Objective:We aim to develop a polymer library consisting of phenylalanine-based poly(ester amide)s(Phe-PEAs)for cancer therapy and investigate the structure–property relationship of these polymers to understand their...Objective:We aim to develop a polymer library consisting of phenylalanine-based poly(ester amide)s(Phe-PEAs)for cancer therapy and investigate the structure–property relationship of these polymers to understand their impact on the drug delivery efficiency of corresponding nanoparticles(NPs).Impact Statement:Our study provides insights into the structure–property relationship of polymers in NP-based drug delivery applications and offers a potential polymer library and NP platform for enhancing cancer therapy.Introduction:Polymer NP-based drug delivery systems have demonstrated substantial potential in cancer therapy by improving drug efficacy and minimizing systemic toxicity.However,successful design and optimization of these systems require a comprehensive understanding of the relationship between polymer structure and physicochemical properties,which directly influence the drug delivery efficiency of the corresponding NPs.Methods:A series of Phe-PEAs with tunable structures was synthesized by varying the length of the methylene group in the diol part of the polymers.Subsequently,Phe-PEAs were formulated into NPs for doxorubicin(DOX)delivery in prostate cancer therapy.Results:Small adjustments in polymer structure induced the changes in the hydrophobicity and thermal properties of the PEAs,consequently NP size,drug loading capacity,cellular uptake efficacy,and cytotoxicity.Additionally,DOXloaded Phe-PEA NPs demonstrated enhanced tumor suppression and reduced side effects in prostate tumor-bearing mice.Conclusion:Phe-PEAs,with their finely tunable structures,show great promise as effective and customizable nanocarriers for cancer therapy.展开更多
Based on the experiments of utilization of garlic processing wastewater in a lotus pond, this study demonstrates that lotus pond wetlands have a remarkable ability to remove organic pollutants and decrease chemical ox...Based on the experiments of utilization of garlic processing wastewater in a lotus pond, this study demonstrates that lotus pond wetlands have a remarkable ability to remove organic pollutants and decrease chemical oxygen demand (CODCr), biochemical oxygen demand (BOD5), and suspended substances (SS) in garlic processing wastewater. Results also show evident effects of lotus roots on absorption of NH3-N. The pH value in a lotus pond with wastewater discharged was relatively stable. The water quality in the lotus pond reached the class Ⅱ emission standard, according to the Integrated Wastewater Discharge Standard (GB8978-1996), seven days after pretreated garlic processing wastewater had been discharged into the lotus pond. Garlic processing wastewater irrigation does not produce pollution in the pond sediment and has no negative effect on the growth of lotus roots. Due to utilization of garlic processing wastewater, the output of lotus roots increased by 3.0% to 8.3%, and the quality of lotus roots was improved. Therefore, better purification and utilization results can be achieved.展开更多
Bi doped n-type SnSe thin films were prepared by chemical vapor deposition(CVD)and their structure and thermoelectric properties were studied.The x-ray diffraction patterns,x-ray photoelectron spectroscopy,and microsc...Bi doped n-type SnSe thin films were prepared by chemical vapor deposition(CVD)and their structure and thermoelectric properties were studied.The x-ray diffraction patterns,x-ray photoelectron spectroscopy,and microscopic images show that the prepared SnSe thin films were composed of pure SnSe crystals.The Seebeck coefficients of the Bi-doped SnSe were greatly improved compared to that of undoped SnSe thin films.Specifically,Sn_(0.99)Bi_(0.01)Se thin film exhibited a Seebeck coefficient of905.8μV·K^(-1) at 600 K,much higher than 285.5μV·K^(-1) of undoped SnSe thin film.Further first-principles calculations reveal that the enhancement of the thermoelectric properties can be explained mainly by the Fermi level lifting and the carrier pockets increasing near the Fermi level due to Bi doping in the SnSe samples.Our results suggest the potentials of the Bi-doped SnSe thin films in thermoelectric applications.展开更多
In this paper, we show how to use the novel extended strand space method to verify Kerberos V. First, we formally model novel semantical features in Kerberos V such as timestamps and protocol mixture in this new frame...In this paper, we show how to use the novel extended strand space method to verify Kerberos V. First, we formally model novel semantical features in Kerberos V such as timestamps and protocol mixture in this new framework. Second, we apply unsolicited authentication test to prove its secrecy and authentication goals of Kerberos V. Our formalization and proof in this case study have been mechanized using Isabelle/HOL.展开更多
