From subject,object and target subsystems,we analyze the rural human resource development system.The subject system includes government,education and training organizations,society,and rural human resource itself.Diff...From subject,object and target subsystems,we analyze the rural human resource development system.The subject system includes government,education and training organizations,society,and rural human resource itself.Different development subject bears different responsibility.Object system includes farmers engaged in farming,farmer workers,rural unemployed people,rural students,rural left-behind people,and other people in rural areas.Different development object has different features.Development target system includes raising quality of rural human resource,keeping reasonable population size,optimizing structure of rural human resource,and improving vitality of rural human resource,etc.展开更多
Nanotechnology in cancer therapy has significantly advanced treatment precision,effectiveness,and safety,improving patient outcomes and personalized care.Engineered smart nanoparticles and cell-based therapies are des...Nanotechnology in cancer therapy has significantly advanced treatment precision,effectiveness,and safety,improving patient outcomes and personalized care.Engineered smart nanoparticles and cell-based therapies are designed to target tumor cells,precisely sensing the tumor microenvironment(TME)and sparing normal cells.These nanoparticles enhance drug accumulation in tumors by solubilizing insoluble compounds or preventing their degradation,and they can also overcome therapy resistance and deliver multiple drugs simultaneously.Despite these benefits,challenges remain in patient-specific responses and regulatory approvals for cell-based or nanoparticle therapies.Cell-based drug delivery systems(DDSs)that primarily utilize the immune-recognition principle between ligands and receptors have shown promise in selectively targeting and destroying cancer cells.This review aims to provide a comprehensive overview of various nanoparticle and cell-based drug delivery system types used in cancer research.It covers approved and experimental nanoparticle therapies,including liposomes,micelles,protein-based and polymeric nanoparticles,as well as cell-based DDSs like macrophages,T-lymphocytes,dendritic cells,viruses,bacterial ghosts,minicells,SimCells,and outer membrane vesicles(OMVs).The review also explains the role of TME and its impact on developing smart DDSs in combination therapies and integrating nanoparticles with cell-based systems for targeting cancer cells.By detailing DDSs at different stages of development,from laboratory research to clinical trials and approved treatments,this review provides the latest insights and a collection of valuable citations of the innovative strategies that can be improved for the precise treatment of cancer.展开更多
Gliomas are the most common intracranial tumors with poor survival and high mortality.Furthermore,the clinical efficacy of current drugs is still not ideal;despite the development of several therapeutic drugs over the...Gliomas are the most common intracranial tumors with poor survival and high mortality.Furthermore,the clinical efficacy of current drugs is still not ideal;despite the development of several therapeutic drugs over the past decades and tumor progression or recurrence is inevitable in many patients.RNAibased therapy presents a novel disease-related gene targeting therapy,including otherwise undruggable genes,and generates therapeutic options.However,the therapeutic effect of siRNA is hindered by multiple biological barriers,primarily the blood-brain barrier(BBB).A glycoprotein-derived peptide-mediated delivery system is the preferred option to resolve this phenomenon.RDP,a polypeptide composed of 15 amino acids derived from rabies virus glycoprotein(RVG),possesses an N-type acetylcholine receptor(nAChR)-binding efficiency similar to that of RVG29.Given its lower cost and small particle size when used as a ligand,RDP should be extensively evaluated.First,we verified the brain-targeting efficacyy of RDP at the cellular and animal levels and further explored the possibility of using the RDP-oligoarginine peptide(designated RDP-5R)as a bio-safe vehicle to deliver therapeutic siRNA into glioma cells in vitro and in vivo.The polypeptide carrier possesses a diblock design composed of oligoarginine for binding siRNA through electrostatic interactions and RDP for cascade BBB-and glioma cell-targeting.The results indicated that RDP-R5/siRNA nanoparticles exhibited stable and suitable physicochemical properties for in vivo application,desirable glioma-targeting effects,and therapeutic efficiency.As a novel and efficient polypeptide carrier,RDP-based polypeptides hold great promise as a noninvasive,safe,and efficient treatment for various brain diseases.展开更多
Objective This study aimed to compare the upgrade rate and cancer detection rate between the 18F-DCFPyL PET/MRI-guided ultrasound fusion targeted biopsy(TB)and systematic biopsy in selected patients with suspected pro...Objective This study aimed to compare the upgrade rate and cancer detection rate between the 18F-DCFPyL PET/MRI-guided ultrasound fusion targeted biopsy(TB)and systematic biopsy in selected patients with suspected prostate cancer(the molecular imaging prostate-specific membrane antigen score of≥2 and multiparametric MRI Prostate Imaging Reporting and Data System score of≥4).Methods Eighty-seven selected biopsy-naive patients were randomized into two groups:TB(n=41)and systematic biopsy(control;n=46).Patients diagnosed with clinically significant prostate cancer proceeded to radical prostatectomy.The primary outcome was the pathological upgrade rate.Secondary outcomes,including the cancer detection rate,incidence of repeat biopsy,positive surgical margin,complications,and prostate-specific antigen level at 6 weeks postoperatively,were compared between the groups using the Pearson or Fisher's exact test,as appropriate.Results In the study,prostate cancer was ultimately detected in all patients.The TB group successfully identified all tumors,whereas five patients in the control group initially missed diagnosis.The pathological upgrade rates for the TB and control groups were 31.7%and 56.5%,respectively.Overall,the detection rate for clinically significant prostate cancer(the International Society of Urological Pathology grade of≥2)was significantly higher in the TB group(92.7%)compared with the control group(76.1%,p=0.035).However,no significant difference was found in the detection rate of all prostate cancer.Complications(Clavien–Dindo grade of≤2)occurred in both the TB group(n=11)and control group(n=13).No statistically significant difference was observed between the groups in terms of the positive surgical margin,complications,or 6-week postoperative prostate-specific antigen level.Conclusion The 18F-DCFPyL PET/MRI-guided ultrasound fusion TB alone was an efficient modality in diagnosing selected patients with prostate cancer.展开更多
Background:Building upon our previous work that developed a folate receptor-mediated,euphaorbia factor L1-loaded PLGA microsphere system integrating active and magnetic targeting for theranostics,further investigation...Background:Building upon our previous work that developed a folate receptor-mediated,euphaorbia factor L1-loaded PLGA microsphere system integrating active and magnetic targeting for theranostics,further investigation into its in vivo pharmacokinetics and tissue distribution is warranted despite its demonstrated biocompatibility and safety.Methods:A UPLC-MS/MS method was established to determine the concentration of euphorbia sterol in rat plasma and mouse tissue homogenates,healthy male SD rats and KM mice were administered in groups,drug concentrations at different time points were determined,pharmacokinetic parameters were analyzed by DAS software,and data were processed by SAS software.Results:The proposed method met the requirements of biological sample detection.The plasma pharmacokinetics of rats showed that the drug concentration in the microsphere group was lower than that in the injection group,and the parameters such as mean residence time(MRT(0–t)),half-life(T1/2z)and apparent volume of distribution(Vz)were significantly different from those in the solution group.The distribution of mouse tissues showed that the drug concentrations in the liver and lung tissues of the microsphere preparation group were higher than those in the injection group,and the drug concentrations in the lung and liver tissues were more distributed.Conclusion:The targeted drug delivery system changed the pharmacokinetic behavior and tissue distribution of euphorbia sterol,slowed down plasma elimination,prolonged the half-life,and improved the targeting of drugs in lung and liver tissues and the magnetic targeting effect of lungs.展开更多
