Cell-free(CF)multiple-input multiple-output(MIMO)is a promising technique to enable the vision of ubiquitous wireless connectivity for next-generation network communications.Compared to traditional co-located massive ...Cell-free(CF)multiple-input multiple-output(MIMO)is a promising technique to enable the vision of ubiquitous wireless connectivity for next-generation network communications.Compared to traditional co-located massive MIMO,CF MIMO allows geographically distributed access points(APs)to serve all users on the same time-frequency resource with spatial multiplexing techniques,resulting in better performance in terms of both spectral efficiency and coverage enhancement.However,the performance gain is achieved at the expense of deploying more APs with high cost and power consumption.To address this issue,the recently proposed reconfigurable intelligent surface(RIS)technique stands out with its unique advantages of low cost,low energy consumption and programmability.In this paper,we provide an overview of RIS-assisted CF MIMO and its interaction with advanced optimization designs and novel applications.Particularly,recent studies on typical performance metrics such as energy efficiency(EE)and spectral efficiency(SE)are surveyed.Besides,the application of RIS-assisted CF MIMO techniques in various future communication systems is also envisioned.Additionally,we briefly discuss the technical challenges and open problems for this area to inspire research direction and fully exploit its potential in meeting the demands of future wireless communication systems.展开更多
Network-assisted full duplex(NAFD)cellfree(CF)massive MIMO has drawn increasing attention in 6G evolvement.In this paper,we build an NAFD CF system in which the users and access points(APs)can flexibly select their du...Network-assisted full duplex(NAFD)cellfree(CF)massive MIMO has drawn increasing attention in 6G evolvement.In this paper,we build an NAFD CF system in which the users and access points(APs)can flexibly select their duplex modes to increase the link spectral efficiency.Then we formulate a joint flexible duplexing and power allocation problem to balance the user fairness and system spectral efficiency.We further transform the problem into a probability optimization to accommodate the shortterm communications.In contrast with the instant performance optimization,the probability optimization belongs to a sequential decision making problem,and thus we reformulate it as a Markov Decision Process(MDP).We utilizes deep reinforcement learning(DRL)algorithm to search the solution from a large state-action space,and propose an asynchronous advantage actor-critic(A3C)-based scheme to reduce the chance of converging to the suboptimal policy.Simulation results demonstrate that the A3C-based scheme is superior to the baseline schemes in term of the complexity,accumulated log spectral efficiency,and stability.展开更多
Objective:With the escalating prevalence of prostate cancer(PCa)in China,there is an urgent demand for novel diagnostic and therapeutic approaches.Extensive investigations have been conducted on the clinical implement...Objective:With the escalating prevalence of prostate cancer(PCa)in China,there is an urgent demand for novel diagnostic and therapeutic approaches.Extensive investigations have been conducted on the clinical implementation of circulating free DNA(cfDNA)in PCa.This review aims to provide a comprehensive overview of the present state of cfDNA as a biomarker for PCa and to examine its merits and obstacles for future clinical utilization.Methods:Relevant peer-reviewed manuscripts on cfDNA as a PCa marker were evaluated by PubMed search(2010-2022)to evaluate the roles of cfDNA in PCa diagnosis,prognosis,and prediction,respectively.Results:cfDNA is primarily released from cells undergoing necrosis and apoptosis,allowing for non-invasive insight into the genomic,transcriptomic,and epigenomic alterations within various PCa disease states.Next-generation sequencing,among other detection methods,enables the assessment of cfDNA abundance,mutation status,fragment characteristics,and epigenetic modifications.Multidimensional analysis based on cfDNA can facilitate early detection of PCa,risk stratification,and treatment monitoring.However,standardization of cfDNA detection methods is still required to expedite its clinical application.Conclusion:cfDNA provides a non-invasive,rapid,and repeatable means of acquiring multidimensional information from PCa patients,which can aid in guiding clinical decisions and enhancing patient management.Overcoming the application barriers of cfDNA necessitates increased data sharing and international collaboration.展开更多
Cell-free Wireless Heterogeneous Networks(HetNets)have emerged as a technological alternative for conventional cellular networks.In this paper,we study the spatially correlative caching strategy,the energy analysis,an...Cell-free Wireless Heterogeneous Networks(HetNets)have emerged as a technological alternative for conventional cellular networks.In this paper,we study the spatially correlative caching strategy,the energy analysis,and the impact of parameter β on the total energy cost of the cell-free wireless HetNets with Access Points distributed by Beta Ginibre Point Process(β-GPP).We derive the approximate expression of Successful Delivery Probability(SDP)based on the Signal-to-Interference-plus-Noise Ratio coverage model.From both analytical and simulation results,it is shown that the proposed caching model based on β-GPP placement,which jointly takes into account path loss,fading,and interference,can closely simulate the caching performance of the cell-free HetNets in terms of SDP.By guaranteeing the outage probability constraints,the analytical expression of the uplink energy cost is also derived.Another conclusion is that with AP locations modeled by β-GPP,the power consumption is not sensitive to β,but is sensitive to the dimension of the kernel function;hence β is less restrictive,and only the truncation of the Ginibre kernel has to be appropriately modified.These findings are new compared with the existing literature where the nodes are commonly assumed to be of Poisson Point Process,Matern Hard-Core Process,or Poisson Cluster Process deployment in cell-free systems.展开更多