In this paper, we present two extensions of the strand space method to model Kerberos V. First, we include time and timestamps to model security protocols with timestamps: we relate a key to a crack time and combine i...In this paper, we present two extensions of the strand space method to model Kerberos V. First, we include time and timestamps to model security protocols with timestamps: we relate a key to a crack time and combine it with timestamps in order to define a notion of recency. Therefore, we can check replay attacks in this new framework. Second, we extend the classic strand space theory to model protocol mixture. The main idea is to introduce a new relation to model the causal relation between one primary protocol session and one of its following secondary protocol session. Accordingly, we also extend the definition of unsolicited authentication test.展开更多
Biological structural materials,despite consisting of limited kinds of compounds,display multifunctionalities due to their complex hierarchical architectures.While some biomimetic strategies have been applied in artif...Biological structural materials,despite consisting of limited kinds of compounds,display multifunctionalities due to their complex hierarchical architectures.While some biomimetic strategies have been applied in artificial materials to enhance their mechanical stability,the simultaneous optimization of other functions along with the mechanical properties via biomimetic designs has not been thoroughly investigated.Herein,iron oxide/carbon nanotube(CNT)-based artificial nacre with both improved mechanical and electromagnetic interference(EMI)shielding performance is fabricated via the mineralization of Fe_(3)O_(4)onto a CNTincorporated matrix.The micro-and nano-structures of the artificial nacre are similar to those of natural nacre,which in turn improves its mechanical properties.The alternating electromagnetic wave-reflective CNT layers and the wave-absorptive iron oxide layers can improve the multiple reflections of the waves on the surfaces of the reflection layers,which then allows sufficient interactions between the waves and the absorption layers.Consequently,compared with the reflection-dependent EMI-shielding of the non-structured material,the artificial nacre exhibits strong absorption-dependent shielding behavior even with a very low content of wave-absorptive phase.Owing to the high mechanical stability,the shielding effectiveness of the artificial nacre that deeply cut by a blade is still maintained at approximately 70%−96%depending on the incident wave frequency.The present work provides a new way for designing structural materials with concurrently enhanced mechanical and functional properties,and a path to combine structural design and intrinsic properties of specific materials via a biomimetic strategy.展开更多
Increasing evidence indicates that N6-methyladenosine(m6A)methylation modification serves important functions in biological metabolism.Dysregulation of m6A regulators is related to the progression of different maligna...Increasing evidence indicates that N6-methyladenosine(m6A)methylation modification serves important functions in biological metabolism.Dysregulation of m6A regulators is related to the progression of different malignancies,including renal cell carcinoma(RCC).Recent studies have reported preliminary findings on the influence of m6A regulator dysregulation on RCC tumorigenesis and development.However,no comprehensive review that integrates and analyzes the roles of m6A modification in RCC has been published to date.In this review,we focus on the dysregulation of m6A regulators as it relates to RCC tumorigenesis and development,as well as possible applications of m6A modification in RCC diagnosis and therapeutics.展开更多
Long-term primary culture of mammalian cells has been always difficult due to unavoidable senescence. Conventional methods for generating immortalized cell lines usually require manipulation of genome which leads to c...Long-term primary culture of mammalian cells has been always difficult due to unavoidable senescence. Conventional methods for generating immortalized cell lines usually require manipulation of genome which leads to change of important biological and genetic characteristics. Recently, conditional reprogramming(CR) emerges as a novel next generation tool for long-term culture of primary epithelium cells derived from almost all origins without alteration of genetic background of primary cells. CR cocultures primary cells with inactivated mouse 3T3-J2 fibroblasts in the presence of RHO-related protein kinase(ROCK) inhibitor Y-27632, enabling primary cells to acquire stem-like characteristics while retain their ability to fully differentiate. With only a few years’ development, CR shows broad prospects in applications in varied areas including disease modeling, regenerative medicine, drug evaluation, drug discovery as well as precision medicine. This review is thus to comprehensively summarize and assess current progress in understanding mechanism of CR and its wide applications, highlighting the value of CR in both basic and translational researches and discussing the challenges faced with CR.展开更多
