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Abstract Post-translational modifications (PTMs) couple feed-fast cycles to diurnal rhythms. However, it remains largely uncharacterized whether and how meal timing organizes diurnal rhythms beyond the transcriptome. Here, we systematically profile the daily rhythms of the proteome, four PTMs (phosphorylation, ubiquitylation, succinylation and N-glycosylation) and the lipidome in the liver from young female mice subjected to either day/sleep time-restricted feeding (DRF) or night/wake time-restricted feeding (NRF). We detect robust daily rhythms among different layers of omics with phosphorylation the most nutrient-responsive and succinylation the least. Integrative analyses reveal that clock regulation of fatty acid metabolism represents a key diurnal feature that is reset by meal timing, as indicated by the rhythmic phosphorylation of the circadian repressor PERIOD2 at Ser971 (PER2-pSer971). We confirm that PER2-pSer971 is activated by nutrient availability in vivo. Together, this dataset represents a comprehensive resource detailing the proteomic and lipidomic responses by the liver to alterations in meal timing.

Tourism motivation and satisfaction are classic themes in tourism research. This study combines latent Dirichlet allocation (LDA) and the Censydiam motivation model to analyze online reviews of tourism in Qinghai, China. The aim of this research is to explore tourist motivation through online reviews and provide innovative service suggestions to improve tourist satisfaction. The LDA model initially extracts six main topics from online comments. Then, using the fuzzy analytic hierarchy process (FAHP), it maps the relationship between topics and tourism motivations to propose strategies for enhancing tourists' enjoyment, conviviality, and other motivating factors. Furthermore, we employ the Kano model to evaluate tourists' satisfaction levels regarding these strategies, demonstrating their positive evaluations. Hence, this study provides tourism industry professionals and service designers with an innovative method for understanding tourists' motivations through online reviews, enabling them to design specific services that enhance tourism experiences.

Fine particulate matter (PM2.5) exposure correlates with airway obstruction, but the mechanism remains to be fully elucidated. We aim to investigate the role of exosomal circular RNAs (circRNAs)-mediated communication between airway epithelial cells and airway smooth muscle cells in PM2.5-induced airway obstruction. RNA sequencing revealed that acute PM2.5 exposure altered the expression profiles of 2904 exosomal circRNAs. Among them, exosomal hsa_circ_0029069 (spliced from CLIP1, thus termed circCLIP1 hereafter) with a loop structure was upregulated by PM2.5 exposure and mainly encapsulated in exosomes. Then, the biological functions and the underlying mechanisms were explored by Western blot, RNA immunoprecipitation and RNA pull-down, etc. Phenotypically, exosomal circCLIP1 entered recipient cells, inducing mucus secretion in recipient HBE cells and contractility of sensitive HBSMCs. Mechanistically, circCLIP1 was upregulated by METTL3-mediated N6-methyladenine (m6A) modification in PM2.5-treated producer HBE cells and exosomes, then enhancing the expression of SEPT10 in recipient HBE cells and sensitive HBSMCs. Our study revealed that exosomal circCLIP1 played a critical role in PM2.5-induced airway obstruction and provided a new potential biomarker for the assessment of PM2.5-related adverse effects.

Background: Meal timing resets circadian clocks in peripheral tissues, such as the liver, in seven days without affecting the phase of the central clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Anterior hypothalamus plays an essential role in energy metabolism, circadian rhythm, and stress response. However, it remains to be elucidated whether and how anterior hypothalamus adapts its circadian rhythms to meal timing. Methods: Here, we applied transcriptomics to profile rhythmic transcripts in the anterior hypothalamus of nocturnal female mice subjected to day- (DRF) or night (NRF)-time restricted feeding for seven days. Results: This global profiling identified 128 and 3,518 rhythmic transcripts in DRF and NRF, respectively. NRF entrained diurnal rhythms among 990 biological processes, including ‘Electron transport chain’ and ‘Hippo signaling’ that reached peak time in the late sleep and late active phase, respectively. By contrast, DRF entrained only 20 rhythmic pathways, including ‘Cellular amino acid catabolic process’, all of which were restricted to the late active phase. The rhythmic transcripts found in both DRF and NRF tissues were largely resistant to phase entrainment by meal timing, which were matched to the action of the circadian clock. Remarkably, DRF for 36 days partially reversed the circadian clock compared to NRF. Conclusions: Collectively, our work generates a useful dataset to explore anterior hypothalamic circadian biology and sheds light on potential rhythmic processes influenced by meal timing in the brain (www.circametdb.org.cn).