Epigenetic changes of DNA, including methylation, have long been recognized as key indicators of various diseases, including aging, cancer, and neurological disorders. Biomarker discoveries based on distinct methylati...Epigenetic changes of DNA, including methylation, have long been recognized as key indicators of various diseases, including aging, cancer, and neurological disorders. Biomarker discoveries based on distinct methylation patterns for both hypermethylation and hypomethylation lead the way in discovery of novel diagnosis and treatment targets. Many different approaches are present to detect the level of methylation in whole genome (whole genome bisulfite sequencing, microarray) as well as at specific loci (methylation specific PCR). Cell-free DNA (cf-DNA) found in body fluids like blood provides information about DNA methylation and serves as a less invasive approach for genetic screening. Cell-free DNA and methylation screening technologies, when combined, have the potential to transform the way we approach genetic screening and personalized therapy. These technologies can help enhance disease diagnostic accuracy and inform the development of targeted therapeutics by providing a non-invasive way for acquiring genomic information and identifying disease-associated methylation patterns. We highlight the clinical benefits of using cell-free DNA (cf-DNA) liquid biopsy analysis and available methylation screening technologies that have been crucial in identifying biomarkers for disease from patients using a non-invasive way. Powering such biomarker discoveries are various methods of cf-DNA methylation analysis such as Bisulfite Sequencing and most recently, Methylation-Specific Restriction Enzyme (MSRE-seq) Analysis, paving the way for novel epigenetic biomarker discoveries for more robust diagnosis such as early disease detection, prognosis, monitoring of disease progression and treatment response as well as discovery of novel drug targets.展开更多
Despite recent advances in surgical techniques and perioperative management, the prognosis of pancreatic cancer(PCa) remains extremely poor. To provide optimal treatment for each patient with Pca, superior biomarkers ...Despite recent advances in surgical techniques and perioperative management, the prognosis of pancreatic cancer(PCa) remains extremely poor. To provide optimal treatment for each patient with Pca, superior biomarkers are urgently needed in all phases of management from early detection to staging, treatment monitoring, and prognosis. In the blood of patients with cancer, circulating tumor cells(CTCs) and cell-free nucleic acids(cf NAs), such as DNA, m RNA, and noncoding RNA have been recognized. In the recent years, their presence in the blood has encouraged researchers to investigate their potential use as novel blood biomarkers, and numerous studies have demonstrated their potential clinical utility as a biomarker for certain types of cancer. This concept, called "liquid biopsy" has been focused on as a less invasive, alternative approach to cancer tissue biopsy for obtaining genetic and epigenetic aberrations that contribute to oncogenesis and cancer progression. In this article, we review the available literature on CTCs and cfN As in patients with cancer, particularly focusing on PCa, and discuss future perspectives in this field.展开更多
Mesenchymal stem cells(MSCs)are multipotent stem cells with marked potential for regenerative medicine because of their strong immunosuppressive and regenerative abilities.The therapeutic effects of MSCs are based in ...Mesenchymal stem cells(MSCs)are multipotent stem cells with marked potential for regenerative medicine because of their strong immunosuppressive and regenerative abilities.The therapeutic effects of MSCs are based in part on their secretion of biologically active factors in extracellular vesicles known as exosomes.Exosomes have a diameter of 30-100 nm and mediate intercellular communication and material exchange.MSC-derived exosomes(MSC-Exos)have potential for cell-free therapy for diseases of,for instance,the kidney,liver,heart,nervous system,and musculoskeletal system.Hence,MSC-Exos are an alternative to MSCbased therapy for regenerative medicine.We review MSC-Exos and their therapeutic potential for a variety of diseases and injuries.展开更多
A key challenge to the scalable deployment of the energy self-sustainability(ESS)Internet of Everything(IoE)for sixth-generation(6G)networks is juggling massive connectivity and high spectral efficiency(SE).Cell-free ...A key challenge to the scalable deployment of the energy self-sustainability(ESS)Internet of Everything(IoE)for sixth-generation(6G)networks is juggling massive connectivity and high spectral efficiency(SE).Cell-free massive multiple-input multiple-output(CF mMIMO)is considered as a promising solution,where many wireless access points perform coherent signal processing to jointly serve the users.However,massive connectivity and high SE are difficult to obtain at the same time because of the limited pilot resource.To solve this problem,we propose a new framework for ESS IoE networks where the user activity detection(UAD)and channel estimation are decoupled.A UAD detector based on deep convolutional neural networks,an initial access scheme,and a scalable power control policy are proposed to enable the practical scalable CF mMIMO implementation.We derive novel and exact closed-form expressions of harvested energy and SE with maximum ratio(MR)processing.Using local partial minimum mean-square error and MR combining,simulation results prove that the proposed framework can serve more users,improve the SE performance,and achieve better user fairness for the considered ESS IoE networks.展开更多