The present study analyzed the predictive value of combined analysis of collapsin response mediator protein 4 (CRMP4) methylation levels and the Cancer of the Prostate Risk Assessment (CAPRA-S) Postsurgical score ...The present study analyzed the predictive value of combined analysis of collapsin response mediator protein 4 (CRMP4) methylation levels and the Cancer of the Prostate Risk Assessment (CAPRA-S) Postsurgical score of patients who required adjuvant hormone therapy (AHT) after radical prostatectomy (RP), We retrospectively analyzed 305 patients with prostate cancer (PCa) who received RP and subsequent androgen deprivation therapy (ADT). Two hundred and thirty patients with clinically high-risk PCa underwent immediate ADT, and 75 patients with intermediate risk PCa underwent deferred ADT. CRMP4 methylation levels in biopsies were determined, and CAPRA-S scores were calculated. In the deferred ADT group, the values of the hazard ratios for tumor progression and cancer-specific mortality (CSM) in patients with 〉15% CRMP4 methylation were 6.81 (95% CI, 2.34-19.80) and 12.83 (95% CI. 2.16-26.10), respectively. Receiver-operating characteristic curve analysis indicated that CRMP4 methylation levels 〉15% served as a significant prognostic marker of tumor progression and CSM. In the immediate ADT group, CAPRA-S scores :〉6 and CRMP4 methylation levels :〉15% were independent predictors of these outcomes (uni- and multi-variable Cox regression analyses). The differences in the 5-year progression-free survival between each combination were statistically significant. Combining CAPRA-S score and CRMP4 methylation levels improved the area under the curve compared with the CRMP4 or CAPRA-S model. Therefore, CRMP4 methylation levels :〉15% were significantly associated with a poor prognosis and their combination with CAPRA-S score accurately predicted tumor progression and metastasis for patients requiring AHT after RP.展开更多
In certified email (CEM) protocols, trusted third party (TTP) transparency is an important security require- ment which helps to avoid bad publicity as well as protecting individual users' privacy. Cederquist et ...In certified email (CEM) protocols, trusted third party (TTP) transparency is an important security require- ment which helps to avoid bad publicity as well as protecting individual users' privacy. Cederquist et al. proposed an opti- mistic certified email protocol, which employs key chains to reduce the storage requirement of the TTE We extend their protocol to satisfy the property of TTP transparency, using existing verifiably encrypted signature schemes. An imple- mentation with the scheme based on bilinear pairing makes our extension one of the most efficient CEM protocols satis- fying strong fairness, timeliness, and TTP transparency. We formally verify the security requirements of the extended pro- tocol. The properties of fairness, timeliness and effectiveness are checked in the model checker Mocha, and TTP trans- parency is formalised and analysed using the toolsets/~CRL and CADE展开更多
Recent development on distributed systems has shown that a variety of fairness constraints (some of which are only recently defined) play vital roles in designing self- stabilizing population protocols. Existing mod...Recent development on distributed systems has shown that a variety of fairness constraints (some of which are only recently defined) play vital roles in designing self- stabilizing population protocols. Existing model checkers are deficient in verifying the systems as only limited kinds of fair- ness are supported with limited verification efficiency. In this work, we support model checking of distributed systems in the toolkit PAT (process analysis toolkit), with a variety of fairness constraints (e.g., process-level weak/strong fairness, event-level weak/strong fairness, strong global fairness). It performs on-the-fly verification against linear temporal prop- erties. We show through empirical evaluation (on recent pop- ulation protocols as well as benchmark systems) that PAT has advantage in model checking with fairness. Previously un- known bugs have been revealed against systems which are designed to function only with strong global fairness.展开更多
