In the information age,electronic documents(e-documents)have become a popular alternative to paper documents due to their lower costs,higher dissemination rates,and ease of knowledge sharing.However,digital copyright ...In the information age,electronic documents(e-documents)have become a popular alternative to paper documents due to their lower costs,higher dissemination rates,and ease of knowledge sharing.However,digital copyright infringements occur frequently due to the ease of copying,which not only infringes on the rights of creators but also weakens their creative enthusiasm.Therefore,it is crucial to establish an e-document sharing system that enforces copyright protection.However,the existing centralized system has outstanding vulnerabilities,and the plagiarism detection algorithm used cannot fully detect the context,semantics,style,and other factors of the text.Digital watermark technology is only used as a means of infringement tracing.This paper proposes a decentralized framework for e-document sharing based on decentralized autonomous organization(DAO)and non-fungible token(NFT)in blockchain.The use of blockchain as a distributed credit base resolves the vulnerabilities inherent in traditional centralized systems.The e-document evaluation and plagiarism detection mechanisms based on the DAO model effectively address challenges in comprehensive text information checks,thereby promoting the enhancement of e-document quality.The mechanism for protecting and circulating e-document copyrights using NFT technology ensures effective safeguarding of users’e-document copyrights and facilitates e-document sharing.Moreover,recognizing the security issues within the DAO governance mechanism,we introduce an innovative optimization solution.Through experimentation,we validate the enhanced security of the optimized governance mechanism,reducing manipulation risks by up to 51%.Additionally,by utilizing evolutionary game analysis to deduce the equilibrium strategies of the framework,we discovered that adjusting the reward and penalty parameters of the incentive mechanism motivates creators to generate superior quality and unique e-documents,while evaluators are more likely to engage in assessments.展开更多
Background:Regulatory proteins involved in human cellular division and proliferation,cyclin-dependent kinases 4 and 6(CDK4/6)are overexpressed in numerous cancers,including triple-negative breast cancer(TNBC).TNBC is ...Background:Regulatory proteins involved in human cellular division and proliferation,cyclin-dependent kinases 4 and 6(CDK4/6)are overexpressed in numerous cancers,including triple-negative breast cancer(TNBC).TNBC is a common pathological subtype of breast cancer that is prone to recurrence and metastasis,and has a single treatment method.As one of the CDK4/6 inhibitors,abemaciclib can effectively inhibit the growth of breast tumors.In this study,we synthesized LA-D-B1,a derivative of Abemaciclib,and investigated its anti-tumor effects in breast cancer.Methods:Cellular viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay.Cell cloning and migration abilities were determined by colony formation assay and wound healing assay.Cell invasion abilities and adhesion were determined by cell invasion assay and cell adhesion assay.The impact of compound LA-D-B1 on cell proliferation and the cell cycle was analyzed through Western blotting,which quantified the levels of proteins associated with the cyclin-dependent kinase(CDK)4/6-cyclin D-Rb-E2F pathway.The in vivo anti-tumor activity of compound LA-D-B1 was investigated using a chick chorioallantoic membrane(CAM)model.Results:The study demonstrated that LA-D-B1 effectively suppressed breast cancer cell proliferation,induced apoptosis,and caused cell cycle arrest.Furthermore,LA-D-B1 reduced the expression of key proteins in the CDK4/6-cyclin D-Rb-E2F pathway,including CDK4,CDK6 and E2F1.The results also indicated significant antitumor activity of LA-D-B1 in a transplanted tumor model.Conclusion:In this study,LA-D-B1 demonstrated a potent anti-tumor effect by effectively suppressing cell proliferation and inhibiting cell cycle progression in breast cancer.These findings highlight the potential of LA-D-B1 as a valuable compound for enhancing therapeutic outcomes and controlling the progression of breast cancer.展开更多
