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
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
Tau plays a crucial role in several neurodegenerative diseases,collectively referred to as tauopathies.Therefore,targeting potential pathological changes in tau could enable useful therapeutic interventions.However,ta...Tau plays a crucial role in several neurodegenerative diseases,collectively referred to as tauopathies.Therefore,targeting potential pathological changes in tau could enable useful therapeutic interventions.However,tau is not an easy target because it dynamically interacts with microtubules and other cellular components,which presents a challenge for tau-targeted drugs.New cellular models could aid the development of mechanism-based tau-targeted therapies.展开更多
Accurate time delay estimation of target echo signals is a critical component of underwater target localization.In active sonar systems,echo signal processing is vulnerable to the effects of reverberation and noise in...Accurate time delay estimation of target echo signals is a critical component of underwater target localization.In active sonar systems,echo signal processing is vulnerable to the effects of reverberation and noise in the maritime environment.This paper proposes a novel method for estimating target time delay using multi-bright spot echoes,assuming the target’s size and depth are known.Aiming to effectively enhance the extraction of geometric features from the target echoes and mitigate the impact of reverberation and noise,the proposed approach employs the fractional order Fourier transform-frequency sliced wavelet transform to extract multi-bright spot echoes.Using the highlighting model theory and the target size information,an observation matrix is constructed to represent multi-angle incident signals and obtain the theoretical scattered echo signals from different angles.Aiming to accurately estimate the target’s time delay,waveform similarity coefficients and mean square error values between the theoretical return signals and received signals are computed across various incident angles and time delays.Simulation results show that,compared to the conventional matched filter,the proposed algorithm reduces the relative error by 65.9%-91.5%at a signal-to noise ratio of-25 dB,and by 66.7%-88.9%at a signal-to-reverberation ratio of−10 dB.This algorithm provides a new approach for the precise localization of submerged targets in shallow water environments.展开更多
This article provides a comprehensive review of various approaches to targeted drug delivery for liver cancer, an area of significant need due to the limited effectiveness of current treatments. The article begins by ...This article provides a comprehensive review of various approaches to targeted drug delivery for liver cancer, an area of significant need due to the limited effectiveness of current treatments. The article begins by highlighting the role of the liver in metabolism and discusses the high mortality associated with hepatocellular carcinoma (HCC). The shortcomings of traditional chemotherapy, such as multidrug resistance and off-target effects, necessitate the exploration of novel therapeutic strategies, with a focus on targeted approaches. The review details both passive and active targeting strategies. Passive targeting leverages the enhanced permeability and retention (EPR) effect and unique features of the tumor microenvironment, while active targeting employs specific ligands, such as peptides, antibodies, and proteins, to bind to overexpressed receptors on liver and tumor cells. The article further details many examples of active targeting using the asialoglycoprotein receptor (ASGPR), glycyrrhetinic acid (GA), transferrin receptor (TfR), and folate receptor (FR) on hepatocytes and tumor cells, demonstrating that there has been significant research effort put into this field. The importance of non-parenchymal cells in the liver is also discussed, and the article examines methods of targeting Kupffer cells, sinusoidal endothelial cells, and hepatic stellate cells for therapeutic benefit. The review goes on to cover the emerging field of subcellular targeting, including specific strategies to target the nucleus, mitochondria, and the endoplasmic reticulum/Golgi apparatus, noting that although there has been some progress, further research is needed in this area. The text finishes with a summary which acknowledges that while targeted therapies, including enzyme-activated prodrugs, such as Pradefovir, and other novel methods for drug delivery have shown significant promise, challenges remain in translating these therapies into clinical use due to limitations in understanding the sequential transport and the mechanisms of action. Ultimately, the article emphasizes the need for in-depth research to fully realize the potential of precision cancer therapies for liver cancer.展开更多
