AIM: To identify the differentially secreted proteins or polypeptides associated with tumorigenesis of esophageal squamous cell carcinoma (ESCC) from serum and to find potential tumor secreted biomarkers.METHODS: Prot...AIM: To identify the differentially secreted proteins or polypeptides associated with tumorigenesis of esophageal squamous cell carcinoma (ESCC) from serum and to find potential tumor secreted biomarkers.METHODS: Proteins from human ESCC tissue and its matched adjacent normal tissue; pre-surgery and postsurgery serum; and pre-surgery and normal control serum were separated by two-dimensional electrophoresis (2-DE)to identify differentially expressed proteins. The silverstained 2-DE were scanned with digital ImageScanner and analyzed with ImageMaster 2D Elite 3.10 software. A cluster of protein spots differentially expressed were selected and identified with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). One of the differentially expressed proteins, clusterin, was downregulated in cancer tissue and pre-surgery serum, but it was reversed in post-surgery serum. The results were confirmed by semi-quantitative reverse-transcription (RT)-PCR and western blot.RESULTS: Comparisons of the protein spots identified on the 2-DE maps from human matched sera showed that some proteins were differentially expressed, with most of them showing no differences in composition, shape or density.Being analyzed by MALDI-TOF-MS and database searching,clusterin was differentially expressed and down-regulated in both cancer tissue and pre-surgery serum compared with their counterparts. The results were also validated by RTPCR and western blot.CONCLUSION: The differentially expressed clusterin may play a key role during tumorigenesis of ESCC. The 2DE-MS based proteomic approach is one of the powerful tools for discovery of secreted markers from peripheral.展开更多
AIM: To investigate the alteration of the annexin I subcellular localization in esophageal squarnous cell carcinoma (ESCC)and the correlation between the translocation and the tumorigenesis of ESCC.METHODS: The protei...AIM: To investigate the alteration of the annexin I subcellular localization in esophageal squarnous cell carcinoma (ESCC)and the correlation between the translocation and the tumorigenesis of ESCC.METHODS: The protein localization of annexin I was detected in both human ESCC tissues and cell line via the indirect immunofluorescence strategy.RESULTS: In the normal esophageal epithelia the annex in I was mainly located on the plasma membrane and formed a consecutive typical trammels net. Annexin I protein also expressed dispersively in cytoplasm and the nuclei without specific localization on the nuclear membrane. In esophageal cancer annexin I decreased very sharply with scattered disappearance on the cellular membrane, however it translocated and highly expressed on the nuclear membrane,which was never found in normal esophageal epithelia. In cultured esophageal cancer cell line annexin I protein was also focused on the nuclear membrane, which was consistent with the result from esophageal cancer tissues.CONCLUSION: This observation suggests that the translocation of annexin I protein in ESCC may correlate with the tumorigenesis of the esophageal cancer.展开更多
AIM: To observe the therapeutic effect of intrasplenic transplantation with embryonic hepatocytes on amelioration of hereditary copper accumulation in toxic milk (TX) mouse modeling Wilson disease. METHODS: Donor hepa...AIM: To observe the therapeutic effect of intrasplenic transplantation with embryonic hepatocytes on amelioration of hereditary copper accumulation in toxic milk (TX) mouse modeling Wilson disease. METHODS: Donor hepatocytes were harvested from 14-d fetal liver of a pregnant homogeneous DL mouse. These cells were successively cultured, labeled with fluorescein dye Hoechst 33342 for 24 h, and sequentially infused into the spleen parenchyma of the recipient TX mice. No host immunosuppression measures were taken. Two and four weeks after transplantation, the recipients were killed for routine histologic investigation and immunohistochemistry study up to 4 wk after transplantation. The serum copper and ceruloplasmin concentrations of the recipient mice were determined by graphite furnace atomic absorption spectroscopy.RESULTS: In the following 2nd and 4th wk after transplantation, the donor hepatocytes could be visualized in the livers of 47.3% recipients. The serum ceruloplasmin and copper concentrations increased by 1.6-fold after 2 wk and 2.0-fold times after 4 wk respectively, which ultimately rose from about 30% of the normal level to nearly 60%(P＜0.01). The hepatic copper concentration decreased 7.2%, 4 wk after transplantation. Pathologic examination showed that there were many actively proliferative hepatocyte precursor cells with specific embryonic hepatocyte marker AFP migrated into hepatic sinusoidsof the recipients. A large number of cells carrying hepatocytes marker and albumin were observed in the recipient spleen tissues.CONCLUSION: Embryonic hepatocytes are capable of differentiating into mature hepatocytes in vivo. After transplantation, the hereditary abnormalities of copper metabolism in TX mice could be corrected partially by intrasplenic transplantation of homogeneous embryonic hepatocytes.展开更多
Background： Blood oxygenation level-dependent magnetic resonance imaging （BOLD-MRI） is a functional MRI technique which involves using the paramagnetic properties of deoxyhemoglobin to image the local tissue oxygen...Background： Blood oxygenation level-dependent magnetic resonance imaging （BOLD-MRI） is a functional MRI technique which involves using the paramagnetic properties of deoxyhemoglobin to image the local tissue oxygen concentration. The purpose of this study was to investigate whether BOLD-MRI could evaluate hypoxia and angiogenesis of breast invasive ductal carcinoma （IDC）. Methods： Ninety-eight female patients with IDC were retrospectively included in this research. All patients underwent breast BOLD-MRI at 3.0 T before surgery. R2＊ values of BOLD-MR1 were measured. The expression of carbonic anhydrase IX （CA IX） and vascular endothelial growth factor （VEGF） was analyzed by immunohistochemistry. Spearman＇s correlation analysis was used to correlate R2＊ value with CA IX and VEGF levels. Results： Heterogeneous intensity on BOLD-MRI images was the main finding of IDCs. The mean R2＊ value was 52.8 ± 18.6 Hz. The R2＊ values in patients with axillary lymph node metastasis were significantly higher than the R2＊ values in patients without axillary lymph node metastasis （t = 2.882, P = 0.005）. R2＊ values increased with CA IX level and positively correlated with the level of CA 1X （r = 0.616, P 〈 0.001）; however, R2＊ value had no significantly correlation with the level of VEGF （r = 0.110, P = 0.281）. Conclusion： B OLD-MRI could noninvasively evaluate chronic hypoxia of IDC, but not angiogenesis.展开更多
