Metformin:A promising clinical therapeutical approach for BPH treatment via inhibiting dysregulated steroid hormones-induced prostatic epithelial cells proliferation

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.

Unloading performances and stabilizing practices for columnar jointed basalt:A case study of Baihetan hydropower station

The columnar jointed rock mass(CJR), composed of polygonal cross-sectional columns cut by several groups of joints in various directions, was exposed during the excavations of the Baihetan hydropower station, China. In order to investigate the unloading performances and the stability conditions during excavation of the columns, an experimental field study was performed. Firstly, on-site investigations indicated that the geotechnical problems, including rock relaxation, cracking and collapse, were the most prominent for the CJR Class I that contains intensive joint network and the smallest column sizes.Comprehensive field tests, including deformation measurement by multi-point extensometers, ultrasonic wave testing, borehole television observation and stress monitoring of rock anchors, revealed that the time-dependent relaxation of the CJRs was marked. The practical excavation experiences for the Baihetan columnar jointed rock masses, such as blasting scheme, supporting time of shotcrete and rock bolts, were presented in the excavations of the diversion tunnels. These detailed investigations and practical construction experiences can provide helpful information for similar geotechnical works in jointed rock mass.

China’s larch stock volume estimation using Sentinel-2 and LiDAR data

Forest Stock Volume(FSV)is one of the key indicators in forestry resource investigation and management on local,regional,and national scales.Limited by the saturation problems of optical satellite remote-sensing imagery in the retrieving of stock volume,and the high cost of Light Detection And Ranging(LiDAR)data,it is still challenging to estimate FSV in a large area using single-sensor remote-sensing data.In this paper,a method integrated multispectral satellite imagery and LiDAR data was developed to map stock volume in a large area.A random forest model was adopted to estimate the stock volume of larch forest in China based on the training samples from the Airborne Laser Scanning(ALS)-derived stock volume and corresponding Sentinel-2 imagery.Validation using National Forest Inventory(NFI)data,ALS-derived stock volume and ground investigation data demonstrated that the estimated stock volume had a high accuracy(R2=0.59,RMSE=59.69 m^(3)/ha,MD=39.96 m^(3)/ha when validated with NFI data;R2 ranged from 0.77 to 0.85,RMSE ranged from 38.68 m^(3)/ha to 67.38 m^(3)/ha,MD ranged from 24.90 m^(3)/ha to 37.27 m^(3)/ha when validated with ALS stock volume;R2=0.42,RMSE=79.10 m^(3)/ha,MD=62.06 m^(3)/ha when validated with field investigation data).Results of this paper indicated the applicability of estimating stock volume of larch forest in a large area by combining Sentinel-2 data and airborne LiDAR data.

H_(2)S promotes developmental brain angiogenesis via the NOS/NO pathway in zebrafish

Background Hydrogen sulphide(H_(2)S)is considered as the third member of the gasotransmitter family,along with nitric oxide(NO)and carbon monoxide.H_(2)S has been reported to induce angiogenesis by promoting the growth,migration and tube-like structure formation of endothelial cells.Those studies were conducted in conditions of cell culture,mouse Matrigel plug assay model,rat wound healing model or rat hindlimb ischaemia model.Recent in vivo studies showed the physiological importance of H_(2)S in muscle angiogenesis.However,the importance of endogenous H_(2)S for brain angiogenesis during development remains unknown.We therefore aimed at determining the role of H_(2)S in brain vascular development.Methods and results Both knockdown and knockout of H2S-producing enzymes,cystathionineβ-synthase(cbs)and cystathionineγ-lyase(cth),using morpholino oligonucleotides and clustered regularly interspaced short palindromic repeats/Cas9-mediated mutation,impaired brain vascular development of larval zebrafish.Incubation with the slow-releasing H_(2)S donor GYY4137 alleviated the defects of brain vascular development in cbs and cth morphants.Quantitative analysis of the midbrain vascular network showed that H_(2)S enhances angiogenesis without affecting the topological structure of the brain vasculature.Mechanically,nitric oxide synthase 2a(nos2a)expression and NO production were decreased in both cbs and cth morphants.Overexpression of nos2a by coinjection of cbs or cth MO with full-length zebrafish nos2a mRNA alleviated the brain vascular developmental defects in cbs and cth morphants.Conclusion We conclude that H_(2)S promotes brain developmental angiogenesis via the NOS/NO pathway in zebrafish.