Prodrugs need to be converted to active drugs to exert their pharmacological activities.Identifying the direct targets of active drugs is essential to elucidate the pharmacological mechanisms of prodrugs,but remains c...Prodrugs need to be converted to active drugs to exert their pharmacological activities.Identifying the direct targets of active drugs is essential to elucidate the pharmacological mechanisms of prodrugs,but remains challenging,especially for active drugs with low stability.展开更多
The potential of messenger RNA(m RNA)as a therapeutic tool for treating diseases has garnered considerable interest,especially in the wake of the successful creation of m RNA vaccines to counter corona virus disease 2...The potential of messenger RNA(m RNA)as a therapeutic tool for treating diseases has garnered considerable interest,especially in the wake of the successful creation of m RNA vaccines to counter corona virus disease 2019(COVID-19).Nucleic acid-based drug gene therapies have emerged as exceptionally promising avenues for combating disease.Furthermore,lipid nanoparticles(LNPs)are ideal carriers for nucleic acid delivery owing to their ionic nature,which enables nucleic acids to electrostatically interact with intracellular membranes,thereby promoting efficient intracellular nucleic acid release.Unfortunately,the effectiveness of LNPs in targeting organs beyond the liver is relatively poor.Thus,enhanced extrahepatic targeting is another important property that would lead to improved in vivo delivery by LNPs.This review focuses on the fundamental characteristics and functions of LNPs developed to facilitate cellular uptake and ensure effective intracellular release of m RNAs.Promising applications,possible advantages and potential challenges associated with use of LNPs in organ specific delivery and release of m RNAs are summarized.Furthermore,the need for future research to address limitations of currently developed LNPs for clinical applications of the m RNA technology is emphasized.展开更多
To address the issues of unknown target size,blurred edges,background interference and low contrast in infrared small target detection,this paper proposes a method based on density peaks searching and weighted multi-f...To address the issues of unknown target size,blurred edges,background interference and low contrast in infrared small target detection,this paper proposes a method based on density peaks searching and weighted multi-feature local difference.Firstly,an improved high-boost filter is used for preprocessing to eliminate background clutter and high-brightness interference,thereby increasing the probability of capturing real targets in the density peak search.Secondly,a triple-layer window is used to extract features from the area surrounding candidate targets,addressing the uncertainty of small target sizes.By calculating multi-feature local differences between the triple-layer windows,the problems of blurred target edges and low contrast are resolved.To balance the contribution of different features,intra-class distance is used to calculate weights,achieving weighted fusion of multi-feature local differences to obtain the weighted multi-feature local differences of candidate targets.The real targets are then extracted using the interquartile range.Experiments on datasets such as SIRST and IRSTD-IK show that the proposed method is suitable for various complex types and demonstrates good robustness and detection performance.展开更多
A measurement system for the scattering characteristics of warhead fragments based on high-speed imaging systems offers advantages such as simple deployment,flexible maneuverability,and high spatiotemporal resolution,...A measurement system for the scattering characteristics of warhead fragments based on high-speed imaging systems offers advantages such as simple deployment,flexible maneuverability,and high spatiotemporal resolution,enabling the acquisition of full-process data of the fragment scattering process.However,mismatches between camera frame rates and target velocities can lead to long motion blur tails of high-speed fragment targets,resulting in low signal-to-noise ratios and rendering conventional detection algorithms ineffective in dynamic strong interference testing environments.In this study,we propose a detection framework centered on dynamic strong interference disturbance signal separation and suppression.We introduce a mixture Gaussian model constrained under a joint spatialtemporal-transform domain Dirichlet process,combined with total variation regularization to achieve disturbance signal suppression.Experimental results demonstrate that the proposed disturbance suppression method can be integrated with certain conventional motion target detection tasks,enabling adaptation to real-world data to a certain extent.Moreover,we provide a specific implementation of this process,which achieves a detection rate close to 100%with an approximate 0%false alarm rate in multiple sets of real target field test data.This research effectively advances the development of the field of damage parameter testing.展开更多