We established a quick and reliable method for recovering cell-free seminal DNA (cfsDNA), by using the binding-washing-elution procedure on the DNA purification column. Low variations (below 15%) among the triplic...We established a quick and reliable method for recovering cell-free seminal DNA (cfsDNA), by using the binding-washing-elution procedure on the DNA purification column. Low variations (below 15%) among the triplicate values of cfsDNA quantity verified the reproducibility of our cfsDNA recovery method. Similar cfsDNA yield and size distribution between seminal plasma acquired by filtration and centrifugation confirmed the presence of cfsDNA. To investigate the general characterization of cfsDNA, the quantitation and size distribution of cfsDNA from normozoospermic and azoospermic semen were analyzed by real-time PCR and electrophoresis, respectively. CfsDNA concentration in semen with normozoospermia (n = 11) was 1.34 ± 0.65 μg ·mL^-1, whereas a higher cfsDNA concentration was observed in azoospermia (2.56 ± 1.43 μg ·mL^-1, n = 9). The continuous distribution of DNA fragments ranging from -1 kb to 15 kb and a spectrum of multiples of 180-bp fragments were observed in each normozoospermic and azoospermic sample. Distinct characteristic DNA ladder fragmentations in some azoospermic samples implicated that cfsDNA originate partly from apoptotic cells. CfsDNAs of 36 selected azoospermic patients with known information of Y chromosome microdeletion were subjected to the same microdeletion analysis by multiplex PCR and PCR amplification of sY114 (1 450 bp). All multiplex PCR reactions with cfsDNA amplified successfully and provided the same result as leukocyte DNA. PCR amplification of sY114 gave a 1 450-bp amplicon as expected. Our data suggested the potential use of cfsDNA in search of biomarker or diagnostic procedures.展开更多
Reconfigurable intelligent surface(RIS)is a promising technology that utilizes massive low-cost elements to reflect incident signals to desired direction.In this paper,we consider a RIS-aided cell free multiple-input ...Reconfigurable intelligent surface(RIS)is a promising technology that utilizes massive low-cost elements to reflect incident signals to desired direction.In this paper,we consider a RIS-aided cell free multiple-input multiple-output(MIMO)network that composed of multiple access points(APs),multiple RISs,multiple information receivers(IRs),and multiple energy receivers(ERs).Under the maximum transmit power constraints of the APs and the minimum total energy harvesting power constraints of the ERs,we aim to maximize the weighted sum-rate(WSR)by jointly optimizing the beamforming matrices and the passive RIS reflection matrices.However,the formulated problem is nonconvex and very challenging to solve.Therefore,we propose an alternating optimization algorithm to obtain a suboptimal solution.Explicitly,the proposed algorithm decomposes the original optimization problem into three subproblems that can be efficiently solved.To overcome the nonconvexity of the subproblems,a successive convex approximation(SCA)based algorithm is proposed to tackle the energy harvesting constraints.Moreover,an alternating direction method of multipliers(ADMM)based algorithm is proposed to optimize the constant modulus constrained RIS reflecting elements.Finally,simulations are conducted to demonstrate the performance advantages of the proposed algorithms.展开更多
Inflammatory bowel diseases(IBD)are chronic inflammatory disorders of the gastrointestinal tract associated with multifactorial conditions such as ulcerative colitis and Crohn’s disease.Although the underlying mechan...Inflammatory bowel diseases(IBD)are chronic inflammatory disorders of the gastrointestinal tract associated with multifactorial conditions such as ulcerative colitis and Crohn’s disease.Although the underlying mechanisms of IBD remain unclear,growing evidence has shown that dysregulated immune system reactions in genetically susceptible individuals contribute to mucosal inflammation.However,conventional treatments have been effective in inducing remission of IBD but not in preventing the relapse of them.In this way,mesenchymal stromal cells(MSC)therapy has been recognized as a promising treatment for IBD due to their immunomodulatory properties,ability to differentiate into several tissues,and homing to inflammatory sites.Even so,literature is conflicted regarding the location and persistence of MSC in the body after transplantation.For this reason,recent studies have focused on the paracrine effect of the biofactors secreted by MSC,especially in relation to the immunomodulatory potential of soluble factors(cytokines,chemokines,and growth factors)and extracellular vehicles that are involved in cell communication and in the transfer of cellular material,such as proteins,lipids,and nucleic acids.Moreover,treatment with interferon-γ,tumor necrosis factor-α,and interleukin-1βcauses MSC to express immunomodulatory molecules that mediate the suppression via cell-contact dependent mechanisms.Taken together,we present an overview of the role of bioactive factors and cell membrane proteins derived from MSC as a cell-free therapy that can improve IBD treatment.展开更多
BACKGROUND Mortality due to septic shock is relatively high.The dynamic monitoring of plasma cell-free DNA(cfDNA)can guide the treatment of septic shock.CASE SUMMARY Herein,we present a typical case of septic shock sy...BACKGROUND Mortality due to septic shock is relatively high.The dynamic monitoring of plasma cell-free DNA(cfDNA)can guide the treatment of septic shock.CASE SUMMARY Herein,we present a typical case of septic shock syndrome caused by the bacilli Acinetobacter baumannii and Pantoea.The patient complained of abdominal pain,fever and chills upon admission to the Emergency Department.Marked decreases in white blood cells and procalcitonin(PCT)were observed after the patient received continuous renal replacement and extracorporeal membrane oxygenation.Plasma cfDNA levels were consistently high,peaking at 1366.40 ng/mL,as measured by a duplex real-time PCR assay with an internal control,which was developed as a novel method for the accurate quantification of cfDNA.The patient died of septic shock on HD 8,suggesting that cfDNA could be used to monitor disease progression more effectively than PCT and the other inflammatory factors measured in this case.CONCLUSION CfDNA may be a promising marker that complements other inflammatory factors to monitor disease progression in patients with septic shock.展开更多
