Inhibitory Effects of Selenium on Telomerase Activity and hTERT Expression in Cadmium-transformed 16HBE Cells

Objective To investigate the effects of sodium selenite on telomerase activity and expression of hTERT mRNA in cadmium-transformed 16HBE cells.Methods Telomerase activity and expression of genes were measured after cultured cadmium-transformed 16HBE cells were exposed to sodium selenite at different doses(0.625,1.25,2.50,5.00 μmol/L)for 24 hours.Results Selenium decreased telomerase activity in cadmium-transformed 16HBE cells.There existed an obvious dose-effect relationship between the selenium concentration and these changes.The expression of hTERT and c-myc mRNA also decreased but the expression of mad1 mRNA increased after exposure to selenium for 24 hours.No difference was found in expression of hTRF1 and hTRF2 mRNA after incubated with sodium selenite for 24 hours,compared with control group.Conclusion Selenium inhibits telomerase activity by decreasing hTERT and c-myc mRNA expression and increasing mad1 mRNA expression in cadmium-transformed 16HBE cells and selenium concentration is significantly correlated with these changes.

Pathological significance of abnormal recepteur d'origine nantais and programmed death ligand 1 expression in colorectal cancer

BACKGROUND Programmed death ligand 1(PD-L1) immunotherapy remains poorly efficacious in colorectal cancer(CRC). The recepteur d'origine nantais(RON) receptor tyrosine kinase plays an important role in regulating tumor immunity.AIM To identify the patterns of RON and PD-L1 expression and explore their clinical significance in CRC.METHODS Gene expression data from the Gene Expression Omnibus database(GEO;n = 290) and patients at the First Affiliated Hospital, Zhejiang University School of Medicine(FAHZUSM;n = 381) were analyzed to determine the prognostic value of RON and PD-L1 expression within the tumor microenvironment of CRC. HT29 cell line was treated with BMS-777607 to explore the relationship between RON activity and PD-L1 expression. Signaling pathways and protein expression perturbed by RON inhibition were evaluated by cellular immunofluorescence and Western blot.RESULTS In the GEO patient cohort, cut-off values for RON and PD-L1 expression were determined to be 7.70 and 4.3, respectively. Stratification of patients based on these cutoffs demonstrated that high expression of RON and PD-L1 was associated with a poor prognosis. In the FAHZUSM cohort, rates of high expression of RON in tumor cells, high PD-L1 expression in tumor cells and tumor infiltrating monocytes, and both high RON and high PD-L1 expression in the tumor microenvironment were 121(32%), 43(11%), 91(24%), and 51(13.4%), respectively. High expression of RON was significantly correlated with high expression of PD-L1 in the tumor cell compartment(P < 0.001). High expression of RON and that of PD-L1 were independent prognostic factors for poorer overall survival. Concurrent high expression of both RON and PD-L1 in the tumor microenvironment was significantly associated with a poor prognosis. In vitro, BMS-777607 inhibited the phosphorylation of RON, inhibited PD-L1 expression, and attenuated activation of the ERK1/2 and AKT signaling pathways in CRC cells.CONCLUSION RON, PD-L1, and their crosstalk are significant in predicting the prognostic value of CRC. Moreover, phosphorylation of RON upregulates PD-L1 expression, which provides a novel approach to immunotherapy in CRC.

Effect of solution treatment on the martensitic transformation behavior of a Ni_(43)Co_7Mn_(39)Sn_(11) polycrystalline alloy

