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
We read with great interest Deng et al.’s study 1 comparing sextant(6-core)and 12-core systematic biopsy in theMRI-targeted era,which valuably challenges the“more cores=higher accuracy”dogma by proposing a precisio...We read with great interest Deng et al.’s study 1 comparing sextant(6-core)and 12-core systematic biopsy in theMRI-targeted era,which valuably challenges the“more cores=higher accuracy”dogma by proposing a precision sampling strategy based on prostate cancer’s spatial distribution,aligning with personalized diagnosis trends.展开更多
Triple-negative breast cancer(TNBC)presents significant diagnostic and therapeutic challenges due to the lack of targeted treatments,rapid progression,high recurrence and metastasis rates,and overall poorer prognosis....Triple-negative breast cancer(TNBC)presents significant diagnostic and therapeutic challenges due to the lack of targeted treatments,rapid progression,high recurrence and metastasis rates,and overall poorer prognosis.Herein,the targeted theranostic platform of cysteine-modified gold nanodots-sulfhydrated luteinizing hormone releasing hormone(CGN-SLR)nanosystem was designed for target recognition and precise dual-mode imaging-guided photothermal therapy(PTT)against TNBC.On the one hand,the CGN-SLR nanosystem can serve as an ideal targeting fluorescent probe and computed tomography(CT)enhancer to facilitate the accurate diagnosis and surgical guidance of TNBC.On the other hand,the CGN-SLR nanosystem with great targeting and PTT ability can significantly inhibit the growth of TNBC,without causing harm to normal tissues and healthy organs.It provides an effective strategy for the diagnosis and treatment of TNBC through the rational design of multifunctional nanoplatform with target recognition,multiple imaging guidance/monitoring,and high-efficiency PTT.展开更多
Within the domain of Intelligent Group Systems(IGSs),this paper develops a resourceaware multitarget Constant False Alarm Rate(CFAR)detection framework for multisite MIMO radar systems.It underscores the necessity of ...Within the domain of Intelligent Group Systems(IGSs),this paper develops a resourceaware multitarget Constant False Alarm Rate(CFAR)detection framework for multisite MIMO radar systems.It underscores the necessity of managing finite transmit and receive antennas and transmit power systematically to enhance detection performance.To tackle the multidimensional resource optimization challenge,we introduce a Cooperative Transmit-Receive Antenna Selection and Power Allocation(CTRSPA)strategy.It employs a perception-action cycle that incorporates uncertain external support information to optimize worst-case detection performance with multiple targets.First,we derive a closed-form expression that incorporates uncertainty for the noncoherent integration squared-law detection probability using the Neyman-Pearson criterion.Subsequently,a joint optimization model for antenna selection and power allocation in CFAR detection is formulated,incorporating practical radar resource constraints.Mathematically,this represents an NPhard problem involving coupled continuous and Boolean variables.We propose a three-stage method—Reformulation,Node Picker,and Convex Power Allocation—that capitalizes on the independent convexity of the optimization model for each variable,ensuring a near-optimal result.Simulations confirm the approach's effectiveness,efficiency,and timeliness,particularly for large-scale radar networks,and reveal the impact of threat levels,system layout,and detection parameters on resource allocation.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
The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of th...The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of these diseases.This paper comprehensively reviews the relationship between mitochondrial dysfunction and chronic neurodegenerative diseases,aiming to uncover the potential use of targeted mitochondrial interventions as viable therapeutic options.We detail five targeted mitochondrial intervention strategies for chronic neurodegenerative diseases that act by promoting mitophagy,inhibiting mitochondrial fission,enhancing mitochondrial biogenesis,applying mitochondria-targeting antioxidants,and transplanting mitochondria.Each method has unique advantages and potential limitations,making them suitable for various therapeutic situations.Therapies that promote mitophagy or inhibit mitochondrial fission could be particularly effective in slowing disease progression,especially in the early stages.In contrast,those that enhance mitochondrial biogenesis and apply mitochondria-targeting antioxidants may offer great benefits during the middle stages of the disease by improving cellular antioxidant capacity and energy metabolism.Mitochondrial transplantation,while still experimental,holds great promise for restoring the function of damaged cells.Future research should focus on exploring the mechanisms and effects of these intervention strategies,particularly regarding their safety and efficacy in clinical settings.Additionally,the development of innovative mitochondria-targeting approaches,such as gene editing and nanotechnology,may provide new solutions for treating chronic neurodegenerative diseases.Implementing combined therapeutic strategies that integrate multiple intervention methods could also enhance treatment outcomes.展开更多