In this paper,the spectral efficiency(SE)of an uplink hardware-constrained cell-free massive multi-input multi-output(MIMO)system with maximal ratio combining(MRC)receiver filters in the context of superimposed pilots...In this paper,the spectral efficiency(SE)of an uplink hardware-constrained cell-free massive multi-input multi-output(MIMO)system with maximal ratio combining(MRC)receiver filters in the context of superimposed pilots(SPs)is investigated.Tractable closed-form SE expressions for the considered system are derived,which share us with opportunities to explore the impacts of the hardware quality coefficient,the length of coherence interval,and the power balance factor between pilot and data signals.Numerical results indicate that the achievable SE deteriorates as the hardware quality decreases and is more susceptible to the hardware impairments at the user equipments(UEs).Besides,we observe that SPs outperform regular pilots(RPs)in terms of SE and this performance gain is heavily dependent on the values of power balance factor and coherence interval.However,the superiorities of SPs over RPs have vanished when severe hardware imperfections are considered.展开更多
Due to advances in modern medicine,liver transplantation has revolutionised the prognosis of many previously incurable liver diseases.This progress has largely been due to advances in immunosuppressant therapy.However...Due to advances in modern medicine,liver transplantation has revolutionised the prognosis of many previously incurable liver diseases.This progress has largely been due to advances in immunosuppressant therapy.However,despite the judicious use of immunosuppression,many liver transplant recipients still experience complications such as rejection,which necessitates diagnosis via invasive liver biopsy.There is a clear need for novel,minimally-invasive tests to optimise immunosuppression and improve patient outcomes.An emerging biomarker in this‘‘precision medicine’‘liver transplantation field is that of donorspecific cell free DNA.In this review,we detail the background and methods of detecting this biomarker,examine its utility in liver transplantation and discuss future research directions that may be most impactful.展开更多
Stem cells are considered as key therapeutic tools in the field of regenerative medicine. In the last decade, based on a growing body of knowledge about their mechanisms of action, a new way of exploring the therapeut...Stem cells are considered as key therapeutic tools in the field of regenerative medicine. In the last decade, based on a growing body of knowledge about their mechanisms of action, a new way of exploring the therapeutic potential of stem cells without the need for cell transplantation has been evidenced. This approach, called cell-free therapy, uses stem cells as a source of therapeutic molecules rather than the therapeutic agent per se, and several studies have shown relevant therapeutic effects under a variety of experimental conditions, including nervous system disorders.展开更多
BACKGROUND Acute ischemic stroke(AIS)is one of the major causes of the continuous increasing rate of global mortality due to the lack of timely diagnosis,prognosis,and management.This study provides a primitive platfo...BACKGROUND Acute ischemic stroke(AIS)is one of the major causes of the continuous increasing rate of global mortality due to the lack of timely diagnosis,prognosis,and management.This study provides a primitive platform for non-invasive and cost-effective diagnosis and prognosis of patients with AIS using circulating cellfree mitochondrial DNA(cf-mtDNA)quantification and validation.AIM To evaluate the role of cf-mtDNA as s non-invasive,and affordable tool for realtime monitoring and prognosticating AIS patients at disease onset and during treatment.METHODS This study enrolled 88 participants including 44 patients with AIS and 44 healthy controls with almost similar mean age group at stroke onset,and at 24 h and 72 h of treatment.Peripheral blood samples were collected from each study participant and plasma was separated using centrifugation.The cf-mtDNA concentration was quantified using nanodrop reading and validated through real-time quantitative polymerase chain reaction(RT-qPCR)of NADH-ubiquinone oxidoreductase chain 1(ND1)relative transcript expression levels.RESULTS Comparative analysis of cf-mtDNA concentration in patients at disease onset showed significantly increased levels compared to control individuals for both nanodrop reading,as well as ND1 relative expression levels(P<0.0001).Intergroup analysis of cf-mtDNA concentration using nanodrop showed significantly reduced levels in patients at 72 h of treatment compared to onset(P<0.01).However,RT-qPCR analysis showed a significant reduction at 24 h and 72 h of treatment compared to the disease onset(P<0.001).The sensitivity and specificity were relatively higher for RT-qPCR than nanodrop-based cfmtDNA quantification.Correlation analysis of both cf-mtDNA concentration as well as ND1 relative expression with National Institute of Health Stroke Scale score at baseline showed a positive trend.CONCLUSION In summary,quantitative estimation of highly pure cf-mtDNA provides a simple,highly sensitive and specific,non-invasive,and affordable approach for real-time monitoring and prognosticating AIS patients at onset and during treatment.展开更多
基金supported in part by ZTE Industry-University-Institute Co⁃operation Funds.
