Objectives:Lung cancer represents a major global healthcare challenge,characterized by high annual incidence and mortality rates worldwide.Although targeted therapies for lung cancer have advanced,treatment outcomes f...Objectives:Lung cancer represents a major global healthcare challenge,characterized by high annual incidence and mortality rates worldwide.Although targeted therapies for lung cancer have advanced,treatment outcomes for advanced-stage patients remain suboptimal.This investigation examines the role of the translocase of the inner mitochondrial membrane(TIMM)8A-TIMM13 complex in lung cancer and evaluates its potential as a novel therapeutic target.Methods:A co-immunoprecipitation(Co-IP)assay was conducted to verify the interaction between TIMM8A and TIMM13.Differential gene expression analysis of TIMM8A or TIMM13 was executed using the TNMplot database,with survival estimates derived from the Kaplan-Meier plotter.Lung cancer cell proliferation was evaluated through Cell Counting Kit 8(CCK-8)and colony formation assays,while cell migration was assessed via Transwell assay.RNA sequencing identified the downstream effectors of TIMM13.RNAi technology facilitated the inhibition of TIMM8A or TIMM13 expression,which was measured through immunoblotting or qRT-PCR.Results:This investigation revealed that components of the TIMM8A-TIMM13 complex exhibited elevated expression in human lung cancer tissues,correlating with disease progression and poor overall survival rates among lung cancer patients.The suppression of either TIMM8A or TIMM13 inhibited cell proliferation and migration.Mechanistic studies through transcriptome analysis identified cell cycle-related pathways as potential key downstream effectors of the TIMM8A-TIMM13 complex.Subsequent experiments confirmed that the TIMM8A-TIMM13 complex significantly regulated the expression of cyclin D1(CCND1)and cyclin-dependent kinase 6(CDK6)complex.Conclusion:The elevated expression of TIMM8A-TIMM13 complex components plays a crucial role in lung cancer cell growth,suggesting its potential as a promising therapeutic target for lung cancer treatment.展开更多
Mosquito-borne flaviviruses,such as Zika virus(ZIKV)and dengue virus(DENV),cause diverse severe clinical manifestations including fever,rash,hepatitis,arthralgia,and congenital anomalies.Here,we identified a host fact...Mosquito-borne flaviviruses,such as Zika virus(ZIKV)and dengue virus(DENV),cause diverse severe clinical manifestations including fever,rash,hepatitis,arthralgia,and congenital anomalies.Here,we identified a host factor,the adaptor protein complex 1 gamma 1 subunit(AP1G1),which plays an important role in both ZIKV and dengue virus 2(DENV2)infections.We explored the role of AP1G1 in ZIKV and DENV2 infections using CRISPR/Cas9 gene editing technology and RNA interference(RNAi)techniques.Knockout or silencing of AP1G1 decreases the replication of ZIKV and DENV2 in multiple human cell lines.Intriguingly,depletion of AP1G1 results in a significant reduction in ZIKV at an early stage,but decreases DENV2 replication levels during the late stage,suggesting that AP1G1 plays distinct roles in the infection by ZIKV and DENV2.Furthermore,we determined that AP1G1 mediates ZIKV-endosomal membrane fusion through inhibitor experiments and fluorescence labeling assays.Mechanistically,we found that AP1G1 exerts its pro-viral effect through binding to the ZIKV envelope glycoprotein(E protein).This interaction promotes the fusion of viral and endosomal membranes,during which the ZIKV genomic RNAs are released from the endosome into the cytoplasm,a process that facilitates viral replication.However,for DENV2 infection,AP1G1 primarily affects its viral RNA replication stage,rather than the fusion of virus-endosomal membrane.Taken together,our work demonstrates that AP1G1 plays a pro-viral role in both ZIKV and DENV2 infections via distinct mechanisms,highlighting its potential as a therapeutic target for antiviral strategies.展开更多
BACKGROUND As a member of the chaperonin-containing tailless complex polypeptide 1(TCP1)complex,which plays a pivotal role in ensuring the accurate folding of numerous proteins,chaperonin-containing TCP1 subunit 6A(CC...BACKGROUND As a member of the chaperonin-containing tailless complex polypeptide 1(TCP1)complex,which plays a pivotal role in ensuring the accurate folding of numerous proteins,chaperonin-containing TCP1 subunit 6A(CCT6A)participates in various physiological and pathological processes.However,its effects on cell death and cancer therapy and the underlying mechanisms need further exploration in colorectal cancer(CRC)cells.AIM To explore the effects of CCT6A on cell death and cancer therapy and the underlying mechanisms in CRC.METHODS Cell proliferation was evaluated using the MTS assay,EdU staining,and