AIM: To investigate the combined effects of K-ras antisense oligodeoxynucleotide (K-ras ASODN) specif ic to GTT point mutation at codon 12 and type Ⅰ insulin-like growth factor receptor (IGF-IR) antisense oligodeoxyn...AIM: To investigate the combined effects of K-ras antisense oligodeoxynucleotide (K-ras ASODN) specif ic to GTT point mutation at codon 12 and type Ⅰ insulin-like growth factor receptor (IGF-IR) antisense oligodeoxynucleotide (IGF-IR ASODN) on proliferation and apoptosis of human pancreatic cancer Patu8988 cells in vitro and in vivo. METHODS: K-ras gene point mutation and its style at codon 12 of human pancreatic cancer cell line Patu8988 were detected by using polymerase chain reaction with special sequence primers (PCR-SSP) and sequence analysis. According to the mutation style, K-ras mutation ASODN specifi c to K-ras point mutation at codon 12 was designed and composed. After K-ras ASODN and IGF-IR ASODN treated on Patu8988 cells respectively or cooperatively, the proliferation and morphological change of Patu8988 cells were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony forming assay andtransmission electron microscopy; the expression of K-ras and IGF-IR mRNA and protein in the treated cells was measured by reverse-transcript polymerase chain reaction (RT-PCR) and flow cytometry respectively; apoptosis was determined by flow cytometry. The combined antitumor activity of K-ras ASODN and IGF-IR ASODN was evaluated in BALB/c nude mice bearing human pancreatic cancer inoculated with Patu8988 cells. RESULTS: The results of PCR-SSP and sequence analysis showed that the human pancreatic cancer cell line Patu8988 had point mutation at codon 12, and the mutation style was GGT→GTT. 2-32 μg/mL K-ras ASODN and 2-32 μg/mL IGF-IR ASODN could inhibit Patu8988 cells' growth, induce apoptosis and decrease the expression of K-ras and IGF-IR mRNA and protein alone. However, there was much more effective inhibition of growth and induction of apoptosis by their combination than by each one alone. In tumor bearing mice, the combination of K-ras ASODN and IGF-IR ASODN showed a signif icant inhibitory effect on the growth of transplanted pancreatic cancer, resulting in a statistically signif icant difference compared with each alone. CONCLUSION: It has been found that K-ras ASODN combined with IGF-IR ASODN could cooperatively inhibit the growth of Patu8988 cells, and induce their apoptosis via reinforcing specific down regulation of K-ras and IGF-IR mRNA and protein expression.展开更多
Background and Aims:Hepatocellular carcinoma(HCC)is the fourth most common cause of cancer-related death and ranks sixth in terms of incident cases worldwide.The purpose of this study was to develop an effective and s...Background and Aims:Hepatocellular carcinoma(HCC)is the fourth most common cause of cancer-related death and ranks sixth in terms of incident cases worldwide.The purpose of this study was to develop an effective and sensitive method to distinguish liver cancer tissues from normal tissues in HCC patients.Integrinα6 is a promising cell surface target for molecular imaging of HCC,where it is overexpressed and is a prognostic biomarker.We previously identified an integrinα6-targeted peptide CRWYDENAC(RWY)that has been used for positron emission tomography(PET)imaging of HCC in mouse models.Methods:We labeled the integrinα6-targeted RWY peptide with cyanine 7(Cy7)to form an optical probe(Cy7-RWY)for near infrared fluorescent(NIRF)and photoacoustic(PA)imaging in HCC.Mice transplanted with subcutaneous HCC-LM3 or orthotopic HCC-H22 cells that overexpressed integrinα6 were intravenously injected with Cy7-RWY and its corresponding Cy7-control.NIRF and PA images of mice were collected from 0 to 48 h after injection.Results:Both NIRF and PA signals started to accumulate in the tumor 2 h after injection of Cy7-RWY and peaked at 24 h.Conclusions:Cy7-RWY is a promising optical probe for NIRF and PA imaging of HCC in mice,and has potential clinical application for HCC detection.展开更多
Continuous top-k query over sliding window is a fundamental problem in database, which retrieves k objects with the highest scores when the window slides. Existing studies mainly adopt exact algorithms to tackle this ...Continuous top-k query over sliding window is a fundamental problem in database, which retrieves k objects with the highest scores when the window slides. Existing studies mainly adopt exact algorithms to tackle this type of queries, whose key idea is to maintain a subset of objects in the window, and try to retrieve answers from it. However, all the existing algorithms are sensitive to query parameters and data distribution. In addition, they suffer from expensive overhead for incremental maintenance, and thus cannot satisfy real-time requirement. In this paper, we define a novel query named (ε, δ)-approximate continuous top-κ query, which returns approximate answers for top-κ query. In order to efficiently support this query, we propose an efficient framework, named PABF (Probabilistic Approximate Based Framework), to support approximate top-κ query over sliding window. We firstly maintain a self-adaptive pruning value, which could filter out newly arrived objects who have a probability less than 1 - 5 of being a query result. For those objects that are not filtered, we combine them together, if the score difference among them is less than a threshold. To efficiently maintain these combined results, the framework PABF also proposes a multi-phase merging algorithm. Theoretical analysis indicates that even in the worst case, we require only logarithmic complexity for maintaining each candidate.展开更多