Background：Strain and strain-rate imaging （SRI） have been found clinically useful in the assessment of cardiac systolic and diastolic function as well as providing new insights in deciphering cardiac physiology and...Background：Strain and strain-rate imaging （SRI） have been found clinically useful in the assessment of cardiac systolic and diastolic function as well as providing new insights in deciphering cardiac physiology and mechanics in cardiomyopathies,and identifying early subclinical changes in various pathologies.The aim of this study was to evaluate the regional and global left ventricular （LV） myocardial function in metabolic syndrome （MS） with SRI so that we can provide more myocardial small lesions in patients with MS,which is robust and reliable basis for early detection of LV function.Methods：Thirty-nine adults with MS were enrolled in the study.There was a control group of 39 healthy adults.In addition to classic echocardiographic assessment of LV global functional changes,SRI was used to evaluate regional and global LV function.Including：Peak systolic strain （S）,peak systolic strain-rate （SR-s）,peak diastolic strain-rate （SR-e）.Results：There were no statistically significant differences between MS and controls in all traditional parameters of LV systolic function.On the other hand,significant differences were observed between MS and the control group in most of the parameters of S,SR-s,SR-e in regional LV function.Multiple stepwise regression analyses revealed that S and SR significantly were negatively correlated with blood pressure,waist circumference,fasting plasma glucose,uric acid,suggesting that risk factories were relevant to regional systolic dysfunction.Conclusion：In MS with normal LV ejection fraction,there was regional myocardial dysfunction,risk factors contributed to the impairment of systolic and diastolic function of the regional myocardium.Assessment of myocardial function using SRI could be more accurate in MS patient evaluation than conventional echocardiography alone.展开更多
AIM: To investigate whether P28 derived from C3d can enhance the immune response to HBV-preS2/S induced by directly injection of naked plasmids containing variable repeats of P28 and HBV-preS2/S in fusion form.METHODS...AIM: To investigate whether P28 derived from C3d can enhance the immune response to HBV-preS2/S induced by directly injection of naked plasmids containing variable repeats of P28 and HBV-preS2/S in fusion form.METHODS: One to four copies of C3d-P28 coding gene,amplified by PCR and modified by restriction endonuclease sdigestion, were subcloned into a eukaryotic expression vector pVAON33 to construct pVAON33-P28, pVAON33-P28.2, pVAON33-P28.3 and pVAON33-P28.4 (pVAON33-P28.[1-4]). HBV-preS2/S coding sequence was then introduced into the pVAON33-P28.[1-4] and identified by both PCR and DNA sequencing. BALB/c mice were primed by intramuscular gene immunization with 100 μg different recombinant plasmids on day 0 and were boosted by subcutaneous inoculation with HBsAg protein (1 μg) 12 wk post-priming. The levels and avidity of specific IgG in sera collected at the indicated times from each group were determined by ELISA and NaSCN-displacement ELISA,respectively.RESULTS: HBsAg specific antibody response was elicited in groups primed with plasmids pVAON33-S2/S-P28.[1-4] and pVAON33-S2/S. However, the response against HBsAg in the groups primed with pVAON33-S2/S-P28.[1-4] was significantly higher than that in pVAON33-S2/S group, the highest level of the specific antibody response was observed in the groups primed with pVAON33-S2/S-P28.4 (P＜0.01).After secondary immunization with specific antigen, the acceleration of antibody levels was significantly higher and faster in the mice primed with DNA expressing preS2/S-P28 fusions than that with DNA expressing preS2/S only (P＜0.05).Interestingly, mice primed with DNA expressing preS2/S-P28.4 fusions maintained the highest levels of anti-HBs antibodies in all animals. The avidity assay showed that the avidity index (AI) collected at 18 wk from mice primed with pVAON33-S2/S-P28.3 and pVAON33-S2/S-P28.4 were significantly higher than that from preS2/S-DNA vaccinated mice (P＜0.01).CONCLUSION: Different repeats of C3d-P28 can enhance both humoral immune response and avidity展开更多
AIM: To compare the distribution of virulence-associatedgenotypes of Helicobacter pylori(H pylori) in two areas of north China with different gastric cancer risk and furthermore probe into the pathogenicity of the bac...AIM: To compare the distribution of virulence-associatedgenotypes of Helicobacter pylori(H pylori) in two areas of north China with different gastric cancer risk and furthermore probe into the pathogenicity of the bacterium. METHODS: Gastric biopsies were taken from 355 subjects from Zhuanghe, a high risk area of gastric cancer, and 136 subjects from Shenyang, a low risk area of gastric cancer. A total of 149 H pylori strains isolated from these patients were studied by PCR for differences in the genotypes of cagA, vac A, and iceA.RESULTS: In patients with high risk for gastric cancer, higher frequencies of vacA s1 or s1m1b genotypes were found as compared to those from the low risk area. CONCLUSION: There is significantly different distribution of H pylori genotypes between Zhuanghe and Shenyang areas in north China.展开更多
Due to the time-varying topology and possible disturbances in a conflict environment,it is still challenging to maintain the mission performance of flying Ad hoc networks(FANET),which limits the application of Unmanne...Due to the time-varying topology and possible disturbances in a conflict environment,it is still challenging to maintain the mission performance of flying Ad hoc networks(FANET),which limits the application of Unmanned Aerial Vehicle(UAV)swarms in harsh environments.This paper proposes an intelligent framework to quickly recover the cooperative coveragemission by aggregating the historical spatio-temporal network with the attention mechanism.The mission resilience metric is introduced in conjunction with connectivity and coverage status information to simplify the optimization model.A spatio-temporal node pooling method is proposed to ensure all node location features can be updated after destruction by capturing the temporal network structure.Combined with the corresponding Laplacian matrix as the hyperparameter,a recovery algorithm based on the multi-head attention graph network is designed to achieve rapid recovery.Simulation results showed that the proposed framework can facilitate rapid recovery of the connectivity and coverage more effectively compared to the existing studies.The results demonstrate that the average connectivity and coverage results is improved by 17.92%and 16.96%,respectively compared with the state-of-the-art model.Furthermore,by the ablation study,the contributions of each different improvement are compared.The proposed model can be used to support resilient network design for real-time mission execution.展开更多
