Chronic sclerosing sialadenitis of the submandibular gland (also known as Küttner tumor) is characterized by concomitant swelling of the submandibular glands secondary to strong lymphocytic infiltration and fibrosis. The pathogenesis of this disease has been unclear, but it is associated with immune disorders. ADAMTS18 is a member of the ADAMTS superfamily of extracellular proteinases. In this study, we showed that Adamts18 is highly expressed in submandibular salivary gland (SMG) during embryonic development and decreases but is retained in adult SMG tissue in mice. Adamts18 deficiency led to reduced cleft formation and epithelial branching in embryonic SMG before embryonic day 15.5 in mice. No significant histologic changes in the later stages of branching or the morphology of SMG were detected in Adamts18−/− mice. However, Adamts18 deficiency causes spontaneous SMG fibrogenesis and fibrosis in adult mice. At 8 wk of age, Adamts18−/− mice began to manifest the first signs of pathologic changes of mild fibrosis and CD11b+ cell infiltration in SMG tissues. At ≥8 mo, all male and female Adamts18−/− mice developed unilateral or bilateral SMG scleroma that is similar to patients with chronic sclerosing sialadenitis of the submandibular gland. Adamts18−/− mice also showed secretory dysfunction and severe dental caries. Histologically, SMG scleroma is characterized by progressive periductal fibrosis, acinar atrophy, irregular duct ectasis, and dense infiltration of IgG-positive plasma cells. A significant infiltration of CD4+ T lymphocytes and CD11b+ monocytes and macrophages was also detected in the SMG scleroma of Adamts18−/− mice. The levels of TGF-β1, IL-6, and IL-33 were significantly increased in Adamts18−/− SMGs, which induces chronic inflammation and myofibroblast activation, ultimately leading to fibrosis. This study indicates that Adamts18 regulates the early branching morphogenesis of embryonic SMG and plays a role in protecting from spontaneous SMG fibrogenesis via modulating local inflammation, autoimmune reaction, and myofibroblast activation in adult mice.

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Pulmonary ground glass nodules (GGNs) have been increasingly identified in past decades and is becoming an important clinical dilemma in oncology. Meanwhile, humans persistently inhale microplastics which are dominant in the air. However, the retention of “non-self” microplastics in human lung and its correlation with pulmonary GGNs remains elusive. In this study, we firstly demonstrated the presence of microfibers and microplastics in human lung, with higher detection rates in GGNs in comparison to those in normal tissue. Moreover, both types and colors of microfibers in tumor were richer than those in normal tissues. Intriguingly, high risk of microfibers exposure predisposes the formation of pulmonary GGN. Further, increased roughness surface was observed in microfibers isolated in human lung, indicating the possible link of surface roughness to the formation of pulmonary GGN. Collectively, our findings reveal an emerging role of environmental microplastics exposure in the etiology of pulmonary GGN.One Sentence SummaryThe exposure of environmental microplastics is a risk factor of pulmonary GGN.

One Sentence Summary: Chronic stress breaks glucose intolerance cycle to resist diet-induced obesity, through myonectin-mediated inhibition of glycemic response to epinephrine (EPI) and activation of insulin signaling in adipose tissues. GraphicalAbstract Stress AAV+ Sympathetic output HFD 2wk Glucose intolerance 4wk Insulin sensitivity ↓ EPI sensitivity ↑ 3wk Glucose intolerance↑ Insulin sensitivity↑ Insulin sensitivity↑↑ P-Akt Ser473↑ EPI sensitivity↑ Thermogenesis↑ Insulin sensitivity↑ P-Akt Ser473↑ EPI sensitivity↑ Lipolysis↑ Myonectin↑ BAT WAT Improved Glycemic Control Stress diet Improved Metabolic Profile Glucose Intolerance Cycle ? ? Obesity Highlights  EPI sensitivity increases after glucose intolerance and with reduced insulin sensitivity in diet-induced obesity  Chronic stress blunts glycemic responses to EPI and increases myonectin levels in serum and skeletal muscle  Myonectin attenuates glycemic response to EPI and improves metabolic profile in HFD-fed mice  Reducing myonectin reverses beneficial effects of stress on glucose homeostasis AbstractInhibiting glycemic response to HPA axis contributes to glycemic control for diabetic patients.Here, mice were subjected to high-fat diet and intermittent chronic stress, and glucose homeostasis and lipolysis were determined during the intervention. Firstly, we found that glucose intolerance appears at the earliest, followed by reduced insulin sensitivity and increased epinephrine (EPI) sensitivity in the early stage of diet-induced obesity. Next we investigated whether chronic stress impairs glycemic control and which mediates its effects. Short-term stress training raises serum and skeletal muscle myonectin (Myn) levels and improves glucose intolerance. Stress attenuates blood glucose and glycerol responses to EPI, but enhances lipolytic response to EPI in adipose tissues. Myn overexpression in vivo improves glucose tolerance and enhances insulin sensitivity at the cost of blunting glycemic responses to EPI. Myn knockdown reduces beneficial effects of stress or exercise on glucose homeostasis. Together, myonectin is a stress-induced myokine that readjusts glycemic and metabolic responses to HPA axis, and thus prevent the progression of glucose intolerance and obesity. Clin Endocrinol Metab 92(7): JS, Samuel VT (2014) Targeting steroid receptor coactivator 1 with antisense oligonucleotides increases insulin-stimulated skeletal muscle glucose uptake in chow-fed and high-fat-fed male rats. Am J Physiol Endocrinol Metab 307(9): E773-E783 Chuang JC, Krishnan V, Yu HG, Mason B, Cui H, Wilkinson MB, Zigman JM, Elmquist JK, Nestler EJ, Lutter M (2010) A beta3-adrenergic-leptin-melanocortin circuit regulates behavioral and metabolic changes induced by chronic stress. Biol Psychiatry 67(11): 1075-1082 Covington JD, Tam CS, Bajpeyi S, Galgani JE, Noland RC, Smith SR, Redman LM, Ravussin E (2016) Myokine Expression in Muscle and Myotubes in Response to Exercise Stimulation. Med Sci Sports Exerc 48(3): 384-390 Crunkhorn S (2018) Metabolic disease: Safely mimicking c...