This research considers the tracking problem of a moving target in distributed sensor networks with a limited sensing range(LSR)affected by non-Gaussian noise.In such sensor networks,observation loss due to LSR is a p...This research considers the tracking problem of a moving target in distributed sensor networks with a limited sensing range(LSR)affected by non-Gaussian noise.In such sensor networks,observation loss due to LSR is a prevalent issue that has received insufficient attention.We introduce a time-varying random variable to describe whether the sensor observes a moving target at each moment.When a single sensor node is unable to receive information from other nodes,it cannot update its state estimation of the moving target once the target moves beyond this node’s observation range.We propose an information flow topology within distributed sensor networks to facilitate the reception of prior state estimation data transmitted by neighboring nodes.Based on this information,a quadratic distributed estimator is designed for each sensor,and an output injection term is introduced to handle unstable systems.Finally,a numerical example is provided to illustrate the effectiveness of the proposed control scheme.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
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
Dual-signal electrochemical sensors have inherent self-correction function to overcome disturbances of experimental and environmental factors,but suffer from electrodes'modification or functional materials'pre...Dual-signal electrochemical sensors have inherent self-correction function to overcome disturbances of experimental and environmental factors,but suffer from electrodes'modification or functional materials'preparation,resulting in cumbersome operation,weak stability and poor recognition efficiency.Herein,we propose a dual-signal electrochemical strategy for microRNA senstive detection based on target-driven T7 exonuclease(T7 Exo)-mediated signal amplification that eliminates the above-mentioned drawbacks.The recognition of methylene(MB)and ferrocene(Fc)co-tagged ssDNA(MB/Fc-ssDNA)by miRNA-155 resulted in the formation of double-stranded nucleic acids,which switched T7 Exo-assisted catalytic digestion on MB/Fc-ssDNA,achieving 1:N amplified generation of MB-mononucleotides(mNs)and Fc-mNs.Compared with MB/Fc-ssDNA,MB-mNs and Fc-mNs exhibited significantly declined electrostatic repulsion force toward working electrode,and then simultaneously generated two signals at distinct potentials,in which dual-signal analysis of miRNA-155 was achieved with limit of detection down to~fM level.This work renders a novel thinking concept to develop high-performance electrochemical sensors for early and reliable diagnosis of miRNA-related diseases,advancing the rapid development of intelligent medicines.展开更多
A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an or...A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an orally administered nanogene delivery system.Designed to achieve in situ,efficient delivery of chimeric antigen receptor(CAR)genes to tumor sites,this approach offers a novel strategy for CAR-macrophage(CAR-M)based immunotherapy.Its key highlights are as follows.展开更多
The prolonged and intricate history of oncological treatments has transitioned significantly since the introduction of chemotherapy.Substantial therapeutic benefits in cancer therapy have been achieved by the integrat...The prolonged and intricate history of oncological treatments has transitioned significantly since the introduction of chemotherapy.Substantial therapeutic benefits in cancer therapy have been achieved by the integration of conventional treatments with molecular biosciences and omics technologies.Human epidermal growth factor receptor,hormone receptors,and angiogenesis factors are among the established therapies in tumor reduction and managing side effects.Novel targeted therapies like KRAS G12C,Claudin-18 isoform 2(CLDN18.2),Trophoblast cell-surface antigen 2(TROP2),and epigenetic regulators emphasize their promise in advancing precision medicine.However,in many cases,the resistance mechanisms associated with these interventions render them ineffective in carrying out their functions.The purpose of this review is to provide a comprehensive and up-to-date examination of both established and emerging drug targets and mechanisms of treatment resistance in oncology.This review seeks to elucidate recent advancements,address persisting challenges,and explore opportunities for innovative developments in cancer target research.Additionally,it explores the growing role of artificial intelligence in reshaping cancer drug discovery and development frameworks as potential avenues for future research.In conclusion,innovative approaches in oncology,supported by pharmacological research,ongoing clinical trials,molecular biosciences,and artificial intelligence,are poised to significantly transform cancer treatment.展开更多