Inoculation with purified specific protein is usually the first step for preparation of monoclonal antibody (mAb). But it is quite difficult to obtain pure proteins especially with natural structures.Here we attempt t...Inoculation with purified specific protein is usually the first step for preparation of monoclonal antibody (mAb). But it is quite difficult to obtain pure proteins especially with natural structures.Here we attempt to replace the protein inoculation with DNA immunization in the preparation of mAb.The eukaryotic expression vectors pcDNA3-PreS2/S and pVAX-PreS2/S encoding the HBV M protein were constructed and prepared for DNA immunization.Female BALB/c mice developed a well antibody response to the target antigen after muscle injection with corresponding plasmids.The mice with effective antibodies induced were used for preparation of mAb.We found the mice immunized with three administrations of pcDNA3-PreS2/S and boosted by intrasplenic injection with the same plasmid could be exploited for preparation of mAb.And positive hybridoma cell 2D3 that can secrete specific mAb was cloned and analyzed.Our studies demonstrate that gene immunization may provide a convenient and efficient way to prepare mAbs.Cellular & Molecular Immunology. 2004;1(4):295-299.展开更多
Primary chemotherapy options for colorectal cancer(CRC)involve four key drugs:fluorouracils(5-FU),oxaliplatin,irinotecan and raltitrexed.The first-line regimen consists of 5-FU and leucovorin combined with oxaliplatin...Primary chemotherapy options for colorectal cancer(CRC)involve four key drugs:fluorouracils(5-FU),oxaliplatin,irinotecan and raltitrexed.The first-line regimen consists of 5-FU and leucovorin combined with oxaliplatin(FOLFOX),while the second-line regimen involves 5-FU and leucovorin combined with irinotecan(FOLFIRI)for metastatic CRC(mCRC)in China[1].展开更多
Cronobacter species are a group of Gram-negative opportunistic pathogens,which cause meningitis,sep-ticemia,and necrotizing enterocolitis in neonates and infants,with neurological sequelae in severe cases.Interest in ...Cronobacter species are a group of Gram-negative opportunistic pathogens,which cause meningitis,sep-ticemia,and necrotizing enterocolitis in neonates and infants,with neurological sequelae in severe cases.Interest in Cronobacter has increased significantly in recent years due to its high virulence in children.In this review,we summarize the current understanding of the prevalence of Cronobacter species in several important food types.We discuss the response mechanisms enabling persistence in adverse growth con-ditions,as well as its pathogenicity.We emphasize the food safety concerns caused by Cronobacter and subsequent control methods and clinical treatments.展开更多
Sexual lifestyles are closely related to overall human health and well-being.Few studies have focused on sexual lifestyles among older adults living with HIV(OALHIV),especially in low-and middle-income countries.This ...Sexual lifestyles are closely related to overall human health and well-being.Few studies have focused on sexual lifestyles among older adults living with HIV(OALHIV),especially in low-and middle-income countries.This study is a part of the sexual well-being among older adults in China(SWELL)study,which is a multicenter cross-sectional study focused on sexual health among older adults aged 50 years and older.Participants were 680 OALHIV(≥50 years old)from the SWELL study conducted from June 2020 to December 2022.Data were collected through one-on-one interviews.We used logistic regression to assess the correlates of sexual activity and sexual satis-faction.Among all participants,37.1%were sexually active.Being older,male,in a steady relationship and employed were associated with being sexually active.The prevalence of sexual satisfaction was 69.8%among sexually active OALHIV.Being homosexual and reporting a better general health status were associated with sexual satisfaction.The OALHIV who have depressive symptoms were less likely to report sexual satisfaction.To support holistic healthy aging among OALHIV,it is important for healthcare providers to be educated about the importance of enquiring about sexual activity,satisfaction and problems and addressing concerns while conveying sex-positive attitudes during clinical reviews,as these are still critical aspects of their health and well-being.展开更多
OBJECTIVE To explore the expression and the function of cell adhesion molecules in invasive micropapillary carcinoma (IMPC) of the breast, and to investigate the metastatic mechanism of IMPC. METHODS The expression of...OBJECTIVE To explore the expression and the function of cell adhesion molecules in invasive micropapillary carcinoma (IMPC) of the breast, and to investigate the metastatic mechanism of IMPC. METHODS The expression of E-cadherin, α-catenin and β-catenin was detected by imrnunohistochemical staining in 64 cases of IMPC, and compared with that of invasive ductal carcinoma (IDC). RESULTS E-cadherin and β-catenin were mainly expressed on the cell membrane of tumors, and cc-catenin was expressed in the cytoplasm and/or on the cell membrane. The expression of E-cadherin in IMPC was significantly higher than that in IDC. Furthermore, the expression of E-cadherin was mainly on the intercellular contact surface of the tumor cell clusters in IMPC, while that on the outer surface of the tumor cell clusters decreased or could not be detected. The degree of lymph nodes metastases in IMPC was significantly higher than that in IDC. The co-expressions of α-catenin and β-catenin in cases of lymph nodes metastases along with the expression of E-cadherin in IMPC were significantly higher than that in IDC. CONCLUSIONS These findings indicated that the adhesiveness of the intercellular contact surfaces of tumor clusters in IMPC was strong, while that of the outer surface of tumor clusters was decreased or lost. It is suggested that the adhesive characteristic of the cells in IMPC might play an important role in its higher metastatic potential.展开更多
Bacterial CpG DNA or synthetic oligonucleotides(ODNs)that contain unmethylated CpG motifs(CpG ODN)can directly activate antigen-presenting cells(APCs)to secrete various cytokines through the intraceilular receptor TLR...Bacterial CpG DNA or synthetic oligonucleotides(ODNs)that contain unmethylated CpG motifs(CpG ODN)can directly activate antigen-presenting cells(APCs)to secrete various cytokines through the intraceilular receptor TLR9.Cytokine profiles elicited by the actions of stimulatory CpG DNA on TLR9 expressed APCs are crucial to the subsequent immune responses.To date,cytokine profiles in APCs upon CpG ODN stimulation in vitro are not fully investigated.In the present study,vector-based siRNA was used to downregulate TLR9 expression.Cytokine profiles were observed in murine macrophage cell line RAW264.7 transfected with TLR9-siRNA plasmid upon CpG ODN stimulation.We found that not all the cytokine expressions by the macrophage were decreased while TLR9 was downregulated. IL-12, TNF-α, IFN-γ and IL-1β expressions were significantly decreased,but IL-6, IFN-β and IL-10 expressions were not affected.Interestingly,the level of IFN-α was even increased.This alteration of cytokines produced by TLR9-downregulated APCs upon CpG ODN stimulation might indicate that the role of CpG DNA is more complicated in the pathogenesis and prevention of diseases.Cellular & Molecular Immunology. 2005;2(2):130-135.展开更多