The acquisition,tracking,and pointing(ATP)system is widely used in target tracking,counter-UAV operations,and other related fields.As UAV technology develops,there is a growing demand to enhance the tracking capabilit...The acquisition,tracking,and pointing(ATP)system is widely used in target tracking,counter-UAV operations,and other related fields.As UAV technology develops,there is a growing demand to enhance the tracking capabilities of ATP systems.However,in practical applications,ATP systems face various design constraints and functional limitations,making it infeasible to indefinitely improve hardware performance to meet tracking requirements.As a result,tracking algorithms are required to execute increasingly complex tasks.This study introduces a multi-rate feedforward predictive controller to address issues such as low image feedback frequency and significant delays in ATP systems,which lead to tracking jitter,poor tracking performance,low precision,and target loss.At the same time,the pro-posed approach aims to improve the tracking capabilities of ATP systems for high-speed and highly maneuverable targets under conditions of low sampling feedback rates and high feedback delays.The method suggested is also characterized by its low order,fast response,and robustness to model parameter variations.In this study,an actual ATP system is built for target tracking test,and the proposed algorithm is fully validated in terms of simulation and actual system application verification.Results from both simulations and experiments demonstrate that the method effectively compensates for delays and low sampling rates.For targets with relative angular velocities ranging from 0 to 90°/s and angular accelerations between 0 and 470°/s^(2),the system improved tracking accuracy by 70.0%-89.9%at a sampling frequency of 50 Hz and a delay of 30 m s.Moreover,the compensation algorithm demonstrated consistent performance across actuators with varying characteristics,further confirming its robustness to model insensitivity.In summary,the proposed algorithm considerably enhances the tracking accuracy and capability of ATP systems for high-speed and highly maneuverable targets,reducing the probability of target loss from high speed.This approach offers a practical solution for future multi-target tracking across diverse operational scenarios.展开更多
As one of the most common gynecological malignancies,peritoneal metastasis is a common feature and cause of high mortality in ovarian cancer(OC).Currently,the standard treatment for OC and its peritoneal metastasis is...As one of the most common gynecological malignancies,peritoneal metastasis is a common feature and cause of high mortality in ovarian cancer(OC).Currently,the standard treatment for OC and its peritoneal metastasis is maximal cytoreductive surgery(CRS)combined with platinum-based chemotherapy.Compared with intravenous chemotherapy,traditional intraperitoneal(IP)chemotherapy exhibits obvious pharmacokinetic(PK)advantages and systemic safety and has shown significant survival benefits in several clinical studies of OC patients.However,there remain several challenges in traditional IP chemotherapy,such as insufficient drug retention,a lack of tumor targeting,inadequate drug penetration,gastrointestinal toxicity,and limited inhibition of tumor metastasis and chemoresistance.Nanomedicine-based IP targeting delivery systems,through specific drug carrier design with tumor cells and tumor environment(TME)targeting,make it possible to overcome these challenges and maximize local therapy efficacy while reducing side effects.In this review article,the rationale and challenges of nanomedicine-based IP chemotherapies,as well as their in vivo fate after IP administration,which are crucial for their rational design and clinical translation,are firstly discussed.Then,current strategies for nanomedicine-based targeting delivery systems and the relevant clinical trials in IP chemotherapy are summarized.Finally,the future directions of the nanomedicine-based IP targeting delivery system for OC and its peritoneal metastasis are proposed,expecting to improve the clinical development of IP chemotherapy.展开更多
Space target imaging simulation technology is an important tool for space target detection and identification,with advantages that include high flexibility and low cost.However,existing space target imaging simulation...Space target imaging simulation technology is an important tool for space target detection and identification,with advantages that include high flexibility and low cost.However,existing space target imaging simulation technologies are mostly based on target magnitudes for simulations,making it difficult to meet image simulation requirements for different signal-to-noise ratio(SNR)needs.Therefore,design of a simulation method that generates target image sequences with various SNRs based on the optical detection system parameters will be important for faint space target detection research.Addressing the SNR calculation issue in optical observation systems,this paper proposes a ground-based detection image SNR calculation method using the optical system parameters.This method calculates the SNR of an observed image precisely using radiative transfer theory,the optical system parameters,and the observation environment parameters.An SNR-based target sequence image simulation method for ground-based detection scenarios is proposed.This method calculates the imaging SNR using the optical system parameters and establishes a model for conversion between the target’s apparent magnitude and image grayscale values,thereby enabling generation of target sequence simulation images with corresponding SNRs for different system parameters.Experiments show that the SNR obtained using this calculation method has an average calculation error of<1 dB when compared with the theoretical SNR of the actual optical system.Additionally,the simulation images generated by the imaging simulation method show high consistency with real images,which meets the requirements of faint space target detection algorithm research and provides reliable data support for development of related technologies.展开更多
This paper develops an economic growth model incorporating China’s Environmental Target Responsibility System(ETRS)to analyze its impact on both economic growth and social welfare.We find that the ETRS’s effect on e...This paper develops an economic growth model incorporating China’s Environmental Target Responsibility System(ETRS)to analyze its impact on both economic growth and social welfare.We find that the ETRS’s effect on economic growth is complex,resulting from the interplay of three key factors:its potential to improve environmental quality,its potential dampening effect on total factor productivity(TFP),and its influence on local government spending on environmental governance.A balanced ETRS can improve environmental quality,promote technological innovation,and enhance social welfare.However,excessively stringent targets and overly emphasized responsibility may lead to declines in both economic growth and social welfare.From the perspective of balancing economic growth and social welfare,we find that the ETRS that maximizes economic growth is less stringent than the ETRS that maximizes social welfare.Crucially,the economic growth cost of shifting from a growth-maximizing to a welfare-maximizing ETRS is minimal.In other words,significant improvements in environmental quality and public well-being can be achieved without substantially sacrificing economic dynamism.This paper attempts to model China’s unique environmental target assessment system within the framework of endogenous growth theory,offering a new perspective for understanding the dynamic relationship between economic growth and environmental quality in China.展开更多
Amyloid-beta clearance plays a key role in the pathogenesis of Alzheimer's disease.H oweve r,the variation in functional proteins involved in amyloid-beta clearance and their correlation with amyloid-beta levels r...Amyloid-beta clearance plays a key role in the pathogenesis of Alzheimer's disease.H oweve r,the variation in functional proteins involved in amyloid-beta clearance and their correlation with amyloid-beta levels remain unclea r.In this study,we conducted meta-analyses and a systematic review using studies from the PubMed,Embase,Web of Science,and Cochrane Library databases,including journal articles published from inception to J une 30,2023.The inclusion criteria included studies comparing the levels of functional proteins associated with amyloid-beta clearance in the blood,cere b rospinal fluid,and brain of healthy controls,patients with mild cognitive impairment,and patients with Alzheimer's disease.Additionally,we analyzed the correlation between these functional proteins and amyloid-beta levels in patients with Alzheimer's disease.The methodological quality of the studies was assessed via the Newcastle-Ottawa Scale.Owing to heterogeneity,we utilized either a fixed-effect or random-effect model to assess the 95%confidence interval(CI)of the standard mean difference(SMD)among healthy controls,patients with mild cognitive impairment,and patients with Alzheimer's disease.The findings revealed significant alterations in the levels of insulin-degrading enzymes,neprilysin,matrix metalloproteinase-9,cathepsin D,receptor for advanced glycation end products,and P-glycoprotein in the brains of patients with Alzheimer's disease,patients with mild cognitive impairment,and healthy controls.In cerebrospinal fluid,the levels of triggering receptor expressed on myeloid cells 2 and ubiquitin C-terminal hydrolase L1 are altered,whereas the levels of TREM2,CD40,CD40L,CD14,CD22,cathepsin D,cystatin C,andα2 M in peripheral blood differ.Notably,TREM2 and cathepsin D showed changes in both brain(SMD=0.31,95%CI:0.16-0.47,P<0.001,I^(2)=78.4%;SMD=1.24,95%CI:0.01-2.48,P=0.048,I^(2)=90.1%)and peripheral blood(SMD=1.01,95%CI:0.35-1.66,P=0.003,I^(2)=96.5%;SMD=7.55,95%CI:3.92-11.18,P<0.001,I^(2)=98.2%)samples.Furthermore,correlations were observed between amyloid-beta levels and the levels of TREM2(r=0.16,95%CI:0.04-0.28,P=0.009,I^(2)=74.7%),neprilysin(r=-0.47,95%CI:-0.80-0.14,P=0.005,I^(2)=76.1%),and P-glycoprotein(r=-0.31,95%CI:-0.51-0.11,P=0.002,I^(2)=0.0%)in patients with Alzheimer's disease.These findings suggest that triggering receptor expressed on myeloid cells 2 and cathepsin D could serve as potential diagnostic biomarkers for Alzheimer's disease,whereas triggering receptor expressed on myeloid cells 2,neprilysin,and P-glycoprotein may represent potential therapeutic targets.展开更多