Objective:Laparoscopic resection is increasingly performed for gastrointestinal stromal tumors(GISTs).However,the laparoscopic approach for GISTs located in the esophagogastric junction(EGJ-GIST)is surgically challeng...Objective:Laparoscopic resection is increasingly performed for gastrointestinal stromal tumors(GISTs).However,the laparoscopic approach for GISTs located in the esophagogastric junction(EGJ-GIST)is surgically challenging.This study compares the efficacy of laparoscopic surgery and the open procedure for EGJ-GIST through the propensity score weighting(PSW)method.Methods:Between April 2006 and April 2018,1,824 surgical patients were diagnosed with primary gastric GIST at four medical centers in South China.Of these patients,228 were identified as EGJ-GISTs and retrospectively reviewed clinicopathological characteristics,operative information,and long-term outcomes.PSW was used to create the balanced cohorts.Results:PSW was carried out in laparoscopic and open-surgery cohorts according to year of surgery,sex,age,body mass index(BMI),tumor size,mitotic rates and recurrence risk.After PSW,438 patients consisting of 213 laparoscopic(L group)and 225 open surgery(O group)patients were enrolled.After PSW,the following measures in the L group were superior to those in the O group:median operative time[interquartile range(IQR)]:100.0(64.5-141.5)vs.149.0(104.0-197.5)min,P<0.001;median blood loss(IQR):30.0(10.0-50.0)vs.50.0(20.0-100.0)mL,P=0.002;median time to liquid intake(IQR):3.0(2.0-4.0)vs.4.0(3.0-5.0)d,P<0.001;median hospital stay(IQR):6.0(4.0-8.0)vs.7.0(5.0-12.0)d,P<0.001;and postoperative complications(10.3%vs.22.7%,P=0.001).The median follow-up was 55(range,2-153)months in the entire cohort.No significant differences were detected in either relapse-free survival(RFS)[hazard ratio(HR):0.372,95%confidence interval(95%CI):0.072-1.910,P=0.236]or overall survival(OS)(HR:0.400,95%CI:0.119-1.343,P=0.138)between the two groups.Conclusions:Laparoscopic surgery for EGJ-GIST is associated with the advantages of shorter operative time,reduced blood loss,shorter time to liquid intake,and shorter length of stay,all without compromising postoperative outcomes and long-term survival.展开更多
This paper proposes a kind of programmable logic element(PLE)based on Sense-Switch pFLASH technology.By programming Sense-Switch pFLASH,all three-bit look-up table(LUT3)functions,partial four-bit look-up table(LUT4)fu...This paper proposes a kind of programmable logic element(PLE)based on Sense-Switch pFLASH technology.By programming Sense-Switch pFLASH,all three-bit look-up table(LUT3)functions,partial four-bit look-up table(LUT4)functions,latch functions,and d flip flop(DFF)with enable and reset functions can be realized.Because PLE uses a choice of operational logic(COOL)approach for the operation of logic functions,it allows any logic circuit to be implemented at any ratio of combinatorial logic to register.This intrinsic property makes it close to the basic application specific integrated circuit(ASIC)cell in terms of fine granularity,thus allowing ASIC-like cell-based mappers to apply all their optimization potential.By measuring Sense-Switch pFLASH and PLE circuits,the results show that the“on”state driving current of the Sense-Switch pFLASH is about 245.52μA,and that the“off”state leakage current is about 0.1 pA.The programmable function of PLE works normally.The delay of the typical combinatorial logic operation AND3 is 0.69 ns,and the delay of the sequential logic operation DFF is 0.65 ns,both of which meet the requirements of the design technical index.展开更多
Interleukin-6(IL-6)is a common pluripotent cytokine that is highly expressed in the tumor microenvironment.The IL-6/JAK/STAT3 signaling directly promotes tumor progression,severely hampering antitumor immunity.Macroph...Interleukin-6(IL-6)is a common pluripotent cytokine that is highly expressed in the tumor microenvironment.The IL-6/JAK/STAT3 signaling directly promotes tumor progression,severely hampering antitumor immunity.Macrophages,the richest innate immune cells within the tumor microenvironment,manipulate tumor progression via phenotypic plasticity.展开更多