Diabetes involves multi-organ complications that seriously threaten human life and health,and has become a major public health problem of global concern.Unfortunately,clinical management strategies for diabetic compli...Diabetes involves multi-organ complications that seriously threaten human life and health,and has become a major public health problem of global concern.Unfortunately,clinical management strategies for diabetic complications are still in their“infancy”,restricted by a limited understanding of their complex pathological mechanism.As is well established,lipid metabolism disorder is the characteristic pathological factors of diabetes,but the detailed molecular mechanisms driving the progression of multi-organ complications remain obscure.Protein S-acylation(often referred to as S-palmitoylation)is a reversible lipid modification that reversibly binds fatty acids to protein-specific cysteine(Cys)residues through palmitoyl acyl transferases(PATs,also known as DHHCs)and deacylation enzymes,which is involved in the pathological progression of a variety of complex diseases such as cancer,neurological disorders and metabolic syndrome.Notably,recent studies have shown that protein S-acylation drives the progression of diabetes and its multiple complications,and targeted intervention in the protein S-acylation process significantly alleviates the progression of diabetes and its complications,suggesting that protein S-acylation may be a common pathological link and intervention target of diabetes complications.Therefore,this review systematically comprehends the contribution of protein S-acylation to the progression of diabetes and its complications,summarizes the influence of the diabetic environment on S-acylation related enzymes,as well as providing an in-depth analysis of current drugs,measures,and challenges in targeting S-acylation.Finally,the accessibility of targeting protein S-acylation to prevent diabetes and its complications and the focus of future in-depth studies are envisioned,with a view to providing comprehensive and in-depth references and rationale for future novel strategies targeting protein S-acylation to prevent and treat diabetes and its multi-organ complications.展开更多
Background:Stomach cancer(SC)is one of the most lethal malignancies worldwide due to late-stage diagnosis and limited treatment.The transcriptomic,epigenomic,and proteomic,etc.,omics datasets generated by high-through...Background:Stomach cancer(SC)is one of the most lethal malignancies worldwide due to late-stage diagnosis and limited treatment.The transcriptomic,epigenomic,and proteomic,etc.,omics datasets generated by high-throughput sequencing technology have become prominent in biomedical research,and they reveal molecular aspects of cancer diagnosis and therapy.Despite the development of advanced sequencing technology,the presence of high-dimensionality in multi-omics data makes it challenging to interpret the data.Methods:In this study,we introduce RankXLAN,an explainable ensemble-based multi-omics framework that integrates feature selection(FS),ensemble learning,bioinformatics,and in-silico validation for robust biomarker detection,potential therapeutic drug-repurposing candidates’identification,and classification of SC.To enhance the interpretability of the model,we incorporated explainable artificial intelligence(SHapley Additive exPlanations analysis),as well as accuracy,precision,F1-score,recall,cross-validation,specificity,likelihood ratio(LR)+,LR−,and Youden index results.Results:The experimental results showed that the top four FS algorithms achieved improved results when applied to the ensemble learning classification model.The proposed ensemble model produced an area under the curve(AUC)score of 0.994 for gene expression,0.97 for methylation,and 0.96 for miRNA expression data.Through the integration of bioinformatics and ML approach of the transcriptomic and epigenomic multi-omics dataset,we identified potential marker genes,namely,UBE2D2,HPCAL4,IGHA1,DPT,and FN3K.In-silico molecular docking revealed a strong binding affinity between ANKRD13C and the FDA-approved drug Everolimus(binding affinity−10.1 kcal/mol),identifying ANKRD13C as a potential therapeutic drug-repurposing target for SC.Conclusion:The proposed framework RankXLAN outperforms other existing frameworks for serum biomarker identification,therapeutic target identification,and SC classification with multi-omics datasets.展开更多
In recent years,proteolysis-targeting chimeras(PROTACs)have gained widespread attention as an emerging therapeutic approach.PROTACs are bifunctional molecules composed of a target protein-binding ligand,an E3 ubiquiti...In recent years,proteolysis-targeting chimeras(PROTACs)have gained widespread attention as an emerging therapeutic approach.PROTACs are bifunctional molecules composed of a target protein-binding ligand,an E3 ubiquitin ligase ligand,and a linker connecting these ligands.By harnessing the cell’s intrinsic ubiquitin-proteasome system(UPS),they promote the ubiquitination of specific target proteins,leading to their degradation and therapeutic effects.PROTACs show exceptional promise in targeting conventional“undruggable”targets compared to traditional small-molecule inhibitors.This review provides an overview of PROTACs,including their molecular mechanism of action,therapeutic benefits,development history,key design aspects,current research and development challenges,and future trends in nextgeneration PROTAC technology.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We read with great interest Deng et al.’s study 1 comparing sextant(6-core)and 12-core systematic biopsy in theMRI-targeted era,which valuably challenges the“more cores=higher accuracy”dogma by proposing a precision sampling strategy based on prostate cancer’s spatial distribution,aligning with personalized diagnosis trends.