High volume conveyor systems in distribution centers have very large footprint and can handlelarge volumes and hold thousands of items.Traditional discrete-event cell-based approach to simulatesuch networks becomes co...High volume conveyor systems in distribution centers have very large footprint and can handlelarge volumes and hold thousands of items.Traditional discrete-event cell-based approach to simulatesuch networks becomes computationally challenging.An alternative approach,in which the traffic isrepresented by segments of fluid flow of different density instead of individual packages,is presentedin this paper to address this challenge.The proposed fluid-based simulation approach is developedusing a Hybrid Petri Nets framework.The underlying model is a combination of an extension of aBatches Petri Nets(BPN)and a Stochastic Petri Nets(SPN).The extensions are in the inclusion ofrandom elements and relaxation of certain structural constraints.Some adaptations are also made to fitthe target system modeling.The approach is presented with an example.展开更多
Using continuous wavelet transform as the analytical tool, the fractal characteristic of nucleotide sequences was studied. The fractal dimension of the exon and intron sequences for different species was calculated. ...Using continuous wavelet transform as the analytical tool, the fractal characteristic of nucleotide sequences was studied. The fractal dimension of the exon and intron sequences for different species was calculated. We use the Mexican hat wavelet function as the mother wavelet and Hurst exponent to describe the long-range correlation. It is found that the Hurst exponent of intron sequence is larger than that of exon sequence for the same gene.展开更多
Given the continuous and growing demand for point of care(POC)diagnostic tests,attention has been shifted toward integration and miniaturization of laboratory protocols into“sample-in-answer-out”devices.Microfluidic...Given the continuous and growing demand for point of care(POC)diagnostic tests,attention has been shifted toward integration and miniaturization of laboratory protocols into“sample-in-answer-out”devices.Microfluidic technologies have been considered an ideal solution to address the requirements of POC diagnostics since many laboratory functions can be miniaturized and incorporated onto a single integrated chip.In this review,we summarize the advances of integrated microfluidic devices for POC diagnostics in the last 3 years.Particularly,we summarize current materials used for microfluidic chip fabrication,discuss the innovation of versatile integrated microfluidic devices,especially the strategies for simplifying sample preparation in manual or self-driven systems,and new detection methods of microfluidic chips.In addition,we describe new integrated microfluidic devices for POC diagnostics of protein-targeted immunodiagnostics,nucleic acid molecular tests,and small molecule metabolites analysis.We also provide future perspectives and current challenges for clinical translation and commercialization of these microfluidic technologies.展开更多
Bacterial genome sequencing is a powerful technique for studying the genetic diversity and evolution ofmicrobial populations.However,the detection of genomic variants from sequencing data is challenging due to the pre...Bacterial genome sequencing is a powerful technique for studying the genetic diversity and evolution ofmicrobial populations.However,the detection of genomic variants from sequencing data is challenging due to the presence of contamination,sequencing errors and multiple strains within the same species.Several bioinformatics tools have been developed to address these issues,but their performance and accuracy have not been systematically evaluated.In this study,we compared 10 variant detection pipelines using 18 simulated and 17 real datasets of high-throughput sequences froma bundle of representative bacteria.We assessed the sensitivity of each pipeline under different conditions of coverage,simulation and strain diversity.We also demonstrated the application of these tools to identify consistentmutations in a 30-time repeated sequencing dataset of Staphylococcus hominis.We found that HaplotypeCaller,but not Mutect2,from the GATK tool set showed the best performance in terms of accuracy and robustness.CFSAN and Snippy performed not as well in several simulated and real sequencing datasets.Our results provided a comprehensive benchmark and guidance for choosing the optimal variant detection pipeline for high-throughput bacterial genome sequencing data.展开更多
基金the Major State Basic Research Development Program of China,No.G19980512 and No.2001CB510201the National Hi-Tech R & D Program of China,No.2001AA227091 and No.2001 AA233061National Natural Science Foundation of China,No.39990570,No.30171049,30225045 and No.39990600
文摘AIM: To identify the differentially secreted proteins or polypeptides associated with tumorigenesis of esophageal squamous cell carcinoma (ESCC) from serum and to find potential tumor secreted biomarkers.METHODS: Proteins from human ESCC tissue and its matched adjacent normal tissue; pre-surgery and postsurgery serum; and pre-surgery and normal control serum were separated by two-dimensional electrophoresis (2-DE)to identify differentially expressed proteins. The silverstained 2-DE were scanned with digital ImageScanner and analyzed with ImageMaster 2D Elite 3.10 software. A cluster of protein spots differentially expressed were selected and identified with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). One of the differentially expressed proteins, clusterin, was downregulated in cancer tissue and pre-surgery serum, but it was reversed in post-surgery serum. The results were confirmed by semi-quantitative reverse-transcription (RT)-PCR and western blot.RESULTS: Comparisons of the protein spots identified on the 2-DE maps from human matched sera showed that some proteins were differentially expressed, with most of them showing no differences in composition, shape or density.Being analyzed by MALDI-TOF-MS and database searching,clusterin was differentially expressed and down-regulated in both cancer tissue and pre-surgery serum compared with their counterparts. The results were also validated by RTPCR and western blot.CONCLUSION: The differentially expressed clusterin may play a key role during tumorigenesis of ESCC. The 2DE-MS based proteomic approach is one of the powerful tools for discovery of secreted markers from peripheral.