Response surface methodology was utilized to model and optimize the operational variables for defluoridation using an electrodialysis process as the treatment of secondary effluent of the graphite industry. Experiment...Response surface methodology was utilized to model and optimize the operational variables for defluoridation using an electrodialysis process as the treatment of secondary effluent of the graphite industry. Experiments were conducted using a Box-Behnken surface statistical design in order to evaluate the effects and the interaction of the influential variables including the operational voltage, initial fluoride concentration and flow rate. The regression models for defluoridation and energy consumption responses were statistically validated using analysis of variance (ANOVA);high coefficient of determination values (R^2 = 0.9772 and R^2 = 0.9814;respectively) were obtained. The quadratic model exhibited high reproducibility and a good fit of the experimental data. The optimum values of the initial fluoride concentration, voltage and flow rate were found to be 13.9 mg/L, 13.4 V, 102.5 L/h, respectively. A fluoride removal efficiency of 99.69% was observed under optimum conditions for the treatment of the secondary effluent of the graphite industry.展开更多
Due to their broad functional plasticity,myeloid cells contribute to both liver injury and recovery during acetaminophen overdose-induced acute liver injury(APAP-ALI).A comprehensive understanding of cellular diversit...Due to their broad functional plasticity,myeloid cells contribute to both liver injury and recovery during acetaminophen overdose-induced acute liver injury(APAP-ALI).A comprehensive understanding of cellular diversity and intercellular crosstalk is essential to elucidate the mechanisms and to develop therapeutic strategies for APAP-ALI treatment.Here,we identified the function of IFN-I in the myeloid compartment during APAP-ALI.Utilizing single-cell RNA sequencing,we characterized the cellular atlas and dynamic progression of liver CD11b+cells post APAP-ALI in WT and STAT2 T403A mice,which was further validated by immunofluorescence staining,bulk RNA-seq,and functional experiments in vitro and in vivo.We identified IFN-I-dependent transcriptional programs in a three-way communication pathway that involved IFN-I synthesis in intermediate restorative macrophages,leading to CSF-1 production in aging neutrophils that ultimately enabled Trem2+restorative macrophage maturation,contributing to efficient liver repair.Overall,we uncovered the heterogeneity of hepatic myeloid cells in APAP-ALI at single-cell resolution and the therapeutic potential of IFN-I in the treatment of APAP-ALI.展开更多
As a group of nonspecific inflammatory diseases affecting the intestine,inflammatory bowel disease(IBD)exhibits the characteristics of chronic recurring inflammation,and was proven to be increasing in incidence(Kaplan...As a group of nonspecific inflammatory diseases affecting the intestine,inflammatory bowel disease(IBD)exhibits the characteristics of chronic recurring inflammation,and was proven to be increasing in incidence(Kaplan,2015).IBD induced by genetic background,environmental changes,immune functions,microbial composition,and toxin exposures(Sasson et al.,2021)primarily includes ulcerative colitis(UC)and Crohn's disease(CD)with complicated clinical symptoms featured by abdominal pain,diarrhea,and even blood in stools(Fan et al.,2021;Huang et al.,2021).展开更多
基金This work is supported by the National Key Research and Development Program(2022YFB2702300)National Natural Science Foundation of China(Grant No.62172115)+2 种基金Innovation Fund Program of the Engineering Research Center for Integration and Application of Digital Learning Technology of Ministry of Education under Grant Number No.1331005Guangdong Higher Education Innovation Group 2020KCXTD007Guangzhou Fundamental Research Plan of Municipal-School Jointly Funded Projects(No.202102010445).
