BACKGROUND Chronic stress during pregnancy may increase visceral hyperalgesia of offspring in a sex-dependent way.Combining adult stress in offspring will increase this sensitivity.Based on the evidence implicating es...BACKGROUND Chronic stress during pregnancy may increase visceral hyperalgesia of offspring in a sex-dependent way.Combining adult stress in offspring will increase this sensitivity.Based on the evidence implicating estrogen in exacerbating visceral hypersensitivity in female rodents in preclinical models,we predicted that chronic prenatal stress(CPS)+chronic adult stress(CAS)will maximize visceral hyperalgesia;and that estrogen plays an important role in colonic hyperalgesia.AIM The aim was to illuminate the role of estrogen in colonic hyperalgesia and its underlying mechanisms.METHODS We established a CPS plus CAS rodent model in which the balloon was used to distend the colorectum.The single-fiber recording in vivo and patch clamp experiments in vitro were used to monitor the colonic neuron’s activity.The reverse transcription-polymerase chain reaction,western blot,and immunofluorescence were used to study the effects of CPS and CAS on colon primary afferent sensitivity.We used ovariectomy and letrozole to reduce estrogen levels of female rats respectively in order to assess the role of estrogen in female-specific enhanced primary afferent sensitization.RESULTS Spontaneous activity and single fiber activity were significantly greater in females than in males.The enhanced sensitization in female rats mainly came from lowthreshold neurons.CPS significantly increased single-unit afferent fiber activity in L6-S2 dorsal roots in response.Activity was further enhanced by CAS.In addition,the excitability of colon-projecting dorsal root ganglion(DRG)neurons increased in CPS+CAS rats and was associated with a decrease in transient Atype K+currents.Compared with ovariectomy,treatment with the aromatase inhibitor letrozole significantly reduced estrogen levels in female rats,confirming the gender difference.Moreover,mice treated with letrozole had decreased colonic DRG neuron excitability.The intrathecal infusion of estrogen increased brain-derived neurotrophic factor(BDNF)protein levels and contributed to the response to visceral pain.Western blotting showed that nerve growth factor protein was upregulated in CPS+CAS mice.CONCLUSION This study adds to the evidence that estrogen-dependent sensitization of primary afferent colon neurons is involved in the development of chronic stress-induced visceral hypersensitivity in female rats.展开更多
In recent years,Deep Learning(DL)technique has been widely used in Internet of Things(IoT)and Industrial Internet of Things(IIoT)for edge computing,and achieved good performances.But more and more studies have shown t...In recent years,Deep Learning(DL)technique has been widely used in Internet of Things(IoT)and Industrial Internet of Things(IIoT)for edge computing,and achieved good performances.But more and more studies have shown the vulnerability of neural networks.So,it is important to test the robustness and vulnerability of neural networks.More specifically,inspired by layer-wise relevance propagation and neural network verification,we propose a novel measurement of sensitive neurons and important neurons,and propose a novel neuron coverage criterion for robustness testing.Based on the novel criterion,we design a novel testing sample generation method,named DeepSI,which involves definitions of sensitive neurons and important neurons.Furthermore,we construct sensitive-decision paths of the neural network through selecting sensitive neurons and important neurons.Finally,we verify our idea by setting up several experiments,then results show our proposed method achieves superior performances.展开更多
Quantitative analyses on phonotactic behavior of the bushcricket have demonstrated that the bushcricket possesses good capability to determine direction of sound source. The morphological structure, laterality and dir...Quantitative analyses on phonotactic behavior of the bushcricket have demonstrated that the bushcricket possesses good capability to determine direction of sound source. The morphological structure, laterality and directional sensitivity of the auditory ascending neuron in the prothoracic ganglion of the bushcricket have been studied. At its best frequency of 15 kHz, the laterality threshold difference of the neuron is great up to about 16 dB. Its directional sensitivity depends closely on stimulus frequency. The higher the stimulus frequency, the greater the directional threshold differences. Spike count and latency shift of the ascending neuron in response to each stimulus depend on the angle of incidence of sound. Therefore, the two parameters can be used as directional cues of sound source by the ascending neuron.展开更多
基金NIDDK,No.5R01DK111819-03 and No.5R01DK032346-28National Natural Science Foundation of China,No.81571326.