colony growth assays.The expression of CCT6A was monitored by immunoblotting and quantitative PCR.CCT6A was knocked out by CRISPR-Cas9,and overexpressed by transfecting plasmids.Autophagy was examined by immunoblotting and the mCherry-GFP-LC3 assay.To monitor apoptosis and necroptosis,immunoblotting,co-immunoprecipitation,and flow cytometry were employed.RESULTS Cisplatin(DDP)exerted cytotoxic effects on CRC cells while simultaneously downregulating the expression of CCT6A.Depletion of CCT6A amplified the cytotoxic effects of DDP,whereas overexpression of CCT6A attenuated these adverse effects.CCT6A suppressed autophagy,apoptosis,and necroptosis under both basal and DDP-treated conditions.Autophagy inhibitors significantly enhanced the cytotoxic effects of DDP,whereas a necroptosis inhibitor partially reversed the cell viability loss induced by DDP.Furthermore,inhibiting autophagy enhanced both apoptosis and necroptosis induced by DDP.CONCLUSION CCT6A negatively modulates autophagy,apoptosis,and necroptosis,and CCT6A confers resistance to DDP therapy in CRC,suggesting its potential as a therapeutic target.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is a leading cause of cancer-related mortality worldwide,with hepatitis B virus(HBV)infection serving as a significant etiological factor in endemic regions.Alpha-fetoprotein(AF...BACKGROUND Hepatocellular carcinoma(HCC)is a leading cause of cancer-related mortality worldwide,with hepatitis B virus(HBV)infection serving as a significant etiological factor in endemic regions.Alpha-fetoprotein(AFP),the most commonly used biomarker,has limited sensitivity,particularly in AFP-negative HCC.Recent studies have identified origin recognition complex subunit 1(ORC1)and extra spindle pole bodies-like 1(ESPL1)as promising serum biomarkers,both linked to HBV DNA integration,a mechanism known to drive hepatocarcinogenesis.AIM To assess serum ORC1’s diagnostic value for HBV-HCC and its link to S gene integration.METHODS In this case-control study,479 HBV-infected patients were enrolled,including 20 hepatitis B,154 with HBV-related cirrhosis,and 96 with HBV-HCC.The control group comprised 73 individuals:29 with non-HBV-HCC and 44 healthy participants.Serum ORC1 and ESPL1 were measured by enzyme-linked immunosorbent assay.HBV integration sites were identified via whole-genome sequencing.Diagnostic performance was assessed using receiver operating characteristic analysis,including in AFP-negative patients.RESULTS HBV integration near the ORC1 locus(chromosome 1p32.3)was detected in 71.4%of HBV-HCC tissues.Serum ORC1 levels were significantly higher in HBV-infected patients than in non-HBV-infected controls(980.11 ng/L vs 746.82 ng/L,P<0.05)and in HBV-HCC compared with non-HBV-HCC(1077.07 ng/L vs 749.54 ng/L,P<0.05).Serum ORC1 and ESPL1 were elevated in HBV-HCC regardless of AFP status,and detected 64.8%and 73.2%of AFP-negative cases,respectively.The combined panel of ORC1[Area under receiver operating characteristic curve(AUC)=0.587],ESPL1(AUC=0.776),and AFP(AUC=0.844)achieved an AUC of 0.887,significantly higher than any single marker(P<0.05),with a sensitivity of 84.44%,specificity of 84.19%,and a negative predictive value of 94.91%.CONCLUSION Serum ORC1,driven by HBV integration,is a promising biomarker especially for AFP-negative HBV-HCC.Its combination with ESPL1 and AFP significantly improves early detection.展开更多
It is of great significance to evaluate the petrophysical properties in shale oil reservoir,which can contribute to geological storage CO_(2).Two-dimensional nuclear magnetic resonance(2D NMR)technology has been appli...It is of great significance to evaluate the petrophysical properties in shale oil reservoir,which can contribute to geological storage CO_(2).Two-dimensional nuclear magnetic resonance(2D NMR)technology has been applied to petrophysical characterization in shale oil reservoir.However,limitations of traditional 2D NMR(T_(1)-T_(2)or T_(2)-D)in detecting short-lived organic matter and the complexity of mineral compositions,pose NMR-based petrophysical challenges.The organic pores were assumed saturated oil and the inorganic pores were assumed saturated water,and the numerical algorithm and theory of T_(1)-T_(2)^(*)in shale oil reservoir were proposed,whose accuracy was validated through T_(2),T_(1)-T_(2)and T_(2)^(*)experiments.The effects of mineral types and contents on the T_(1)-T_(2)^(*)responses were firstly simulated by the random walk algorithm,revealing the NMR response mechanisms in shale oil reservoir with complex mineral compositions at different magnetic field frequency(f).The results indicate that when the pyrite content is 5.43%,dwell time is 4μs,the f is 200 MHz,and echo spacing is 0.4 ms,the T_(1)-T_(2)^(*)-based porosity is 2.39 times that of T_(1)-T_(2)-based porosity.The T_(2LM)^(*)is 0.015 ms,which is 0.015 times that of T_(2)LM.The T_(1LM)is 8.84 ms,which is 0.63 times that of T_(1LM).The T_(1)-T_(2)^(*)-based petrophysical conversion models were firstly created,and the foundation of petrophysical conversion was laid at different f.展开更多