基金the Major State Basic Research Development Program of China,No.G1998051205the National Hi-Tech R & D Program of China,No.2001AA227091+1 种基金the National Natural Science Foundation of China,No.39990570(Major Program)and No.30171049(General Program)the National Science Fund for Distinguished Young Scholars(No.30225045)
文摘AIM: To investigate the alteration of the annexin I subcellular localization in esophageal squarnous cell carcinoma (ESCC)and the correlation between the translocation and the tumorigenesis of ESCC.METHODS: The protein localization of annexin I was detected in both human ESCC tissues and cell line via the indirect immunofluorescence strategy.RESULTS: In the normal esophageal epithelia the annex in I was mainly located on the plasma membrane and formed a consecutive typical trammels net. Annexin I protein also expressed dispersively in cytoplasm and the nuclei without specific localization on the nuclear membrane. In esophageal cancer annexin I decreased very sharply with scattered disappearance on the cellular membrane, however it translocated and highly expressed on the nuclear membrane,which was never found in normal esophageal epithelia. In cultured esophageal cancer cell line annexin I protein was also focused on the nuclear membrane, which was consistent with the result from esophageal cancer tissues.CONCLUSION: This observation suggests that the translocation of annexin I protein in ESCC may correlate with the tumorigenesis of the esophageal cancer.
基金Supported by the National Natural Science Foundation of China, No. 30400147211 Project of Sun Yat-Sen University, No. 98138and the Key Subject Support Grants from Ministry of Public Health No. 2001321
文摘AIM: To observe the therapeutic effect of intrasplenic transplantation with embryonic hepatocytes on amelioration of hereditary copper accumulation in toxic milk (TX) mouse modeling Wilson disease. METHODS: Donor hepatocytes were harvested from 14-d fetal liver of a pregnant homogeneous DL mouse. These cells were successively cultured, labeled with fluorescein dye Hoechst 33342 for 24 h, and sequentially infused into the spleen parenchyma of the recipient TX mice. No host immunosuppression measures were taken. Two and four weeks after transplantation, the recipients were killed for routine histologic investigation and immunohistochemistry study up to 4 wk after transplantation. The serum copper and ceruloplasmin concentrations of the recipient mice were determined by graphite furnace atomic absorption spectroscopy.RESULTS: In the following 2nd and 4th wk after transplantation, the donor hepatocytes could be visualized in the livers of 47.3% recipients. The serum ceruloplasmin and copper concentrations increased by 1.6-fold after 2 wk and 2.0-fold times after 4 wk respectively, which ultimately rose from about 30% of the normal level to nearly 60%(P＜0.01). The hepatic copper concentration decreased 7.2%, 4 wk after transplantation. Pathologic examination showed that there were many actively proliferative hepatocyte precursor cells with specific embryonic hepatocyte marker AFP migrated into hepatic sinusoidsof the recipients. A large number of cells carrying hepatocytes marker and albumin were observed in the recipient spleen tissues.CONCLUSION: Embryonic hepatocytes are capable of differentiating into mature hepatocytes in vivo. After transplantation, the hereditary abnormalities of copper metabolism in TX mice could be corrected partially by intrasplenic transplantation of homogeneous embryonic hepatocytes.
文摘Background： Blood oxygenation level-dependent magnetic resonance imaging （BOLD-MRI） is a functional MRI technique which involves using the paramagnetic properties of deoxyhemoglobin to image the local tissue oxygen concentration. The purpose of this study was to investigate whether BOLD-MRI could evaluate hypoxia and angiogenesis of breast invasive ductal carcinoma （IDC）. Methods： Ninety-eight female patients with IDC were retrospectively included in this research. All patients underwent breast BOLD-MRI at 3.0 T before surgery. R2＊ values of BOLD-MR1 were measured. The expression of carbonic anhydrase IX （CA IX） and vascular endothelial growth factor （VEGF） was analyzed by immunohistochemistry. Spearman＇s correlation analysis was used to correlate R2＊ value with CA IX and VEGF levels. Results： Heterogeneous intensity on BOLD-MRI images was the main finding of IDCs. The mean R2＊ value was 52.8 ± 18.6 Hz. The R2＊ values in patients with axillary lymph node metastasis were significantly higher than the R2＊ values in patients without axillary lymph node metastasis （t = 2.882, P = 0.005）. R2＊ values increased with CA IX level and positively correlated with the level of CA 1X （r = 0.616, P 〈 0.001）; however, R2＊ value had no significantly correlation with the level of VEGF （r = 0.110, P = 0.281）. Conclusion： B OLD-MRI could noninvasively evaluate chronic hypoxia of IDC, but not angiogenesis.
