BACKGROUND Currently,intrahepatic cholangiocarcinoma(ICC)poses a continuing,significant health challenge,but the relationship has yet to be established between ICC and the proteasome 26S subunit non-ATPase 6(PSMD6).AI...BACKGROUND Currently,intrahepatic cholangiocarcinoma(ICC)poses a continuing,significant health challenge,but the relationship has yet to be established between ICC and the proteasome 26S subunit non-ATPase 6(PSMD6).AIM To investigate the protein expression and clinicopathological significance of PSMD6 in ICC.METHODS The potential impact of the PSMD6 gene on the growth of ICC cell lines was analyzed using clustered regularly interspaced short palindromic repeat knockout screening technology.Forty-two paired specimens of ICC and adjacent noncancerous tissues were collected.PSMD6 protein expression was determined by immunohistochemistry.Receiver operating characteristic curve analysis was performed to validate PSMD6 expression level,and its association with ICC patients’various clinicopathological characteristics was investigated.RESULTS The PSMD6 gene was found to be essential for the growth of ICC cell lines.PSMD6 protein was significantly overexpressed in ICC tissues(P<0.001),but showed no significant association with patient age,gender,pathological grade,or tumor-node-metastasis stage(P>0.05).CONCLUSION PSMD6 can promote the growth of ICC cells,thus playing a pro-oncogenic role.展开更多
In this editorial we comment on the article by Tang et al published in the recent issue of World Journal of Hepatology.Drug therapy of intrahepatic cholangiocarcinoma(iCCA)poses an enormous challenge since only a smal...In this editorial we comment on the article by Tang et al published in the recent issue of World Journal of Hepatology.Drug therapy of intrahepatic cholangiocarcinoma(iCCA)poses an enormous challenge since only a small proportion of patients demonstrate beneficial responses to therapeutic agents.Thus,there has been a sustained search for novel molecular targets for iCCA.The study by Tang et al evaluated the role of 26S proteasome non-ATPase regulatory subunit 6(PSMD6),a 19S regulatory subunit of the proteasome,in human iCCA cells and specimens.The authors employed clustered regularly interspaced short palindromic repeat(CRISPR)knockout screening technology integrated with the computational CERES algorithm,and analyzed the human protein atlas(THPA)database and tissue microarrays.The results show that PSMD6 is a gene essential for the proliferation of 17 iCCA cell lines,and PSMD6 protein was overexpressed in iCCA tissues without a significant correlation with the clinicopathological parameters.The authors conclude that PSMD6 may play a promoting role in iCCA.The major limitations and defects of this study are the lack of detailed information of CRISPR knockout screening,in vivo experiments,and a discussion of plausible mechanistic cues,which,therefore,dampen the significance of the results.Further studies are required to verify PSMD6 as a molecular target for developing novel therapeutics for iCCA.In addition,the editorial article summarizes the latest advances in molecular targeted drugs and recently emerging immunotherapy in the clinical management of iCCA,development of proteasome inhibitors for cancer therapy,and advantages of CRISPR screening technology,computational methods,and THPA database as experimental tools for fighting cancer.We hope that these comments may provide some clues for those engaged in the field of basic and clinical research into iCCA.展开更多
The Ag clusters have been investigated widely theoretically and experimentally. In particular, it has recently shown that the neutral Ag8 clusters embedded in an argon matrix have a strong fluorescence signal. As we c...The Ag clusters have been investigated widely theoretically and experimentally. In particular, it has recently shown that the neutral Ag8 clusters embedded in an argon matrix have a strong fluorescence signal. As we can know, the metal clusters may have important effects on the structures and properties of biomolecules. More and more attention is paid to the interaction between nanomaterials and biomolecules. In this work, the B3LYP method in density functional theory was used on the complexes between the 6-mercaptopurine（6MP） and Ag8 clusters combined with 6-311＋＋G＊＊ as well as LANL2DZ base sets. The geometries of all the complexes were optimized with full degree of freedom and the structures, chemical bonds, orbital properties as well as Mulliken charges for ten possible complexes were analyzed based on the same theory level. In addition, the influence of temperature and pressure on the stabilities of the four complexes was further explored using standard statistical thermodynamic methods ranging from 50 to 500 K and at 100 kPa or 100 bar. The results show that the complex Ag8-6 MP-7-5 can be the most stable one among the investigated complexes, in which the Ag（11） atom interacts with the S（10） atom forming the strong chemical bond. The Mulliken charges also show that the Ag–S chemical bond is formed and the related charge has transferred. Additionally, the temperature and pressure can significantly influence the stability of the four stable complexes.展开更多
The events from 157 globular clusters(GCs)are analyzed by using 12 yr long-term Pass 8 data from Fermi Large Area Telescope.Besides the 34 GCs reported in previous literatures,four additional GCs(ESO 452-SC11,NGC6380,...The events from 157 globular clusters(GCs)are analyzed by using 12 yr long-term Pass 8 data from Fermi Large Area Telescope.Besides the 34 GCs reported in previous literatures,four additional GCs(ESO 452-SC11,NGC6380,Palomar 6 and UKS 1)in the Milky Way are detected as gamma-ray GC candidates.Especially for UKS 1,these are known as the faintest GCs in long-wavelength bands.Further data analysis has been performed for the four GCs.While no pulsars are determined in radio and/or X-ray wavelengths so far,their gamma-ray pulsation emissions are not found,and no significant gamma-ray flux variability is detected.The numbers of MSPs within the four GCs are estimated based on the assumption that the MSPs within each GC emit similar amounts of gamma-rays.The gamma-ray results reported here could help us better understand the nature of gamma-ray emission origins for GCs.展开更多
文摘BACKGROUND Currently,intrahepatic cholangiocarcinoma(ICC)poses a continuing,significant health challenge,but the relationship has yet to be established between ICC and the proteasome 26S subunit non-ATPase 6(PSMD6).AIM To investigate the protein expression and clinicopathological significance of PSMD6 in ICC.METHODS The potential impact of the PSMD6 gene on the growth of ICC cell lines was analyzed using clustered regularly interspaced short palindromic repeat knockout screening technology.Forty-two paired specimens of ICC and adjacent noncancerous tissues were collected.PSMD6 protein expression was determined by immunohistochemistry.Receiver operating characteristic curve analysis was performed to validate PSMD6 expression level,and its association with ICC patients’various clinicopathological characteristics was investigated.RESULTS The PSMD6 gene was found to be essential for the growth of ICC cell lines.PSMD6 protein was significantly overexpressed in ICC tissues(P<0.001),but showed no significant association with patient age,gender,pathological grade,or tumor-node-metastasis stage(P>0.05).CONCLUSION PSMD6 can promote the growth of ICC cells,thus playing a pro-oncogenic role.