Objective To explore the role of HIV-1 tat gene variations in AIDS dementia complex （ADC） pathogenesis. Methods HIV-1 tat genes derived from peripheral spleen and central basal ganglia of an AIDS patient with ADC an...Objective To explore the role of HIV-1 tat gene variations in AIDS dementia complex （ADC） pathogenesis. Methods HIV-1 tat genes derived from peripheral spleen and central basal ganglia of an AIDS patient with ADC and an AIDS patient without ADC were cloned for sequence analysis. HIV-1 tat gene sequence alignment was performed by using CLUSTAL W and the phylogentic analysis was conducted by using Neighbor-joining with MEGA4 software. All tat genes were used to construct recombinant retroviral expressing vector MSCV-IRES-GFP/tat. The MSCV-IRES-GFP/tat was cotransfected into 293T cells with pCMV-VSV-G and pUMVC vectors to assemble the recombinant retrovirus. After infection of gliomas U87 cells with equal amount of the recombinant retrovirus, TNF-α, and IL-1β concentrations in the supernatant of U87 cells were determined with ELISA. Results HIV-1 tat genes derived from peripheral spleen and central basal ganglia of the AIDS patient with ADC and the other one without ADC exhibited genetic variations. Tat variations and amino acid mutation sites existed mainly at Tat protein core functional area （38-47aa）. All Tat proteins could induce ug7 cells to produce TNF-α and IL-1β, but the level of IL-1β production was different among Tat proteins derived from the ADC patient＇s spleen, basal ganglia, and the non-ADC patient＇s spleen. The level of Tat proteins derived from the ADC patient＇s spleen, basal ganglia, and the non-ADC patient＇s spleen were obviously higher than that from the non-ADC patient＇s basal ganglia. Conclusion Tat protein core functional area （38-47aa） may serve as the key area of enhancing the secretion of IL-1β. This may be related with the neurotoxicity of HIV-1 Tat.展开更多
Metal (Me=Fe(III), Mo(VI), Mn(II), Co(II), Ni(II), Zn(II) and Cu(II)) 2-hydroxy-1-naphthaldehyde thiosemicarbazone complexes (MeHNT) were synthesized and used as mimic-enzyme catalysts to mimic the active group of hor...Metal (Me=Fe(III), Mo(VI), Mn(II), Co(II), Ni(II), Zn(II) and Cu(II)) 2-hydroxy-1-naphthaldehyde thiosemicarbazone complexes (MeHNT) were synthesized and used as mimic-enzyme catalysts to mimic the active group of horseradish peroxidase (HRP). The results showed that Fe-HNT, Mo-HNT are effective catalysts, which have similar catalytic activity as HRP. The sequence of catalytic activities of tested biomimic peroxidas is Mo-HNT > Fe-HNT > Zn-HNT > Ni-HNT > Mn-HNT. Among them, Fe-HNT is used as a mimic-enzyme catalyst in determination of ascorbic acid and glucose by coupling the catalytic reaction of glucose oxidase.展开更多
A novel cyclometalated iridium complex with 1, 3, 4-oxadiazole moiety was synthesizedand characterized. Its UV and photoluminescent properties were studied. The strong UVabsorption intensity around 462 nm attributed t...A novel cyclometalated iridium complex with 1, 3, 4-oxadiazole moiety was synthesizedand characterized. Its UV and photoluminescent properties were studied. The strong UVabsorption intensity around 462 nm attributed to spin-forbidden triplet metal–ligand charge transferband and photoluminescence at 518 nm were observed. This indicated that achieved iridiumcomplex could be used as an efficient electrophosphorescent material.展开更多
A novel heterometallic complex,[Zn4Ni（OH）2（btec）2（titb）2（H2O）2]·2H2O（1）（H4btec=1,2,4,5-benzenetetracarboxylic acid,titb=1,3,5-tris（imidazol-1-ylmethyl）-2,4,6-trime-thylbenzene）,has been hydrothermal...A novel heterometallic complex,[Zn4Ni（OH）2（btec）2（titb）2（H2O）2]·2H2O（1）（H4btec=1,2,4,5-benzenetetracarboxylic acid,titb=1,3,5-tris（imidazol-1-ylmethyl）-2,4,6-trime-thylbenzene）,has been hydrothermally prepared and characterized by IR spectroscopy,elemental analysis and single-crystal X-ray diffraction.The crystal is of triclinic system,space group P1 with a=10.817（10）,b=11.878（11）,c=14.569（14）,α=71.762（12）,β=76.122（13）,γ=71.493（13）°,V=1665（3）3,C62H62N12O22Zn4Ni,Mr=1647.43,Dc=1.643 g/cm3,F（000）=842,μ=1.784 mm-1 and Z=1.The final R=0.0531 and wR=0.0890 for 3545 observed reflections（Ⅰ 2σ（Ⅰ））.In the title complex,the btec ligand acts as a five-dentate bridging ligand to link up zinc and nickel atoms into a lamellar framework,which are further interlinked into a 3-D framework via the titb ligands.展开更多
