With rapid development of marine infrastructures,materials with better biocorrosion resistance and antibiofouling performance will be highly demanded.Ti6Al4V alloy is susceptible to the above.The inhibition to the mic...With rapid development of marine infrastructures,materials with better biocorrosion resistance and antibiofouling performance will be highly demanded.Ti6Al4V alloy is susceptible to the above.The inhibition to the microbiologically influenced corrosion of Ti6Al4V-5Cu alloy against Pseudomonas aeruginosa was investigated using antibacterial test,electrochemical techniques,surface analysis,and weight loss test conducted for 2.5 months.At a sputtering depth of 0 nm,the passive film of Ti6Al4V-5Cu alloy was mainly composed of ideal oxide TiO_(2).With increasing sputtering thickness to 6 nm,Ti_(2)O_(3)and TiO were detected with a relative fraction of 14.6%and 14.8%,respectively,in the oxide layer of Ti6Al4V-5Cu alloy.In contrast,the outermost layer of Ti6AlV alloy was predominantly composed of TiO_(2)but Ti_(2)O_(3)(22.8%),Al_(2)O_(3)and V_(2)O_(5) were also detected.With increasing sputtering depth to 6 nm,fitting revealed the presence of Ti_(2)O_(3)and TiO with relative fractions of 25.3%and 35.8%,respectively.Yet,a spot of TiO(8%)was also observed at 12 nm in the oxide layer of Ti6Al4V alloy.Although the addition of Cu into Ti6Al4V alloy generated the self-healing property of passive film in the presence of P.aeruginosa,it also reduced resistance to corrosion in general condition.展开更多
More than 85%of patients with uveal melanoma(UM)carry a GNAQ or GNA11 mutation at a hotspot codon(Q209)that encodes G proteinαsubunit q/11 polypeptides(Gα_(q/11)).GNAQ/11 relies on palmitoylation for membrane associ...More than 85%of patients with uveal melanoma(UM)carry a GNAQ or GNA11 mutation at a hotspot codon(Q209)that encodes G proteinαsubunit q/11 polypeptides(Gα_(q/11)).GNAQ/11 relies on palmitoylation for membrane association and signal transduction.Despite the palmitoylation of GNAQ/11 was discovered long before,its implication in UM remains unclear.Here,results of palmitoylation-targeted mutagenesis and chemical interference approaches revealed that the loss of GNAQ/11 palmitoylation substantially affected tumor cell proliferation and survival in UM cells.Palmitoylation inhibition through the mutation of palmitoylation sites suppressed GNAQ/11^(Q209L)-induced malignant transformation in NIH3T3 cells.Importantly,the palmitoylation-deficient oncogenic GNAQ/11 failed to rescue the cell death initiated by the knock down of endogenous GNAQ/11 oncogenes in UM cells,which are much more dependent on Gα_(q/11) signaling for cell survival and proliferation than other melanoma cells without GNAQ/11 mutations.Furthermore,the palmitoylation inhibitor,2-bromopalmitate,also specifically disrupted Gα_(q/11) downstream signaling by interfering with the MAPK pathway and BCL2 survival pathway in GNAQ/11-mutant UM cells and showed a notable synergistic effect when applied in combination with the BCL2 inhibitor,ABT-199,in vitro.The findings validate that GNAQ/11 palmitoylation plays a critical role in UM and may serve as a promising therapeutic target for GNAQ/11-driven UM.展开更多
The influence of hot-deformation on the microstructure,crystalline orientation,and texture evolution of Ti6Al4V-5Cu,an antibacterial(α+β)titanium alloy,was investigated.The alloy was deformed using a hot rolling pro...The influence of hot-deformation on the microstructure,crystalline orientation,and texture evolution of Ti6Al4V-5Cu,an antibacterial(α+β)titanium alloy,was investigated.The alloy was deformed using a hot rolling process in 15%,58%,and 73%thickness reduction ratios.It was found that the basal<α→>and pyramidal<c→+α→>type slip planes could be activated in theαphase,which dominated the deformation behavior of Ti6Al4V-5Cu alloy.Under various deformation conditions,the alloy revealed different microstructure features.On the 15%hot rolled alloy,the deformation was performed by the breakdown of priorβgrain boundaries(GBβ),which was attributed to the formation of coarseαgrains,rotated nearly 45°with respect to the transversal and rolling directions.The presence of different sub-structure geometries made the interior grain size distribution heterogeneous.On the 58%hot rolled alloy,Ti2Cu intermetallic compound was found at theα/βinterface.High-resolution transmission electron microscopy investigation