Although patients benefit from surgical transurethral resection of bladder cancers,some niduses are missed or incompletely resected,and small malignant lesions may recur.Intravesical chemotherapy and immunotherapy are...Although patients benefit from surgical transurethral resection of bladder cancers,some niduses are missed or incompletely resected,and small malignant lesions may recur.Intravesical chemotherapy and immunotherapy are universally accepted as adjuvant treatments after surgery to avoid recurrence and progression.However,these treatments still have limitations,including an insufficient retention period,inefficient permeability of chemotherapeutic agents,and dilution of the agents by urine.Nanostructure-based smart therapeutic platforms can be tailored to be responsive to internal or external stimuli to ameliorate this situation.This unparalleled capability empowers the precise aggregation of stimulus–responsive nanocarriers in the target regions,namely,the tumors,and subsequent release of the anticancer materials.This review summarizes the current nanostructure-based therapeutic platforms,especially stimulus–responsive nanocarriers,and highlights their benefits and limitations in bladder cancer therapy.Novel innovations in nanotechnology have undoubtedly arrived at a new height and have become useful for practical applications.Nanotechnology will positively promote the development of anticancer agents not only for bladder cancer but also for other solid tumors.展开更多
Interaction detection in large-scale genetic asso- ciation studies has attracted intensive research interest, since many diseases have complex traits. Various approaches have been developed for finding significant gen...Interaction detection in large-scale genetic asso- ciation studies has attracted intensive research interest, since many diseases have complex traits. Various approaches have been developed for finding significant genetic interactions. In this article, we propose a novel framework SRMiner to detect interacting susceptible and protective genotype patterns. SR- Miner can discover not only probable combination of single nucleotide polymorphisms (SNPs) causing diseases but also the corresponding SNPs suppressing their pathogenic func- tions, which provides a better prospective to uncover the un- derlying relevance between genetic variants and complex dis- eases. We have performed extensive experiments on several real WeUcome Trust Case Control Consortium (WTCCC) datasets. We use the pathway-based and the protein-protein interaction (PPI) network-based evaluation methods to verify the discovered patterns. The results show that SRMiner successfully identifies many disease-related genes verified by the existing work. Furthermore, SRMiner can also infer some uncomfirmed but highly possible disease-related genes.展开更多
Current cancer therapies have encountered adverse response due to poor therapeutic efficiency,severe side effects and acquired resistance to multiple drugs.Thus,there are urgent needs for finding new cancer-targeted p...Current cancer therapies have encountered adverse response due to poor therapeutic efficiency,severe side effects and acquired resistance to multiple drugs.Thus,there are urgent needs for finding new cancer-targeted pharmacological strategies.In this review,we summarized the current understanding with THZ1,a covalent inhibitor of cyclin-dependent kinase 7(CDK7),which demonstrated promising anti-tumor activity against different cancer types.By introducing the anti-tumor behaviors and the potential targets for different cancers,this review aims to provide more effective approaches to CDK7 inhibitor-based therapeutic agents and deeper insight into the diverse tumor proliferation mechanisms.展开更多
1 Introduction and main contributions Link prediction for temporal networks aims to evaluate the likelihood of the future linkage among nodes,which has significant applications in social networks,biological networks a...1 Introduction and main contributions Link prediction for temporal networks aims to evaluate the likelihood of the future linkage among nodes,which has significant applications in social networks,biological networks and traffic analysis[1],etc.Network embedding[2]is an important analytical tool for temporal network link prediction,which helps us better understand network evolution[3].How to encode high-dimensional and non-Euclidean network information is a crucial problem for node embedding in temporal networks.One of the challenges is to reveal the spatial structure at each timestamp and the temporal property over time[4].Some existing work[5]shows that extracting the spatial relation of each node can be used as a valid feature representation for each node.Moreover,the emergence of deep learning techniques[4,5]brings new insights for learning temporal properties,but most models using deep learning still fail to achieve satisfying prediction accuracy.展开更多
基金This work was funded by the National Natural Science Foundation of China(52173150,51973243,and 82272689)the National Key R&D Program of China(2018YFA0902800)+5 种基金the Medical Science and Technology Foundation of Guangdong Province(A2020543)the Shenzhen Science and Technology Program(RCYX20200714114645131)the Shenzhen Fundamental Research Program(JCYJ20210324115212033 and JCYJ20190809164617205)the Sanming Project of Medicine in Shenzhen(SZSM202011011)the China Postdoctoral Science Foundation(2022M723670)the Research Start-up Fund of the Seventh Affiliated Hospital,Sun Yat-sen University(ZSQYJZPI202003 and ZSQYBRJH0011).