Six new transition metal complexes, [Zn（HBTC）（PYTPY）]n·n PYTPY（1）, [Cu（HBTC）（PYTPY）]n·n PYTPY（2）, [Co（HBTC）（PYTPY）]n·n DMF（3）, [Mn（HBTC）（PYTPY）]n·n DMF（4）, [Cd（HBTC）（PYTP...Six new transition metal complexes, [Zn（HBTC）（PYTPY）]n·n PYTPY（1）, [Cu（HBTC）（PYTPY）]n·n PYTPY（2）, [Co（HBTC）（PYTPY）]n·n DMF（3）, [Mn（HBTC）（PYTPY）]n·n DMF（4）, [Cd（HBTC）（PYTPY）（H2O）]n·2nH2O（5）, and [Co（HBTC）（PYTPY）（H2O）2]（6）,（H3BTC = 1,3,5-benzenetricarboxylic acid, PYTPY = 4＇-（4-pyridyl）-2,2＇：6＇,2＇＇-terpyridine, DMF = N,N？-dimethylformamide）, have been synthesized and characterized by elemental analysis, IR and X-ray single-crystal diffraction. Complexes 1~5 all feature one-dimensional chain structures, and complex 6 exhibits a zero-dimensional structure. Complexes 1~5 present three-dimensional（3D） supramolecular frameworks via π-π stacking interactions, whenas 6 has also a 3D supramolecular structure assembled by hydrogen bonding. Meanwhile, complexes 1 ~ 6 exhibit the thermal stabilities and photoluminescent properties.展开更多
Two new metal-organic complexes [Cd2（1,4-BDC）（4-pytyp）（H2O）4]·（1,4-BDC）（1） and [Cu2（1,4-BDC）（4-pytyp）2（H2O）2]·（1,4-BDC）·8H2O（2）（4-pytyp = 4＇-（4＇＇-pyridyl）-2,2＇：6＇,2＇＇-terp...Two new metal-organic complexes [Cd2（1,4-BDC）（4-pytyp）（H2O）4]·（1,4-BDC）（1） and [Cu2（1,4-BDC）（4-pytyp）2（H2O）2]·（1,4-BDC）·8H2O（2）（4-pytyp = 4＇-（4＇＇-pyridyl）-2,2＇：6＇,2＇＇-terpyridine, 1,4-H2 BDC = 1,4-benzenedicarboxylic acid） have been synthesized under hydrothermal conditions and characterized by elemental analysis, infrared analysis and X-ray single-crystal diffraction. The scrutiny of single-crystal structure reveals that complex 1 forms to a 3D supramolecular network linked by π-π stacking interactions and hydrogen bonds. X-ray diffraction analysis reveals that complex 2 exhibits a 3D supramolecular network linked through complicated hydrogen bonds. The thermogravimetric analysis and photoluminescent properties of 1 and 2 are discussed in detail.展开更多
The inclusion-complex of CD-MCP （β-cyclodextrin （β-CD） including 1-methylcyclopropene （1-MCP）） was prepared and characterized. Basing on programmed-heating procedure and weight-temperature analysis, as well as...The inclusion-complex of CD-MCP （β-cyclodextrin （β-CD） including 1-methylcyclopropene （1-MCP）） was prepared and characterized. Basing on programmed-heating procedure and weight-temperature analysis, as well as the application of Satava-Sestak＇s, Ozawa＇s and Kissinger＇s methods, the mechanism and kinetics of thermal dissociation of this inclusion complex were studied. An additional mass loss is found at 170-180℃. The mechanism of thermal dissociation of CD-MCP is dominated by a one-dimensional random nucleation and subsequent growth process （A2/3）. The activation energy Es and the pre-exponential factor AS for the process are 102.14 kJ/mol and 3.63×10^10s^-1, respectively. This ES value shows that there is no strong chemical intere, ctions between β-CD and 1-MC;P,展开更多
Urinary prothrombin fragment 1 （UPTFl） is a potent inhibitor of urinary stone formation. UPTF1 exerts such inhibitory effect by effective 7-carboxylation in which vitamin K epoxide reductase complex subunit 1 （VKO...Urinary prothrombin fragment 1 （UPTFl） is a potent inhibitor of urinary stone formation. UPTF1 exerts such inhibitory effect by effective 7-carboxylation in which vitamin K epoxide reductase complex subunit 1 （VKORC1）, the rate-limiting enzyme, is involved. This study examined the correlation between VKORC1 expression and calcium oxalate urolithiasis. The renal cortex samples were obtained from patients undergoing nephrectomy and then divided into 3 groups： urolithiasis group, control group A [hydronephrosis-without-stone （HWS） group], control group B （normal control group）, The localization and expression of VKORC1 in renal tissues were determined by using immunohistochemistry, immunofluorescence microscopy, Western blotting and SYBR Green I real-time reverse-transcription PCR. The rapid amplification of cDNA ends （RACE） were conducted to obtain the 3＇- and 5＇-untranslated region （UTR） of VKORC1. The results showed that VKORC1 was located in the cytoplasm of renal tubular epithelial cells. The expression of VKORC1 in the uro- lithiasis group was significantly lower than that in the other two control groups （P〈0.05）. Moreover, the 3＇- and 5＇-UTR sequence of the VKORC1 gene was successfully cloned. No insertion or deletion was found in the 3＇- and 5＇-UTR. However, a 171-bp new base sequence was discovered in the up- stream of 5＇-UTR end in the urolithiasis group. It was concluded that the decreased expression of VKORC 1 may contribute to the development of calcium oxalate urolithiasis in the kidney.展开更多
基金supported by Beijing Natural Science Foundation(7242268)Beijing Hospitals Authority Youth Programme(QML20230807)Training Fund for Open Projects at Clinical Institutes and Departments of Capital Medical University(CCMU2023ZKYXZ007).