基金Supported by The National Key Research and Development Program of China,No.2017YFC1308602The Research Funds by the Fifth Affiliated Hospital of Harbin Medical University,No.2022-002 and No.2023-001.
文摘In this editorial we comment on the article by Tang et al published in the recent issue of World Journal of Hepatology.Drug therapy of intrahepatic cholangiocarcinoma(iCCA)poses an enormous challenge since only a small proportion of patients demonstrate beneficial responses to therapeutic agents.Thus,there has been a sustained search for novel molecular targets for iCCA.The study by Tang et al evaluated the role of 26S proteasome non-ATPase regulatory subunit 6(PSMD6),a 19S regulatory subunit of the proteasome,in human iCCA cells and specimens.The authors employed clustered regularly interspaced short palindromic repeat(CRISPR)knockout screening technology integrated with the computational CERES algorithm,and analyzed the human protein atlas(THPA)database and tissue microarrays.The results show that PSMD6 is a gene essential for the proliferation of 17 iCCA cell lines,and PSMD6 protein was overexpressed in iCCA tissues without a significant correlation with the clinicopathological parameters.The authors conclude that PSMD6 may play a promoting role in iCCA.The major limitations and defects of this study are the lack of detailed information of CRISPR knockout screening,in vivo experiments,and a discussion of plausible mechanistic cues,which,therefore,dampen the significance of the results.Further studies are required to verify PSMD6 as a molecular target for developing novel therapeutics for iCCA.In addition,the editorial article summarizes the latest advances in molecular targeted drugs and recently emerging immunotherapy in the clinical management of iCCA,development of proteasome inhibitors for cancer therapy,and advantages of CRISPR screening technology,computational methods,and THPA database as experimental tools for fighting cancer.We hope that these comments may provide some clues for those engaged in the field of basic and clinical research into iCCA.
基金supported by the National Natural Science Foundation of China(No.21643014)the Special Natural Science Foundation of Science and Technology Bureau of Xi’an City Government(No.2016CXWL02 and SGH17H249)
文摘The Ag clusters have been investigated widely theoretically and experimentally. In particular, it has recently shown that the neutral Ag8 clusters embedded in an argon matrix have a strong fluorescence signal. As we can know, the metal clusters may have important effects on the structures and properties of biomolecules. More and more attention is paid to the interaction between nanomaterials and biomolecules. In this work, the B3LYP method in density functional theory was used on the complexes between the 6-mercaptopurine（6MP） and Ag8 clusters combined with 6-311＋＋G＊＊ as well as LANL2DZ base sets. The geometries of all the complexes were optimized with full degree of freedom and the structures, chemical bonds, orbital properties as well as Mulliken charges for ten possible complexes were analyzed based on the same theory level. In addition, the influence of temperature and pressure on the stabilities of the four complexes was further explored using standard statistical thermodynamic methods ranging from 50 to 500 K and at 100 kPa or 100 bar. The results show that the complex Ag8-6 MP-7-5 can be the most stable one among the investigated complexes, in which the Ag（11） atom interacts with the S（10） atom forming the strong chemical bond. The Mulliken charges also show that the Ag–S chemical bond is formed and the related charge has transferred. Additionally, the temperature and pressure can significantly influence the stability of the four stable complexes.
基金supported in part by the National Key R&D Program of China under Grant No.2018YFA0404204the National Natural Science Foundation of China(NSFC,Grant No.12163006)+1 种基金the Basic Research Program of Yunnan Province No.202101AT070394the Joint Foundation of Department of Science and Technology of Yunnan Province and Yunnan University(2018FY001(-003))。
文摘The events from 157 globular clusters(GCs)are analyzed by using 12 yr long-term Pass 8 data from Fermi Large Area Telescope.Besides the 34 GCs reported in previous literatures,four additional GCs(ESO 452-SC11,NGC6380,Palomar 6 and UKS 1)in the Milky Way are detected as gamma-ray GC candidates.Especially for UKS 1,these are known as the faintest GCs in long-wavelength bands.Further data analysis has been performed for the four GCs.While no pulsars are determined in radio and/or X-ray wavelengths so far,their gamma-ray pulsation emissions are not found,and no significant gamma-ray flux variability is detected.The numbers of MSPs within the four GCs are estimated based on the assumption that the MSPs within each GC emit similar amounts of gamma-rays.The gamma-ray results reported here could help us better understand the nature of gamma-ray emission origins for GCs.