文摘In the information age,electronic documents(e-documents)have become a popular alternative to paper documents due to their lower costs,higher dissemination rates,and ease of knowledge sharing.However,digital copyright infringements occur frequently due to the ease of copying,which not only infringes on the rights of creators but also weakens their creative enthusiasm.Therefore,it is crucial to establish an e-document sharing system that enforces copyright protection.However,the existing centralized system has outstanding vulnerabilities,and the plagiarism detection algorithm used cannot fully detect the context,semantics,style,and other factors of the text.Digital watermark technology is only used as a means of infringement tracing.This paper proposes a decentralized framework for e-document sharing based on decentralized autonomous organization(DAO)and non-fungible token(NFT)in blockchain.The use of blockchain as a distributed credit base resolves the vulnerabilities inherent in traditional centralized systems.The e-document evaluation and plagiarism detection mechanisms based on the DAO model effectively address challenges in comprehensive text information checks,thereby promoting the enhancement of e-document quality.The mechanism for protecting and circulating e-document copyrights using NFT technology ensures effective safeguarding of users’e-document copyrights and facilitates e-document sharing.Moreover,recognizing the security issues within the DAO governance mechanism,we introduce an innovative optimization solution.Through experimentation,we validate the enhanced security of the optimized governance mechanism,reducing manipulation risks by up to 51%.Additionally,by utilizing evolutionary game analysis to deduce the equilibrium strategies of the framework,we discovered that adjusting the reward and penalty parameters of the incentive mechanism motivates creators to generate superior quality and unique e-documents,while evaluators are more likely to engage in assessments.
基金supported by the National Natural Science Foundation of China(82273167,82104174,81602626,12271068,82172558 and 82373112)Jiangsu Province Basic Research Program Natural Science Foundation(Outstanding Youth Fund Project,BK20220063)+7 种基金the Key Program of Basic Science(Natural Science)of Jiangsu Province(22KJA350001)“Huaguo Mountain Talent Plan”of Lianyungang City(Innovative Talents Liu Bin)Qing Lan Project of Jiangsu Universities(Outstanding Young Backbone Teachers,Ji Jing)the Natural Science Foundation of Jiangsu Higher Education Institutions of China(No.20KJB350008)Priority Academic Program Development of Jiangsu Higher Education Institutions,College Students’Innovative Entrepreneurial Training Plan Program(Project Nos.SY202211641640011,SY202311641640002 and SZ202311641640002)Chen Xiao-Ping Foundation for the Development of Science and Technology of Hubei Province(Project No.CXPJJH123003-027)the Distinguished Young Scholars of Nanjing(JQX20008)Scientific Research Foundation for Returned Scholars of Tongji Hospital(Project 2022hgry021).
文摘Background:Regulatory proteins involved in human cellular division and proliferation,cyclin-dependent kinases 4 and 6(CDK4/6)are overexpressed in numerous cancers,including triple-negative breast cancer(TNBC).TNBC is a common pathological subtype of breast cancer that is prone to recurrence and metastasis,and has a single treatment method.As one of the CDK4/6 inhibitors,abemaciclib can effectively inhibit the growth of breast tumors.In this study,we synthesized LA-D-B1,a derivative of Abemaciclib,and investigated its anti-tumor effects in breast cancer.Methods:Cellular viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay.Cell cloning and migration abilities were determined by colony formation assay and wound healing assay.Cell invasion abilities and adhesion were determined by cell invasion assay and cell adhesion assay.The impact of compound LA-D-B1 on cell proliferation and the cell cycle was analyzed through Western blotting,which quantified the levels of proteins associated with the cyclin-dependent kinase(CDK)4/6-cyclin D-Rb-E2F pathway.The in vivo anti-tumor activity of compound LA-D-B1 was investigated using a chick chorioallantoic membrane(CAM)model.Results:The study demonstrated that LA-D-B1 effectively suppressed breast cancer cell proliferation,induced apoptosis,and caused cell cycle arrest.Furthermore,LA-D-B1 reduced the expression of key proteins in the CDK4/6-cyclin D-Rb-E2F pathway,including CDK4,CDK6 and E2F1.The results also indicated significant antitumor activity of LA-D-B1 in a transplanted tumor model.Conclusion:In this study,LA-D-B1 demonstrated a potent anti-tumor effect by effectively suppressing cell proliferation and inhibiting cell cycle progression in breast cancer.These findings highlight the potential of LA-D-B1 as a valuable compound for enhancing therapeutic outcomes and controlling the progression of breast cancer.
