Objective To study changes in expression of claudin-11 and proteins related to mitogen-activated protein kinase (MAPK) signaling pathways, as well as the ultrastructure of the blood testis barrier(BTB), in male ICR mice exposed to decabromodiphenyl ether (BDE-209). Methods Fifty-two mice, 4 weeks of age, weighing 15-21 g, were provided with adaptive feeding for 1 week. Mice were randomly divided into 4 groups, named control, low-dose, medium-dose and high-dose groups. The treated groups received BDE-209, by intragastric gavage, at doses, respectively, of 100, 300 and 500 mg/kg. Mice were sacrificed after 6 weeks and organs harvested on ice, weighed and stored at-80 °C. The ultrastructure of testicular tissues was examined by electron microscopy. Western blotting was used to detect proteins related to the MAPK pathway, including p38 mitogen activated protein kinase (p38), phosphorylated p38 (p-p38), extracellular regulated protein kinase 1/2 (ERK1/2) , phosphorylated ERK1/2 (p-ERK1/2) , c-jun N-terminal kinase (JNK), phosphorylated JNK (p-JNK) and the BTB tight junction protein claudin-11. Analyze the difference between each groups. Results At sacrifice, the body weights in each treated group were compared with those in the control group weighing (41.14 ± 0.60) g. Compared with controls, body weights were significantly different (P<0.05) in the middle dose, at (39.97 ± 0.66) g and high dose, at (39.98± 0.55) g in control group. The coefficients of the testis were significantly lower (P<0.05) in each treated group than in controls, with values of (0.37±0.0)%, (0.31±0.05)% and (0.31±0.04)% for low- dose, medium-dose and high-dose groups, respectively. The epidymus coefficient values were also significantly lower than controls (P<0.05), with values of (0.16±0.06)%, (0.11±0.05)% and (0.07±0.03)%, respectively in the same three dose groups. Electron microscopy ultrastructure showed that, compared with the control group, the testes in the middle and high dose groups had closely connected fractures, cell edema and more vacuoles. Compared with in the control group, levels of p-p38 and p-JNK in testicular tissue were significantly increased (P<0.05). In the control group and in low-, medium- and high-dose groups, the p-p38/p38 ratios were 1.35±0.13, 3.46±0.10, 5.71±0.26 and 4.79±0.21, respectively. The corresponding p-JNK/JNK ratios were 2.07±0.0, 4.77±0.18, 3.63±0.06 and 4.85±0.15. Claudin-11 levels were significantly lower (P<0.05) than control values in each dosed group. The corresponding values in control, low-dose, medium-dose and high-dose groups were 8.33±0.36, 2.06±0.27, 3.37±0.27 and 1.55±0.19, respectively. Conclusion BDE-209 increased expression of proteins in the MAPK pathway and decreased expression of the BTB tight junction protein claudin-11 in testicular tissue. It also caused ultrastructural damage to the Sertoli cell BTB tight junctions.This suggested that BDE-209 might damage Sertolicells BTB through effects on the MAPK pathway.

Objective To study changes in expression of claudin-11 and proteins related to mitogen-activated protein kinase (MAPK) signaling pathways, as well as the ultrastructure of the blood testis barrier(BTB), in male ICR mice exposed to decabromodiphenyl ether (BDE-209). Methods Fifty-two mice, 4 weeks of age, weighing 15-21 g, were provided with adaptive feeding for 1 week. Mice were randomly divided into 4 groups, named control, low-dose, medium-dose and high-dose groups. The treated groups received BDE-209, by intragastric gavage, at doses, respectively, of 100, 300 and 500 mg/kg. Mice were sacrificed after 6 weeks and organs harvested on ice, weighed and stored at-80 °C. The ultrastructure of testicular tissues was examined by electron microscopy. Western blotting was used to detect proteins related to the MAPK pathway, including p38 mitogen activated protein kinase (p38), phosphorylated p38 (p-p38), extracellular regulated protein kinase 1/2 (ERK1/2) , phosphorylated ERK1/2 (p-ERK1/2) , c-jun N-terminal kinase (JNK), phosphorylated JNK (p-JNK) and the BTB tight junction protein claudin-11. Analyze the difference between each groups. Results At sacrifice, the body weights in each treated group were compared with those in the control group weighing (41.14 ± 0.60) g. Compared with controls, body weights were significantly different (P<0.05) in the middle dose, at (39.97 ± 0.66) g and high dose, at (39.98± 0.55) g in control group. The coefficients of the testis were significantly lower (P<0.05) in each treated group than in controls, with values of (0.37±0.0)%, (0.31±0.05)% and (0.31±0.04)% for low- dose, medium-dose and high-dose groups, respectively. The epidymus coefficient values were also significantly lower than controls (P<0.05), with values of (0.16±0.06)%, (0.11±0.05)% and (0.07±0.03)%, respectively in the same three dose groups. Electron microscopy ultrastructure showed that, compared with the control group, the testes in the middle and high dose groups had closely connected fractures, cell edema and more vacuoles. Compared with in the control group, levels of p-p38 and p-JNK in testicular tissue were significantly increased (P<0.05). In the control group and in low-, medium- and high-dose groups, the p-p38/p38 ratios were 1.35±0.13, 3.46±0.10, 5.71±0.26 and 4.79±0.21, respectively. The corresponding p-JNK/JNK ratios were 2.07±0.0, 4.77±0.18, 3.63±0.06 and 4.85±0.15. Claudin-11 levels were significantly lower (P<0.05) than control values in each dosed group. The corresponding values in control, low-dose, medium-dose and high-dose groups were 8.33±0.36, 2.06±0.27, 3.37±0.27 and 1.55±0.19, respectively. Conclusion BDE-209 increased expression of proteins in the MAPK pathway and decreased expression of the BTB tight junction protein claudin-11 in testicular tissue. It also caused ultrastructural damage to the Sertoli cell BTB tight junctions.This suggested that BDE-209 might damage Sertolicells BTB through effects on the MAPK pathway.

