with 131I entered the study. According to the results of 131I whole-body scan (WBS), pulmonary metastases were classified as 131I-avid and non-131I-avid. For patients with 131I-avid lung metastases, treatment response was measured by three parameters: serum thyroglobulin (Tg) levels, chest computed tomography (CT) and post-therapeutic 131I-WBS. Overall survival was calculated by the Kaplan-Meier method. Factors predictive of the outcome were determined by multivariate analyses. Results: Among patients demonstrating 131I-avid pulmonary metastases (256/372, 68.8%), 156 cases (156/256, 60.9%) showed a significant decrease in serum Tg levels after 131I therapy and 138 cases (138/229, 60.3%) showed a reduction in pulmonary metastases on follow-up CT. A complete cure, however, was only achieved in 62 cases (62/256, 24.2%). Multivariate analysis showed that only age, the presence of multiple distant metastases and pulmonary metastatic node size were significant independent variables between the groups of 131I-avid and non-131I-avid. Conclusion: This study indicated that, most 131I-avid pulmonary metastases from DTC can obtain partial or complete remission after131I therapy. Younger patients (<40 years old) with only pulmonary metastases and small ('fine miliaric' or micronodular) metastases appear to have relative favorite outcomes. Patients who do not respond to 131I treatment have a worse prognosis. [ABSTRACT FROM AUTHOR]

Differentiated thyroid cancer (DTC) is usually indolent with good prognosis and long-term survival. However, DTC distant metastasis is often a grave event and accounts for most of its disease-specific mortality. The major sites of distant metastases are the lung and bone. Metastases to the brain, breast, liver, kidney, muscle, and skin are rare or relatively rare. Nevertheless, recognizing rare metastases from DTC has a significant impact on the clinical decision making and prognosis of patients. 131I single photon emission computed tomography/computed tomography (131I-SPECT/CT) can provide both metabolic and anatomic information about a lesion; therefore, it can better localize and define the 131I-WBS findings in DTC patients. In this pictorial review, the imaging features of a range of rare metastases from DTC are demonstrated, with a particular emphasis on the 131I-SPECT/CT diagnostic aspect. [ABSTRACT FROM AUTHOR]

The residents' consumption tilting motive is one of the most important factors that determine the balance of current accounts. If the residents of a country are comparatively patient in consumption and tend to tilt their income for future consumption, current accounts will increase. Conversely, if the residents are relatively impatient and tend to consume in advance, current accounts will drop. Based on a co-integration analysis of the balance of current accounts and the value of net foreign assets in China, we have found that in our country the subjective discount factor of the residents is larger than the discount factor in the world market, so the Chinese residents are more patient in consumption. It can be concluded that the consumption tilting motive is one of the important factors affecting the current account surplus in China. [ABSTRACT FROM AUTHOR]

Background. Parapharyngeal metastasis is a rare event in differentiated thyroid carcinoma (DTC). The 131I-single photon emission CT (SPECT)/CT allows better localization and definition for metastases in DTC. The aim of this study was to assess the value of 131I-SPECT/CT for the diagnosis of parapharyngeal metastasis in patients with DTC. Methods. Consecutive patients with DTC (n = 561) treated with 131I for the ablation of remnant or treatment of metastases were enrolled. A 131I-SPECT/CT was performed when there were abnormal findings indicative of parapharyngeal metastasis on 131I-whole-body scan (WBS). Results. A total of 15 lesions were found to be parapharyngeal metastasis in 14 of 561 patients with DTC after the use of 131I-SPECT/CT. The incidence rate of parapharyngeal metastasis was about 2.5% in DTC. Of the 15 lesions, only 5 lesions were CT-positive. The remaining 10 lesions were either ignored or indeterminate by the CT alone. Conclusion. The 131I-SPECT/CT can identify parapharyngeal metastasis at an early stage. Parapharyngeal metastasis in DTC is relatively frequent after the use of 131I-SPECT/CT. [ABSTRACT FROM AUTHOR]