Target-based and phenotype-based methods are the two main approaches for drug screening.Target-based drug screening focuses on specific targets CPA highly correlated with disease mechanisms,by detecting protein-ligand...Target-based and phenotype-based methods are the two main approaches for drug screening.Target-based drug screening focuses on specific targets CPA highly correlated with disease mechanisms,by detecting protein-ligand binding structure,dynamics and affinity.Currently,the four mainstream drug targets are G protein-coupled receptors(GPCRs),kinases,ion channels,and nuclear receptors,accounting for over 70%of effective drug targets,most of which are membrane proteins and enzymes.In recent years,various new drug targets have been continuously discovered,and the research focus has shifted from simple affinity analysis to high-throughput and high-content screening,as well as exploring drug-target interaction modes.These deepen reliance on the analytical techniques to have higher sensitivity,recognition specificity,and applicability to diversified target structures,which promoting the rapid development of novel screening methods.展开更多
We investigate the spatial and temporal correlations of hot-electron generation in high-intensity laser interaction with massive and thin copper targets under conditions relevant to inertial confinement fusion.Using K...We investigate the spatial and temporal correlations of hot-electron generation in high-intensity laser interaction with massive and thin copper targets under conditions relevant to inertial confinement fusion.Using Ka time-resolved imaging,it is found that in the case of massive targets,the hot-electron generation follows the laser pulse intensity with a short delay needed for favorable plasma formation.Conversely,a significant delay in the x-ray emission compared with the laser pulse intensity profile is observed in the case of thin targets.Theoretical analysis and numerical simulations suggest that this is related to radiation preheating of the foil and the increase in hot-electron lifetime in a hot expanding plasma.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 application of deep learning for target detection in aerial images captured by Unmanned Aerial Vehicles(UAV)has emerged as a prominent research focus.Due to the considerable distance between UAVs and the photograp...The application of deep learning for target detection in aerial images captured by Unmanned Aerial Vehicles(UAV)has emerged as a prominent research focus.Due to the considerable distance between UAVs and the photographed objects,coupled with complex shooting environments,existing models often struggle to achieve accurate real-time target detection.In this paper,a You Only Look Once v8(YOLOv8)model is modified from four aspects:the detection head,the up-sampling module,the feature extraction module,and the parameter optimization of positive sample screening,and the YOLO-S3DT model is proposed to improve the performance of the model for detecting small targets in aerial images.Experimental results show that all detection indexes of the proposed model are significantly improved without increasing the number of model parameters and with the limited growth of computation.Moreover,this model also has the best performance compared to other detecting models,demonstrating its advancement within this category of tasks.展开更多
The paper presents a two-layer,disturbance-resistant,and fault-tolerant affine formation maneuver control scheme that accomplishes the surrounding of a dynamic target with multiple underactuated Quadrotor Unmanned Aer...The paper presents a two-layer,disturbance-resistant,and fault-tolerant affine formation maneuver control scheme that accomplishes the surrounding of a dynamic target with multiple underactuated Quadrotor Unmanned Aerial Vehicles(QUAVs).This scheme mainly consists of predefinedtime estimators and fixed-time tracking controllers,with a hybrid Laplacian matrix describing the communication among these QUAVs.At the first layer,we devise predefined time estimators for leading and following QUAVs,enabling accurate estimation of desired information.In the second layer,we initially devise a fixed-time hybrid observer to estimate unknown disturbances and actuator faults.Fixedtime translational tracking controllers are then proposed,and the intermediary control input from these controllers is used to extract the desired attitude and angular velocities for the fixed-time rotational tracking controllers.We employ an exact tracking differentiator to handle variables that are challenging to differentiate directly.The paper includes a demonstration of the control system stability through mathematical proof,as well as the presentation of simulation results and comparative simulations.展开更多