Ulcerative colitis(UC)is a common progressive inflammatory disease whose incidence has increased rapidly in recent years,and can develop into colorectal cancer in severe cases.There are currently no adequate or effect...Ulcerative colitis(UC)is a common progressive inflammatory disease whose incidence has increased rapidly in recent years,and can develop into colorectal cancer in severe cases.There are currently no adequate or effective treatments for UC due to the fact that some patients have found suboptimal results after repeated administration,while others have experienced adverse effects.With the rapid development of nanotechnology,developing innovative colon-targeting platforms is essential to improving efficacy,reducing side effects,and improving patient compliance.In this review,we summarize the pathophysiological characteristics of UC and the most recent status of numerous nanodrug delivery systems based on different targeting mechanisms in treating UC.Oral,intravenous,and rectal drug delivery nanoparticles targeting the colon are discussed,which can provide ideas for the design of colon-targeting nanoparticles for the treatment of colon diseases,especially for the treatment of UC.Last but not least,we provide a glimpse into the future of colon-targeted delivery systems,as well as future advancements in the field.展开更多
Cellular senescence is the results of aging and age-related diseases,and the development of anti-aging methods may improve health and extend longevity.The natural flavonol fisetin has been shown to antagonize senescen...Cellular senescence is the results of aging and age-related diseases,and the development of anti-aging methods may improve health and extend longevity.The natural flavonol fisetin has been shown to antagonize senescence in vitro and increases longevity in vivo,but has poor water solubility and limited bioavailability.In this study,a food-grade and senescent cell-targeted delivery system for fisetin was developed based on whey protein isolate-galactooligosaccharides(WPI-GOS)Maillard conjugate,which could recognize senescence associatedβ-galactosidase in senescent cells.The fisetin nanoparticles possessed a high encapsulation efficiency,excellent dispersibility in water,good storage stability and well biocompatibility.Moreover,they could effectively accumulate and retain in senescent cells with excellent senescent cell-targeting efficacy,and inhibit the oxidative stress-induced cellular senescence in vitro.Thus,this novel nanoparticle system based on WPI-GOS Maillard conjugate showed promise to deliver hydrophobic bioactive ingredients like fisetin to senescent cells to improve their bioavailability and anti-senescence effect.展开更多
BACKGROUND Gliomas pose a significant challenge to effective treatment despite advancements in chemotherapy and radiotherapy.Glioma stem cells(GSCs),a subset within tumors,contribute to resistance,tumor heterogeneity,...BACKGROUND Gliomas pose a significant challenge to effective treatment despite advancements in chemotherapy and radiotherapy.Glioma stem cells(GSCs),a subset within tumors,contribute to resistance,tumor heterogeneity,and plasticity.Recent studies reveal GSCs’role in therapeutic resistance,driven by DNA repair mechanisms and dynamic transitions between cellular states.Resistance mechanisms can involve different cellular pathways,most of which have been recently reported in the literature.Despite progress,targeted therapeutic approaches lack consensus due to GSCs’high plasticity.AIM To analyze targeted therapies against GSC-mediated resistance to radio-and chemotherapy in gliomas,focusing on underlying mechanisms.METHODS A systematic search was conducted across major medical databases(PubMed,Embase,and Cochrane Library)up to September 30,2023.The search strategy utilized relevant Medical Subject Heading terms and keywords related to including“glioma stem cells”,“radiotherapy”,“chemotherapy”,“resistance”,and“targeted therapies”.Studies included in this review were publications focusing on targeted therapies against the molecular mechanism of GSC-mediated re-sistance to radiotherapy resistance(RTR).RESULTS In a comprehensive review of 66 studies on stem cell therapies for SCI,452 papers were initially identified,with 203 chosen for full-text analysis.Among them,201 were deemed eligible after excluding 168 for various reasons.The temporal breakdown of studies illustrates this trend:2005-2010(33.3%),2011-2015(36.4%),and 2016-2022(30.3%).Key GSC models,particularly U87(33.3%),U251(15.2%),and T98G(15.2%),emerge as significant in research,reflecting their representativeness of glioma characteristics.Pathway analysis indicates a focus on phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(mTOR)(27.3%)and Notch(12.1%)pathways,suggesting their crucial roles in resistance development.Targeted molecules with mTOR(18.2%),CHK1/2(15.2%),and ATP binding cassette G2(12.1%)as frequent targets underscore their importance in overcoming GSC-mediated resistance.Various therapeutic agents,notably RNA inhibitor/short hairpin RNA(27.3%),inhibitors(e.g.,LY294002,NVP-BEZ235)(24.2%),and monoclonal antibodies(e.g.,cetuximab)(9.1%),demonstrate versatility in targeted therapies.among 20 studies(60.6%),the most common effect on the chemotherapy resistance response is a reduction in temozolomide resistance(51.5%),followed by reductions in carmustine resistance(9.1%)and doxorubicin resistance(3.0%),while resistance to RTR is reduced in 42.4%of studies.CONCLUSION GSCs play a complex role in mediating radioresistance and chemoresistance,emphasizing the necessity for precision therapies that consider the heterogeneity within the GSC population and the dynamic tumor microenvironment to enhance outcomes for glioblastoma patients.展开更多
Regulated cell death is a form of cell death that is actively controlled by biomolecules.Several studies have shown that regulated cell death plays a key role after spinal cord injury.Pyroptosis and ferroptosis are ne...Regulated cell death is a form of cell death that is actively controlled by biomolecules.Several studies have shown that regulated cell death plays a key role after spinal cord injury.Pyroptosis and ferroptosis are newly discovered types of regulated cell deaths that have been shown to exacerbate inflammation and lead to cell death in damaged spinal cords.Autophagy,a complex form of cell death that is interconnected with various regulated cell death mechanisms,has garnered significant attention in the study of spinal cord injury.This injury triggers not only cell death but also cellular survival responses.Multiple signaling pathways play pivotal roles in influencing the processes of both deterioration and repair in spinal cord injury by regulating pyroptosis,ferroptosis,and autophagy.Therefore,this review aims to comprehensively examine the mechanisms underlying regulated cell deaths,the signaling pathways that modulate these mechanisms,and the potential therapeutic targets for spinal cord injury.Our analysis suggests that targeting the common regulatory signaling pathways of different regulated cell deaths could be a promising strategy to promote cell survival and enhance the repair of spinal cord injury.Moreover,a holistic approach that incorporates multiple regulated cell deaths and their regulatory pathways presents a promising multi-target therapeutic strategy for the management of spinal cord injury.展开更多
Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities.Research on the pathogenesis of peripheral nerve injury has focused on pathological changes...Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities.Research on the pathogenesis of peripheral nerve injury has focused on pathological changes at individual injury sites,neglecting multilevel pathological analysis of the overall nervous system and target organs.This has led to restrictions on current therapeutic approaches.In this paper,we first summarize the potential mechanisms of peripheral nerve injury from a holistic perspective,covering the central nervous system,peripheral nervous system,and target organs.After peripheral nerve injury,the cortical plasticity of the brain is altered due to damage to and regeneration of peripheral nerves;changes such as neuronal apoptosis and axonal demyelination occur in the spinal cord.The nerve will undergo axonal regeneration,activation of Schwann cells,inflammatory response,and vascular system regeneration at the injury site.Corresponding damage to target organs can occur,including skeletal muscle atrophy and sensory receptor disruption.We then provide a brief review of the research advances in therapeutic approaches to peripheral nerve injury.The main current treatments are conducted passively and include physical factor rehabilitation,pharmacological treatments,cell-based therapies,and physical exercise.However,most treatments only partially address the problem and cannot complete the systematic recovery of the entire central nervous system-peripheral nervous system-target organ pathway.Therefore,we should further explore multilevel treatment options that produce effective,long-lasting results,perhaps requiring a combination of passive(traditional)and active(novel)treatment methods to stimulate rehabilitation at the central-peripheral-target organ levels to achieve better functional recovery.展开更多
The aim of this study was to compare the accuracies of cognitive fusion-guided targeted biopsy(TB),systematic biopsy(SB),and combined TB+SB for the detection of prostate cancer(PCa)and clinically significant PCa(csPCa...The aim of this study was to compare the accuracies of cognitive fusion-guided targeted biopsy(TB),systematic biopsy(SB),and combined TB+SB for the detection of prostate cancer(PCa)and clinically significant PCa(csPCa)in males with lesions detected by magnetic resonance imaging(MRI).We conducted a retrospective analysis of individuals who underwent prostate biopsy at Peking University People's Hospital(Beijing,China),with an emphasis on patients with both transrectal TB and SB.The main objective was to determine the precisions of SB,TB,and TB+SB for diagnosing PCa and csPCa.We also evaluated the detection rates of TB,SB,TB+ipsilateral-SB(ipsi-SB),TB+contralateral-SB(contra-SB),and TB+SB for PCa and csPCa in patients with unilateral MRI lesions.We compared the diagnostic yields of the various biopsy schemes using the McNemar’s test.A total of 180 patients were enrolled.The rates of PCa detection using TB,SB,and TB+SB were 52.8%,62.2%,and 66.7%,respectively,and the corresponding rates for csPCa were 46.1%,56.7%,and 58.3%,respectively.Among patients with unilateral MRI lesions,the PCa detection rates for TB,SB,TB+ipsi-SB,TB+contra-SB,and TB+SB were 53.3%,64.8%,65.6%,61.5%,and 68.0%,respectively.TB+ipsi-SB detected 96.4%of PCa and 95.9%of csPCa cases.These findings suggest that the combination of TB+SB has better diagnostic accuracy compared with SB or TB alone.For patients with unilateral MRI lesions,the combination of TB+ipsi-SB may be suitable in clinical settings.展开更多
Glutamine is one of the most abundant non-essential amino acids in human plasma and plays a crucial role in many biological processes of the human body.Tumor cells take up a large amount of glutamine to meet their rap...Glutamine is one of the most abundant non-essential amino acids in human plasma and plays a crucial role in many biological processes of the human body.Tumor cells take up a large amount of glutamine to meet their rapid proliferation requirements,which is supported by the upregulation of glutamine transporters.Targeted inhibition of glutamine transporters effectively inhibits cell growth and proliferation in tumors.Among all cancers,digestive system malignant tumors(DSMTs)have the highest incidence and mortality rates,and the current therapeutic strategies for DSMTs are mainly surgical resection and chemotherapy.Due to the relatively low survival rate and severe side effects associated with DSMTs treatment,new treatment strategies are urgently required.This article summarizes the glutamine transporters involved in DSMTs and describes their role in DSMTs.Additionally,glutamine transportertarget drugs are discussed,providing theoretical guidance for the further development of drugs DSMTs treatment.展开更多
To address the current problems of poor generality,low real-time,and imperfect information transmission of the battlefield target intelligence system,this paper studies the battlefield target intelligence system from ...To address the current problems of poor generality,low real-time,and imperfect information transmission of the battlefield target intelligence system,this paper studies the battlefield target intelligence system from the top-level perspective of multi-service joint warfare.First,an overall planning and analysis method of architecture modeling is proposed with the idea of a bionic analogy for battlefield target intelligence system architecture modeling,which reduces the difficulty of the planning and design process.The method introduces the Department of Defense architecture framework(DoDAF)modeling method,the multi-living agent(MLA)theory modeling method,and other combinations for planning and modeling.A set of rapid planning methods that can be applied to model the architecture of various types of complex systems is formed.Further,the liveness analysis of the battlefield target intelligence system is carried out,and the problems of the existing system are presented from several aspects.And the technical prediction of the development and construction is given,which provides directional ideas for the subsequent research and development of the battlefield target intelligence system.In the end,the proposed architecture model of the battlefield target intelligence system is simulated and verified by applying the colored Petri nets(CPN)simulation software.The analysis demonstrates the reasonable integrity of its logic.展开更多
This paper investigates the problem of Joint Radar Node Selection and Power Allocation(JRNSPA)in the Multiple Radar System(MRS)in the blanket jamming environment.Each radar node independently tracks moving target and ...This paper investigates the problem of Joint Radar Node Selection and Power Allocation(JRNSPA)in the Multiple Radar System(MRS)in the blanket jamming environment.Each radar node independently tracks moving target and subsequently transmits the raw observation data to the fusion center,which formulates a centralized tracking network structure.In order to establish a practical blanket jamming environment,we suppose that each target carries the self-defense jammer which automatically implements blanket jamming to the radar nodes that exceed the preset interception probability.Subsequently,the Predicted Conditional Cramer-Rao Lower Bound(PC-CRLB)is derived and utilized as the tracking accuracy criterion.Aimed at ensuring both the tracking performance and the Low Probability of Intercept(LPI)performance,the resource-saving scheduling model is formulated to minimize the transmit power consumption while meeting the requirements of tracking accuracy.Finally,the Modified Zoutendijk Method Of Feasible Directions(MZMFD)-based two-stage solution technique is adopted to solve the formulated non-convex optimization model.Simulation results show the effectiveness of the proposed JRNSPA scheme.展开更多
By critically examining the work,we conducted a comprehensive bibliometric analysis on the role of nuclear factor erythroid 2-related factor 2(NRF2)in nervous system diseases.We also proposed suggestions for future bi...By critically examining the work,we conducted a comprehensive bibliometric analysis on the role of nuclear factor erythroid 2-related factor 2(NRF2)in nervous system diseases.We also proposed suggestions for future bibliometric studies,including the integration of multiple websites,analytical tools,and analytical approaches,The findings presented provide compelling evidence that ferroptosis is closely associated with the therapeutic challenges of nervous system diseases.Targeted modulation of NRF2 to regulate ferroptosis holds substantial potential for effectively treating these diseases.Future NRF2-related research should not only focus on discovering new drugs but also on designing rational drug delivery systems.In particular,nanocarriers offer substantial potential for facilitating the clinical translation of NRF2 research and addressing existing issues related to NRF2-related drugs.展开更多
基金Supported by Project of National Social Science Foundation(09XMZ055)General Program of Scientific Research Project of Guangxi Provincial Department of Education (200911MS104)
文摘From subject,object and target subsystems,we analyze the rural human resource development system.The subject system includes government,education and training organizations,society,and rural human resource itself.Different development subject bears different responsibility.Object system includes farmers engaged in farming,farmer workers,rural unemployed people,rural students,rural left-behind people,and other people in rural areas.Different development object has different features.Development target system includes raising quality of rural human resource,keeping reasonable population size,optimizing structure of rural human resource,and improving vitality of rural human resource,etc.