The generation of new neurons from neural stem cells is restricted to two regions of the adult mammalian central nervous system: the subventricular zone of the lateral ventricle, and the subgranular zone of the hippocampal dentate gyrus. In both regions, signals provided by the microenvironment regulate the maintenance, proliferation and neuronal fate commitment of the local stem cell population. The identity of these signals is largely unknown. Here we show that adult hippocampal stem/progenitor cells (AHPs) express receptors and signalling components for Wnt proteins, which are key regulators of neural stem cell behaviour in embryonic development. We also show that the Wnt/β-catenin pathway is active and that Wnt3 is expressed in the hippocampal neurogenic niche. Overexpression of Wnt3 is sufficient to increase neurogenesis from AHPs in vitro and in vivo. By contrast, blockade of Wnt signalling reduces neurogenesis from AHPs in vitro and abolishes neurogenesis almost completely in vivo. Our data show that Wnt signalling is a principal regulator of adult hippocampal neurogenesis and provide evidence that Wnt proteins have a role in adult hippocampal function. [ABSTRACT FROM AUTHOR]

Netrins are a family of secreted molecules that are important for axonal outgrowth and guidance in the developing nervous system. However, the signaling mechanisms that lie immediately downstream of netrin receptors remain poorly understood. Here we report that the netrin receptor DCC (deleted in colorectal cancer) interacts with the focal adhesion kinase (FAK), a kinase implicated in regulating cell adhesion and migration. FAK was expressed in developing brains and was localized with DCC in cultured neurons. Netrin-1 induced FAK and DCC tyrosine phosphorylation. Disruption of FAK signaling abolished netrin-1-induced neurite outgrowth and attractive growth cone turning. Taken together, these results indicate a new signaling mechanism for DCC, in which FAK is activated upon netrin-1 stimulation and mediates netrin-1 function; they also identify a critical role for FAK in axon navigation. [ABSTRACT FROM AUTHOR]

Examines the role of gradients of extracellular guidance factors in axonal growth. Adaptation of spinal neurons in chemotactic migration; Sensitization in increasing basal concentrations of the guidance factor netrin-1; Benefits of the adaptive behavior of neurons in long-range chemotaxis.

More aggressive thyroid cancer cells show a higher activity of glycometabolism. Targeting cancer cell metabolism has emerged as a novel approach to prevent or treat malignant tumors. Glucose metabolism regulation effect of metformin in papillary thyroid cancer was investigated in the current study. Human papillary thyroid carcinoma (PTC) cell lines BCPAP and KTC1 were used. Cell viability was detected by CCK8 assay. Glucose uptake and relative gene expression were measured in metformin (0-10 mM for 48 h)-treated cells by 18F-FDG uptake assay and western blotting analysis, respectively. MicroPET/CT imaging was performed to detect 18F-FDG uptake in vivo. After treatment with metformin at 0, 2.5, 5 and 10 mM for 48 h, the ratio of p-AMPK to total AMPK showed significant rising in a dose-dependent manner in both BCPAP and KTC1, whereas p-AKT and p-mTOR expression level were downregulated. 18F-FDG uptake reduced after metformin treatment in a dose-dependent manner, corresponding to the reduced expression level of HK2 and GLUT1 in vitro. Xenograft model of PTC using BCPAP cells was achieved successfully. MicroPET/CT imaging showed that in vivo 18F-FDG uptake decreased after treatment with metformin. Immunohistochemistry staining further confirmed the reduction of HK2 and GLUT1 expression in the tumor tissue of metformintreated PTC xenograft model. In conclusion, metformin could reduce glucose metabolism of PTC in vitro and in vivo. Metformin, by targeting glycometabolism of cancer cells, could be a promising adjuvant therapy alternative in the treatment modality of advanced thyroid carcinoma. [ABSTRACT FROM AUTHOR]