基金supported by the Natural Science Foundation of Jilin Province(No.SKL202302002).
文摘Triple-negative breast cancer(TNBC)presents significant diagnostic and therapeutic challenges due to the lack of targeted treatments,rapid progression,high recurrence and metastasis rates,and overall poorer prognosis.Herein,the targeted theranostic platform of cysteine-modified gold nanodots-sulfhydrated luteinizing hormone releasing hormone(CGN-SLR)nanosystem was designed for target recognition and precise dual-mode imaging-guided photothermal therapy(PTT)against TNBC.On the one hand,the CGN-SLR nanosystem can serve as an ideal targeting fluorescent probe and computed tomography(CT)enhancer to facilitate the accurate diagnosis and surgical guidance of TNBC.On the other hand,the CGN-SLR nanosystem with great targeting and PTT ability can significantly inhibit the growth of TNBC,without causing harm to normal tissues and healthy organs.It provides an effective strategy for the diagnosis and treatment of TNBC through the rational design of multifunctional nanoplatform with target recognition,multiple imaging guidance/monitoring,and high-efficiency PTT.
基金supported by the National Natural Science Foundation of China(Nos.62071482 and 62471348)the Shaanxi Association of Science and Technology Youth Talent Support Program Project,China(No.20230137)+1 种基金the Innovative Talents Cultivate Program for Technology Innovation Team of Shaanxi Province,China(No.2024RS-CXTD-08)the Youth Innovation Team of Shaanxi Universities,China。
文摘Within the domain of Intelligent Group Systems(IGSs),this paper develops a resourceaware multitarget Constant False Alarm Rate(CFAR)detection framework for multisite MIMO radar systems.It underscores the necessity of managing finite transmit and receive antennas and transmit power systematically to enhance detection performance.To tackle the multidimensional resource optimization challenge,we introduce a Cooperative Transmit-Receive Antenna Selection and Power Allocation(CTRSPA)strategy.It employs a perception-action cycle that incorporates uncertain external support information to optimize worst-case detection performance with multiple targets.First,we derive a closed-form expression that incorporates uncertainty for the noncoherent integration squared-law detection probability using the Neyman-Pearson criterion.Subsequently,a joint optimization model for antenna selection and power allocation in CFAR detection is formulated,incorporating practical radar resource constraints.Mathematically,this represents an NPhard problem involving coupled continuous and Boolean variables.We propose a three-stage method—Reformulation,Node Picker,and Convex Power Allocation—that capitalizes on the independent convexity of the optimization model for each variable,ensuring a near-optimal result.Simulations confirm the approach's effectiveness,efficiency,and timeliness,particularly for large-scale radar networks,and reveal the impact of threat levels,system layout,and detection parameters on resource allocation.
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partly supported by the Yan’an University Qin Chuanyuan“Scientist+Engineer”Team Special Fund,No.2023KXJ-012(to YL)Yan’an University Transformation of Scientific and Technological Achievements Fund,No.2023CGZH-001(to YL)+2 种基金College Students Innovation and Entrepreneurship Training Program,Nos.D2023158,202410719056(to XS,JM)Yan’an University Production and Cultivation Project,No.CXY202001(to YL)Kweichow Moutai Hospital Research and Talent Development Fund Project,No.MTyk2022-25(to XO)。
文摘The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of these diseases.This paper comprehensively reviews the relationship between mitochondrial dysfunction and chronic neurodegenerative diseases,aiming to uncover the potential use of targeted mitochondrial interventions as viable therapeutic options.We detail five targeted mitochondrial intervention strategies for chronic neurodegenerative diseases that act by promoting mitophagy,inhibiting mitochondrial fission,enhancing mitochondrial biogenesis,applying mitochondria-targeting antioxidants,and transplanting mitochondria.Each method has unique advantages and potential limitations,making them suitable for various therapeutic situations.Therapies that promote mitophagy or inhibit mitochondrial fission could be particularly effective in slowing disease progression,especially in the early stages.In contrast,those that enhance mitochondrial biogenesis and apply mitochondria-targeting antioxidants may offer great benefits during the middle stages of the disease by improving cellular antioxidant capacity and energy metabolism.Mitochondrial transplantation,while still experimental,holds great promise for restoring the function of damaged cells.Future research should focus on exploring the mechanisms and effects of these intervention strategies,particularly regarding their safety and efficacy in clinical settings.Additionally,the development of innovative mitochondria-targeting approaches,such as gene editing and nanotechnology,may provide new solutions for treating chronic neurodegenerative diseases.Implementing combined therapeutic strategies that integrate multiple intervention methods could also enhance treatment outcomes.