文摘Objective:We aim to develop a polymer library consisting of phenylalanine-based poly(ester amide)s(Phe-PEAs)for cancer therapy and investigate the structure–property relationship of these polymers to understand their impact on the drug delivery efficiency of corresponding nanoparticles(NPs).Impact Statement:Our study provides insights into the structure–property relationship of polymers in NP-based drug delivery applications and offers a potential polymer library and NP platform for enhancing cancer therapy.Introduction:Polymer NP-based drug delivery systems have demonstrated substantial potential in cancer therapy by improving drug efficacy and minimizing systemic toxicity.However,successful design and optimization of these systems require a comprehensive understanding of the relationship between polymer structure and physicochemical properties,which directly influence the drug delivery efficiency of the corresponding NPs.Methods:A series of Phe-PEAs with tunable structures was synthesized by varying the length of the methylene group in the diol part of the polymers.Subsequently,Phe-PEAs were formulated into NPs for doxorubicin(DOX)delivery in prostate cancer therapy.Results:Small adjustments in polymer structure induced the changes in the hydrophobicity and thermal properties of the PEAs,consequently NP size,drug loading capacity,cellular uptake efficacy,and cytotoxicity.Additionally,DOXloaded Phe-PEA NPs demonstrated enhanced tumor suppression and reduced side effects in prostate tumor-bearing mice.Conclusion:Phe-PEAs,with their finely tunable structures,show great promise as effective and customizable nanocarriers for cancer therapy.
基金supported by the Key Project of Environmental Science and Technology of Shandong Province(Grant No.2006003-2)
文摘Based on the experiments of utilization of garlic processing wastewater in a lotus pond, this study demonstrates that lotus pond wetlands have a remarkable ability to remove organic pollutants and decrease chemical oxygen demand (CODCr), biochemical oxygen demand (BOD5), and suspended substances (SS) in garlic processing wastewater. Results also show evident effects of lotus roots on absorption of NH3-N. The pH value in a lotus pond with wastewater discharged was relatively stable. The water quality in the lotus pond reached the class Ⅱ emission standard, according to the Integrated Wastewater Discharge Standard (GB8978-1996), seven days after pretreated garlic processing wastewater had been discharged into the lotus pond. Garlic processing wastewater irrigation does not produce pollution in the pond sediment and has no negative effect on the growth of lotus roots. Due to utilization of garlic processing wastewater, the output of lotus roots increased by 3.0% to 8.3%, and the quality of lotus roots was improved. Therefore, better purification and utilization results can be achieved.
基金Project supported by the National Key Research and Development Program of China(Grant No.2017YFB0405702)the National Natural Science Foundation of China(Grant No.51672179).
文摘Bi doped n-type SnSe thin films were prepared by chemical vapor deposition(CVD)and their structure and thermoelectric properties were studied.The x-ray diffraction patterns,x-ray photoelectron spectroscopy,and microscopic images show that the prepared SnSe thin films were composed of pure SnSe crystals.The Seebeck coefficients of the Bi-doped SnSe were greatly improved compared to that of undoped SnSe thin films.Specifically,Sn_(0.99)Bi_(0.01)Se thin film exhibited a Seebeck coefficient of905.8μV·K^(-1) at 600 K,much higher than 285.5μV·K^(-1) of undoped SnSe thin film.Further first-principles calculations reveal that the enhancement of the thermoelectric properties can be explained mainly by the Fermi level lifting and the carrier pockets increasing near the Fermi level due to Bi doping in the SnSe samples.Our results suggest the potentials of the Bi-doped SnSe thin films in thermoelectric applications.