文摘Objective:Laparoscopic resection is increasingly performed for gastrointestinal stromal tumors(GISTs).However,the laparoscopic approach for GISTs located in the esophagogastric junction(EGJ-GIST)is surgically challenging.This study compares the efficacy of laparoscopic surgery and the open procedure for EGJ-GIST through the propensity score weighting(PSW)method.Methods:Between April 2006 and April 2018,1,824 surgical patients were diagnosed with primary gastric GIST at four medical centers in South China.Of these patients,228 were identified as EGJ-GISTs and retrospectively reviewed clinicopathological characteristics,operative information,and long-term outcomes.PSW was used to create the balanced cohorts.Results:PSW was carried out in laparoscopic and open-surgery cohorts according to year of surgery,sex,age,body mass index(BMI),tumor size,mitotic rates and recurrence risk.After PSW,438 patients consisting of 213 laparoscopic(L group)and 225 open surgery(O group)patients were enrolled.After PSW,the following measures in the L group were superior to those in the O group:median operative time[interquartile range(IQR)]:100.0(64.5-141.5)vs.149.0(104.0-197.5)min,P<0.001;median blood loss(IQR):30.0(10.0-50.0)vs.50.0(20.0-100.0)mL,P=0.002;median time to liquid intake(IQR):3.0(2.0-4.0)vs.4.0(3.0-5.0)d,P<0.001;median hospital stay(IQR):6.0(4.0-8.0)vs.7.0(5.0-12.0)d,P<0.001;and postoperative complications(10.3%vs.22.7%,P=0.001).The median follow-up was 55(range,2-153)months in the entire cohort.No significant differences were detected in either relapse-free survival(RFS)[hazard ratio(HR):0.372,95%confidence interval(95%CI):0.072-1.910,P=0.236]or overall survival(OS)(HR:0.400,95%CI:0.119-1.343,P=0.138)between the two groups.Conclusions:Laparoscopic surgery for EGJ-GIST is associated with the advantages of shorter operative time,reduced blood loss,shorter time to liquid intake,and shorter length of stay,all without compromising postoperative outcomes and long-term survival.
基金supported by the National Natural Science Foundation of China(No.62174150)the Natural Science Foundation of Jiangsu Province,China(Nos.BK20211040 and BK20211041)。
文摘This paper proposes a kind of programmable logic element(PLE)based on Sense-Switch pFLASH technology.By programming Sense-Switch pFLASH,all three-bit look-up table(LUT3)functions,partial four-bit look-up table(LUT4)functions,latch functions,and d flip flop(DFF)with enable and reset functions can be realized.Because PLE uses a choice of operational logic(COOL)approach for the operation of logic functions,it allows any logic circuit to be implemented at any ratio of combinatorial logic to register.This intrinsic property makes it close to the basic application specific integrated circuit(ASIC)cell in terms of fine granularity,thus allowing ASIC-like cell-based mappers to apply all their optimization potential.By measuring Sense-Switch pFLASH and PLE circuits,the results show that the“on”state driving current of the Sense-Switch pFLASH is about 245.52μA,and that the“off”state leakage current is about 0.1 pA.The programmable function of PLE works normally.The delay of the typical combinatorial logic operation AND3 is 0.69 ns,and the delay of the sequential logic operation DFF is 0.65 ns,both of which meet the requirements of the design technical index.