Peripheral immunity forms the foundation of tumor immunity,while tumor immunity represents a more refined adaptation of peripheral immune responses.The tumor microenvironment(TME),a localized niche surrounding tumor c...Peripheral immunity forms the foundation of tumor immunity,while tumor immunity represents a more refined adaptation of peripheral immune responses.The tumor microenvironment(TME),a localized niche surrounding tumor cells,is inherently immunosuppressive(1,2).Effective tumor therapy necessitates the dismantling of this microenvironment,aiming to eradicate tumors from the host system.展开更多
An improved model based on you only look once version 8(YOLOv8)is proposed to solve the problem of low detection accuracy due to the diversity of object sizes in optical remote sensing images.Firstly,the feature pyram...An improved model based on you only look once version 8(YOLOv8)is proposed to solve the problem of low detection accuracy due to the diversity of object sizes in optical remote sensing images.Firstly,the feature pyramid network(FPN)structure of the original YOLOv8 mode is replaced by the generalized-FPN(GFPN)structure in GiraffeDet to realize the"cross-layer"and"cross-scale"adaptive feature fusion,to enrich the semantic information and spatial information on the feature map to improve the target detection ability of the model.Secondly,a pyramid-pool module of multi atrous spatial pyramid pooling(MASPP)is designed by using the idea of atrous convolution and feature pyramid structure to extract multi-scale features,so as to improve the processing ability of the model for multi-scale objects.The experimental results show that the detection accuracy of the improved YOLOv8 model on DIOR dataset is 92%and mean average precision(mAP)is 87.9%,respectively 3.5%and 1.7%higher than those of the original model.It is proved the detection and classification ability of the proposed model on multi-dimensional optical remote sensing target has been improved.展开更多
Osteoarthritis(OA)is one of the most common degenerative and age-related diseases in joints,which affects 654 million people worldwide.Current therapies could not fundamentally reverse the pathologic process of OA due...Osteoarthritis(OA)is one of the most common degenerative and age-related diseases in joints,which affects 654 million people worldwide.Current therapies could not fundamentally reverse the pathologic process of OA due to the complex pathogenesis.Although OA mechanisms have been investigated on a large scale over the past decade,the OA pathology correlated with aging-associated changes is still largely unrevealed.Therefore,in-depth analysis of the aging microenvironment and aging-related molecular mechanisms in OA may offer additional strategies for clinical prevention and treatment.In this review,we discuss the potential pathogenesis of OA in light of aging-associated changes and summarize three main components of the aging microenvironment of the OA joint:immune homeostatic imbalance,cellular senescence,and stem cell exhaustion,which could be induced by aging and further exacerbate OA progression.Additionally,it is emphasized that immune homeostatic imbalance appears before established OA,which occurs in the early stage and is the therapeutic window of opportunity for better clinical outcomes.Importantly,we evaluate recent therapeutic targets and promising interventions against these components,as well as the challenges and prospects for precise and individualized therapies of OA patients,which we believe would guide the construction of novel combined strategies targeting aging-related factors against OA for better treatments in the future.展开更多
Small interfering RNA(siRNA),a promising revolutionary therapy,faces delivery obstacles due to its poor targeting,strong charge negativity and macromolecular nature.Clinical-approved siRNAs can now only be delivered t...Small interfering RNA(siRNA),a promising revolutionary therapy,faces delivery obstacles due to its poor targeting,strong charge negativity and macromolecular nature.Clinical-approved siRNAs can now only be delivered to the liver mediated by the chemically conjugated N-acetylgalactosamine(GalNAc)ligand,the conjugate can be effectively uptaken into cells through interaction with asialoglycoprotein receptor(ASGPR)highly expressed on liver hepatocytes.To further explore an efficient non-hepatic targeted delivery strategy,in this study,we designed a delivery system that chemically conjugated p53 siRNA to renal tubular cell-targeting peptides for targeting the kidney,which was suitable for industrial transformation.Results showed that peptide-siRNA conjugate could specifically enter renal tubular epithelial cells and silence target genes.In cisplatin-induced acute kidney injury(AKI)mice,peptide-siRNA conjugate blocked the p53-mediated apoptotic pathway and alleviated renal damage.The innovative proposed system to conjugate kidney-targeting peptides with siRNA achieved the efficient kidney-targeted delivery of si RNA and provided a prospective choice for treating AKI.展开更多