文摘In this paper, we show how to use the novel extended strand space method to verify Kerberos V. First, we formally model novel semantical features in Kerberos V such as timestamps and protocol mixture in this new framework. Second, we apply unsolicited authentication test to prove its secrecy and authentication goals of Kerberos V. Our formalization and proof in this case study have been mechanized using Isabelle/HOL.
文摘In this paper, we present two extensions of the strand space method to model Kerberos V. First, we include time and timestamps to model security protocols with timestamps: we relate a key to a crack time and combine it with timestamps in order to define a notion of recency. Therefore, we can check replay attacks in this new framework. Second, we extend the classic strand space theory to model protocol mixture. The main idea is to introduce a new relation to model the causal relation between one primary protocol session and one of its following secondary protocol session. Accordingly, we also extend the definition of unsolicited authentication test.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(Nos.XDB 0470303 and XDB 0450402)the National Key Research and Development Program of China(Nos.2018YFE0202201 and 2021YFA0715700)+2 种基金the National Natural Science Foundation of China(Nos.22293044,U1932213,and 22305240)the New Cornerstone Investigator Program.Y.-F.M.acknowledges the Major Basic Research Project of Anhui Province(No.2023z04020009)the Double First-Class University Construction Fund from USTC(No.YD2060002037).
文摘Biological structural materials,despite consisting of limited kinds of compounds,display multifunctionalities due to their complex hierarchical architectures.While some biomimetic strategies have been applied in artificial materials to enhance their mechanical stability,the simultaneous optimization of other functions along with the mechanical properties via biomimetic designs has not been thoroughly investigated.Herein,iron oxide/carbon nanotube(CNT)-based artificial nacre with both improved mechanical and electromagnetic interference(EMI)shielding performance is fabricated via the mineralization of Fe_(3)O_(4)onto a CNTincorporated matrix.The micro-and nano-structures of the artificial nacre are similar to those of natural nacre,which in turn improves its mechanical properties.The alternating electromagnetic wave-reflective CNT layers and the wave-absorptive iron oxide layers can improve the multiple reflections of the waves on the surfaces of the reflection layers,which then allows sufficient interactions between the waves and the absorption layers.Consequently,compared with the reflection-dependent EMI-shielding of the non-structured material,the artificial nacre exhibits strong absorption-dependent shielding behavior even with a very low content of wave-absorptive phase.Owing to the high mechanical stability,the shielding effectiveness of the artificial nacre that deeply cut by a blade is still maintained at approximately 70%−96%depending on the incident wave frequency.The present work provides a new way for designing structural materials with concurrently enhanced mechanical and functional properties,and a path to combine structural design and intrinsic properties of specific materials via a biomimetic strategy.
基金funded by Shenzhen Basic Science Research(JCYJ20190809164617205)Sanming Project of Medicine in Shenzhen(SZSM202011011)Part-time PI Research Start-up Fund of SAHSYSU(ZSQYJZPI202003).
文摘Increasing evidence indicates that N6-methyladenosine(m6A)methylation modification serves important functions in biological metabolism.Dysregulation of m6A regulators is related to the progression of different malignancies,including renal cell carcinoma(RCC).Recent studies have reported preliminary findings on the influence of m6A regulator dysregulation on RCC tumorigenesis and development.However,no comprehensive review that integrates and analyzes the roles of m6A modification in RCC has been published to date.In this review,we focus on the dysregulation of m6A regulators as it relates to RCC tumorigenesis and development,as well as possible applications of m6A modification in RCC diagnosis and therapeutics.