文摘Nanotechnology in cancer therapy has significantly advanced treatment precision,effectiveness,and safety,improving patient outcomes and personalized care.Engineered smart nanoparticles and cell-based therapies are designed to target tumor cells,precisely sensing the tumor microenvironment(TME)and sparing normal cells.These nanoparticles enhance drug accumulation in tumors by solubilizing insoluble compounds or preventing their degradation,and they can also overcome therapy resistance and deliver multiple drugs simultaneously.Despite these benefits,challenges remain in patient-specific responses and regulatory approvals for cell-based or nanoparticle therapies.Cell-based drug delivery systems(DDSs)that primarily utilize the immune-recognition principle between ligands and receptors have shown promise in selectively targeting and destroying cancer cells.This review aims to provide a comprehensive overview of various nanoparticle and cell-based drug delivery system types used in cancer research.It covers approved and experimental nanoparticle therapies,including liposomes,micelles,protein-based and polymeric nanoparticles,as well as cell-based DDSs like macrophages,T-lymphocytes,dendritic cells,viruses,bacterial ghosts,minicells,SimCells,and outer membrane vesicles(OMVs).The review also explains the role of TME and its impact on developing smart DDSs in combination therapies and integrating nanoparticles with cell-based systems for targeting cancer cells.By detailing DDSs at different stages of development,from laboratory research to clinical trials and approved treatments,this review provides the latest insights and a collection of valuable citations of the innovative strategies that can be improved for the precise treatment of cancer.
基金supported by CAMS Innovation Fund for Medical Sciences(No.2021-I2M-1-026,China).
文摘Gliomas are the most common intracranial tumors with poor survival and high mortality.Furthermore,the clinical efficacy of current drugs is still not ideal;despite the development of several therapeutic drugs over the past decades and tumor progression or recurrence is inevitable in many patients.RNAibased therapy presents a novel disease-related gene targeting therapy,including otherwise undruggable genes,and generates therapeutic options.However,the therapeutic effect of siRNA is hindered by multiple biological barriers,primarily the blood-brain barrier(BBB).A glycoprotein-derived peptide-mediated delivery system is the preferred option to resolve this phenomenon.RDP,a polypeptide composed of 15 amino acids derived from rabies virus glycoprotein(RVG),possesses an N-type acetylcholine receptor(nAChR)-binding efficiency similar to that of RVG29.Given its lower cost and small particle size when used as a ligand,RDP should be extensively evaluated.First,we verified the brain-targeting efficacyy of RDP at the cellular and animal levels and further explored the possibility of using the RDP-oligoarginine peptide(designated RDP-5R)as a bio-safe vehicle to deliver therapeutic siRNA into glioma cells in vitro and in vivo.The polypeptide carrier possesses a diblock design composed of oligoarginine for binding siRNA through electrostatic interactions and RDP for cascade BBB-and glioma cell-targeting.The results indicated that RDP-R5/siRNA nanoparticles exhibited stable and suitable physicochemical properties for in vivo application,desirable glioma-targeting effects,and therapeutic efficiency.As a novel and efficient polypeptide carrier,RDP-based polypeptides hold great promise as a noninvasive,safe,and efficient treatment for various brain diseases.
基金supported by the Youth support Program of Chinese General Hospital (Grand Number: 22QNFC044 to Niu S).
文摘Objective This study aimed to compare the upgrade rate and cancer detection rate between the 18F-DCFPyL PET/MRI-guided ultrasound fusion targeted biopsy(TB)and systematic biopsy in selected patients with suspected prostate cancer(the molecular imaging prostate-specific membrane antigen score of≥2 and multiparametric MRI Prostate Imaging Reporting and Data System score of≥4).Methods Eighty-seven selected biopsy-naive patients were randomized into two groups:TB(n=41)and systematic biopsy(control;n=46).Patients diagnosed with clinically significant prostate cancer proceeded to radical prostatectomy.The primary outcome was the pathological upgrade rate.Secondary outcomes,including the cancer detection rate,incidence of repeat biopsy,positive surgical margin,complications,and prostate-specific antigen level at 6 weeks postoperatively,were compared between the groups using the Pearson or Fisher's exact test,as appropriate.Results In the study,prostate cancer was ultimately detected in all patients.The TB group successfully identified all tumors,whereas five patients in the control group initially missed diagnosis.The pathological upgrade rates for the TB and control groups were 31.7%and 56.5%,respectively.Overall,the detection rate for clinically significant prostate cancer(the International Society of Urological Pathology grade of≥2)was significantly higher in the TB group(92.7%)compared with the control group(76.1%,p=0.035).However,no significant difference was found in the detection rate of all prostate cancer.Complications(Clavien–Dindo grade of≤2)occurred in both the TB group(n=11)and control group(n=13).No statistically significant difference was observed between the groups in terms of the positive surgical margin,complications,or 6-week postoperative prostate-specific antigen level.Conclusion The 18F-DCFPyL PET/MRI-guided ultrasound fusion TB alone was an efficient modality in diagnosing selected patients with prostate cancer.
基金sponsored by the Fundamental Research Funds forthe Central Universities(No.2024-JYB-JBZD-047)High Level Key Discipline Construction of Traditional Chinese Medicine(zyyzdxk-2023272).
文摘Background:Building upon our previous work that developed a folate receptor-mediated,euphaorbia factor L1-loaded PLGA microsphere system integrating active and magnetic targeting for theranostics,further investigation into its in vivo pharmacokinetics and tissue distribution is warranted despite its demonstrated biocompatibility and safety.Methods:A UPLC-MS/MS method was established to determine the concentration of euphorbia sterol in rat plasma and mouse tissue homogenates,healthy male SD rats and KM mice were administered in groups,drug concentrations at different time points were determined,pharmacokinetic parameters were analyzed by DAS software,and data were processed by SAS software.Results:The proposed method met the requirements of biological sample detection.The plasma pharmacokinetics of rats showed that the drug concentration in the microsphere group was lower than that in the injection group,and the parameters such as mean residence time(MRT(0–t)),half-life(T1/2z)and apparent volume of distribution(Vz)were significantly different from those in the solution group.The distribution of mouse tissues showed that the drug concentrations in the liver and lung tissues of the microsphere preparation group were higher than those in the injection group,and the drug concentrations in the lung and liver tissues were more distributed.Conclusion:The targeted drug delivery system changed the pharmacokinetic behavior and tissue distribution of euphorbia sterol,slowed down plasma elimination,prolonged the half-life,and improved the targeting of drugs in lung and liver tissues and the magnetic targeting effect of lungs.
基金supported by the National Natural Science Foun-dation of China(Grant No.52275099).
