Abstract Background Overweight and obesity are among the leading chronic diseases worldwide. Environmental phenols have been renowned as endocrine disruptors that contribute to weight changes; however, the effects of exposure to mixed phenols on obesity are not well established. Methods Using data from adults in National Health and Nutrition Examination Survey, this study examined the individual and combined effects of four phenols on obesity. A combination of traditional logistic regression and two mixed models (weighted quantile sum (WQS) regression and Bayesian kernel-machine regression (BKMR)) were used together to assess the role of phenols in the development of obesity. The potential mediation of cholesterol on these effects was analyzed through a parallel mediation model. Results The results demonstrated that solitary phenols except triclosan were inversely associated with obesity (P-value < 0.05). The WQS index was also negatively correlated with general obesity (β: 0.770, 95% CI: 0.644–0.919, P-value = 0.004) and abdominal obesity (β: 0.781, 95% CI: 0.658–0.928, P-value = 0.004). Consistently, the BKMR model demonstrated the significant joint negative effects of phenols on obesity. The parallel mediation analysis revealed that high-density lipoprotein mediated the effects of all four single phenols on obesity, whereas low-density lipoprotein only mediated the association between benzophenol-3 and obesity. Moreover, Cholesterol acts as a mediator of the association between mixed phenols and obesity. Exposure to single and mixed phenols significantly and negatively correlated with obesity. Cholesterol mediated the association of single and mixed environmental phenols with obesity. Conclusions Assessing the potential public health risks of mixed phenols helps to incorporate this information into practical health advice and guidance.

Thyroid hormone (TH) and/or its receptors (TRs) are essential for hearing, cochlear late-stage development and maintaining endocochlear potential (EP). The mechanism underlying the EP reduction upon deficiency of TH or TRs remains unknown. The cochlear outer sulcus (root cell) is considered to be important for the maintenance of endolymph homeostasis and EP, and undergoes dramatic morphological changes during cochlear late-stage developmental window. It has been long neglected whether TH and/or TRs are required for root cell differentiation and function. Here we demonstrate a key role for TH or TRs in postnatal root cell development and survival in mice. Anti-thyroid drug-induced developmental hypothyroidism results in severe retardation in root cell differentiation. Targeted deletion of both TRα and TRβ but not individual TRβ in cochlear epithelium causes a similar impairment, compounded with an early-onset degeneration of root cells and a reduced EP, without obvious alterations in stria vascularis. Furthermore, we demonstrate that TH signaling acts in parallel with ZBTB20 in the outer sulcus, a transcription factor which we have recently reported to be essential for the outer sulcus differentiation. Our results support that TRα and TRβ act redundantly in promoting root cell late-stage differentiation and maintaining its cellular homeostasis, and root cell dysfunction at least partially contribute to a reduced EP upon deficiency of TH or TRs. These findings imply that root cells may play an important role in maintaining the health of cochlear sensory epithelium and normal EP.Significance Statement Thyroid hormone (TH) and/or its receptors (TRs) are essential for hearing and cochlear development. The cochlear outer sulcus (root cell) is considered to be important for cochlear ionic and metabolic homeostasis. We found that combined deletion of both TRα and TRβ but not individual TRβ results in severe retardation in root cell differentiation accompanied by an early-onset degeneration and a reduced endocochlear potential (EP), suggesting TRα and TRβ act redundantly in promoting root cell differentiation and maintaining its cellular homeostasis. Our findings suggest that root cell dysfunction may at least partially contribute to a reduced EP upon deficiency of TRs, and root cells may play an important role in maintaining the health of cochlear sensory epithelium and EP.### Competing Interest StatementThe authors have declared no competing interest.

Background: It is well accepted that repetitive resveratrol (RV) pretreatment (PRC) exerts neuroprotective effect on ischemic stroke. RV was shown to be able to enhance the production of T regulatory cells (Tregs) in autoimmune diseases whereas Tregs are considered to be the cerebroprotective immunomodulator in ischemic stroke. Thus, we hypothesized whether Tregs contributed to PRC-induced neuroprotection against cerebral ischemia/reperfusion (I/R) injury. Methods: Cerebral I/R injury was induced by middle cerebral artery occlusion for 90 minutes in rats. Adult male Sprague-Dawley rats were randomly assigned to 2 groups: I/R and RV I/R. RV (50 mg/kg) was administrated intraperitoneally once a day for 7 days prior to ischemia onset. Results: PRC significantly ameliorated neurological defects and reduced cerebral infarct volume, accompanied by the significantly increased frequencies of Tregs in the spleens and ischemic hemisphere, the significantly increased levels of interleukin-10 (IL-10) in the plasma and ischemic hemisphere, and the significantly decreased levels of tumor necrosis factor-alpha and IL-6 in the plasma and ischemic hemisphere at 24 hours after ischemia onset. In addition, we also found that PRC significantly improved the frequency and suppressive function of Tregs in the spleens prior to ischemia onset. Conclusions: Thus, PRC-induced neuroprotection was in part mediated by more Treg accumulation and activation in vivo prior to ischemia onset except for less inflammation response at 24 hours after ischemia onset.

Objective To observe the expression of a two-pore domain K+ channel KCNK16 in rat islets,and to explore its regulation by insulin secretagogues.Methods Real time-PCR and immunohistochemistry were employed to observe the expression of KCNK16 in rat islets and other tissues.Rat islets were exposed to glucose,prolactin,palmitate,and trichostatin A (TSA) for 24 h and KCNK16 expression were determined by realtime-PCR and Western blot.Glucose-and KCl-stimulated insulin secretion were assayed by ELISA after islets were exposed to TSA for 24 h.The dose-and time-dependent effects of TSA on KCNK16 expression in INS1-E cells were determined by RTPCR.Results KCNK16 was highly expressed in rat islets.Glucose,prolactin,and palmitate did not affect the expression of KCNK16 in rat islets.TSA treatment significantly potentiated glucose-and KCl-stimulated insulin secretion in isolated rat islets (P ＜ 0.05),along with decreased KCNK16 mRNA and protein expressions (P ＜ 0.01).TSA inhibited KCNK16 expression in a dose-and time-dependent manner in INS1-E cells (P＜0.05).Conclusion KCNK16 is exclusively and highly expressed in rat islets and its expression can be down-regulated by TSA treatment.It is possible that TSA enhances insulin secretion via decreasing KCNK16 expression.