Neurogenesis decline in hippocampal dentate gyrus(DG)participates in stress-induced depressive-like behaviors,but the underlying mechanism remains poorly understood.Here,we observed low-expression of NOD-like receptor...Neurogenesis decline in hippocampal dentate gyrus(DG)participates in stress-induced depressive-like behaviors,but the underlying mechanism remains poorly understood.Here,we observed low-expression of NOD-like receptor family pyrin domain containing 6(NLRP6)in hippocampus of stress-stimulated mice,being consistent with high corticosterone level.NLRP6 was found to be abundantly expressed in neural stem cells(NSCs)of DG.Both Nlrp6 knockout(Nlrp6^(-/-))and NSCconditional Nlrp6 knockout(Nlrp6CKO)mice were susceptible to stress,being more likely to develop depressive-like behaviors.Interestingly,NLRP6 was required for NSC proliferation in sustaining hippocampal neurogenesis and reinforcing stress resilience during growing up.Nlrp6 deficiency promoted esophageal cancer-related gene 4(ECRG4)expression and caused mitochondrial dysfunction.Corticosterone as a stress factor significantly down-regulated NLRP6 expression,damaged mitochondrial function and suppressed cell proliferation in NSCs,which were blocked by Nlrp6 overexpression.ECRG4 knockdown reversed corticosterone-induced NSC mitochondrial function and cell proliferation disorders.Pioglitazone,a well-known clinical drug,up-regulated NLRP6 expression to inhibit ECRG4 expression in its protection against corticosterone-induced NSC mitochondrial dysfunction and proliferation restriction.In conclusion,this study demonstrates that NLRP6 is essential to maintain mitochondrial homeostasis and proliferation in NSCs,and identifies NLRP6 as a promising therapeutic target for hippocampal neurogenesis decline linked to depression.展开更多
Mechanical biological treatment(MBT)technology has attracted increasing attention because it can reduce the volume of waste produced.To deal with the current trend of increasing waste,MBT practices are being adopted t...Mechanical biological treatment(MBT)technology has attracted increasing attention because it can reduce the volume of waste produced.To deal with the current trend of increasing waste,MBT practices are being adopted to address waste generated in developing urban societies.In this study,a total of 20 specimens of consolidated undrained triaxial tests were conducted on waste obtained from the Hangzhou Tianziling landfill,China,to evaluate the effect of loading rate on the shear strength parameters of MBT waste.The MBT waste samples exhibited an evident strain-hardening behavior,and no peak was observed even when the axial strain exceeded 25%.Further,the shear strength increased with an increase in the loading rate;the effect of loading rate on shear strength under a low confining pressure was greater than that under a high confining pressure.Furthermore,the shear strength parameters of MBT waste were related to the loading rate.The relationship between the cohesion,internal friction angle,and logarithm of the loading rate could be fitted to a linear relationship,which was established in this study.Finally,the ranges of shear strength parameters cohesion c and effective cohesion c′were determined as 1.0–8.2 kPa and 2.1–14.9 kPa,respectively;the ranges of the internal friction angleφand effective internal friction angleφ’were determined as 16.2°–29°and 19.8°–43.9°,respectively.These results could be used as a valuable reference for conducting stability analyses of MBT landfills.展开更多
基金National Key R&D Program of China(2022YFC3500303)National Natural Science Foundation of China(81991522)partly by the Open Project of State Key Laboratory of Natural Medicine,No.SKLNMKF202204,China。
文摘Neurogenesis decline in hippocampal dentate gyrus(DG)participates in stress-induced depressive-like behaviors,but the underlying mechanism remains poorly understood.Here,we observed low-expression of NOD-like receptor family pyrin domain containing 6(NLRP6)in hippocampus of stress-stimulated mice,being consistent with high corticosterone level.NLRP6 was found to be abundantly expressed in neural stem cells(NSCs)of DG.Both Nlrp6 knockout(Nlrp6^(-/-))and NSCconditional Nlrp6 knockout(Nlrp6CKO)mice were susceptible to stress,being more likely to develop depressive-like behaviors.Interestingly,NLRP6 was required for NSC proliferation in sustaining hippocampal neurogenesis and reinforcing stress resilience during growing up.Nlrp6 deficiency promoted esophageal cancer-related gene 4(ECRG4)expression and caused mitochondrial dysfunction.Corticosterone as a stress factor significantly down-regulated NLRP6 expression,damaged mitochondrial function and suppressed cell proliferation in NSCs,which were blocked by Nlrp6 overexpression.ECRG4 knockdown reversed corticosterone-induced NSC mitochondrial function and cell proliferation disorders.Pioglitazone,a well-known clinical drug,up-regulated NLRP6 expression to inhibit ECRG4 expression in its protection against corticosterone-induced NSC mitochondrial dysfunction and proliferation restriction.In conclusion,this study demonstrates that NLRP6 is essential to maintain mitochondrial homeostasis and proliferation in NSCs,and identifies NLRP6 as a promising therapeutic target for hippocampal neurogenesis decline linked to depression.
基金funded by the National Natural Science Foundation of China(Nos.51978625 and 51678532)the Zhejiang Provincial Natural Science Foundation of China(No.LZ21E080003)。
文摘Mechanical biological treatment(MBT)technology has attracted increasing attention because it can reduce the volume of waste produced.To deal with the current trend of increasing waste,MBT practices are being adopted to address waste generated in developing urban societies.In this study,a total of 20 specimens of consolidated undrained triaxial tests were conducted on waste obtained from the Hangzhou Tianziling landfill,China,to evaluate the effect of loading rate on the shear strength parameters of MBT waste.The MBT waste samples exhibited an evident strain-hardening behavior,and no peak was observed even when the axial strain exceeded 25%.Further,the shear strength increased with an increase in the loading rate;the effect of loading rate on shear strength under a low confining pressure was greater than that under a high confining pressure.Furthermore,the shear strength parameters of MBT waste were related to the loading rate.The relationship between the cohesion,internal friction angle,and logarithm of the loading rate could be fitted to a linear relationship,which was established in this study.Finally,the ranges of shear strength parameters cohesion c and effective cohesion c′were determined as 1.0–8.2 kPa and 2.1–14.9 kPa,respectively;the ranges of the internal friction angleφand effective internal friction angleφ’were determined as 16.2°–29°and 19.8°–43.9°,respectively.These results could be used as a valuable reference for conducting stability analyses of MBT landfills.