文摘Background：Strain and strain-rate imaging （SRI） have been found clinically useful in the assessment of cardiac systolic and diastolic function as well as providing new insights in deciphering cardiac physiology and mechanics in cardiomyopathies,and identifying early subclinical changes in various pathologies.The aim of this study was to evaluate the regional and global left ventricular （LV） myocardial function in metabolic syndrome （MS） with SRI so that we can provide more myocardial small lesions in patients with MS,which is robust and reliable basis for early detection of LV function.Methods：Thirty-nine adults with MS were enrolled in the study.There was a control group of 39 healthy adults.In addition to classic echocardiographic assessment of LV global functional changes,SRI was used to evaluate regional and global LV function.Including：Peak systolic strain （S）,peak systolic strain-rate （SR-s）,peak diastolic strain-rate （SR-e）.Results：There were no statistically significant differences between MS and controls in all traditional parameters of LV systolic function.On the other hand,significant differences were observed between MS and the control group in most of the parameters of S,SR-s,SR-e in regional LV function.Multiple stepwise regression analyses revealed that S and SR significantly were negatively correlated with blood pressure,waist circumference,fasting plasma glucose,uric acid,suggesting that risk factories were relevant to regional systolic dysfunction.Conclusion：In MS with normal LV ejection fraction,there was regional myocardial dysfunction,risk factors contributed to the impairment of systolic and diastolic function of the regional myocardium.Assessment of myocardial function using SRI could be more accurate in MS patient evaluation than conventional echocardiography alone.
基金Supported by the Major State Basic Research Development Program of China,No.2001CB510006 National Science Found for Distinguished Young Scholars from NSFC,No.39925031 and Key Research Program of STCSM, No.03DZ19229
文摘AIM: To investigate whether P28 derived from C3d can enhance the immune response to HBV-preS2/S induced by directly injection of naked plasmids containing variable repeats of P28 and HBV-preS2/S in fusion form.METHODS: One to four copies of C3d-P28 coding gene,amplified by PCR and modified by restriction endonuclease sdigestion, were subcloned into a eukaryotic expression vector pVAON33 to construct pVAON33-P28, pVAON33-P28.2, pVAON33-P28.3 and pVAON33-P28.4 (pVAON33-P28.[1-4]). HBV-preS2/S coding sequence was then introduced into the pVAON33-P28.[1-4] and identified by both PCR and DNA sequencing. BALB/c mice were primed by intramuscular gene immunization with 100 μg different recombinant plasmids on day 0 and were boosted by subcutaneous inoculation with HBsAg protein (1 μg) 12 wk post-priming. The levels and avidity of specific IgG in sera collected at the indicated times from each group were determined by ELISA and NaSCN-displacement ELISA,respectively.RESULTS: HBsAg specific antibody response was elicited in groups primed with plasmids pVAON33-S2/S-P28.[1-4] and pVAON33-S2/S. However, the response against HBsAg in the groups primed with pVAON33-S2/S-P28.[1-4] was significantly higher than that in pVAON33-S2/S group, the highest level of the specific antibody response was observed in the groups primed with pVAON33-S2/S-P28.4 (P＜0.01).After secondary immunization with specific antigen, the acceleration of antibody levels was significantly higher and faster in the mice primed with DNA expressing preS2/S-P28 fusions than that with DNA expressing preS2/S only (P＜0.05).Interestingly, mice primed with DNA expressing preS2/S-P28.4 fusions maintained the highest levels of anti-HBs antibodies in all animals. The avidity assay showed that the avidity index (AI) collected at 18 wk from mice primed with pVAON33-S2/S-P28.3 and pVAON33-S2/S-P28.4 were significantly higher than that from preS2/S-DNA vaccinated mice (P＜0.01).CONCLUSION: Different repeats of C3d-P28 can enhance both humoral immune response and avidity
基金Supported by the National Key Basic Research Program of China (G1998051203)National Key Technologies R&D Program of China during the 10th Five-year Plan Period,2001BA703B06(B)
文摘AIM: To compare the distribution of virulence-associatedgenotypes of Helicobacter pylori(H pylori) in two areas of north China with different gastric cancer risk and furthermore probe into the pathogenicity of the bacterium. METHODS: Gastric biopsies were taken from 355 subjects from Zhuanghe, a high risk area of gastric cancer, and 136 subjects from Shenyang, a low risk area of gastric cancer. A total of 149 H pylori strains isolated from these patients were studied by PCR for differences in the genotypes of cagA, vac A, and iceA.RESULTS: In patients with high risk for gastric cancer, higher frequencies of vacA s1 or s1m1b genotypes were found as compared to those from the low risk area. CONCLUSION: There is significantly different distribution of H pylori genotypes between Zhuanghe and Shenyang areas in north China.
基金the National Natural Science Foundation of China(NNSFC)(Grant Nos.72001213 and 72301292)the National Social Science Fund of China(Grant No.19BGL297)the Basic Research Program of Natural Science in Shaanxi Province(Grant No.2021JQ-369).