基金National Natural Science Foundation of China(No.61803081)。
文摘This research considers the tracking problem of a moving target in distributed sensor networks with a limited sensing range(LSR)affected by non-Gaussian noise.In such sensor networks,observation loss due to LSR is a prevalent issue that has received insufficient attention.We introduce a time-varying random variable to describe whether the sensor observes a moving target at each moment.When a single sensor node is unable to receive information from other nodes,it cannot update its state estimation of the moving target once the target moves beyond this node’s observation range.We propose an information flow topology within distributed sensor networks to facilitate the reception of prior state estimation data transmitted by neighboring nodes.Based on this information,a quadratic distributed estimator is designed for each sensor,and an output injection term is introduced to handle unstable systems.Finally,a numerical example is provided to illustrate the effectiveness of the proposed control scheme.
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 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 National Natural Science Foundation of China(82304197 and 21605093)Hebei Natural Science Foundation(B2023201013)+4 种基金Science Research Project of Hebei Education Department(QN2024135)Hebei Province Innovation Capability Enhancement Plan Project(22567620H)Interdisciplinary Research Program of Hebei University(DXK202411)Medical Science Foundation of Hebei University(2023A02)Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education(MCMDZR-2024002)。
文摘Dual-signal electrochemical sensors have inherent self-correction function to overcome disturbances of experimental and environmental factors,but suffer from electrodes'modification or functional materials'preparation,resulting in cumbersome operation,weak stability and poor recognition efficiency.Herein,we propose a dual-signal electrochemical strategy for microRNA senstive detection based on target-driven T7 exonuclease(T7 Exo)-mediated signal amplification that eliminates the above-mentioned drawbacks.The recognition of methylene(MB)and ferrocene(Fc)co-tagged ssDNA(MB/Fc-ssDNA)by miRNA-155 resulted in the formation of double-stranded nucleic acids,which switched T7 Exo-assisted catalytic digestion on MB/Fc-ssDNA,achieving 1:N amplified generation of MB-mononucleotides(mNs)and Fc-mNs.Compared with MB/Fc-ssDNA,MB-mNs and Fc-mNs exhibited significantly declined electrostatic repulsion force toward working electrode,and then simultaneously generated two signals at distinct potentials,in which dual-signal analysis of miRNA-155 was achieved with limit of detection down to~fM level.This work renders a novel thinking concept to develop high-performance electrochemical sensors for early and reliable diagnosis of miRNA-related diseases,advancing the rapid development of intelligent medicines.
文摘A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an orally administered nanogene delivery system.Designed to achieve in situ,efficient delivery of chimeric antigen receptor(CAR)genes to tumor sites,this approach offers a novel strategy for CAR-macrophage(CAR-M)based immunotherapy.Its key highlights are as follows.
文摘The prolonged and intricate history of oncological treatments has transitioned significantly since the introduction of chemotherapy.Substantial therapeutic benefits in cancer therapy have been achieved by the integration of conventional treatments with molecular biosciences and omics technologies.Human epidermal growth factor receptor,hormone receptors,and angiogenesis factors are among the established therapies in tumor reduction and managing side effects.Novel targeted therapies like KRAS G12C,Claudin-18 isoform 2(CLDN18.2),Trophoblast cell-surface antigen 2(TROP2),and epigenetic regulators emphasize their promise in advancing precision medicine.However,in many cases,the resistance mechanisms associated with these interventions render them ineffective in carrying out their functions.The purpose of this review is to provide a comprehensive and up-to-date examination of both established and emerging drug targets and mechanisms of treatment resistance in oncology.This review seeks to elucidate recent advancements,address persisting challenges,and explore opportunities for innovative developments in cancer target research.Additionally,it explores the growing role of artificial intelligence in reshaping cancer drug discovery and development frameworks as potential avenues for future research.In conclusion,innovative approaches in oncology,supported by pharmacological research,ongoing clinical trials,molecular biosciences,and artificial intelligence,are poised to significantly transform cancer treatment.