The effect of solution treatment on the martensitic transformation behavior of a Ni43Co7Mn39Sn11 polycrystalline alloy fabricated by an arc melting method was investigated by scanning electron microscopy(SEM), energy-dispersive X-ray spectroscopy(EDS), and differential scanning calorimetry(DSC). The examination indicates the presence of severe chemical segregation in the dendritic as-cast structure because of solidification. This chemical segregation completely impedes the intrinsic martensitic transformation. Annealing at 1223 K for 24 h is identified as the threshold annealing condition to eliminate the microstructural segregation and begin the martensitic transformation, as indicated by a broad and obscure feature. Annealing at 1273 K for 24–48 h is found to be effective at promoting notably the martensitic transformation, but the martensitic transformation exhibits a multiple-step feature. Complete homogeneity is achieved by annealing at 1273 K for 72 h, which produces a sharp, single-step martensitic transformation. The microstructural evolution and the valence electron concentrations of alloys(e/a ratio) are evaluated, which are reflective of the degree of compositional homogeneity of alloys, confirming that high annealing temperature and long holding time are vital to reveal the intrinsic martensitic behavior of this alloy. The adequately homogenized alloy displays a martensitic transformation at 292 K and an enthalpy of 11.2 J/g.

Will male semen quality improve with environmental quality?

Wenzhou has improved its environmental quality because of comprehensive environmental remediation;nevertheless,the semen quality of infertile males remains unclear.This study determined whether better environmental quality improved semen quality in this region.We recorded semen quality data from 22962 infertile males from January 2014 to November 2019 at the Center for Reproductive Health of The First Affiliated Hospital of Wenzhou Medical University(Wenzhou,China).Patients were predominantly 30–35 years old(33.1%)and workers(82.0%),with high school education or lower(77.6%);more than a half of the patients(52.6%)were Wenzhou household registration;and most patients(77.5%)had abnormal semen quality.Patients who were older than 40 years and workers,and those with Wenzhou household registration,had significantly worse semen quality(all P<0.05).From 2014 to 2019,progressive sperm motility,total sperm motility,and semen volume showed increasing linear trends in all patients(P=0.021,0.030,and 0.005,respectively),yet normal sperm morphology showed a linearly decreasing trend(P=0.046).Sensitivity analyses for subgroups yielded similar results.In conclusion,the improvement of environmental quality and better function of the accessory glands are associated with progressive sperm motility,total sperm motility,and semen volume.Normal sperm morphology is influenced by occupational exposures and personal lifestyle and does not improve with environmental quality.

Analysis of semen quality of 38 905 infertile male patients during 2008- 2016 in Wenzhou, China

This study analyzed the trend in semen quality of infertile male patients in Wenzhou,China,based on the data obtained from 38905 patients during 2008-2016 in The First Affiliated Hospital of Wenzhou Medical University(Wenzhou,China).The results showed that only 24.9%of the patients had normal semen quality.For the semen quality of infertile male patients,that of the workers and 40-year-olds was significantly worse than the other occupational and age groups.For all the infertile patients,low semen volume,asthenozoospermia,and teratozoospermia accounted for 8.4%,50.5%,and 54.1%,respectively.During 2008-2016,the annual mean percentage of fast forward motile spermatozoa,percentage of total forward motile spermatozoa,and percentage of spermatozoa with normal morphology decreased linearly with slopes of-2.11,-2.59,and-0.70,respectively.The proportion of patients with asthenozoospermia and multi-abnormal spermatozoa increased during 2008-2016 with slopes of 4.70 and 4.87,respectively,while for low semen volume,it decreased with a slope of-0.47 in the same time period.The proportion of patients with teratozoospermia increased from 2008 to 2011 and from 2011 to 2016 with slopes of 17.10 and 2.09,respectively.In general,the deteriorating trend of semen quality of infertile male patients in Wenzhou was obvious.Future efforts should be made to reveal the adverse influences on semen quality,such as occupational exposure,environmental quality,and living habits.Furthermore,more pervasive reproduction health education is necessary.

Review of the genus Eugauria Snellen(Lepidoptera:Crambidae:Musotiminae) in China,with descriptions of two new species

Three species of the genus Eugauria Snellen are reported, in which two species are described as new to science, named E. arcuosa Chen & Wu, sp. nov. and E. crenata Chen & Wu, sp. nov. The adults and genitalia structures of all species are described and illustrated. A key to the species of the genus is provided.