文摘Objectives:Lung cancer represents a major global healthcare challenge,characterized by high annual incidence and mortality rates worldwide.Although targeted therapies for lung cancer have advanced,treatment outcomes for advanced-stage patients remain suboptimal.This investigation examines the role of the translocase of the inner mitochondrial membrane(TIMM)8A-TIMM13 complex in lung cancer and evaluates its potential as a novel therapeutic target.Methods:A co-immunoprecipitation(Co-IP)assay was conducted to verify the interaction between TIMM8A and TIMM13.Differential gene expression analysis of TIMM8A or TIMM13 was executed using the TNMplot database,with survival estimates derived from the Kaplan-Meier plotter.Lung cancer cell proliferation was evaluated through Cell Counting Kit 8(CCK-8)and colony formation assays,while cell migration was assessed via Transwell assay.RNA sequencing identified the downstream effectors of TIMM13.RNAi technology facilitated the inhibition of TIMM8A or TIMM13 expression,which was measured through immunoblotting or qRT-PCR.Results:This investigation revealed that components of the TIMM8A-TIMM13 complex exhibited elevated expression in human lung cancer tissues,correlating with disease progression and poor overall survival rates among lung cancer patients.The suppression of either TIMM8A or TIMM13 inhibited cell proliferation and migration.Mechanistic studies through transcriptome analysis identified cell cycle-related pathways as potential key downstream effectors of the TIMM8A-TIMM13 complex.Subsequent experiments confirmed that the TIMM8A-TIMM13 complex significantly regulated the expression of cyclin D1(CCND1)and cyclin-dependent kinase 6(CDK6)complex.Conclusion:The elevated expression of TIMM8A-TIMM13 complex components plays a crucial role in lung cancer cell growth,suggesting its potential as a promising therapeutic target for lung cancer treatment.
基金supported by the National Natural Science Foundation of China(No.82471389,No.32470986,No.82271385)Natural Science Foundation of Guangdong Province(No.2024A1515010471).
文摘Mosquito-borne flaviviruses,such as Zika virus(ZIKV)and dengue virus(DENV),cause diverse severe clinical manifestations including fever,rash,hepatitis,arthralgia,and congenital anomalies.Here,we identified a host factor,the adaptor protein complex 1 gamma 1 subunit(AP1G1),which plays an important role in both ZIKV and dengue virus 2(DENV2)infections.We explored the role of AP1G1 in ZIKV and DENV2 infections using CRISPR/Cas9 gene editing technology and RNA interference(RNAi)techniques.Knockout or silencing of AP1G1 decreases the replication of ZIKV and DENV2 in multiple human cell lines.Intriguingly,depletion of AP1G1 results in a significant reduction in ZIKV at an early stage,but decreases DENV2 replication levels during the late stage,suggesting that AP1G1 plays distinct roles in the infection by ZIKV and DENV2.Furthermore,we determined that AP1G1 mediates ZIKV-endosomal membrane fusion through inhibitor experiments and fluorescence labeling assays.Mechanistically,we found that AP1G1 exerts its pro-viral effect through binding to the ZIKV envelope glycoprotein(E protein).This interaction promotes the fusion of viral and endosomal membranes,during which the ZIKV genomic RNAs are released from the endosome into the cytoplasm,a process that facilitates viral replication.However,for DENV2 infection,AP1G1 primarily affects its viral RNA replication stage,rather than the fusion of virus-endosomal membrane.Taken together,our work demonstrates that AP1G1 plays a pro-viral role in both ZIKV and DENV2 infections via distinct mechanisms,highlighting its potential as a therapeutic target for antiviral strategies.
基金Supported by Shandong Provincial Natural Science Foundation,No.ZR2023MH329Project of Shandong Province Higher Educational Youth Innovation Science and Technology Program,No.2023KJ263and Natural Science Foundation of Gansu Province,China,No.22JR5RA953.