文摘Cell-free(CF)multiple-input multiple-output(MIMO)is a promising technique to enable the vision of ubiquitous wireless connectivity for next-generation network communications.Compared to traditional co-located massive MIMO,CF MIMO allows geographically distributed access points(APs)to serve all users on the same time-frequency resource with spatial multiplexing techniques,resulting in better performance in terms of both spectral efficiency and coverage enhancement.However,the performance gain is achieved at the expense of deploying more APs with high cost and power consumption.To address this issue,the recently proposed reconfigurable intelligent surface(RIS)technique stands out with its unique advantages of low cost,low energy consumption and programmability.In this paper,we provide an overview of RIS-assisted CF MIMO and its interaction with advanced optimization designs and novel applications.Particularly,recent studies on typical performance metrics such as energy efficiency(EE)and spectral efficiency(SE)are surveyed.Besides,the application of RIS-assisted CF MIMO techniques in various future communication systems is also envisioned.Additionally,we briefly discuss the technical challenges and open problems for this area to inspire research direction and fully exploit its potential in meeting the demands of future wireless communication systems.
基金supported by the National Key R&D Program of China under Grant 2020YFB1807204the BUPT Excellent Ph.D.Students Foundation under Grant CX2022306。
文摘Network-assisted full duplex(NAFD)cellfree(CF)massive MIMO has drawn increasing attention in 6G evolvement.In this paper,we build an NAFD CF system in which the users and access points(APs)can flexibly select their duplex modes to increase the link spectral efficiency.Then we formulate a joint flexible duplexing and power allocation problem to balance the user fairness and system spectral efficiency.We further transform the problem into a probability optimization to accommodate the shortterm communications.In contrast with the instant performance optimization,the probability optimization belongs to a sequential decision making problem,and thus we reformulate it as a Markov Decision Process(MDP).We utilizes deep reinforcement learning(DRL)algorithm to search the solution from a large state-action space,and propose an asynchronous advantage actor-critic(A3C)-based scheme to reduce the chance of converging to the suboptimal policy.Simulation results demonstrate that the A3C-based scheme is superior to the baseline schemes in term of the complexity,accumulated log spectral efficiency,and stability.
基金Shanghai Sailing Program to Yasheng Zhu(20YF1448100)the Science and Technology Commission of Shanghai Municipality(22Y11905200 to Yasheng Zhu,18410750200 to Shancheng Ren)+1 种基金National Natural Science Foundation of China(82203450 to Yasheng Zhu,82125025 to Shancheng Ren,81872105 to Shancheng Ren)Valuable discussions and suggestions were contributed by Xiaomin Zhang(Department of Urology,The First Affiliated Hospital,Naval Medical University,Shanghai 200433,China).
文摘Objective:With the escalating prevalence of prostate cancer(PCa)in China,there is an urgent demand for novel diagnostic and therapeutic approaches.Extensive investigations have been conducted on the clinical implementation of circulating free DNA(cfDNA)in PCa.This review aims to provide a comprehensive overview of the present state of cfDNA as a biomarker for PCa and to examine its merits and obstacles for future clinical utilization.Methods:Relevant peer-reviewed manuscripts on cfDNA as a PCa marker were evaluated by PubMed search(2010-2022)to evaluate the roles of cfDNA in PCa diagnosis,prognosis,and prediction,respectively.Results:cfDNA is primarily released from cells undergoing necrosis and apoptosis,allowing for non-invasive insight into the genomic,transcriptomic,and epigenomic alterations within various PCa disease states.Next-generation sequencing,among other detection methods,enables the assessment of cfDNA abundance,mutation status,fragment characteristics,and epigenetic modifications.Multidimensional analysis based on cfDNA can facilitate early detection of PCa,risk stratification,and treatment monitoring.However,standardization of cfDNA detection methods is still required to expedite its clinical application.Conclusion:cfDNA provides a non-invasive,rapid,and repeatable means of acquiring multidimensional information from PCa patients,which can aid in guiding clinical decisions and enhancing patient management.Overcoming the application barriers of cfDNA necessitates increased data sharing and international collaboration.
基金supported in part by the National Natural Science Foundation of China(NSFC)under the grant number 61901075the Natural Science Foundation of Chongqing,China,under the grant number cstc2019jcyj-msxmX0602+1 种基金Chongqing Basic and Cutting edge Project under the grant number cstc2018jcyjAX0507Chongqing University of Posts and Telecommunications Doctoral Candidates High-end Talent Training Project(No.BYJS2017001).