A series of core-expanded naphthalene diimides(NDI-DTYM) and thiophene-based derivatives(1a-c)were designed and synthesized to investigate the relationship between molecular structures and the highest occupied mol...A series of core-expanded naphthalene diimides(NDI-DTYM) and thiophene-based derivatives(1a-c)were designed and synthesized to investigate the relationship between molecular structures and the highest occupied molecular orbital(HOMO) energy levels but has little impact on the lowest unoccupied molecular orbital(LUMO) energy levels.The results demonstrated that increasing the number of thiophene units can gradually elevate the HOMO energy levels but had little impact on the LUMO energy levels.The n-channel organic field-effect transistors(OFETs) based on 1b and 1c have demonstrated that these almost unchanged LUMO energy levels are proper to transport electrons.展开更多
Two copolymers of P1 and P2 comprising benzothiadiazole, 1,4-bis(dodecyloxy)-benzene units were synthesized by Sonogashira coupling polymerization based on ethynyl-linked 1,2,5,6-naphthalenediimide. Their thermal, o...Two copolymers of P1 and P2 comprising benzothiadiazole, 1,4-bis(dodecyloxy)-benzene units were synthesized by Sonogashira coupling polymerization based on ethynyl-linked 1,2,5,6-naphthalenediimide. Their thermal, optical, electrochemical as well as charge transport properties were studied. Bottom-gate top-contact organic field-effect transistors (OFETs) measurements of P1 and P2 thin films showed different charge transport behaviors. P1 displayed pure electron transport behaviors in OFETs with electron mobility up to 10^-3 cm^2·V-1·s^-1, while P2 exhibited hole transport features. The molecular structure analysis revealed that the structure of P1 has the acceptor-linker-acceptor' (A-L-A') characteristic, and P2 possesses the donor-linker-acceptor (D-L-A) structure feature. The results demonstrate that different molecular structures lead them to have distinct charge transport behaviors. In particular, the first pure electron transport copolymer in OFETs based on 1,2,5,6-naphthalenediimide is achieved.展开更多
基金Social development foundation of Suzhou, China, No. SZD0614Young teacher foundation of Soochow UniversityFoundation of health department of Jiangsu Province, China, No. Z200622
文摘AIM: To investigate the combined effects of K-ras antisense oligodeoxynucleotide (K-ras ASODN) specif ic to GTT point mutation at codon 12 and type Ⅰ insulin-like growth factor receptor (IGF-IR) antisense oligodeoxynucleotide (IGF-IR ASODN) on proliferation and apoptosis of human pancreatic cancer Patu8988 cells in vitro and in vivo. METHODS: K-ras gene point mutation and its style at codon 12 of human pancreatic cancer cell line Patu8988 were detected by using polymerase chain reaction with special sequence primers (PCR-SSP) and sequence analysis. According to the mutation style, K-ras mutation ASODN specifi c to K-ras point mutation at codon 12 was designed and composed. After K-ras ASODN and IGF-IR ASODN treated on Patu8988 cells respectively or cooperatively, the proliferation and morphological change of Patu8988 cells were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony forming assay andtransmission electron microscopy; the expression of K-ras and IGF-IR mRNA and protein in the treated cells was measured by reverse-transcript polymerase chain reaction (RT-PCR) and flow cytometry respectively; apoptosis was determined by flow cytometry. The combined antitumor activity of K-ras ASODN and IGF-IR ASODN was evaluated in BALB/c nude mice bearing human pancreatic cancer inoculated with Patu8988 cells. RESULTS: The results of PCR-SSP and sequence analysis showed that the human pancreatic cancer cell line Patu8988 had point mutation at codon 12, and the mutation style was GGT→GTT. 2-32 μg/mL K-ras ASODN and 2-32 μg/mL IGF-IR ASODN could inhibit Patu8988 cells' growth, induce apoptosis and decrease the expression of K-ras and IGF-IR mRNA and protein alone. However, there was much more effective inhibition of growth and induction of apoptosis by their combination than by each one alone. In tumor bearing mice, the combination of K-ras ASODN and IGF-IR ASODN showed a signif icant inhibitory effect on the growth of transplanted pancreatic cancer, resulting in a statistically signif icant difference compared with each alone. CONCLUSION: It has been found that K-ras ASODN combined with IGF-IR ASODN could cooperatively inhibit the growth of Patu8988 cells, and induce their apoptosis via reinforcing specific down regulation of K-ras and IGF-IR mRNA and protein expression.