Conventional nutritional supplements frequently demonstrate limited clinical effectiveness due to the harsh milieu of the gastrointestinal tract,inefficient transepithelial transport,and rapid systemic clearance.Nanol...Conventional nutritional supplements frequently demonstrate limited clinical effectiveness due to the harsh milieu of the gastrointestinal tract,inefficient transepithelial transport,and rapid systemic clearance.Nanoliposomal delivery platforms-lipid bilayer vesicles on the nanometer scale-have attracted attention as an adaptive strategy to shield sensitive nutrients,navigate biological barriers,and deliver payloads directly to target tissues or even sub-cellular organelles.Despite a growing body of literature,a consolidated appraisal of design principles,targeting modalities,and translational hurdles is still needed to guide future nutraceutical innovation.We aim to:(1)Summarize the physicochemical foundations of nanoliposomal nutrient carriers;(2)Delineate state-of-the-art approaches for organ-specific and organelle-specific targeting,with particular emphasis on renal and mitochondrial delivery;(3)Evaluate current evidence supporting therapeutic benefits in cardiometabolic,neuroprotective,and renal-repair contexts;and(4)Map unresolved challenges-including manufacturing scale-up,cost,and regulatory oversight-to inform a roadmap for clinical translation.A systematic literature search was performed across PubMed,Web of Science,and Scopus through May 2025 using Boolean combinations of“nanoliposome”,“nutrient”,“targeted delivery”,“bioavailability”,and organ-specific terms(e.g.,“kidney”,“mitochondria”).Primary research articles,systematic reviews,and relevant meta-analyses written in English were included.Data were extracted on liposomal composition,particle size,surface modifications(e.g.,polyethylene glycol,ligand conjugation),in vitro and in vivo bio-distribution,efficacy outcomes,and safety profiles.Key design variables were mapped against reported biological performance to identify convergent principles.Sixty-four original studies and twenty-one reviews met inclusion criteria.Encapsulation within phosphatidylcholine-rich bilayers consistently enhanced nutrient stability in simulated gastric fluid and improved Caco-2 trans-epithelial transport two-fold to ten-fold compared with free compound controls.Ligand-mediated strategies-such as folate,lactoferrin,or peptide conjugation-achieved organ-specific accumulation,with kidney-directed liposomes demonstrating up to a four-fold increase in renal cortex uptake.Mitochondrial targeting using amphipathic peptides(e.g.,SS-31)or triphenylphosphonium moieties delivered antioxidant nutrients to the organelle,restoring mitochondrial membrane potential and reducing reactive oxygen species(ROS)in preclinical cardiomyopathy and neurodegeneration models.Endosomal escape was most effectively triggered by fusogenic lipids(e.g.,dioleoylphosphatidylethanolamine)or pH-responsive polymers.PEGylation prolonged circulation half-life by 3-6 hours but elicited anti-polyethylene glycol antibodies in approximately one-quarter of recipients;emerging natural sterol-mimetic or collagen-mimetic coatings showed comparable stealth behavior with superior biodegradability.Scalability remains limited:Only three studies reported pilot-scale(>10 L)batches with Good Manufacturing Practice-compliant reproducibility.Targeted nanoliposomal systems substantially improve nutrient stability,absorption,and tissue specificity,offering a credible route to transform supplement efficacy for cardiometabolic,renal,and neuroprotective indications.Optimization of lipid composition,escape mechanisms,and biocompatible surface chemistries can further enhance therapeutic indices.Nonetheless,industrial-scale manufacturing,cost containment,and immunogenicity mitigation remain critical obstacles.Addressing these gaps through standardized characterization protocols,head-to-head clinical trials,and biomaterial innovation will be essential to unlock the full potential of nanoliposomal nutraceuticals in routine healthcare practice.展开更多
Adelphocoris suturalis is a polyphagous pest that is increasingly causing severe economic damage due to more frequent outbreaks.The development of non-target resistance to commercial Bacillus thuringiensis(Bt)cotton h...Adelphocoris suturalis is a polyphagous pest that is increasingly causing severe economic damage due to more frequent outbreaks.The development of non-target resistance to commercial Bacillus thuringiensis(Bt)cotton has further exacerbated its pest status and amplified the need for more sustainable methods of control.RNA interference(RNAi)-based pest management strategies,such as root soaking and transgenic plants that express dsRNAs,have proven to be reliable,eco-friendly pest control strategies.To identify new RNAi targets for potential A.suturalis population control,we investigated the target of rapamycin(TOR)signaling pathway.A critical role for this pathway in A.suturalis reproductive regulation was suggested by pharmacological analyses.Subsequent RNAi-mediated knockdown of the A.suturalis TOR pathway genes TOR,Ras homolog enriched in the brain(Rheb),and ribosomal S6 kinase(S6K)reduced fertility.Moreover,a spray-induced and nanocarrier-delivered gene silencing(SI-NDGS)system targeting TOR successfully suppressed ovarian development,which demonstrates its effectiveness as a pest control target.These results provide a critical foundation for understanding reproductive regulation in A.suturalis and introduce new candidates for RNAi-based A.suturalis management.展开更多