文摘The acquisition,tracking,and pointing(ATP)system is widely used in target tracking,counter-UAV operations,and other related fields.As UAV technology develops,there is a growing demand to enhance the tracking capabilities of ATP systems.However,in practical applications,ATP systems face various design constraints and functional limitations,making it infeasible to indefinitely improve hardware performance to meet tracking requirements.As a result,tracking algorithms are required to execute increasingly complex tasks.This study introduces a multi-rate feedforward predictive controller to address issues such as low image feedback frequency and significant delays in ATP systems,which lead to tracking jitter,poor tracking performance,low precision,and target loss.At the same time,the pro-posed approach aims to improve the tracking capabilities of ATP systems for high-speed and highly maneuverable targets under conditions of low sampling feedback rates and high feedback delays.The method suggested is also characterized by its low order,fast response,and robustness to model parameter variations.In this study,an actual ATP system is built for target tracking test,and the proposed algorithm is fully validated in terms of simulation and actual system application verification.Results from both simulations and experiments demonstrate that the method effectively compensates for delays and low sampling rates.For targets with relative angular velocities ranging from 0 to 90°/s and angular accelerations between 0 and 470°/s^(2),the system improved tracking accuracy by 70.0%-89.9%at a sampling frequency of 50 Hz and a delay of 30 m s.Moreover,the compensation algorithm demonstrated consistent performance across actuators with varying characteristics,further confirming its robustness to model insensitivity.In summary,the proposed algorithm considerably enhances the tracking accuracy and capability of ATP systems for high-speed and highly maneuverable targets,reducing the probability of target loss from high speed.This approach offers a practical solution for future multi-target tracking across diverse operational scenarios.
基金supported by the National Key R&D Program of China(No.2020YFE0201700)the Liaoning Revitalization Talents Program(No.XLYC1908031)。
文摘As one of the most common gynecological malignancies,peritoneal metastasis is a common feature and cause of high mortality in ovarian cancer(OC).Currently,the standard treatment for OC and its peritoneal metastasis is maximal cytoreductive surgery(CRS)combined with platinum-based chemotherapy.Compared with intravenous chemotherapy,traditional intraperitoneal(IP)chemotherapy exhibits obvious pharmacokinetic(PK)advantages and systemic safety and has shown significant survival benefits in several clinical studies of OC patients.However,there remain several challenges in traditional IP chemotherapy,such as insufficient drug retention,a lack of tumor targeting,inadequate drug penetration,gastrointestinal toxicity,and limited inhibition of tumor metastasis and chemoresistance.Nanomedicine-based IP targeting delivery systems,through specific drug carrier design with tumor cells and tumor environment(TME)targeting,make it possible to overcome these challenges and maximize local therapy efficacy while reducing side effects.In this review article,the rationale and challenges of nanomedicine-based IP chemotherapies,as well as their in vivo fate after IP administration,which are crucial for their rational design and clinical translation,are firstly discussed.Then,current strategies for nanomedicine-based targeting delivery systems and the relevant clinical trials in IP chemotherapy are summarized.Finally,the future directions of the nanomedicine-based IP targeting delivery system for OC and its peritoneal metastasis are proposed,expecting to improve the clinical development of IP chemotherapy.
基金supported by Open Fund of National Key Laboratory of Deep Space Exploration(NKDSEL2024014)by Civil Aerospace Pre-research Project of State Administration of Science,Technology and Industry for National Defence,PRC(D040103).
文摘Space target imaging simulation technology is an important tool for space target detection and identification,with advantages that include high flexibility and low cost.However,existing space target imaging simulation technologies are mostly based on target magnitudes for simulations,making it difficult to meet image simulation requirements for different signal-to-noise ratio(SNR)needs.Therefore,design of a simulation method that generates target image sequences with various SNRs based on the optical detection system parameters will be important for faint space target detection research.Addressing the SNR calculation issue in optical observation systems,this paper proposes a ground-based detection image SNR calculation method using the optical system parameters.This method calculates the SNR of an observed image precisely using radiative transfer theory,the optical system parameters,and the observation environment parameters.An SNR-based target sequence image simulation method for ground-based detection scenarios is proposed.This method calculates the imaging SNR using the optical system parameters and establishes a model for conversion between the target’s apparent magnitude and image grayscale values,thereby enabling generation of target sequence simulation images with corresponding SNRs for different system parameters.Experiments show that the SNR obtained using this calculation method has an average calculation error of<1 dB when compared with the theoretical SNR of the actual optical system.Additionally,the simulation images generated by the imaging simulation method show high consistency with real images,which meets the requirements of faint space target detection algorithm research and provides reliable data support for development of related technologies.
基金supported by the National Social Science Fund of China(NSSFC)Project“Research on Economic Growth Theory”(Grant No.22VRC176)the National Natural Science Foundation of China(NSFC)Project“Economic Dynamic Equilibrium and Optimal Regulation Policy Framework Design in the Process of Population Aging”(Grant No.72342033)+1 种基金NSFC Project“Research on the Macroeconomic Impact Mechanism of Local Government Land Allocation Behavior”(Grant No.72003211)the Central University of Finance and Economics Youth Research Innovation Team Support Program Project“Research on Data-Based Platform Anti-Monopoly Regulation”(Grant No.20230047).
文摘This paper develops an economic growth model incorporating China’s Environmental Target Responsibility System(ETRS)to analyze its impact on both economic growth and social welfare.We find that the ETRS’s effect on economic growth is complex,resulting from the interplay of three key factors:its potential to improve environmental quality,its potential dampening effect on total factor productivity(TFP),and its influence on local government spending on environmental governance.A balanced ETRS can improve environmental quality,promote technological innovation,and enhance social welfare.However,excessively stringent targets and overly emphasized responsibility may lead to declines in both economic growth and social welfare.From the perspective of balancing economic growth and social welfare,we find that the ETRS that maximizes economic growth is less stringent than the ETRS that maximizes social welfare.Crucially,the economic growth cost of shifting from a growth-maximizing to a welfare-maximizing ETRS is minimal.In other words,significant improvements in environmental quality and public well-being can be achieved without substantially sacrificing economic dynamism.This paper attempts to model China’s unique environmental target assessment system within the framework of endogenous growth theory,offering a new perspective for understanding the dynamic relationship between economic growth and environmental quality in China.
基金supported by the National Natural Science Foundation of China,No.81571046(to KZ)Key Project of Educational Department of Liaoning Province,No.LJKZ0755(to KZ)+2 种基金Project of Department of Science&Technology of Liaoning Province,No.2023JH2/20200116(to KZ)Shenyang Young and Middleaged Innovative Talents Support Program,No.RC210240(to KZ)the 345 Talent Project of Shengjing Hospital of China Medical University(to LH)。
文摘Amyloid-beta clearance plays a key role in the pathogenesis of Alzheimer's disease.H oweve r,the variation in functional proteins involved in amyloid-beta clearance and their correlation with amyloid-beta levels remain unclea r.In this study,we conducted meta-analyses and a systematic review using studies from the PubMed,Embase,Web of Science,and Cochrane Library databases,including journal articles published from inception to J une 30,2023.The inclusion criteria included studies comparing the levels of functional proteins associated with amyloid-beta clearance in the blood,cere b rospinal fluid,and brain of healthy controls,patients with mild cognitive impairment,and patients with Alzheimer's disease.Additionally,we analyzed the correlation between these functional proteins and amyloid-beta levels in patients with Alzheimer's disease.The methodological quality of the studies was assessed via the Newcastle-Ottawa Scale.Owing to heterogeneity,we utilized either a fixed-effect or random-effect model to assess the 95%confidence interval(CI)of the standard mean difference(SMD)among healthy controls,patients with mild cognitive impairment,and patients with Alzheimer's disease.The findings revealed significant alterations in the levels of insulin-degrading enzymes,neprilysin,matrix metalloproteinase-9,cathepsin D,receptor for advanced glycation end products,and P-glycoprotein in the brains of patients with Alzheimer's disease,patients with mild cognitive impairment,and healthy controls.In cerebrospinal fluid,the levels of triggering receptor expressed on myeloid cells 2 and ubiquitin C-terminal hydrolase L1 are altered,whereas the levels of TREM2,CD40,CD40L,CD14,CD22,cathepsin D,cystatin C,andα2 M in peripheral blood differ.Notably,TREM2 and cathepsin D showed changes in both brain(SMD=0.31,95%CI:0.16-0.47,P<0.001,I^(2)=78.4%;SMD=1.24,95%CI:0.01-2.48,P=0.048,I^(2)=90.1%)and peripheral blood(SMD=1.01,95%CI:0.35-1.66,P=0.003,I^(2)=96.5%;SMD=7.55,95%CI:3.92-11.18,P<0.001,I^(2)=98.2%)samples.Furthermore,correlations were observed between amyloid-beta levels and the levels of TREM2(r=0.16,95%CI:0.04-0.28,P=0.009,I^(2)=74.7%),neprilysin(r=-0.47,95%CI:-0.80-0.14,P=0.005,I^(2)=76.1%),and P-glycoprotein(r=-0.31,95%CI:-0.51-0.11,P=0.002,I^(2)=0.0%)in patients with Alzheimer's disease.These findings suggest that triggering receptor expressed on myeloid cells 2 and cathepsin D could serve as potential diagnostic biomarkers for Alzheimer's disease,whereas triggering receptor expressed on myeloid cells 2,neprilysin,and P-glycoprotein may represent potential therapeutic targets.