基金supported by the National Natural Science Foundation of China(Nos.81703807 and 81803237)grants from the Sichuan Science and Technology Program(No.2019YJ0485)the Joint Funds of the Southwest Medical University&Luzhou(Nos.2018LZXNYD-ZK34 and 2017LZXNYD-J02,China)
文摘Long-term primary culture of mammalian cells has been always difficult due to unavoidable senescence. Conventional methods for generating immortalized cell lines usually require manipulation of genome which leads to change of important biological and genetic characteristics. Recently, conditional reprogramming(CR) emerges as a novel next generation tool for long-term culture of primary epithelium cells derived from almost all origins without alteration of genetic background of primary cells. CR cocultures primary cells with inactivated mouse 3T3-J2 fibroblasts in the presence of RHO-related protein kinase(ROCK) inhibitor Y-27632, enabling primary cells to acquire stem-like characteristics while retain their ability to fully differentiate. With only a few years’ development, CR shows broad prospects in applications in varied areas including disease modeling, regenerative medicine, drug evaluation, drug discovery as well as precision medicine. This review is thus to comprehensively summarize and assess current progress in understanding mechanism of CR and its wide applications, highlighting the value of CR in both basic and translational researches and discussing the challenges faced with CR.
文摘The present study analyzed the predictive value of combined analysis of collapsin response mediator protein 4 (CRMP4) methylation levels and the Cancer of the Prostate Risk Assessment (CAPRA-S) Postsurgical score of patients who required adjuvant hormone therapy (AHT) after radical prostatectomy (RP), We retrospectively analyzed 305 patients with prostate cancer (PCa) who received RP and subsequent androgen deprivation therapy (ADT). Two hundred and thirty patients with clinically high-risk PCa underwent immediate ADT, and 75 patients with intermediate risk PCa underwent deferred ADT. CRMP4 methylation levels in biopsies were determined, and CAPRA-S scores were calculated. In the deferred ADT group, the values of the hazard ratios for tumor progression and cancer-specific mortality (CSM) in patients with 〉15% CRMP4 methylation were 6.81 (95% CI, 2.34-19.80) and 12.83 (95% CI. 2.16-26.10), respectively. Receiver-operating characteristic curve analysis indicated that CRMP4 methylation levels 〉15% served as a significant prognostic marker of tumor progression and CSM. In the immediate ADT group, CAPRA-S scores :〉6 and CRMP4 methylation levels :〉15% were independent predictors of these outcomes (uni- and multi-variable Cox regression analyses). The differences in the 5-year progression-free survival between each combination were statistically significant. Combining CAPRA-S score and CRMP4 methylation levels improved the area under the curve compared with the CRMP4 or CAPRA-S model. Therefore, CRMP4 methylation levels :〉15% were significantly associated with a poor prognosis and their combination with CAPRA-S score accurately predicted tumor progression and metastasis for patients requiring AHT after RP.
文摘In certified email (CEM) protocols, trusted third party (TTP) transparency is an important security require- ment which helps to avoid bad publicity as well as protecting individual users' privacy. Cederquist et al. proposed an opti- mistic certified email protocol, which employs key chains to reduce the storage requirement of the TTE We extend their protocol to satisfy the property of TTP transparency, using existing verifiably encrypted signature schemes. An imple- mentation with the scheme based on bilinear pairing makes our extension one of the most efficient CEM protocols satis- fying strong fairness, timeliness, and TTP transparency. We formally verify the security requirements of the extended pro- tocol. The properties of fairness, timeliness and effectiveness are checked in the model checker Mocha, and TTP trans- parency is formalised and analysed using the toolsets/~CRL and CADE
文摘Recent development on distributed systems has shown that a variety of fairness constraints (some of which are only recently defined) play vital roles in designing self- stabilizing population protocols. Existing model checkers are deficient in verifying the systems as only limited kinds of fair- ness are supported with limited verification efficiency. In this work, we support model checking of distributed systems in the toolkit PAT (process analysis toolkit), with a variety of fairness constraints (e.g., process-level weak/strong fairness, event-level weak/strong fairness, strong global fairness). It performs on-the-fly verification against linear temporal prop- erties. We show through empirical evaluation (on recent pop- ulation protocols as well as benchmark systems) that PAT has advantage in model checking with fairness. Previously un- known bugs have been revealed against systems which are designed to function only with strong global fairness.