基金supported by National Natural Science Foundation of China(No.82304909)National Natural Science Foundation of China(No.82174112)Tianjin Science and Technology Innovation Base Construction(No.24ZYJDSY00280).
文摘Diabetes involves multi-organ complications that seriously threaten human life and health,and has become a major public health problem of global concern.Unfortunately,clinical management strategies for diabetic complications are still in their“infancy”,restricted by a limited understanding of their complex pathological mechanism.As is well established,lipid metabolism disorder is the characteristic pathological factors of diabetes,but the detailed molecular mechanisms driving the progression of multi-organ complications remain obscure.Protein S-acylation(often referred to as S-palmitoylation)is a reversible lipid modification that reversibly binds fatty acids to protein-specific cysteine(Cys)residues through palmitoyl acyl transferases(PATs,also known as DHHCs)and deacylation enzymes,which is involved in the pathological progression of a variety of complex diseases such as cancer,neurological disorders and metabolic syndrome.Notably,recent studies have shown that protein S-acylation drives the progression of diabetes and its multiple complications,and targeted intervention in the protein S-acylation process significantly alleviates the progression of diabetes and its complications,suggesting that protein S-acylation may be a common pathological link and intervention target of diabetes complications.Therefore,this review systematically comprehends the contribution of protein S-acylation to the progression of diabetes and its complications,summarizes the influence of the diabetic environment on S-acylation related enzymes,as well as providing an in-depth analysis of current drugs,measures,and challenges in targeting S-acylation.Finally,the accessibility of targeting protein S-acylation to prevent diabetes and its complications and the focus of future in-depth studies are envisioned,with a view to providing comprehensive and in-depth references and rationale for future novel strategies targeting protein S-acylation to prevent and treat diabetes and its multi-organ complications.
基金the Deanship of Research and Graduate Studies at King Khalid University,KSA,for funding this work through the Large Research Project under grant number RGP2/164/46.
文摘Background:Stomach cancer(SC)is one of the most lethal malignancies worldwide due to late-stage diagnosis and limited treatment.The transcriptomic,epigenomic,and proteomic,etc.,omics datasets generated by high-throughput sequencing technology have become prominent in biomedical research,and they reveal molecular aspects of cancer diagnosis and therapy.Despite the development of advanced sequencing technology,the presence of high-dimensionality in multi-omics data makes it challenging to interpret the data.Methods:In this study,we introduce RankXLAN,an explainable ensemble-based multi-omics framework that integrates feature selection(FS),ensemble learning,bioinformatics,and in-silico validation for robust biomarker detection,potential therapeutic drug-repurposing candidates’identification,and classification of SC.To enhance the interpretability of the model,we incorporated explainable artificial intelligence(SHapley Additive exPlanations analysis),as well as accuracy,precision,F1-score,recall,cross-validation,specificity,likelihood ratio(LR)+,LR−,and Youden index results.Results:The experimental results showed that the top four FS algorithms achieved improved results when applied to the ensemble learning classification model.The proposed ensemble model produced an area under the curve(AUC)score of 0.994 for gene expression,0.97 for methylation,and 0.96 for miRNA expression data.Through the integration of bioinformatics and ML approach of the transcriptomic and epigenomic multi-omics dataset,we identified potential marker genes,namely,UBE2D2,HPCAL4,IGHA1,DPT,and FN3K.In-silico molecular docking revealed a strong binding affinity between ANKRD13C and the FDA-approved drug Everolimus(binding affinity−10.1 kcal/mol),identifying ANKRD13C as a potential therapeutic drug-repurposing target for SC.Conclusion:The proposed framework RankXLAN outperforms other existing frameworks for serum biomarker identification,therapeutic target identification,and SC classification with multi-omics datasets.
文摘In recent years,proteolysis-targeting chimeras(PROTACs)have gained widespread attention as an emerging therapeutic approach.PROTACs are bifunctional molecules composed of a target protein-binding ligand,an E3 ubiquitin ligase ligand,and a linker connecting these ligands.By harnessing the cell’s intrinsic ubiquitin-proteasome system(UPS),they promote the ubiquitination of specific target proteins,leading to their degradation and therapeutic effects.PROTACs show exceptional promise in targeting conventional“undruggable”targets compared to traditional small-molecule inhibitors.This review provides an overview of PROTACs,including their molecular mechanism of action,therapeutic benefits,development history,key design aspects,current research and development challenges,and future trends in nextgeneration PROTAC technology.