基金financially supported by Beijing Nova Program(Nos.Z211100002121127 and 20220484219)Beijing Natural Science Foundation(No.L212059)+1 种基金Fundamental Research Funds for the Central Universities(No.3332021101)CAMS Innovation Fund for Medical Sciences(CIFMS,Nos.2021-I2M-1-026 and 2021-I2M-1-028).
文摘Ulcerative colitis(UC)is a common progressive inflammatory disease whose incidence has increased rapidly in recent years,and can develop into colorectal cancer in severe cases.There are currently no adequate or effective treatments for UC due to the fact that some patients have found suboptimal results after repeated administration,while others have experienced adverse effects.With the rapid development of nanotechnology,developing innovative colon-targeting platforms is essential to improving efficacy,reducing side effects,and improving patient compliance.In this review,we summarize the pathophysiological characteristics of UC and the most recent status of numerous nanodrug delivery systems based on different targeting mechanisms in treating UC.Oral,intravenous,and rectal drug delivery nanoparticles targeting the colon are discussed,which can provide ideas for the design of colon-targeting nanoparticles for the treatment of colon diseases,especially for the treatment of UC.Last but not least,we provide a glimpse into the future of colon-targeted delivery systems,as well as future advancements in the field.
基金supported by Dalian Youth Science and Technology Star Project(2020RQ121)the National Science Fund for Distinguished Young Scholars of China(31925031)+1 种基金Doctoral Scientific Research Foundation of Liaoning Province(2020-BS-211)Liaoning Province Education Administration(J2020101)。
文摘Cellular senescence is the results of aging and age-related diseases,and the development of anti-aging methods may improve health and extend longevity.The natural flavonol fisetin has been shown to antagonize senescence in vitro and increases longevity in vivo,but has poor water solubility and limited bioavailability.In this study,a food-grade and senescent cell-targeted delivery system for fisetin was developed based on whey protein isolate-galactooligosaccharides(WPI-GOS)Maillard conjugate,which could recognize senescence associatedβ-galactosidase in senescent cells.The fisetin nanoparticles possessed a high encapsulation efficiency,excellent dispersibility in water,good storage stability and well biocompatibility.Moreover,they could effectively accumulate and retain in senescent cells with excellent senescent cell-targeting efficacy,and inhibit the oxidative stress-induced cellular senescence in vitro.Thus,this novel nanoparticle system based on WPI-GOS Maillard conjugate showed promise to deliver hydrophobic bioactive ingredients like fisetin to senescent cells to improve their bioavailability and anti-senescence effect.
文摘BACKGROUND Gliomas pose a significant challenge to effective treatment despite advancements in chemotherapy and radiotherapy.Glioma stem cells(GSCs),a subset within tumors,contribute to resistance,tumor heterogeneity,and plasticity.Recent studies reveal GSCs’role in therapeutic resistance,driven by DNA repair mechanisms and dynamic transitions between cellular states.Resistance mechanisms can involve different cellular pathways,most of which have been recently reported in the literature.Despite progress,targeted therapeutic approaches lack consensus due to GSCs’high plasticity.AIM To analyze targeted therapies against GSC-mediated resistance to radio-and chemotherapy in gliomas,focusing on underlying mechanisms.METHODS A systematic search was conducted across major medical databases(PubMed,Embase,and Cochrane Library)up to September 30,2023.The search strategy utilized relevant Medical Subject Heading terms and keywords related to including“glioma stem cells”,“radiotherapy”,“chemotherapy”,“resistance”,and“targeted therapies”.Studies included in this review were publications focusing on targeted therapies against the molecular mechanism of GSC-mediated re-sistance to radiotherapy resistance(RTR).RESULTS In a comprehensive review of 66 studies on stem cell therapies for SCI,452 papers were initially identified,with 203 chosen for full-text analysis.Among them,201 were deemed eligible after excluding 168 for various reasons.The temporal breakdown of studies illustrates this trend:2005-2010(33.3%),2011-2015(36.4%),and 2016-2022(30.3%).Key GSC models,particularly U87(33.3%),U251(15.2%),and T98G(15.2%),emerge as significant in research,reflecting their representativeness of glioma characteristics.Pathway analysis indicates a focus on phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(mTOR)(27.3%)and Notch(12.1%)pathways,suggesting their crucial roles in resistance development.Targeted molecules with mTOR(18.2%),CHK1/2(15.2%),and ATP binding cassette G2(12.1%)as frequent targets underscore their importance in overcoming GSC-mediated resistance.Various therapeutic agents,notably RNA inhibitor/short hairpin RNA(27.3%),inhibitors(e.g.,LY294002,NVP-BEZ235)(24.2%),and monoclonal antibodies(e.g.,cetuximab)(9.1%),demonstrate versatility in targeted therapies.among 20 studies(60.6%),the most common effect on the chemotherapy resistance response is a reduction in temozolomide resistance(51.5%),followed by reductions in carmustine resistance(9.1%)and doxorubicin resistance(3.0%),while resistance to RTR is reduced in 42.4%of studies.CONCLUSION GSCs play a complex role in mediating radioresistance and chemoresistance,emphasizing the necessity for precision therapies that consider the heterogeneity within the GSC population and the dynamic tumor microenvironment to enhance outcomes for glioblastoma patients.
基金supported by the Natural Science Foundation of Fujian Province,No.2021J02035(to WX).
文摘Regulated cell death is a form of cell death that is actively controlled by biomolecules.Several studies have shown that regulated cell death plays a key role after spinal cord injury.Pyroptosis and ferroptosis are newly discovered types of regulated cell deaths that have been shown to exacerbate inflammation and lead to cell death in damaged spinal cords.Autophagy,a complex form of cell death that is interconnected with various regulated cell death mechanisms,has garnered significant attention in the study of spinal cord injury.This injury triggers not only cell death but also cellular survival responses.Multiple signaling pathways play pivotal roles in influencing the processes of both deterioration and repair in spinal cord injury by regulating pyroptosis,ferroptosis,and autophagy.Therefore,this review aims to comprehensively examine the mechanisms underlying regulated cell deaths,the signaling pathways that modulate these mechanisms,and the potential therapeutic targets for spinal cord injury.Our analysis suggests that targeting the common regulatory signaling pathways of different regulated cell deaths could be a promising strategy to promote cell survival and enhance the repair of spinal cord injury.Moreover,a holistic approach that incorporates multiple regulated cell deaths and their regulatory pathways presents a promising multi-target therapeutic strategy for the management of spinal cord injury.