Colorectal adenocarcinoma (CRC) is the third most common malignancy worldwide. Metastatic CRC has a poor prognosis because of chemotherapy resistance. Our previous study demonstrated that semaphorin 3F (SEMA3F) signaling may contribute to reversing chemotherapy resistance in CRC cells by reducing E-cadherin and integrin αvβ3 expression levels. Another study showed that upregulation of p27 significantly increase the expression of E-cadherin and integrin. This study aimed to evaluate the effect of SEMA3F on P27 and whether it can reverse resistance in CRC cells. We compared the chemosensitivity of human colorectal cancer cell lines with different SEMA3F expression levels to 5-Fu through cell experiment and animal experiment. Then the interaction between SEMA3F and p27 and its possible mechanism were explored by Western Blot, immunofluorescence and immunocoprecipitation. We also compared the disease-free survival of 118 CRC patients with high or low expression of SEMA3F.The results showed that overexpresstion of SEMA3F enhanced the chemotherapy sensitivity and apoptosis of CRC cells in vitro and in vivo. Among 118 postoperative CRC specimens, the disease-free survival of patients with positive SEMA3F expression was significantly longer than that with negative SEMA3F expression after adjuvant treatment. Upregulation of SEMA3F in multicellular spheroid culture (MSC) could increase p27 phosphorylation at serine 10 (Ser10), subsequently promote the cytosolic translocation of P27. Overall, our results reveal a novel molecular mechanism: SEMA3F mediates the degradation of p27 and regulates its subcellular localization to enhance chemosensitivity to 5-Fu in CRC cells, rather than inhibits p27 expression.

Summary: Inverted feeding is a paradigm to study synchronization of circadian clocks by feeding rhythm in tissues more directly. Here, we provide a protocol for performing inverted feeding in mice and analyzing circadian rhythmicity in mouse tissues. We describe setting up inverted feeding and performing tissue dissection, followed by RNA extraction and gene expression analysis, and lastly R software-based analysis of circadian rhythmicity. This protocol can be combined with the use of CircaMetDB database for mechanistic studies of inverted feeding.For complete details on the use and execution of this protocol, please refer to Xin et al. (2021).

Dysregulation of long noncoding RNA (lncRNA) is known to be involved in numerous human diseases, including lung cancer. However, the precise biological functions of most lncRNA remain to be elucidated. Here, we identified a novel up‐regulated lncRNA, LINC01436 (RefSeq: NR_110419.1), in non‐small cell lung cancer (NSCLC). High expression of LINC01436 was significantly associated with poor overall survival. Notably, LINC01436 expression was transcriptionally repressed by E2F6 under normoxia, and the inhibitory effect was relieved in a hypoxic microenvironment. Gain‐ and loss‐of‐function studies revealed that LINC01436 acted as a proto‐oncogene by promoting lung cancer cell growth, migration and invasion in vitro. Xenograft tumor assays in nude mice confirmed that LINC01436 promoted tumor growth and metastasis in vivo. Mechanistically, LINC01436 exerted biological functions by acting as a microRNA (miR)‐30a‐3p sponge to regulate the expression of its target gene EPAS1. Our findings characterize LINC01436 as a new hypoxia‐sensitive lncRNA with oncogenic function in NSCLC, suggesting that LINC01436 may be a potential biomarker for prognosis and a potential target for treatment.

Summary: Time of eating synchronizes circadian rhythms of metabolism and physiology. Inverted feeding can uncouple peripheral circadian clocks from the central clock located in the suprachiasmatic nucleus. However, system-wide changes of circadian metabolism and physiology entrained to inverted feeding in peripheral tissues remain largely unexplored. Here, we performed a 24-h global profiling of transcripts and metabolites in mouse peripheral tissues to study the transition kinetics during inverted feeding, and revealed distinct kinetics in phase entrainment of diurnal transcriptomes by inverted feeding, which graded from fat tissue (near-completely entrained), liver, kidney, to heart. Phase kinetics of tissue clocks tracked with those of transcriptomes and were gated by light-related cues. Integrated analysis of transcripts and metabolites demonstrated that fatty acid oxidation entrained completely to inverted feeding in heart despite the slow kinetics/resistance of the heart clock to entrainment by feeding. This multi-omics resource defines circadian signatures of inverted feeding in peripheral tissues (www.CircaMetDB.org.cn).

Background: Meal timing resets circadian clocks in peripheral tissues, such as the liver, in seven days without affecting the phase of the central clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Anterior hypothalamus plays an essential role in energy metabolism, circadian rhythm, and stress response. However, it remains to be elucidated whether and how anterior hypothalamus adapts its circadian rhythms to meal timing. Methods: Here, we applied transcriptomics to profile rhythmic transcripts in the anterior hypothalamus of nocturnal female mice subjected to day- (DRF) or night (NRF)-time restricted feeding for seven days. Results: This global profiling identified 128 and 3,518 rhythmic transcripts in DRF and NRF, respectively. NRF entrained diurnal rhythms among 990 biological processes, including ‘Electron transport chain’ and ‘Hippo signaling’ that reached peak time in the late sleep and late active phase, respectively. By contrast, DRF entrained only 20 rhythmic pathways, including ‘Cellular amino acid catabolic process’, all of which were restricted to the late active phase. The rhythmic transcripts found in both DRF and NRF tissues were largely resistant to phase entrainment by meal timing, which were matched to the action of the circadian clock. Remarkably, DRF for 36 days partially reversed the circadian clock compared to NRF. Conclusions: Collectively, our work generates a useful dataset to explore anterior hypothalamic circadian biology and sheds light on potential rhythmic processes influenced by meal timing in the brain (www.circametdb.org.cn).