OBJECTIVE To investigate the effects of andrographolide （Andro） on angiogenesis in rats with diabetic foot and to explore its mechanism of action based on the Hippo-Yes-associated protein （YAP） signaling pathway. METHODS The rat model of type 2 diabetes was established by using low-dose streptozotocin combined with high-fat and high-glucose diet. On the basis of successful modeling， the rat model of diabetes foot was established by scalding. Model rats were randomly divided into 5 groups with 12 rats in each group： model group， Andro low-dose， medium-dose， and high-dose groups （1， 10， and 20 mg/kg）， as well as inhibitor group （20 mg/kg Andro+100 mg/kg of verteporfin， an specific inhibitor of Hippo-YAP signaling pathway）； other 12 healthy rats were included in the Control group. Rats in each group were intragastrically and intraperitoneally injected with solvents or corresponding drugs， once a day， for 2 consecutive weeks. The wound healing， fasting blood glucose （FBG） and fasting insulin （FINS） were detected in rats after medication. HE staining was performed to observe the tissue damage and capillary number of rat trauma； the number of endothelial progenitor cells （EPCs） in peripheral blood of rats was counted by using flow cytometry； the contents of serum total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C） and low-density lipoprotein cholesterol （LDL-C） in rats were determined by fully automatic biochemical analyzer； the expressions of hypoxia- inducible factor 1α （HIF-1α）， vascular endothelial growth factor （VEGF） and Hippo-YAP signaling pathway-related proteins in the traumatic tissues of rats in each group were detected by Western blot. RESULTS Compared with Control group， the wound healing rate， capillary number， the proportion of EPCs， HDL-C content， as well as the protein expression levels of HIF-1α and VEGF and the phosphorylation levels of mammalian Ste20-like kinase 1， large tumor suppressor gene 1 and YAP proteins were significantly reduced in the model group， while the FBG， FINS levels and TC， TG and LDL-C contents were significantly increased （P＜0.05）. Compared with model group， the above indexes were significantly reversed in Andro low-dose， medium-dose and high-dose group， in a dose-dependent manner （P＜ 0.05）； verteporfin attenuated the above reversal effect of Andro （P＜0.05）. CONCLUSIONS Andro has the effects of lowering blood glucose and blood lipids， promoting blood vessel formation and wound healing in rats with diabetic foot， and its mechanism of action may be related to the activation of Hippo-YAP signaling pathway.

Monitoring neuronal activity in vivo is critical to understanding the physiological or pathological functions of the brain. Two-photon Ca imaging in vivo using a cranial window and specific neuronal labeling enables real-time, in situ, and long-term imaging of the living brain. Here, we constructed a recombinant rabies virus containing the Ca indicator GCaMP6s along with the fluorescent protein DsRed2 as a baseline reference to ensure GCaMP6s signal reliability. This functional tracer was applied to retrogradely label specific V1-thalamus circuits and detect spontaneous Ca activity in the dendrites of V1 corticothalamic neurons by in vivo two-photon Ca imaging. Notably, we were able to record single-spine spontaneous Ca activity in specific circuits. Distinct spontaneous Ca dynamics in dendrites of V1 corticothalamic neurons were found for different V1-thalamus circuits. Our method can be applied to monitor Ca dynamics in specific input circuits in vivo, and contribute to functional studies of defined neural circuits and the dissection of functional circuit connections.