showed the occurrence of grain rotation in different crystallographic directions.At room temperature,the percentage elongation(El)of the alloy reached 23.15%on the 58%hot rolled sample.On the 73%deformed alloy,refined and randomly oriented characteristics of grains were obtained due to higher thickness reduction,which resulted from the segregation of very fine granules.The influence of grain rotation during a hot rolling process revealed that theα/βtexture fiber separation angle to maintain the Burger orientation relationship of{0001}α//{110}βplanes decreased with increase of the thickness reduction ratio when Ti6Al4V-5Cu alloy was deformed by a hot rolling mechanism.Activation of tensile{1012}<1011>and compressive{1122}<1123>twins on the deformation of the alloy was also studied.展开更多
Cullin-RING E3 ubiquitin ligase(CRL)-4 is a member of the large CRL family in eukaryotes.It plays important roles in a wide range of cellular processes,organismal development,and physiological and pathological conditi...Cullin-RING E3 ubiquitin ligase(CRL)-4 is a member of the large CRL family in eukaryotes.It plays important roles in a wide range of cellular processes,organismal development,and physiological and pathological conditions.DDB1-and CUL4-associated factor 8(DCAF8)is a WD40 repeat-containing protein,which serves as a substrate receptor for CRL4.The physiological role of DCAF8 is unknown.In this study,we constructed Dcaf8 knockout mice.Homozygous mice were viable with no noticeable abnormalities.However,the fertility of Dcaf8-deficient male mice was markedly impaired,consistent with the high expression of DCAF8 in adult mouse testis.Sperm movement characteristics,including progressive motility,path velocity,progressive velocity,and track speed,were significantly lower in Dcaf8 knockout mice than in wild-type(WT)mice.However,the total motility was similar between WT and Dcaf8 knockout sperm.More than 40%of spermatids in Dcaf8 knockout mice showed pronounced morphological abnormalities with typical bent head malformation.The acrosome and nucleus of Dcaf8 knockout sperm looked similar to those of WT sperm.In vitro tests showed that the fertilization rate of Dcaf8 knockout mice was significantly reduced.The results demonstrated that DCAF8 plays a critical role in spermatogenesis,and DCAF8 is a key component of CRL4 function in the reproductive system.展开更多
基金financially supported by the National Natural Science Foundation of China(No.U1906226)the United Research&Development Program(No.E049A201)+1 种基金the National Key Research and Development Program(No.2017YFB0306201)the support of CAS-TWAS President Fellowship。
文摘With rapid development of marine infrastructures,materials with better biocorrosion resistance and antibiofouling performance will be highly demanded.Ti6Al4V alloy is susceptible to the above.The inhibition to the microbiologically influenced corrosion of Ti6Al4V-5Cu alloy against Pseudomonas aeruginosa was investigated using antibacterial test,electrochemical techniques,surface analysis,and weight loss test conducted for 2.5 months.At a sputtering depth of 0 nm,the passive film of Ti6Al4V-5Cu alloy was mainly composed of ideal oxide TiO_(2).With increasing sputtering thickness to 6 nm,Ti_(2)O_(3)and TiO were detected with a relative fraction of 14.6%and 14.8%,respectively,in the oxide layer of Ti6Al4V-5Cu alloy.In contrast,the outermost layer of Ti6AlV alloy was predominantly composed of TiO_(2)but Ti_(2)O_(3)(22.8%),Al_(2)O_(3)and V_(2)O_(5) were also detected.With increasing sputtering depth to 6 nm,fitting revealed the presence of Ti_(2)O_(3)and TiO with relative fractions of 25.3%and 35.8%,respectively.Yet,a spot of TiO(8%)was also observed at 12 nm in the oxide layer of Ti6Al4V alloy.Although the addition of Cu into Ti6Al4V alloy generated the self-healing property of passive film in the presence of P.aeruginosa,it also reduced resistance to corrosion in general condition.
基金This work was supported by the Key Project of National Natural Science Foundation of China(No.81530006 to Ruibao Ren)Shanghai Collaborative Innovation Program on Regenerative Medicine and Stem Cell Research(No.2019CXJQ01 to Ruibao Ren)+2 种基金National Natural ScienceFoundation of China(No.81870112 to Ruibao Ren,No.81770171 to Bo Jiao,and No.81970134 to Ping Liu)Samuel Waxman Cancer Research Foundation(to Ruibao Ren)the Innovative Research Team of High-level Local Universities in Shanghai.