基金the National Natural Science Foundation of China(Nos.21704104 and 81772754)Shenzhen Science and Technology Innovation Commission(Nos.RCYX20200714114645131 and JCYJ20190809164617205)+4 种基金Guangdong Basic and Applied Basic Research Foundation(Nos.2020A1515011443 and 2021A1515010669)Major Basic Research and Cultivation Program of Natural Science Foundation of Guangdong Province(No.2017A03038009)the Fundamental Research Funds for the Central Universities,Sun Yat-sen University(No.20ykpy17)Sanming Project of Medicine in Shenzhen(No.SZSM202011011)Research Start-up Fund of Part-time PI,SAHSYSU(No.ZSQYJZPI202003).
文摘Although patients benefit from surgical transurethral resection of bladder cancers,some niduses are missed or incompletely resected,and small malignant lesions may recur.Intravesical chemotherapy and immunotherapy are universally accepted as adjuvant treatments after surgery to avoid recurrence and progression.However,these treatments still have limitations,including an insufficient retention period,inefficient permeability of chemotherapeutic agents,and dilution of the agents by urine.Nanostructure-based smart therapeutic platforms can be tailored to be responsive to internal or external stimuli to ameliorate this situation.This unparalleled capability empowers the precise aggregation of stimulus–responsive nanocarriers in the target regions,namely,the tumors,and subsequent release of the anticancer materials.This review summarizes the current nanostructure-based therapeutic platforms,especially stimulus–responsive nanocarriers,and highlights their benefits and limitations in bladder cancer therapy.Novel innovations in nanotechnology have undoubtedly arrived at a new height and have become useful for practical applications.Nanotechnology will positively promote the development of anticancer agents not only for bladder cancer but also for other solid tumors.
文摘Interaction detection in large-scale genetic asso- ciation studies has attracted intensive research interest, since many diseases have complex traits. Various approaches have been developed for finding significant genetic interactions. In this article, we propose a novel framework SRMiner to detect interacting susceptible and protective genotype patterns. SR- Miner can discover not only probable combination of single nucleotide polymorphisms (SNPs) causing diseases but also the corresponding SNPs suppressing their pathogenic func- tions, which provides a better prospective to uncover the un- derlying relevance between genetic variants and complex dis- eases. We have performed extensive experiments on several real WeUcome Trust Case Control Consortium (WTCCC) datasets. We use the pathway-based and the protein-protein interaction (PPI) network-based evaluation methods to verify the discovered patterns. The results show that SRMiner successfully identifies many disease-related genes verified by the existing work. Furthermore, SRMiner can also infer some uncomfirmed but highly possible disease-related genes.
文摘Current cancer therapies have encountered adverse response due to poor therapeutic efficiency,severe side effects and acquired resistance to multiple drugs.Thus,there are urgent needs for finding new cancer-targeted pharmacological strategies.In this review,we summarized the current understanding with THZ1,a covalent inhibitor of cyclin-dependent kinase 7(CDK7),which demonstrated promising anti-tumor activity against different cancer types.By introducing the anti-tumor behaviors and the potential targets for different cancers,this review aims to provide more effective approaches to CDK7 inhibitor-based therapeutic agents and deeper insight into the diverse tumor proliferation mechanisms.
基金This work has been supported by Chongqing Graduate Student Research and Innovation Project(CYB19096)the China Scholarship Council(202006990041)+2 种基金the Fundamental Research Funds for the Central Universities(XDJK2020D021)the Capacity Development Grant of Southwest University(SWU116007)the National Natural Science Foundation of China(Grant Nos.61672435,61732019,61811530327)。
文摘1 Introduction and main contributions Link prediction for temporal networks aims to evaluate the likelihood of the future linkage among nodes,which has significant applications in social networks,biological networks and traffic analysis[1],etc.Network embedding[2]is an important analytical tool for temporal network link prediction,which helps us better understand network evolution[3].How to encode high-dimensional and non-Euclidean network information is a crucial problem for node embedding in temporal networks.One of the challenges is to reveal the spatial structure at each timestamp and the temporal property over time[4].Some existing work[5]shows that extracting the spatial relation of each node can be used as a valid feature representation for each node.Moreover,the emergence of deep learning techniques[4,5]brings new insights for learning temporal properties,but most models using deep learning still fail to achieve satisfying prediction accuracy.