Carnitine palmitoyltransferase 1C (CPT1C) is a sensor of malonyl-CoA and is located in the ER of neurons. AMPA receptors (AMPARs) mediate fast excitatory neurotransmission in the brain and play a key role in synaptic plasticity. In the present study, we demonstrate across different metabolic stress conditions that modulate malonyl-CoA levels in cortical neurons that CPT1C regulates the trafficking of the major AMPAR subunit, GluA1, through the phosphatidyl-inositol-4-phosphate (PI(4)P) phosphatase SAC1. https://www.selleckchem.com/ In normal conditions, CPT1C down-regulates SAC1 catalytic activity, allowing efficient GluA1 trafficking to the plasma membrane. However, under low malonyl-CoA levels, such as during glucose depletion, CPT1C-dependent inhibition of SAC1 is released, facilitating SAC1's translocation to ER-TGN contact sites to decrease TGN PI(4)P pools and trigger GluA1 retention at the TGN. Results reveal that GluA1 trafficking is regulated by CPT1C sensing of malonyl-CoA and provide the first report of a SAC1 inhibitor. Moreover, they shed light on how nutrients can affect synaptic function and cognition. Clustering analysis in a biological network is to group biological entities into functional modules, thus providing valuable insight into the understanding of complex biological systems. Existing clustering techniques make use of lower-order connectivity patterns at the level of individual biological entities and their connections, but few of them can take into account of higher-order connectivity patterns at the level of small network motifs. Here, we present a novel clustering framework, namely HiSCF, to identify functional modules based on the higher-order structure information available in a biological network. Taking advantage of higher-order Markov stochastic process, HiSCF is able to perform the clustering analysis by exploiting a variety of network motifs. Compared with several state-of-the-art clustering models, HiSCF yields the best performance for two practical clustering applications, i.e., protein complex identification and gene co-expression module detection, in terms of accuracy. The promising performance of HiSCF demonstrates that the consideration of higher-order network motifs gains new insight into the analysis of biological networks, such as the identification of overlapping protein complexes and the inference of new signaling pathways, and also reveals the rich higher-order organizational structures presented in biological networks. HiSCF is available at https//github.com/allenv5/HiSCF. Supplementary data are available at Bioinformatics online. Supplementary data are available at Bioinformatics online. Loneliness is common in older adults, and it is associated with unhealthy behaviours, including substance use. We evaluated the association between loneliness and self-reported use of opioids and benzodiazepines in older adults. We used data from the Canadian Community Health Survey's 'Healthy Aging' sub-survey and included adults 65years or older who administered their own medications. We classified individuals as lonely if they scored 6 or more on the three -item University of California, Los Angeles's Loneliness Scale. We used multinomial logistic regression models, adjusting for demographics and self-reported comorbidities, to describe the association between loneliness and daily or occasional use of opioids, benzodiazepines and non-opioid analgesics. We also explored the association between loneliness and polypharmacy. Our cohort included 15,302 older adults, of whom 2,096 (13.7%) were classified as lonely. Daily use of opioids (4.1%) and benzodiazepines (1.7%) were less common than daily use of non-opioid analgesics (33.9%). Lonely older adults had higher daily use of opioids (odds ratio [OR] 1.61, 1.31-1.98) and benzodiazepines (OR 1.66, 1.21-2.28), but not non-opioid analgesics (OR 1.05, 0.92-1.19). Loneliness was not associated with occasional use of opioids, benzodiazepines or non-opioid analgesics in older adults, but was associated with polypharmacy (OR 1.27, 1.06-1.52). Loneliness in older adults is associated with increased daily use of opioids and benzodiazepines. Further research should evaluate patient- and physician-level factors that mediate this association, and develop strategies to mitigate loneliness and its attendant adverse outcomes. Loneliness in older adults is associated with increased daily use of opioids and benzodiazepines. Further research should evaluate patient- and physician-level factors that mediate this association, and develop strategies to mitigate loneliness and its attendant adverse outcomes. Previous longitudinal studies have found that cognitive function affected oral health, and vice versa. However, research is lacking on the reciprocal relationships between cognitive function and edentulism simultaneously, especially in developing countries. The present study aimed to examine the reciprocal relationship between cognitive function and edentulism among middle-aged and older adults in China. Data were derived from the 2011 and 2015 waves of the China Health and Retirement Longitudinal Study. The sample included 14,038 respondents aged 45 or older. A two-wave cross-lagged analysis was adopted to test the hypothesized model. Among respondents aged 45-59, baseline cognitive function was associated with subsequent edentulism [b = -0.017, standard deviation (SD) = 0.006, P < 0.01]. In contrast, baseline edentulism was not significantly associated with poorer cognitive function at the follow-up wave (b = -0.744, SD = 0.383, P > 0.05). However, among respondents aged 60 or older, baseline cognitive function was associated with subsequent edentulism (b = -0.017, SD = 0.005, P < 0.01), and baseline edentulism was also associated with follow-up lower levels of cognitive function (b = -0.419, SD = 0.143, P < 0.01). These findings demonstrated the reciprocal relationships of cognitive function and edentulism. However, such relationships varied across age groups. This study demonstrates the importance of developing programs and services to promote both cognitive and oral health, especially for those in older age. These findings demonstrated the reciprocal relationships of cognitive function and edentulism. However, such relationships varied across age groups. This study demonstrates the importance of developing programs and services to promote both cognitive and oral health, especially for those in older age.