文摘Cell-free Wireless Heterogeneous Networks(HetNets)have emerged as a technological alternative for conventional cellular networks.In this paper,we study the spatially correlative caching strategy,the energy analysis,and the impact of parameter β on the total energy cost of the cell-free wireless HetNets with Access Points distributed by Beta Ginibre Point Process(β-GPP).We derive the approximate expression of Successful Delivery Probability(SDP)based on the Signal-to-Interference-plus-Noise Ratio coverage model.From both analytical and simulation results,it is shown that the proposed caching model based on β-GPP placement,which jointly takes into account path loss,fading,and interference,can closely simulate the caching performance of the cell-free HetNets in terms of SDP.By guaranteeing the outage probability constraints,the analytical expression of the uplink energy cost is also derived.Another conclusion is that with AP locations modeled by β-GPP,the power consumption is not sensitive to β,but is sensitive to the dimension of the kernel function;hence β is less restrictive,and only the truncation of the Ginibre kernel has to be appropriately modified.These findings are new compared with the existing literature where the nodes are commonly assumed to be of Poisson Point Process,Matern Hard-Core Process,or Poisson Cluster Process deployment in cell-free systems.
文摘Epigenetic changes of DNA, including methylation, have long been recognized as key indicators of various diseases, including aging, cancer, and neurological disorders. Biomarker discoveries based on distinct methylation patterns for both hypermethylation and hypomethylation lead the way in discovery of novel diagnosis and treatment targets. Many different approaches are present to detect the level of methylation in whole genome (whole genome bisulfite sequencing, microarray) as well as at specific loci (methylation specific PCR). Cell-free DNA (cf-DNA) found in body fluids like blood provides information about DNA methylation and serves as a less invasive approach for genetic screening. Cell-free DNA and methylation screening technologies, when combined, have the potential to transform the way we approach genetic screening and personalized therapy. These technologies can help enhance disease diagnostic accuracy and inform the development of targeted therapeutics by providing a non-invasive way for acquiring genomic information and identifying disease-associated methylation patterns. We highlight the clinical benefits of using cell-free DNA (cf-DNA) liquid biopsy analysis and available methylation screening technologies that have been crucial in identifying biomarkers for disease from patients using a non-invasive way. Powering such biomarker discoveries are various methods of cf-DNA methylation analysis such as Bisulfite Sequencing and most recently, Methylation-Specific Restriction Enzyme (MSRE-seq) Analysis, paving the way for novel epigenetic biomarker discoveries for more robust diagnosis such as early disease detection, prognosis, monitoring of disease progression and treatment response as well as discovery of novel drug targets.
文摘Despite recent advances in surgical techniques and perioperative management, the prognosis of pancreatic cancer(PCa) remains extremely poor. To provide optimal treatment for each patient with Pca, superior biomarkers are urgently needed in all phases of management from early detection to staging, treatment monitoring, and prognosis. In the blood of patients with cancer, circulating tumor cells(CTCs) and cell-free nucleic acids(cf NAs), such as DNA, m RNA, and noncoding RNA have been recognized. In the recent years, their presence in the blood has encouraged researchers to investigate their potential use as novel blood biomarkers, and numerous studies have demonstrated their potential clinical utility as a biomarker for certain types of cancer. This concept, called "liquid biopsy" has been focused on as a less invasive, alternative approach to cancer tissue biopsy for obtaining genetic and epigenetic aberrations that contribute to oncogenesis and cancer progression. In this article, we review the available literature on CTCs and cfN As in patients with cancer, particularly focusing on PCa, and discuss future perspectives in this field.
文摘Mesenchymal stem cells(MSCs)are multipotent stem cells with marked potential for regenerative medicine because of their strong immunosuppressive and regenerative abilities.The therapeutic effects of MSCs are based in part on their secretion of biologically active factors in extracellular vesicles known as exosomes.Exosomes have a diameter of 30-100 nm and mediate intercellular communication and material exchange.MSC-derived exosomes(MSC-Exos)have potential for cell-free therapy for diseases of,for instance,the kidney,liver,heart,nervous system,and musculoskeletal system.Hence,MSC-Exos are an alternative to MSCbased therapy for regenerative medicine.We review MSC-Exos and their therapeutic potential for a variety of diseases and injuries.
文摘A key challenge to the scalable deployment of the energy self-sustainability(ESS)Internet of Everything(IoE)for sixth-generation(6G)networks is juggling massive connectivity and high spectral efficiency(SE).Cell-free massive multiple-input multiple-output(CF mMIMO)is considered as a promising solution,where many wireless access points perform coherent signal processing to jointly serve the users.However,massive connectivity and high SE are difficult to obtain at the same time because of the limited pilot resource.To solve this problem,we propose a new framework for ESS IoE networks where the user activity detection(UAD)and channel estimation are decoupled.A UAD detector based on deep convolutional neural networks,an initial access scheme,and a scalable power control policy are proposed to enable the practical scalable CF mMIMO implementation.We derive novel and exact closed-form expressions of harvested energy and SE with maximum ratio(MR)processing.Using local partial minimum mean-square error and MR combining,simulation results prove that the proposed framework can serve more users,improve the SE performance,and achieve better user fairness for the considered ESS IoE networks.