文摘More than 85%of patients with uveal melanoma(UM)carry a GNAQ or GNA11 mutation at a hotspot codon(Q209)that encodes G proteinαsubunit q/11 polypeptides(Gα_(q/11)).GNAQ/11 relies on palmitoylation for membrane association and signal transduction.Despite the palmitoylation of GNAQ/11 was discovered long before,its implication in UM remains unclear.Here,results of palmitoylation-targeted mutagenesis and chemical interference approaches revealed that the loss of GNAQ/11 palmitoylation substantially affected tumor cell proliferation and survival in UM cells.Palmitoylation inhibition through the mutation of palmitoylation sites suppressed GNAQ/11^(Q209L)-induced malignant transformation in NIH3T3 cells.Importantly,the palmitoylation-deficient oncogenic GNAQ/11 failed to rescue the cell death initiated by the knock down of endogenous GNAQ/11 oncogenes in UM cells,which are much more dependent on Gα_(q/11) signaling for cell survival and proliferation than other melanoma cells without GNAQ/11 mutations.Furthermore,the palmitoylation inhibitor,2-bromopalmitate,also specifically disrupted Gα_(q/11) downstream signaling by interfering with the MAPK pathway and BCL2 survival pathway in GNAQ/11-mutant UM cells and showed a notable synergistic effect when applied in combination with the BCL2 inhibitor,ABT-199,in vitro.The findings validate that GNAQ/11 palmitoylation plays a critical role in UM and may serve as a promising therapeutic target for GNAQ/11-driven UM.
基金supported by the National Natural Science Foundation of China(No.51631009)the authors acknowledge the CAS-TWAS presidential scholarship program.
文摘The influence of hot-deformation on the microstructure,crystalline orientation,and texture evolution of Ti6Al4V-5Cu,an antibacterial(α+β)titanium alloy,was investigated.The alloy was deformed using a hot rolling process in 15%,58%,and 73%thickness reduction ratios.It was found that the basal<α→>and pyramidal<c→+α→>type slip planes could be activated in theαphase,which dominated the deformation behavior of Ti6Al4V-5Cu alloy.Under various deformation conditions,the alloy revealed different microstructure features.On the 15%hot rolled alloy,the deformation was performed by the breakdown of priorβgrain boundaries(GBβ),which was attributed to the formation of coarseαgrains,rotated nearly 45°with respect to the transversal and rolling directions.The presence of different sub-structure geometries made the interior grain size distribution heterogeneous.On the 58%hot rolled alloy,Ti2Cu intermetallic compound was found at theα/βinterface.High-resolution transmission electron microscopy investigation showed the occurrence of grain rotation in different crystallographic directions.At room temperature,the percentage elongation(El)of the alloy reached 23.15%on the 58%hot rolled sample.On the 73%deformed alloy,refined and randomly oriented characteristics of grains were obtained due to higher thickness reduction,which resulted from the segregation of very fine granules.The influence of grain rotation during a hot rolling process revealed that theα/βtexture fiber separation angle to maintain the Burger orientation relationship of{0001}α//{110}βplanes decreased with increase of the thickness reduction ratio when Ti6Al4V-5Cu alloy was deformed by a hot rolling mechanism.Activation of tensile{1012}<1011>and compressive{1122}<1123>twins on the deformation of the alloy was also studied.
基金the Key Program of Natural Science Foundation of China(Nos.8153006 and 81870112 to Ruibao Ren,No.81970134 to Ping Liu)Shanghai Science and Technology Development Funds(No.18ZR1423600 to Ruibao Ren)+1 种基金Shanghai Collaborative Innovation Program on Regenerative Medicine and Stem Cell Research(No.2019CXJQ01 to Ruibao Ren)the Samuel Waxman Cancer Research Foundation and Innovative Research Team of High-level Local Universities in Shanghai(to Ruibao Ren).
文摘Cullin-RING E3 ubiquitin ligase(CRL)-4 is a member of the large CRL family in eukaryotes.It plays important roles in a wide range of cellular processes,organismal development,and physiological and pathological conditions.DDB1-and CUL4-associated factor 8(DCAF8)is a WD40 repeat-containing protein,which serves as a substrate receptor for CRL4.The physiological role of DCAF8 is unknown.In this study,we constructed Dcaf8 knockout mice.Homozygous mice were viable with no noticeable abnormalities.However,the fertility of Dcaf8-deficient male mice was markedly impaired,consistent with the high expression of DCAF8 in adult mouse testis.Sperm movement characteristics,including progressive motility,path velocity,progressive velocity,and track speed,were significantly lower in Dcaf8 knockout mice than in wild-type(WT)mice.However,the total motility was similar between WT and Dcaf8 knockout sperm.More than 40%of spermatids in Dcaf8 knockout mice showed pronounced morphological abnormalities with typical bent head malformation.The acrosome and nucleus of Dcaf8 knockout sperm looked similar to those of WT sperm.In vitro tests showed that the fertilization rate of Dcaf8 knockout mice was significantly reduced.The results demonstrated that DCAF8 plays a critical role in spermatogenesis,and DCAF8 is a key component of CRL4 function in the reproductive system.