The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.However,whether Met exert...The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.However,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive relationship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met’s anti-proliferative effects were blocked by AMPK inhibitor or YAP1 overexpression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.展开更多
Background:A variety of experimental animal models are used in basic ophthalmological research to elucidate physiological mechanisms of vision and disease pathogenesis.The choice of animal model is based on the measur...Background:A variety of experimental animal models are used in basic ophthalmological research to elucidate physiological mechanisms of vision and disease pathogenesis.The choice of animal model is based on the measurability of specific parameters or structures,the applicability of clinical measurement technologies,and the similarity to human eye function.Studies of eye pathology usually compare optical parameters between a healthy and altered state,so accurate baseline assessments are critical,but few reports have comprehensively examined the normal anatomical structures and physiological functions in these models.Methods:Three cynomolgus monkeys,six New Zealand rabbits,ten Sprague Dawley(SD)rats,and BALB/c mice were examined by fundus photography(FP),fundus fluorescein angiography(FFA),and optical coherence tomography(OCT).Results:Most retinal structures of cynomolgus monkey were anatomically similar to the corresponding human structures as revealed by FP,FFA,and OCT.New Zealand rabbits have large eyeballs,but they have large optic disc and myelinated retinal nerve fibers in their retinas,and the growth pattern of retinal vessels were also different to the human retinas.Unlike monkeys and rabbits,the retinal vessels of SD rats and BALB/c mice were widely distributed and clear.The OCT performance of them were similar with human beings except the macular.Conclusions:Monkey is a good model to study changes in retinal structure associated with fundus disease,rabbits are not suitable for studies on retinal vessel diseases and optic nerve diseases,and rats and mice are good models for retinal vascular diseases.These measures will help guide the choice of model and measurement technology and reduce the number of experimental animals required.展开更多
Van der Waals （vdW） heterojunctions are equipped to avert dangling bonds due to weak, inter-layer vdW force, and ensure strong in-plane covalent bonding for two-dimensional layered structures. We fabricated four het...Van der Waals （vdW） heterojunctions are equipped to avert dangling bonds due to weak, inter-layer vdW force, and ensure strong in-plane covalent bonding for two-dimensional layered structures. We fabricated four heterojunctions devices of different layers based on p-type distorted 1T-MX2 ReSe2 and n-type hexagonal MoS2 nanoflakes, and measured their electronic and optoelectronic properties. The device showed a high rectification coefficient of 500 for the diode, a high ON/OFF ratio and higher electron mobility for the field-effect transistor （FET） compared with the individual components, and a high current responsivity （Rλ） and external quantum efficiency （EQE） of 6.75 A/W and 1,266%, respectively, for the photodetector.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.:81973377,81903689,82073906 and 82273987)the Key Natural Science Foundation of Jiangsu Higher Education Institutions of China(Grant Nos.:19KJB350006 and 19KJA460008)+1 种基金Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),the initializing Fund of Xuzhou Medical University(Grant No.:D2018011)Postgraduate Research Practice Innovation Program of Jiangsu Province(Grant Nos.:KYCX21-2733 and KYCX22-2966).
文摘The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.However,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive relationship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met’s anti-proliferative effects were blocked by AMPK inhibitor or YAP1 overexpression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.
基金This study was funded by Science and Technology Projects of Guangdong Province(Nos.2019A030317002,2017A030303013,2013B060300003).
文摘Background:A variety of experimental animal models are used in basic ophthalmological research to elucidate physiological mechanisms of vision and disease pathogenesis.The choice of animal model is based on the measurability of specific parameters or structures,the applicability of clinical measurement technologies,and the similarity to human eye function.Studies of eye pathology usually compare optical parameters between a healthy and altered state,so accurate baseline assessments are critical,but few reports have comprehensively examined the normal anatomical structures and physiological functions in these models.Methods:Three cynomolgus monkeys,six New Zealand rabbits,ten Sprague Dawley(SD)rats,and BALB/c mice were examined by fundus photography(FP),fundus fluorescein angiography(FFA),and optical coherence tomography(OCT).Results:Most retinal structures of cynomolgus monkey were anatomically similar to the corresponding human structures as revealed by FP,FFA,and OCT.New Zealand rabbits have large eyeballs,but they have large optic disc and myelinated retinal nerve fibers in their retinas,and the growth pattern of retinal vessels were also different to the human retinas.Unlike monkeys and rabbits,the retinal vessels of SD rats and BALB/c mice were widely distributed and clear.The OCT performance of them were similar with human beings except the macular.Conclusions:Monkey is a good model to study changes in retinal structure associated with fundus disease,rabbits are not suitable for studies on retinal vessel diseases and optic nerve diseases,and rats and mice are good models for retinal vascular diseases.These measures will help guide the choice of model and measurement technology and reduce the number of experimental animals required.
基金This work was supported by the ＂Hundred Talents Program＂ of Chinese Academy of Sciences （CAS）,the National Natural Science Foundation of China （No. 91233120）, and the CAS/SAFEA International Partnership Program for Creative Research Teams.
文摘Van der Waals （vdW） heterojunctions are equipped to avert dangling bonds due to weak, inter-layer vdW force, and ensure strong in-plane covalent bonding for two-dimensional layered structures. We fabricated four heterojunctions devices of different layers based on p-type distorted 1T-MX2 ReSe2 and n-type hexagonal MoS2 nanoflakes, and measured their electronic and optoelectronic properties. The device showed a high rectification coefficient of 500 for the diode, a high ON/OFF ratio and higher electron mobility for the field-effect transistor （FET） compared with the individual components, and a high current responsivity （Rλ） and external quantum efficiency （EQE） of 6.75 A/W and 1,266%, respectively, for the photodetector.
