The associations between sugar-sweetened beverage (SSB) consumption and the risk of stroke, depression, cancer, and cause-specific mortality have not been determined, and the quantitative aspects of this link remain unclear. This meta-analysis therefore conducted a systematic review and dose-response analysis to determine their causal links. The database searches were conducted in PubMed, Cochrane library, Embase, Web of Science up to Nov 10, 2021. The intervention effects were evaluated by relative risk (RR) with 95% confidences (CIs). Thirty-two articles met the inclusion criteria. Higher levels of SSB consumption significantly increased the risk of stroke (RR 1.12, 95% Cs 1.03–1.23), depression (1.25, 1.11–1.41), cancer (1.10, 1.03–1.17), and all-cause mortality (1.08, 1.05–1.11) compared with none or lower SSB intake. The associations were dose-dependent, with per 250 mL increment of SSB intake daily increasing the risk of stroke, depression, cancer, and all-cause mortality by RR 1.09 (1.03–1.15), 1.08 (1.06–1.10), 1.17 (1.04–1.32), and 1.07 (1.03–1.11), respectively. The link was curved for depression and cancer risk (pnon-linear < 0.05). Subgroup analysis suggested that higher SSB intake increased ischemic stroke by 10%, CVD-caused mortality by 13%, and cancer-caused mortality by 6.0% than none or lower SSB consumption. It is suggested that SSB accounts for a leading risk factor of stroke, depression, cancer, and mortality, and that the risk rises in parallel with the increment of SSB intake (and is affected by participant characteristics).

Lymphatic metastasis is the leading cause responsible for recurrence and progression in papillary thyroid cancer (PTC), where dysregulation of lncRNAs have been extensively demonstrated to be implicated. However, the specific lymphatic node metastatsis-related (LNM) lncRNAs remain not identified in PTC yet. LNM lncRNA, MFSD4A-AS1, were explored in PTC dataset from TCGA, and our clinical samples. The roles of MFSD4A-AS1 in lymphatic metastasis were investigated by in vitro, and in vivo. Bioinformatic analysis, Luciferase assay and RIP assay were performed to identify the potential targets and the underlying pathway of MFSD4A-AS1 in lymphatic metastasis of PTC. MFSD4A-AS1 was specifically upregulated in PTC tissues with lymphatic metastasis. Upregulating MFSD4A-AS1 promoted mesh formation and migration of HUVECs and invasion and migration of PTC cells. Importantly and consistently, MFSD4A-AS1 promoted lymphatic metastasis of PTC cells in vivo by inducing the lymphangiogenic formation and enhancing invasive capability of PTC cells. Mechanistic dissection further revealed that MFSD4A-AS1 functioned as ceRNA to sequester miR-30c-2-3p, miR-145-3p and miR-139-5p to disrupt the miRNAs-mediated inhibition of VEGFA and VEGFC, and further activated TGF-β signaling by sponging miR-30c-2-3p that targeted TGFBR2 and USP15, both of which synergistically promoted lymphangiogenesis and lymphatic metastasis of PTC. Our results unravel a novel dual mechanisms by which MFSD4A-AS1 promotes lymphatic metastasis of PTC, which will facilitate the development of anti-lymphatic metastatic therapeutic strategy in PTC.

Insulin resistance is recognized as one major feature of metabolic syndrome, and frequently emerges as a difficult problem encountered during long-term pharmacological treatment of diabetes. Insulin resistance often causes organs or tissues, such as skeletal muscle, adipose, and liver, to become less responsive or resistant to insulin. Exercise can promote the physiological function of those organs and tissues and benefits insulin action via increasing insulin receptor sensitivity, glucose uptake, and mitochondrial function. This is done by decreasing adipose tissue deposition, inflammatory cytokines, and oxidative stress. However, understanding the mechanism that regulates the interaction between exercise and insulin function becomes a challenging task. As a novel myokine, irisin is activated by exercise, released from the muscle, and affects multi-organ functions. Recent evidence indicates that it can promote glucose uptake, improve mitochondrial function, alleviate obesity, and decrease inflammation, as a result leading to the improvement of insulin action. We here will review the current evidence concerning the signaling pathways by which irisin regulates the effect of exercise on the up-regulation of insulin action in humans and animals.

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