文摘BACKGROUND As a member of the chaperonin-containing tailless complex polypeptide 1(TCP1)complex,which plays a pivotal role in ensuring the accurate folding of numerous proteins,chaperonin-containing TCP1 subunit 6A(CCT6A)participates in various physiological and pathological processes.However,its effects on cell death and cancer therapy and the underlying mechanisms need further exploration in colorectal cancer(CRC)cells.AIM To explore the effects of CCT6A on cell death and cancer therapy and the underlying mechanisms in CRC.METHODS Cell proliferation was evaluated using the MTS assay,EdU staining,and colony growth assays.The expression of CCT6A was monitored by immunoblotting and quantitative PCR.CCT6A was knocked out by CRISPR-Cas9,and overexpressed by transfecting plasmids.Autophagy was examined by immunoblotting and the mCherry-GFP-LC3 assay.To monitor apoptosis and necroptosis,immunoblotting,co-immunoprecipitation,and flow cytometry were employed.RESULTS Cisplatin(DDP)exerted cytotoxic effects on CRC cells while simultaneously downregulating the expression of CCT6A.Depletion of CCT6A amplified the cytotoxic effects of DDP,whereas overexpression of CCT6A attenuated these adverse effects.CCT6A suppressed autophagy,apoptosis,and necroptosis under both basal and DDP-treated conditions.Autophagy inhibitors significantly enhanced the cytotoxic effects of DDP,whereas a necroptosis inhibitor partially reversed the cell viability loss induced by DDP.Furthermore,inhibiting autophagy enhanced both apoptosis and necroptosis induced by DDP.CONCLUSION CCT6A negatively modulates autophagy,apoptosis,and necroptosis,and CCT6A confers resistance to DDP therapy in CRC,suggesting its potential as a therapeutic target.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a leading cause of cancer-related mortality worldwide,with hepatitis B virus(HBV)infection serving as a significant etiological factor in endemic regions.Alpha-fetoprotein(AFP),the most commonly used biomarker,has limited sensitivity,particularly in AFP-negative HCC.Recent studies have identified origin recognition complex subunit 1(ORC1)and extra spindle pole bodies-like 1(ESPL1)as promising serum biomarkers,both linked to HBV DNA integration,a mechanism known to drive hepatocarcinogenesis.AIM To assess serum ORC1’s diagnostic value for HBV-HCC and its link to S gene integration.METHODS In this case-control study,479 HBV-infected patients were enrolled,including 20 hepatitis B,154 with HBV-related cirrhosis,and 96 with HBV-HCC.The control group comprised 73 individuals:29 with non-HBV-HCC and 44 healthy participants.Serum ORC1 and ESPL1 were measured by enzyme-linked immunosorbent assay.HBV integration sites were identified via whole-genome sequencing.Diagnostic performance was assessed using receiver operating characteristic analysis,including in AFP-negative patients.RESULTS HBV integration near the ORC1 locus(chromosome 1p32.3)was detected in 71.4%of HBV-HCC tissues.Serum ORC1 levels were significantly higher in HBV-infected patients than in non-HBV-infected controls(980.11 ng/L vs 746.82 ng/L,P<0.05)and in HBV-HCC compared with non-HBV-HCC(1077.07 ng/L vs 749.54 ng/L,P<0.05).Serum ORC1 and ESPL1 were elevated in HBV-HCC regardless of AFP status,and detected 64.8%and 73.2%of AFP-negative cases,respectively.The combined panel of ORC1[Area under receiver operating characteristic curve(AUC)=0.587],ESPL1(AUC=0.776),and AFP(AUC=0.844)achieved an AUC of 0.887,significantly higher than any single marker(P<0.05),with a sensitivity of 84.44%,specificity of 84.19%,and a negative predictive value of 94.91%.CONCLUSION Serum ORC1,driven by HBV integration,is a promising biomarker especially for AFP-negative HBV-HCC.Its combination with ESPL1 and AFP significantly improves early detection.
基金funded by the National Natural Science Foundation of China(42174131)。
文摘It is of great significance to evaluate the petrophysical properties in shale oil reservoir,which can contribute to geological storage CO_(2).Two-dimensional nuclear magnetic resonance(2D NMR)technology has been applied to petrophysical characterization in shale oil reservoir.However,limitations of traditional 2D NMR(T_(1)-T_(2)or T_(2)-D)in detecting short-lived organic matter and the complexity of mineral compositions,pose NMR-based petrophysical challenges.The organic pores were assumed saturated oil and the inorganic pores were assumed saturated water,and the numerical algorithm and theory of T_(1)-T_(2)^(*)in shale oil reservoir were proposed,whose accuracy was validated through T_(2),T_(1)-T_(2)and T_(2)^(*)experiments.The effects of mineral types and contents on the T_(1)-T_(2)^(*)responses were firstly simulated by the random walk algorithm,revealing the NMR response mechanisms in shale oil reservoir with complex mineral compositions at different magnetic field frequency(f).The results indicate that when the pyrite content is 5.43%,dwell time is 4μs,the f is 200 MHz,and echo spacing is 0.4 ms,the T_(1)-T_(2)^(*)-based porosity is 2.39 times that of T_(1)-T_(2)-based porosity.The T_(2LM)^(*)is 0.015 ms,which is 0.015 times that of T_(2)LM.The T_(1LM)is 8.84 ms,which is 0.63 times that of T_(1LM).The T_(1)-T_(2)^(*)-based petrophysical conversion models were firstly created,and the foundation of petrophysical conversion was laid at different f.