基金Acknowledgment The investigation was supported by grants from the National Natural Science Foundation of China (No. 30801144), by the Specialized Research Fund for the Doctoral Program of Higher Education (No. 200804871092) and by the National Key Technology Research and Development Program for the 10th Five- Year Plan, China (No. 2004BA720A33-01).
文摘We established a quick and reliable method for recovering cell-free seminal DNA (cfsDNA), by using the binding-washing-elution procedure on the DNA purification column. Low variations (below 15%) among the triplicate values of cfsDNA quantity verified the reproducibility of our cfsDNA recovery method. Similar cfsDNA yield and size distribution between seminal plasma acquired by filtration and centrifugation confirmed the presence of cfsDNA. To investigate the general characterization of cfsDNA, the quantitation and size distribution of cfsDNA from normozoospermic and azoospermic semen were analyzed by real-time PCR and electrophoresis, respectively. CfsDNA concentration in semen with normozoospermia (n = 11) was 1.34 ± 0.65 μg ·mL^-1, whereas a higher cfsDNA concentration was observed in azoospermia (2.56 ± 1.43 μg ·mL^-1, n = 9). The continuous distribution of DNA fragments ranging from -1 kb to 15 kb and a spectrum of multiples of 180-bp fragments were observed in each normozoospermic and azoospermic sample. Distinct characteristic DNA ladder fragmentations in some azoospermic samples implicated that cfsDNA originate partly from apoptotic cells. CfsDNAs of 36 selected azoospermic patients with known information of Y chromosome microdeletion were subjected to the same microdeletion analysis by multiplex PCR and PCR amplification of sY114 (1 450 bp). All multiplex PCR reactions with cfsDNA amplified successfully and provided the same result as leukocyte DNA. PCR amplification of sY114 gave a 1 450-bp amplicon as expected. Our data suggested the potential use of cfsDNA in search of biomarker or diagnostic procedures.
基金National Natural Science Foundation of China(Fund number 61620106001)。
文摘Reconfigurable intelligent surface(RIS)is a promising technology that utilizes massive low-cost elements to reflect incident signals to desired direction.In this paper,we consider a RIS-aided cell free multiple-input multiple-output(MIMO)network that composed of multiple access points(APs),multiple RISs,multiple information receivers(IRs),and multiple energy receivers(ERs).Under the maximum transmit power constraints of the APs and the minimum total energy harvesting power constraints of the ERs,we aim to maximize the weighted sum-rate(WSR)by jointly optimizing the beamforming matrices and the passive RIS reflection matrices.However,the formulated problem is nonconvex and very challenging to solve.Therefore,we propose an alternating optimization algorithm to obtain a suboptimal solution.Explicitly,the proposed algorithm decomposes the original optimization problem into three subproblems that can be efficiently solved.To overcome the nonconvexity of the subproblems,a successive convex approximation(SCA)based algorithm is proposed to tackle the energy harvesting constraints.Moreover,an alternating direction method of multipliers(ADMM)based algorithm is proposed to optimize the constant modulus constrained RIS reflecting elements.Finally,simulations are conducted to demonstrate the performance advantages of the proposed algorithms.
文摘Inflammatory bowel diseases(IBD)are chronic inflammatory disorders of the gastrointestinal tract associated with multifactorial conditions such as ulcerative colitis and Crohn’s disease.Although the underlying mechanisms of IBD remain unclear,growing evidence has shown that dysregulated immune system reactions in genetically susceptible individuals contribute to mucosal inflammation.However,conventional treatments have been effective in inducing remission of IBD but not in preventing the relapse of them.In this way,mesenchymal stromal cells(MSC)therapy has been recognized as a promising treatment for IBD due to their immunomodulatory properties,ability to differentiate into several tissues,and homing to inflammatory sites.Even so,literature is conflicted regarding the location and persistence of MSC in the body after transplantation.For this reason,recent studies have focused on the paracrine effect of the biofactors secreted by MSC,especially in relation to the immunomodulatory potential of soluble factors(cytokines,chemokines,and growth factors)and extracellular vehicles that are involved in cell communication and in the transfer of cellular material,such as proteins,lipids,and nucleic acids.Moreover,treatment with interferon-γ,tumor necrosis factor-α,and interleukin-1βcauses MSC to express immunomodulatory molecules that mediate the suppression via cell-contact dependent mechanisms.Taken together,we present an overview of the role of bioactive factors and cell membrane proteins derived from MSC as a cell-free therapy that can improve IBD treatment.