基金funded by the National Natural Science Foundation of China (Grant:81972531)Fundamental Research Funds for the Central Universities (Grant:19ykpy174)+1 种基金GuangDong Basic and Applied Basic Research Foundation (Grant:2020A1515011374)GuangDong Basic and Applied Basic Research Foundation (Grant:202102020138).
文摘Background and Aims:Hepatocellular carcinoma(HCC)is the fourth most common cause of cancer-related death and ranks sixth in terms of incident cases worldwide.The purpose of this study was to develop an effective and sensitive method to distinguish liver cancer tissues from normal tissues in HCC patients.Integrinα6 is a promising cell surface target for molecular imaging of HCC,where it is overexpressed and is a prognostic biomarker.We previously identified an integrinα6-targeted peptide CRWYDENAC(RWY)that has been used for positron emission tomography(PET)imaging of HCC in mouse models.Methods:We labeled the integrinα6-targeted RWY peptide with cyanine 7(Cy7)to form an optical probe(Cy7-RWY)for near infrared fluorescent(NIRF)and photoacoustic(PA)imaging in HCC.Mice transplanted with subcutaneous HCC-LM3 or orthotopic HCC-H22 cells that overexpressed integrinα6 were intravenously injected with Cy7-RWY and its corresponding Cy7-control.NIRF and PA images of mice were collected from 0 to 48 h after injection.Results:Both NIRF and PA signals started to accumulate in the tumor 2 h after injection of Cy7-RWY and peaked at 24 h.Conclusions:Cy7-RWY is a promising optical probe for NIRF and PA imaging of HCC in mice,and has potential clinical application for HCC detection.
基金This work is partially supported by the National Natural Science Fund for Distinguish Young Scholars of China under Grant No. 61322208, the National Basic Research 973 Program of China under Grant No. 2012CB316201, the National Natural Science Foundation of China under Grant Nos. 61272178 and 61572122, and the Key Program of the National Natural Science Foundation of China under Grant No. 61532021.
文摘Continuous top-k query over sliding window is a fundamental problem in database, which retrieves k objects with the highest scores when the window slides. Existing studies mainly adopt exact algorithms to tackle this type of queries, whose key idea is to maintain a subset of objects in the window, and try to retrieve answers from it. However, all the existing algorithms are sensitive to query parameters and data distribution. In addition, they suffer from expensive overhead for incremental maintenance, and thus cannot satisfy real-time requirement. In this paper, we define a novel query named (ε, δ)-approximate continuous top-κ query, which returns approximate answers for top-κ query. In order to efficiently support this query, we propose an efficient framework, named PABF (Probabilistic Approximate Based Framework), to support approximate top-κ query over sliding window. We firstly maintain a self-adaptive pruning value, which could filter out newly arrived objects who have a probability less than 1 - 5 of being a query result. For those objects that are not filtered, we combine them together, if the score difference among them is less than a threshold. To efficiently maintain these combined results, the framework PABF also proposes a multi-phase merging algorithm. Theoretical analysis indicates that even in the worst case, we require only logarithmic complexity for maintaining each candidate.
基金supported financially by the National Natural Science Foundation of China (Nos. 21302212 and 21522209)the ‘‘Strategic Priority Research Program’’ (No. XDB12010100)
文摘A series of core-expanded naphthalene diimides(NDI-DTYM) and thiophene-based derivatives(1a-c)were designed and synthesized to investigate the relationship between molecular structures and the highest occupied molecular orbital(HOMO) energy levels but has little impact on the lowest unoccupied molecular orbital(LUMO) energy levels.The results demonstrated that increasing the number of thiophene units can gradually elevate the HOMO energy levels but had little impact on the LUMO energy levels.The n-channel organic field-effect transistors(OFETs) based on 1b and 1c have demonstrated that these almost unchanged LUMO energy levels are proper to transport electrons.
基金financially supported by the National Natural Science Foundation of China(No.21674126)the"Strategic Priority Research Program"(No.XDB12010100)the Shanghai Science and Technology Committee(No.16JC1400603)
文摘Two copolymers of P1 and P2 comprising benzothiadiazole, 1,4-bis(dodecyloxy)-benzene units were synthesized by Sonogashira coupling polymerization based on ethynyl-linked 1,2,5,6-naphthalenediimide. Their thermal, optical, electrochemical as well as charge transport properties were studied. Bottom-gate top-contact organic field-effect transistors (OFETs) measurements of P1 and P2 thin films showed different charge transport behaviors. P1 displayed pure electron transport behaviors in OFETs with electron mobility up to 10^-3 cm^2·V-1·s^-1, while P2 exhibited hole transport features. The molecular structure analysis revealed that the structure of P1 has the acceptor-linker-acceptor' (A-L-A') characteristic, and P2 possesses the donor-linker-acceptor (D-L-A) structure feature. The results demonstrate that different molecular structures lead them to have distinct charge transport behaviors. In particular, the first pure electron transport copolymer in OFETs based on 1,2,5,6-naphthalenediimide is achieved.