基金supported by the Science&Technology Development Program of Shandong Province(Grant No.2007GG30002003)
文摘Objective To explore the role of HIV-1 tat gene variations in AIDS dementia complex （ADC） pathogenesis. Methods HIV-1 tat genes derived from peripheral spleen and central basal ganglia of an AIDS patient with ADC and an AIDS patient without ADC were cloned for sequence analysis. HIV-1 tat gene sequence alignment was performed by using CLUSTAL W and the phylogentic analysis was conducted by using Neighbor-joining with MEGA4 software. All tat genes were used to construct recombinant retroviral expressing vector MSCV-IRES-GFP/tat. The MSCV-IRES-GFP/tat was cotransfected into 293T cells with pCMV-VSV-G and pUMVC vectors to assemble the recombinant retrovirus. After infection of gliomas U87 cells with equal amount of the recombinant retrovirus, TNF-α, and IL-1β concentrations in the supernatant of U87 cells were determined with ELISA. Results HIV-1 tat genes derived from peripheral spleen and central basal ganglia of the AIDS patient with ADC and the other one without ADC exhibited genetic variations. Tat variations and amino acid mutation sites existed mainly at Tat protein core functional area （38-47aa）. All Tat proteins could induce ug7 cells to produce TNF-α and IL-1β, but the level of IL-1β production was different among Tat proteins derived from the ADC patient＇s spleen, basal ganglia, and the non-ADC patient＇s spleen. The level of Tat proteins derived from the ADC patient＇s spleen, basal ganglia, and the non-ADC patient＇s spleen were obviously higher than that from the non-ADC patient＇s basal ganglia. Conclusion Tat protein core functional area （38-47aa） may serve as the key area of enhancing the secretion of IL-1β. This may be related with the neurotoxicity of HIV-1 Tat.
文摘Metal (Me=Fe(III), Mo(VI), Mn(II), Co(II), Ni(II), Zn(II) and Cu(II)) 2-hydroxy-1-naphthaldehyde thiosemicarbazone complexes (MeHNT) were synthesized and used as mimic-enzyme catalysts to mimic the active group of horseradish peroxidase (HRP). The results showed that Fe-HNT, Mo-HNT are effective catalysts, which have similar catalytic activity as HRP. The sequence of catalytic activities of tested biomimic peroxidas is Mo-HNT > Fe-HNT > Zn-HNT > Ni-HNT > Mn-HNT. Among them, Fe-HNT is used as a mimic-enzyme catalyst in determination of ascorbic acid and glucose by coupling the catalytic reaction of glucose oxidase.
基金This work was supported by the National Natural Science Foundation of China(No.20272014)the Project of National Education Ministry(Project No.204097)National 973 Project of China(Project No.2002CB613400-5).
文摘A novel cyclometalated iridium complex with 1, 3, 4-oxadiazole moiety was synthesizedand characterized. Its UV and photoluminescent properties were studied. The strong UVabsorption intensity around 462 nm attributed to spin-forbidden triplet metal–ligand charge transferband and photoluminescence at 518 nm were observed. This indicated that achieved iridiumcomplex could be used as an efficient electrophosphorescent material.
基金supported by the National Natural Science Foundation of China (No. 20971004)the Key Project of Chinese Ministry of Education (No. 210102)
文摘A novel heterometallic complex,[Zn4Ni（OH）2（btec）2（titb）2（H2O）2]·2H2O（1）（H4btec=1,2,4,5-benzenetetracarboxylic acid,titb=1,3,5-tris（imidazol-1-ylmethyl）-2,4,6-trime-thylbenzene）,has been hydrothermally prepared and characterized by IR spectroscopy,elemental analysis and single-crystal X-ray diffraction.The crystal is of triclinic system,space group P1 with a=10.817（10）,b=11.878（11）,c=14.569（14）,α=71.762（12）,β=76.122（13）,γ=71.493（13）°,V=1665（3）3,C62H62N12O22Zn4Ni,Mr=1647.43,Dc=1.643 g/cm3,F（000）=842,μ=1.784 mm-1 and Z=1.The final R=0.0531 and wR=0.0890 for 3545 observed reflections（Ⅰ 2σ（Ⅰ））.In the title complex,the btec ligand acts as a five-dentate bridging ligand to link up zinc and nickel atoms into a lamellar framework,which are further interlinked into a 3-D framework via the titb ligands.