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Tau plays a crucial role in several neurodegenerative diseases,collectively referred to as tauopathies.Therefore,targeting potential pathological changes in tau could enable useful therapeutic interventions.However,tau is not an easy target because it dynamically interacts with microtubules and other cellular components,which presents a challenge for tau-targeted drugs.New cellular models could aid the development of mechanism-based tau-targeted therapies.
基金Supported by the State Key Laboratory of Acoustics and Marine Information Chinese Academy of Sciences(SKL A202507).
文摘Accurate time delay estimation of target echo signals is a critical component of underwater target localization.In active sonar systems,echo signal processing is vulnerable to the effects of reverberation and noise in the maritime environment.This paper proposes a novel method for estimating target time delay using multi-bright spot echoes,assuming the target’s size and depth are known.Aiming to effectively enhance the extraction of geometric features from the target echoes and mitigate the impact of reverberation and noise,the proposed approach employs the fractional order Fourier transform-frequency sliced wavelet transform to extract multi-bright spot echoes.Using the highlighting model theory and the target size information,an observation matrix is constructed to represent multi-angle incident signals and obtain the theoretical scattered echo signals from different angles.Aiming to accurately estimate the target’s time delay,waveform similarity coefficients and mean square error values between the theoretical return signals and received signals are computed across various incident angles and time delays.Simulation results show that,compared to the conventional matched filter,the proposed algorithm reduces the relative error by 65.9%-91.5%at a signal-to noise ratio of-25 dB,and by 66.7%-88.9%at a signal-to-reverberation ratio of−10 dB.This algorithm provides a new approach for the precise localization of submerged targets in shallow water environments.
文摘This article provides a comprehensive review of various approaches to targeted drug delivery for liver cancer, an area of significant need due to the limited effectiveness of current treatments. The article begins by highlighting the role of the liver in metabolism and discusses the high mortality associated with hepatocellular carcinoma (HCC). The shortcomings of traditional chemotherapy, such as multidrug resistance and off-target effects, necessitate the exploration of novel therapeutic strategies, with a focus on targeted approaches. The review details both passive and active targeting strategies. Passive targeting leverages the enhanced permeability and retention (EPR) effect and unique features of the tumor microenvironment, while active targeting employs specific ligands, such as peptides, antibodies, and proteins, to bind to overexpressed receptors on liver and tumor cells. The article further details many examples of active targeting using the asialoglycoprotein receptor (ASGPR), glycyrrhetinic acid (GA), transferrin receptor (TfR), and folate receptor (FR) on hepatocytes and tumor cells, demonstrating that there has been significant research effort put into this field. The importance of non-parenchymal cells in the liver is also discussed, and the article examines methods of targeting Kupffer cells, sinusoidal endothelial cells, and hepatic stellate cells for therapeutic benefit. The review goes on to cover the emerging field of subcellular targeting, including specific strategies to target the nucleus, mitochondria, and the endoplasmic reticulum/Golgi apparatus, noting that although there has been some progress, further research is needed in this area. The text finishes with a summary which acknowledges that while targeted therapies, including enzyme-activated prodrugs, such as Pradefovir, and other novel methods for drug delivery have shown significant promise, challenges remain in translating these therapies into clinical use due to limitations in understanding the sequential transport and the mechanisms of action. Ultimately, the article emphasizes the need for in-depth research to fully realize the potential of precision cancer therapies for liver cancer.
