Chelating this magnesium influx or inhibiting P38 mitogen-activated protein kinase (p38 MAPK) blocked the delayed pCREB by NMDA. Finally, we found that NMDAR signaling in the absence of extracellular calcium activates p38 MAPK. Our studies thus indicate that magnesium influx, dependent on NMDA receptor opening, can transduce a signaling pathway to activate CREB in neurons.Amyotrophic lateral sclerosis (ALS) is a devastating disease that like multiple other neurologic diseases has no curative treatment currently available. Environmental exposures to known neurotoxic compounds (e.g., pesticides, heavy metals, cyanobacterial toxins, etc.) are identified as risk factors associated with ALS. Assuming these environmental factors have causative roles in disease risk and given the ubiquity of these types of exposures for the modern human, why are not more people afflicted with ALS? Herein is proposed an energy balance moderation framework (EBMF)-a framework that postulates energy balance as a key moderator of neurologic disease risk. The EBMF proposes that the ability of the body to handle toxic compound exposures through excretion, metabolism, and/or storage impacts the acute and chronic tissue-specific toxicity which is moderated by energy balance. In this model, positive energy balance (weight gain or excess body weight/mass) would be protective against acute neurotoxic exposure permitting the assimilation and sequestration of toxic compounds within body stores separate from the nervous system. However, this protective buffering could be lost during sustained negative energy balance (weight loss) with the release of sequestered compounds redistributing to the nervous system. The EBMF may have relevance beyond ALS for other neurologic diseases with demonstrated environmental risks (such as Alzheimer's and Parkinson's disease) and offers new insights into potential strategies to reduce disease risk and develop novel treatments.BACKGROUND AND AIMS Hypoxia represents one of the most pervasive microenvironmental stresses in HCC due to the overwhelming growth and inadequate blood supply. HIF1α as an important transcription factor participates in the regulation of various biological behaviors of HCC cells under hypoxia. Our previous study indicated that miR-375 is a hypoxia-associated miRNA. However, the interaction between miR-375 and HIF1α remains unclear. METHODS Bioinformatic analysis was performed for miRNA screening. qRT-PCR, western blotting, and immunohistochemical staining were used to detect the expression of related molecules. Bioinformatic analysis and dual luciferase assay were used to predict and further confirm the target association. Transwell chamber assay and flow cytometry were, respectively, used to detect migration, invasion and apoptosis of hepatoma cells. RESULTS MiR-375 presented an obviously differential expression in human HCCs versus background livers (BLs) and HCCs versus normal liver tissues (NLTs). In rat models, miR-375 was gradually declined during hepatocarcinogenesis. HIF1α was remarkably upregulated at protein level rather than at mRNA level in human HCCs versus BLs, HCCs versus NLTs, BLs versus NLTs, and in rat fibrotic livers versus NLTs. HIF1α was determined to be a target of miR-375. MiR-375 inhibitor induced the migration and invasive capabilities and attenuated apoptosis of hepatoma cells under hypoxia. Depriving HIF1α by siRNA could partially reverse the function of miR-375 inhibitor under hypoxia.  https://www.selleckchem.com/products/talabostat.html  CONCLUSIONS MiR-375 impairs the invasive capabilities of HCC cells by targeting HIF1α under hypoxia.The last two decades have witnessed the rising prevalence of both co-publishing and retraction. Focusing on research collaboration, this paper utilizes a unique dataset to investigate factors contributing to retraction probability and elapsed time between publication and retraction. Data analysis reveals that the majority of retracted papers are multi-authored and that repeat offenders are collaboration prone. Yet, all things being equal, collaboration, in and of itself, does not increase the likelihood of producing flawed or fraudulent research, at least in the form of retraction. That holds for all retractions and also retractions due to falsification, fabrication, and plagiarism (FFP). The research also finds that publications with authors from elite universities are less likely to be retracted, which is particularly true for retractions due to FFP. China stands out with the fastest retracting speed compared to other countries. Possible explanations, limitations, and policy implications are also discussed.PURPOSE The role of thyroid autoimmunity in the association between obesity and hyperthyrotropinaemia remains unclear. We aimed to assess the relationship between obesity, autoimmunity, and hyperthyrotropinaemia. METHODS In this population-based cross-sectional study, 12531 Chinese individuals (18-80 years) with thyroid function test were categorized into three groups by body mass index (BMI) and were categorized into three layers by thyroid autoantibodies. Multivariate logistic regression was employed to assess the correlation and interaction effect. RESULTS There was no significant difference in prevalence of hyperthyrotropinaemia (P = 0.637) among three BMI groups. After stratification, the difference of serum thyrotropin (P  less then  0.01) and prevalence of hyperthyrotropinaemia (P  less then  0.01) between the three groups have significant linear trends at the positive levels of thyroid peroxidase antibody (TPOAb) or/and thyroglobulin antibody (TgAb). When TPOAb and TgAb were positive, the risk of hyperthyrotropinaemia increased 1.857-fold in overweight group and 2.201-fold in obese group compared with normal group. Compared with negative TPOAb and TgAb, the risk of hyperthyrotropinaemia for individuals with two positive antibodies increased 3.310-fold, 4.969-fold, and 5.122-fold in the three BMI groups. The adjusted OR (95% CI) for interaction were 1.033 (0.752-1.419) for overweight and one positive antibodies, 1.935 (1.252-2.990) for overweight and two positive antibodies, 1.435 (0.978-2.105) for obesity and one positive antibodies and 2.191 (1.252-3.832) for obesity and two positive antibodies. CONCLUSION Overweight and obesity were associated with hyperthyrotropinaemia only in presence of thyroid autoimmunity, and obesity might aggravate the pathogenic effect of autoimmunity on hyperthyrotropinaemia. There was an interaction effect between obesity and autoimmunity on the prevalence of hyperthyrotropinaemia.