基金Supported by the National Natural Science Foundation of China(No.21576112)Natural Science Foundation of Jilin Province(20150623024TC-19,20170520147JH)the Science and Technology Development Plan of Siping City(2015049)
文摘Six new transition metal complexes, [Zn（HBTC）（PYTPY）]n·n PYTPY（1）, [Cu（HBTC）（PYTPY）]n·n PYTPY（2）, [Co（HBTC）（PYTPY）]n·n DMF（3）, [Mn（HBTC）（PYTPY）]n·n DMF（4）, [Cd（HBTC）（PYTPY）（H2O）]n·2nH2O（5）, and [Co（HBTC）（PYTPY）（H2O）2]（6）,（H3BTC = 1,3,5-benzenetricarboxylic acid, PYTPY = 4＇-（4-pyridyl）-2,2＇：6＇,2＇＇-terpyridine, DMF = N,N？-dimethylformamide）, have been synthesized and characterized by elemental analysis, IR and X-ray single-crystal diffraction. Complexes 1~5 all feature one-dimensional chain structures, and complex 6 exhibits a zero-dimensional structure. Complexes 1~5 present three-dimensional（3D） supramolecular frameworks via π-π stacking interactions, whenas 6 has also a 3D supramolecular structure assembled by hydrogen bonding. Meanwhile, complexes 1 ~ 6 exhibit the thermal stabilities and photoluminescent properties.
基金Supported by the Program for New Century Excellent Talents in University(NCET-10-0176)the Natural Science Foundation of Jilin Province(No.20130521019JH)the fund of Jilin Provincial Education Department of China(No.2014154)
文摘Two new metal-organic complexes [Cd2（1,4-BDC）（4-pytyp）（H2O）4]·（1,4-BDC）（1） and [Cu2（1,4-BDC）（4-pytyp）2（H2O）2]·（1,4-BDC）·8H2O（2）（4-pytyp = 4＇-（4＇＇-pyridyl）-2,2＇：6＇,2＇＇-terpyridine, 1,4-H2 BDC = 1,4-benzenedicarboxylic acid） have been synthesized under hydrothermal conditions and characterized by elemental analysis, infrared analysis and X-ray single-crystal diffraction. The scrutiny of single-crystal structure reveals that complex 1 forms to a 3D supramolecular network linked by π-π stacking interactions and hydrogen bonds. X-ray diffraction analysis reveals that complex 2 exhibits a 3D supramolecular network linked through complicated hydrogen bonds. The thermogravimetric analysis and photoluminescent properties of 1 and 2 are discussed in detail.
文摘The inclusion-complex of CD-MCP （β-cyclodextrin （β-CD） including 1-methylcyclopropene （1-MCP）） was prepared and characterized. Basing on programmed-heating procedure and weight-temperature analysis, as well as the application of Satava-Sestak＇s, Ozawa＇s and Kissinger＇s methods, the mechanism and kinetics of thermal dissociation of this inclusion complex were studied. An additional mass loss is found at 170-180℃. The mechanism of thermal dissociation of CD-MCP is dominated by a one-dimensional random nucleation and subsequent growth process （A2/3）. The activation energy Es and the pre-exponential factor AS for the process are 102.14 kJ/mol and 3.63×10^10s^-1, respectively. This ES value shows that there is no strong chemical intere, ctions between β-CD and 1-MC;P,
基金supported by a grant from the National Natural Science Foundation of China(No.30901482)
文摘Urinary prothrombin fragment 1 （UPTFl） is a potent inhibitor of urinary stone formation. UPTF1 exerts such inhibitory effect by effective 7-carboxylation in which vitamin K epoxide reductase complex subunit 1 （VKORC1）, the rate-limiting enzyme, is involved. This study examined the correlation between VKORC1 expression and calcium oxalate urolithiasis. The renal cortex samples were obtained from patients undergoing nephrectomy and then divided into 3 groups： urolithiasis group, control group A [hydronephrosis-without-stone （HWS） group], control group B （normal control group）, The localization and expression of VKORC1 in renal tissues were determined by using immunohistochemistry, immunofluorescence microscopy, Western blotting and SYBR Green I real-time reverse-transcription PCR. The rapid amplification of cDNA ends （RACE） were conducted to obtain the 3＇- and 5＇-untranslated region （UTR） of VKORC1. The results showed that VKORC1 was located in the cytoplasm of renal tubular epithelial cells. The expression of VKORC1 in the uro- lithiasis group was significantly lower than that in the other two control groups （P〈0.05）. Moreover, the 3＇- and 5＇-UTR sequence of the VKORC1 gene was successfully cloned. No insertion or deletion was found in the 3＇- and 5＇-UTR. However, a 171-bp new base sequence was discovered in the up- stream of 5＇-UTR end in the urolithiasis group. It was concluded that the decreased expression of VKORC 1 may contribute to the development of calcium oxalate urolithiasis in the kidney.