文摘BACKGROUND Chronic stress during pregnancy may increase visceral hyperalgesia of offspring in a sex-dependent way.Combining adult stress in offspring will increase this sensitivity.Based on the evidence implicating estrogen in exacerbating visceral hypersensitivity in female rodents in preclinical models,we predicted that chronic prenatal stress(CPS)+chronic adult stress(CAS)will maximize visceral hyperalgesia;and that estrogen plays an important role in colonic hyperalgesia.AIM The aim was to illuminate the role of estrogen in colonic hyperalgesia and its underlying mechanisms.METHODS We established a CPS plus CAS rodent model in which the balloon was used to distend the colorectum.The single-fiber recording in vivo and patch clamp experiments in vitro were used to monitor the colonic neuron’s activity.The reverse transcription-polymerase chain reaction,western blot,and immunofluorescence were used to study the effects of CPS and CAS on colon primary afferent sensitivity.We used ovariectomy and letrozole to reduce estrogen levels of female rats respectively in order to assess the role of estrogen in female-specific enhanced primary afferent sensitization.RESULTS Spontaneous activity and single fiber activity were significantly greater in females than in males.The enhanced sensitization in female rats mainly came from lowthreshold neurons.CPS significantly increased single-unit afferent fiber activity in L6-S2 dorsal roots in response.Activity was further enhanced by CAS.In addition,the excitability of colon-projecting dorsal root ganglion(DRG)neurons increased in CPS+CAS rats and was associated with a decrease in transient Atype K+currents.Compared with ovariectomy,treatment with the aromatase inhibitor letrozole significantly reduced estrogen levels in female rats,confirming the gender difference.Moreover,mice treated with letrozole had decreased colonic DRG neuron excitability.The intrathecal infusion of estrogen increased brain-derived neurotrophic factor(BDNF)protein levels and contributed to the response to visceral pain.Western blotting showed that nerve growth factor protein was upregulated in CPS+CAS mice.CONCLUSION This study adds to the evidence that estrogen-dependent sensitization of primary afferent colon neurons is involved in the development of chronic stress-induced visceral hypersensitivity in female rats.
基金supported by the National Key R&DProgram of China(No.2021YFF0602104-2)。
文摘In recent years,Deep Learning(DL)technique has been widely used in Internet of Things(IoT)and Industrial Internet of Things(IIoT)for edge computing,and achieved good performances.But more and more studies have shown the vulnerability of neural networks.So,it is important to test the robustness and vulnerability of neural networks.More specifically,inspired by layer-wise relevance propagation and neural network verification,we propose a novel measurement of sensitive neurons and important neurons,and propose a novel neuron coverage criterion for robustness testing.Based on the novel criterion,we design a novel testing sample generation method,named DeepSI,which involves definitions of sensitive neurons and important neurons.Furthermore,we construct sensitive-decision paths of the neural network through selecting sensitive neurons and important neurons.Finally,we verify our idea by setting up several experiments,then results show our proposed method achieves superior performances.
文摘Quantitative analyses on phonotactic behavior of the bushcricket have demonstrated that the bushcricket possesses good capability to determine direction of sound source. The morphological structure, laterality and directional sensitivity of the auditory ascending neuron in the prothoracic ganglion of the bushcricket have been studied. At its best frequency of 15 kHz, the laterality threshold difference of the neuron is great up to about 16 dB. Its directional sensitivity depends closely on stimulus frequency. The higher the stimulus frequency, the greater the directional threshold differences. Spike count and latency shift of the ascending neuron in response to each stimulus depend on the angle of incidence of sound. Therefore, the two parameters can be used as directional cues of sound source by the ascending neuron.