文摘Due to the time-varying topology and possible disturbances in a conflict environment,it is still challenging to maintain the mission performance of flying Ad hoc networks(FANET),which limits the application of Unmanned Aerial Vehicle(UAV)swarms in harsh environments.This paper proposes an intelligent framework to quickly recover the cooperative coveragemission by aggregating the historical spatio-temporal network with the attention mechanism.The mission resilience metric is introduced in conjunction with connectivity and coverage status information to simplify the optimization model.A spatio-temporal node pooling method is proposed to ensure all node location features can be updated after destruction by capturing the temporal network structure.Combined with the corresponding Laplacian matrix as the hyperparameter,a recovery algorithm based on the multi-head attention graph network is designed to achieve rapid recovery.Simulation results showed that the proposed framework can facilitate rapid recovery of the connectivity and coverage more effectively compared to the existing studies.The results demonstrate that the average connectivity and coverage results is improved by 17.92%and 16.96%,respectively compared with the state-of-the-art model.Furthermore,by the ablation study,the contributions of each different improvement are compared.The proposed model can be used to support resilient network design for real-time mission execution.
基金supported by National High Technology Research and Development Program of China(863 program 2004AA215242)National Science Found for Distinguished Young Scholars from NSFC(No.39925031)Science and Technology commission of Shanghai municipality(024319112).
文摘Inoculation with purified specific protein is usually the first step for preparation of monoclonal antibody (mAb). But it is quite difficult to obtain pure proteins especially with natural structures.Here we attempt to replace the protein inoculation with DNA immunization in the preparation of mAb.The eukaryotic expression vectors pcDNA3-PreS2/S and pVAX-PreS2/S encoding the HBV M protein were constructed and prepared for DNA immunization.Female BALB/c mice developed a well antibody response to the target antigen after muscle injection with corresponding plasmids.The mice with effective antibodies induced were used for preparation of mAb.We found the mice immunized with three administrations of pcDNA3-PreS2/S and boosted by intrasplenic injection with the same plasmid could be exploited for preparation of mAb.And positive hybridoma cell 2D3 that can secrete specific mAb was cloned and analyzed.Our studies demonstrate that gene immunization may provide a convenient and efficient way to prepare mAbs.Cellular & Molecular Immunology. 2004;1(4):295-299.
文摘Primary chemotherapy options for colorectal cancer(CRC)involve four key drugs:fluorouracils(5-FU),oxaliplatin,irinotecan and raltitrexed.The first-line regimen consists of 5-FU and leucovorin combined with oxaliplatin(FOLFOX),while the second-line regimen involves 5-FU and leucovorin combined with irinotecan(FOLFIRI)for metastatic CRC(mCRC)in China[1].
基金the financial support of National Key Research and Development program, China (2017YFC1601202 and 2017YFC1601200)China Postdoctoral Science Foundation (2021M690854)+2 种基金National Natural Science Foundation of China (31671951 and 31972175)Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program (2017BT01S174)Fundamental Research Funds for the Central Universities, China (JZ2020HGQA0151)
文摘Cronobacter species are a group of Gram-negative opportunistic pathogens,which cause meningitis,sep-ticemia,and necrotizing enterocolitis in neonates and infants,with neurological sequelae in severe cases.Interest in Cronobacter has increased significantly in recent years due to its high virulence in children.In this review,we summarize the current understanding of the prevalence of Cronobacter species in several important food types.We discuss the response mechanisms enabling persistence in adverse growth con-ditions,as well as its pathogenicity.We emphasize the food safety concerns caused by Cronobacter and subsequent control methods and clinical treatments.
基金supported by the Natural Science Foundation of China International/Regional Research Collaboration Project(72061137001)Natural Science Foundation of China Excellent Young Scientists Fund(82022064)+2 种基金Chongqing Talents Program for Innovative and Entrepreneurial Pioneers(cstc2021ycjh-bgzxm0097)Chongqing Natural Science Foundation Project(cstc2021jcyj-msxmX1171)Chinese State Key Laboratory of Infectious Disease Prevention and Control(2021SKLID303).
文摘Sexual lifestyles are closely related to overall human health and well-being.Few studies have focused on sexual lifestyles among older adults living with HIV(OALHIV),especially in low-and middle-income countries.This study is a part of the sexual well-being among older adults in China(SWELL)study,which is a multicenter cross-sectional study focused on sexual health among older adults aged 50 years and older.Participants were 680 OALHIV(≥50 years old)from the SWELL study conducted from June 2020 to December 2022.Data were collected through one-on-one interviews.We used logistic regression to assess the correlates of sexual activity and sexual satis-faction.Among all participants,37.1%were sexually active.Being older,male,in a steady relationship and employed were associated with being sexually active.The prevalence of sexual satisfaction was 69.8%among sexually active OALHIV.Being homosexual and reporting a better general health status were associated with sexual satisfaction.The OALHIV who have depressive symptoms were less likely to report sexual satisfaction.To support holistic healthy aging among OALHIV,it is important for healthcare providers to be educated about the importance of enquiring about sexual activity,satisfaction and problems and addressing concerns while conveying sex-positive attitudes during clinical reviews,as these are still critical aspects of their health and well-being.
文摘OBJECTIVE To explore the expression and the function of cell adhesion molecules in invasive micropapillary carcinoma (IMPC) of the breast, and to investigate the metastatic mechanism of IMPC. METHODS The expression of E-cadherin, α-catenin and β-catenin was detected by imrnunohistochemical staining in 64 cases of IMPC, and compared with that of invasive ductal carcinoma (IDC). RESULTS E-cadherin and β-catenin were mainly expressed on the cell membrane of tumors, and cc-catenin was expressed in the cytoplasm and/or on the cell membrane. The expression of E-cadherin in IMPC was significantly higher than that in IDC. Furthermore, the expression of E-cadherin was mainly on the intercellular contact surface of the tumor cell clusters in IMPC, while that on the outer surface of the tumor cell clusters decreased or could not be detected. The degree of lymph nodes metastases in IMPC was significantly higher than that in IDC. The co-expressions of α-catenin and β-catenin in cases of lymph nodes metastases along with the expression of E-cadherin in IMPC were significantly higher than that in IDC. CONCLUSIONS These findings indicated that the adhesiveness of the intercellular contact surfaces of tumor clusters in IMPC was strong, while that of the outer surface of tumor clusters was decreased or lost. It is suggested that the adhesive characteristic of the cells in IMPC might play an important role in its higher metastatic potential.