基金Supported by National Natural Science Foundation of China,No.81672100 and No.81671836the Key Laboratory for Laboratory Medicine of Jiangsu Province of China,No.ZDXKB2016005
文摘BACKGROUND Mortality due to septic shock is relatively high.The dynamic monitoring of plasma cell-free DNA(cfDNA)can guide the treatment of septic shock.CASE SUMMARY Herein,we present a typical case of septic shock syndrome caused by the bacilli Acinetobacter baumannii and Pantoea.The patient complained of abdominal pain,fever and chills upon admission to the Emergency Department.Marked decreases in white blood cells and procalcitonin(PCT)were observed after the patient received continuous renal replacement and extracorporeal membrane oxygenation.Plasma cfDNA levels were consistently high,peaking at 1366.40 ng/mL,as measured by a duplex real-time PCR assay with an internal control,which was developed as a novel method for the accurate quantification of cfDNA.The patient died of septic shock on HD 8,suggesting that cfDNA could be used to monitor disease progression more effectively than PCT and the other inflammatory factors measured in this case.CONCLUSION CfDNA may be a promising marker that complements other inflammatory factors to monitor disease progression in patients with septic shock.
基金This work was supported in part by the National Natural Science Foundation of China under Grants 62071246,61771252,61861039,and 61427801in part by the National Key Research and Development Program of China under Grants 2020YFB1806608 and 2018YFC1314903+2 种基金in part by the Jiangsu Province Special Fund Project for Transformation of Scientific and Technological Achievements under Grant BA2019058in part by the Major Natural Science Research Project of Jiangsu Higher Education Institutions under Grant 18KJA510005in part by the Postgraduate Research&Practice Innovation Program of Jiangsu Province under Grants SJKY190740 and KYCX200709.
文摘In this paper,the spectral efficiency(SE)of an uplink hardware-constrained cell-free massive multi-input multi-output(MIMO)system with maximal ratio combining(MRC)receiver filters in the context of superimposed pilots(SPs)is investigated.Tractable closed-form SE expressions for the considered system are derived,which share us with opportunities to explore the impacts of the hardware quality coefficient,the length of coherence interval,and the power balance factor between pilot and data signals.Numerical results indicate that the achievable SE deteriorates as the hardware quality decreases and is more susceptible to the hardware impairments at the user equipments(UEs).Besides,we observe that SPs outperform regular pilots(RPs)in terms of SE and this performance gain is heavily dependent on the values of power balance factor and coherence interval.However,the superiorities of SPs over RPs have vanished when severe hardware imperfections are considered.
基金The University of Melbourne,Parkville 3000,VIC,Australia。
文摘Due to advances in modern medicine,liver transplantation has revolutionised the prognosis of many previously incurable liver diseases.This progress has largely been due to advances in immunosuppressant therapy.However,despite the judicious use of immunosuppression,many liver transplant recipients still experience complications such as rejection,which necessitates diagnosis via invasive liver biopsy.There is a clear need for novel,minimally-invasive tests to optimise immunosuppression and improve patient outcomes.An emerging biomarker in this‘‘precision medicine’‘liver transplantation field is that of donorspecific cell free DNA.In this review,we detail the background and methods of detecting this biomarker,examine its utility in liver transplantation and discuss future research directions that may be most impactful.
文摘Stem cells are considered as key therapeutic tools in the field of regenerative medicine. In the last decade, based on a growing body of knowledge about their mechanisms of action, a new way of exploring the therapeutic potential of stem cells without the need for cell transplantation has been evidenced. This approach, called cell-free therapy, uses stem cells as a source of therapeutic molecules rather than the therapeutic agent per se, and several studies have shown relevant therapeutic effects under a variety of experimental conditions, including nervous system disorders.
文摘BACKGROUND Acute ischemic stroke(AIS)is one of the major causes of the continuous increasing rate of global mortality due to the lack of timely diagnosis,prognosis,and management.This study provides a primitive platform for non-invasive and cost-effective diagnosis and prognosis of patients with AIS using circulating cellfree mitochondrial DNA(cf-mtDNA)quantification and validation.AIM To evaluate the role of cf-mtDNA as s non-invasive,and affordable tool for realtime monitoring and prognosticating AIS patients at disease onset and during treatment.METHODS This study enrolled 88 participants including 44 patients with AIS and 44 healthy controls with almost similar mean age group at stroke onset,and at 24 h and 72 h of treatment.Peripheral blood samples were collected from each study participant and plasma was separated using centrifugation.The cf-mtDNA concentration was quantified using nanodrop reading and validated through real-time quantitative polymerase chain reaction(RT-qPCR)of NADH-ubiquinone oxidoreductase chain 1(ND1)relative transcript expression levels.RESULTS Comparative analysis of cf-mtDNA concentration in patients at disease onset showed significantly increased levels compared to control individuals for both nanodrop reading,as well as ND1 relative expression levels(P<0.0001).Intergroup analysis of cf-mtDNA concentration using nanodrop showed significantly reduced levels in patients at 72 h of treatment compared to onset(P<0.01).However,RT-qPCR analysis showed a significant reduction at 24 h and 72 h of treatment compared to the disease onset(P<0.001).The sensitivity and specificity were relatively higher for RT-qPCR than nanodrop-based cfmtDNA quantification.Correlation analysis of both cf-mtDNA concentration as well as ND1 relative expression with National Institute of Health Stroke Scale score at baseline showed a positive trend.CONCLUSION In summary,quantitative estimation of highly pure cf-mtDNA provides a simple,highly sensitive and specific,non-invasive,and affordable approach for real-time monitoring and prognosticating AIS patients at onset and during treatment.