基金supported by grants from the Natural Science Foundation of Tianjin(General Program),Nos.23JCYBJC01390(to RL),22JCYBJC00220(to XC),and 22JCYBJC00210(to QL).
文摘Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities.Research on the pathogenesis of peripheral nerve injury has focused on pathological changes at individual injury sites,neglecting multilevel pathological analysis of the overall nervous system and target organs.This has led to restrictions on current therapeutic approaches.In this paper,we first summarize the potential mechanisms of peripheral nerve injury from a holistic perspective,covering the central nervous system,peripheral nervous system,and target organs.After peripheral nerve injury,the cortical plasticity of the brain is altered due to damage to and regeneration of peripheral nerves;changes such as neuronal apoptosis and axonal demyelination occur in the spinal cord.The nerve will undergo axonal regeneration,activation of Schwann cells,inflammatory response,and vascular system regeneration at the injury site.Corresponding damage to target organs can occur,including skeletal muscle atrophy and sensory receptor disruption.We then provide a brief review of the research advances in therapeutic approaches to peripheral nerve injury.The main current treatments are conducted passively and include physical factor rehabilitation,pharmacological treatments,cell-based therapies,and physical exercise.However,most treatments only partially address the problem and cannot complete the systematic recovery of the entire central nervous system-peripheral nervous system-target organ pathway.Therefore,we should further explore multilevel treatment options that produce effective,long-lasting results,perhaps requiring a combination of passive(traditional)and active(novel)treatment methods to stimulate rehabilitation at the central-peripheral-target organ levels to achieve better functional recovery.
基金supported by the National Natural Science Foundation of China(No.82071777)Peking University People's Hospital Scientific Research Development Funds(No.RDJP2022-10).
文摘The aim of this study was to compare the accuracies of cognitive fusion-guided targeted biopsy(TB),systematic biopsy(SB),and combined TB+SB for the detection of prostate cancer(PCa)and clinically significant PCa(csPCa)in males with lesions detected by magnetic resonance imaging(MRI).We conducted a retrospective analysis of individuals who underwent prostate biopsy at Peking University People's Hospital(Beijing,China),with an emphasis on patients with both transrectal TB and SB.The main objective was to determine the precisions of SB,TB,and TB+SB for diagnosing PCa and csPCa.We also evaluated the detection rates of TB,SB,TB+ipsilateral-SB(ipsi-SB),TB+contralateral-SB(contra-SB),and TB+SB for PCa and csPCa in patients with unilateral MRI lesions.We compared the diagnostic yields of the various biopsy schemes using the McNemar’s test.A total of 180 patients were enrolled.The rates of PCa detection using TB,SB,and TB+SB were 52.8%,62.2%,and 66.7%,respectively,and the corresponding rates for csPCa were 46.1%,56.7%,and 58.3%,respectively.Among patients with unilateral MRI lesions,the PCa detection rates for TB,SB,TB+ipsi-SB,TB+contra-SB,and TB+SB were 53.3%,64.8%,65.6%,61.5%,and 68.0%,respectively.TB+ipsi-SB detected 96.4%of PCa and 95.9%of csPCa cases.These findings suggest that the combination of TB+SB has better diagnostic accuracy compared with SB or TB alone.For patients with unilateral MRI lesions,the combination of TB+ipsi-SB may be suitable in clinical settings.
基金the National Natural Science Foundation of China(No.82003846)the Administration of Traditional Chinese Medicine of Guangdong Province,China(No.20212124).
文摘Glutamine is one of the most abundant non-essential amino acids in human plasma and plays a crucial role in many biological processes of the human body.Tumor cells take up a large amount of glutamine to meet their rapid proliferation requirements,which is supported by the upregulation of glutamine transporters.Targeted inhibition of glutamine transporters effectively inhibits cell growth and proliferation in tumors.Among all cancers,digestive system malignant tumors(DSMTs)have the highest incidence and mortality rates,and the current therapeutic strategies for DSMTs are mainly surgical resection and chemotherapy.Due to the relatively low survival rate and severe side effects associated with DSMTs treatment,new treatment strategies are urgently required.This article summarizes the glutamine transporters involved in DSMTs and describes their role in DSMTs.Additionally,glutamine transportertarget drugs are discussed,providing theoretical guidance for the further development of drugs DSMTs treatment.
基金supported by the National Natural Science Foundation of China(41927801).
文摘To address the current problems of poor generality,low real-time,and imperfect information transmission of the battlefield target intelligence system,this paper studies the battlefield target intelligence system from the top-level perspective of multi-service joint warfare.First,an overall planning and analysis method of architecture modeling is proposed with the idea of a bionic analogy for battlefield target intelligence system architecture modeling,which reduces the difficulty of the planning and design process.The method introduces the Department of Defense architecture framework(DoDAF)modeling method,the multi-living agent(MLA)theory modeling method,and other combinations for planning and modeling.A set of rapid planning methods that can be applied to model the architecture of various types of complex systems is formed.Further,the liveness analysis of the battlefield target intelligence system is carried out,and the problems of the existing system are presented from several aspects.And the technical prediction of the development and construction is given,which provides directional ideas for the subsequent research and development of the battlefield target intelligence system.In the end,the proposed architecture model of the battlefield target intelligence system is simulated and verified by applying the colored Petri nets(CPN)simulation software.The analysis demonstrates the reasonable integrity of its logic.
基金This study was supported by the National Natural Science Foundation of China(No.62001506).
文摘This paper investigates the problem of Joint Radar Node Selection and Power Allocation(JRNSPA)in the Multiple Radar System(MRS)in the blanket jamming environment.Each radar node independently tracks moving target and subsequently transmits the raw observation data to the fusion center,which formulates a centralized tracking network structure.In order to establish a practical blanket jamming environment,we suppose that each target carries the self-defense jammer which automatically implements blanket jamming to the radar nodes that exceed the preset interception probability.Subsequently,the Predicted Conditional Cramer-Rao Lower Bound(PC-CRLB)is derived and utilized as the tracking accuracy criterion.Aimed at ensuring both the tracking performance and the Low Probability of Intercept(LPI)performance,the resource-saving scheduling model is formulated to minimize the transmit power consumption while meeting the requirements of tracking accuracy.Finally,the Modified Zoutendijk Method Of Feasible Directions(MZMFD)-based two-stage solution technique is adopted to solve the formulated non-convex optimization model.Simulation results show the effectiveness of the proposed JRNSPA scheme.
基金Supported by The Guangdong Basic and Applied Basic Research Foundation,China,No.2024A1515011236.
文摘By critically examining the work,we conducted a comprehensive bibliometric analysis on the role of nuclear factor erythroid 2-related factor 2(NRF2)in nervous system diseases.We also proposed suggestions for future bibliometric studies,including the integration of multiple websites,analytical tools,and analytical approaches,The findings presented provide compelling evidence that ferroptosis is closely associated with the therapeutic challenges of nervous system diseases.Targeted modulation of NRF2 to regulate ferroptosis holds substantial potential for effectively treating these diseases.Future NRF2-related research should not only focus on discovering new drugs but also on designing rational drug delivery systems.In particular,nanocarriers offer substantial potential for facilitating the clinical translation of NRF2 research and addressing existing issues related to NRF2-related drugs.