基金Financial support for this work was provided by the National High Technology Research and Development Program of China(2004AA215242)by Science and Technology Commission of Shanghai Municipality(04XD14003).
文摘Bacterial CpG DNA or synthetic oligonucleotides(ODNs)that contain unmethylated CpG motifs(CpG ODN)can directly activate antigen-presenting cells(APCs)to secrete various cytokines through the intraceilular receptor TLR9.Cytokine profiles elicited by the actions of stimulatory CpG DNA on TLR9 expressed APCs are crucial to the subsequent immune responses.To date,cytokine profiles in APCs upon CpG ODN stimulation in vitro are not fully investigated.In the present study,vector-based siRNA was used to downregulate TLR9 expression.Cytokine profiles were observed in murine macrophage cell line RAW264.7 transfected with TLR9-siRNA plasmid upon CpG ODN stimulation.We found that not all the cytokine expressions by the macrophage were decreased while TLR9 was downregulated. IL-12, TNF-α, IFN-γ and IL-1β expressions were significantly decreased,but IL-6, IFN-β and IL-10 expressions were not affected.Interestingly,the level of IFN-α was even increased.This alteration of cytokines produced by TLR9-downregulated APCs upon CpG ODN stimulation might indicate that the role of CpG DNA is more complicated in the pathogenesis and prevention of diseases.Cellular & Molecular Immunology. 2005;2(2):130-135.
文摘High volume conveyor systems in distribution centers have very large footprint and can handlelarge volumes and hold thousands of items.Traditional discrete-event cell-based approach to simulatesuch networks becomes computationally challenging.An alternative approach,in which the traffic isrepresented by segments of fluid flow of different density instead of individual packages,is presentedin this paper to address this challenge.The proposed fluid-based simulation approach is developedusing a Hybrid Petri Nets framework.The underlying model is a combination of an extension of aBatches Petri Nets(BPN)and a Stochastic Petri Nets(SPN).The extensions are in the inclusion ofrandom elements and relaxation of certain structural constraints.Some adaptations are also made to fitthe target system modeling.The approach is presented with an example.
基金This work was supported by the Provincial Natural Science Foundation of Guangdong(Contract 990944)the National Natural Science Foundation of China(Contract 20205003,29975033).
文摘Using continuous wavelet transform as the analytical tool, the fractal characteristic of nucleotide sequences was studied. The fractal dimension of the exon and intron sequences for different species was calculated. We use the Mexican hat wavelet function as the mother wavelet and Hurst exponent to describe the long-range correlation. It is found that the Hurst exponent of intron sequence is larger than that of exon sequence for the same gene.
基金Fundamental Research Funds for the Central Universities,Grant/Award Number:ZQN-818State Key Laboratory of Chemo/Biosensing and Chemometrics,Grant/Award Number:2019006+1 种基金Natural Science Foundation of Fujian Province,China,Grant/Award Number:2021J01310National Natural Science Foundation of China,Grant/Award Numbers:21775128,21804022。
文摘Given the continuous and growing demand for point of care(POC)diagnostic tests,attention has been shifted toward integration and miniaturization of laboratory protocols into“sample-in-answer-out”devices.Microfluidic technologies have been considered an ideal solution to address the requirements of POC diagnostics since many laboratory functions can be miniaturized and incorporated onto a single integrated chip.In this review,we summarize the advances of integrated microfluidic devices for POC diagnostics in the last 3 years.Particularly,we summarize current materials used for microfluidic chip fabrication,discuss the innovation of versatile integrated microfluidic devices,especially the strategies for simplifying sample preparation in manual or self-driven systems,and new detection methods of microfluidic chips.In addition,we describe new integrated microfluidic devices for POC diagnostics of protein-targeted immunodiagnostics,nucleic acid molecular tests,and small molecule metabolites analysis.We also provide future perspectives and current challenges for clinical translation and commercialization of these microfluidic technologies.
基金supported by Zhejiang Provincial Natural Science Foundation(LY20H030006)Key Research&Development Program of Zhejiang(2023C03045)+2 种基金Fundamental Research Funds for the Central Universities(2022ZFJH003)Jinan Microecological Biomedicine Shandong Laboratory(JNL-2022036C)Public Welfare Project of Jinhua City,Zhejiang(2021-4-359).
文摘Bacterial genome sequencing is a powerful technique for studying the genetic diversity and evolution ofmicrobial populations.However,the detection of genomic variants from sequencing data is challenging due to the presence of contamination,sequencing errors and multiple strains within the same species.Several bioinformatics tools have been developed to address these issues,but their performance and accuracy have not been systematically evaluated.In this study,we compared 10 variant detection pipelines using 18 simulated and 17 real datasets of high-throughput sequences froma bundle of representative bacteria.We assessed the sensitivity of each pipeline under different conditions of coverage,simulation and strain diversity.We also demonstrated the application of these tools to identify consistentmutations in a 30-time repeated sequencing dataset of Staphylococcus hominis.We found that HaplotypeCaller,but not Mutect2,from the GATK tool set showed the best performance in terms of accuracy and robustness.CFSAN and Snippy performed not as well in several simulated and real sequencing datasets.Our results provided a comprehensive benchmark and guidance for choosing the optimal variant detection pipeline for high-throughput bacterial genome sequencing data.