基金supported by the Shandong Province Major Scientific and Technological Innovation Project(China)(No.2020CXGC010503)the Shandong Provincial Key Laboratory Platform Project(China)(No.2021ZDSYS11)the National Natural Science Foundation of China Major Project(No.81991525).
文摘Interleukin-6(IL-6)is a common pluripotent cytokine that is highly expressed in the tumor microenvironment.The IL-6/JAK/STAT3 signaling directly promotes tumor progression,severely hampering antitumor immunity.Macrophages,the richest innate immune cells within the tumor microenvironment,manipulate tumor progression via phenotypic plasticity.
基金financially supported by the Key Research Project of Shandong Province (No. 2017CXGC1004)the National Natural Science Foundation of China (Grant No. 21878178)+1 种基金the Shandong Science and Technology Development Plan (No. 2018GGX107001)the Young Taishan Scholars Program of Shandong Province.
文摘Response surface methodology was utilized to model and optimize the operational variables for defluoridation using an electrodialysis process as the treatment of secondary effluent of the graphite industry. Experiments were conducted using a Box-Behnken surface statistical design in order to evaluate the effects and the interaction of the influential variables including the operational voltage, initial fluoride concentration and flow rate. The regression models for defluoridation and energy consumption responses were statistically validated using analysis of variance (ANOVA);high coefficient of determination values (R^2 = 0.9772 and R^2 = 0.9814;respectively) were obtained. The quadratic model exhibited high reproducibility and a good fit of the experimental data. The optimum values of the initial fluoride concentration, voltage and flow rate were found to be 13.9 mg/L, 13.4 V, 102.5 L/h, respectively. A fluoride removal efficiency of 99.69% was observed under optimum conditions for the treatment of the secondary effluent of the graphite industry.
基金supported by the Key R&D Program of Shandong Province(2020CXGC010503)Shandong Provincial Key Laboratory Platform Project(2021ZDSYS11)Major Program of National Natural Science Foundation of China(81991525).
文摘Due to their broad functional plasticity,myeloid cells contribute to both liver injury and recovery during acetaminophen overdose-induced acute liver injury(APAP-ALI).A comprehensive understanding of cellular diversity and intercellular crosstalk is essential to elucidate the mechanisms and to develop therapeutic strategies for APAP-ALI treatment.Here,we identified the function of IFN-I in the myeloid compartment during APAP-ALI.Utilizing single-cell RNA sequencing,we characterized the cellular atlas and dynamic progression of liver CD11b+cells post APAP-ALI in WT and STAT2 T403A mice,which was further validated by immunofluorescence staining,bulk RNA-seq,and functional experiments in vitro and in vivo.We identified IFN-I-dependent transcriptional programs in a three-way communication pathway that involved IFN-I synthesis in intermediate restorative macrophages,leading to CSF-1 production in aging neutrophils that ultimately enabled Trem2+restorative macrophage maturation,contributing to efficient liver repair.Overall,we uncovered the heterogeneity of hepatic myeloid cells in APAP-ALI at single-cell resolution and the therapeutic potential of IFN-I in the treatment of APAP-ALI.
基金supported by the Zhenjiang Key Research and Development Plan(Social Development)(No.SH2021066)the Clinical Medical Science and Technology Development Fund Project of Jiangsu University in 2018(No.JLY20180031)the Taicang Science and Technology Planning Project(No.TC2020JCYL17),China。
文摘As a group of nonspecific inflammatory diseases affecting the intestine,inflammatory bowel disease(IBD)exhibits the characteristics of chronic recurring inflammation,and was proven to be increasing in incidence(Kaplan,2015).IBD induced by genetic background,environmental changes,immune functions,microbial composition,and toxin exposures(Sasson et al.,2021)primarily includes ulcerative colitis(UC)and Crohn's disease(CD)with complicated clinical symptoms featured by abdominal pain,diarrhea,and even blood in stools(Fan et al.,2021;Huang et al.,2021).