基金support from the National Natural Science Foundation of China(Grant Nos.:U21A20407 and 81973467).
文摘Prodrugs need to be converted to active drugs to exert their pharmacological activities.Identifying the direct targets of active drugs is essential to elucidate the pharmacological mechanisms of prodrugs,but remains challenging,especially for active drugs with low stability.
基金supported by Guang Dong Basic and Applied Basic Research Foundation(No.2023B1515120001)Shenzhen University 2035 Program for Excellent Research(Nos.00000208 and 00000225)。
文摘The potential of messenger RNA(m RNA)as a therapeutic tool for treating diseases has garnered considerable interest,especially in the wake of the successful creation of m RNA vaccines to counter corona virus disease 2019(COVID-19).Nucleic acid-based drug gene therapies have emerged as exceptionally promising avenues for combating disease.Furthermore,lipid nanoparticles(LNPs)are ideal carriers for nucleic acid delivery owing to their ionic nature,which enables nucleic acids to electrostatically interact with intracellular membranes,thereby promoting efficient intracellular nucleic acid release.Unfortunately,the effectiveness of LNPs in targeting organs beyond the liver is relatively poor.Thus,enhanced extrahepatic targeting is another important property that would lead to improved in vivo delivery by LNPs.This review focuses on the fundamental characteristics and functions of LNPs developed to facilitate cellular uptake and ensure effective intracellular release of m RNAs.Promising applications,possible advantages and potential challenges associated with use of LNPs in organ specific delivery and release of m RNAs are summarized.Furthermore,the need for future research to address limitations of currently developed LNPs for clinical applications of the m RNA technology is emphasized.
基金supported by the National Natural Science Foundation of China (No.52205548)。
文摘To address the issues of unknown target size,blurred edges,background interference and low contrast in infrared small target detection,this paper proposes a method based on density peaks searching and weighted multi-feature local difference.Firstly,an improved high-boost filter is used for preprocessing to eliminate background clutter and high-brightness interference,thereby increasing the probability of capturing real targets in the density peak search.Secondly,a triple-layer window is used to extract features from the area surrounding candidate targets,addressing the uncertainty of small target sizes.By calculating multi-feature local differences between the triple-layer windows,the problems of blurred target edges and low contrast are resolved.To balance the contribution of different features,intra-class distance is used to calculate weights,achieving weighted fusion of multi-feature local differences to obtain the weighted multi-feature local differences of candidate targets.The real targets are then extracted using the interquartile range.Experiments on datasets such as SIRST and IRSTD-IK show that the proposed method is suitable for various complex types and demonstrates good robustness and detection performance.
文摘A measurement system for the scattering characteristics of warhead fragments based on high-speed imaging systems offers advantages such as simple deployment,flexible maneuverability,and high spatiotemporal resolution,enabling the acquisition of full-process data of the fragment scattering process.However,mismatches between camera frame rates and target velocities can lead to long motion blur tails of high-speed fragment targets,resulting in low signal-to-noise ratios and rendering conventional detection algorithms ineffective in dynamic strong interference testing environments.In this study,we propose a detection framework centered on dynamic strong interference disturbance signal separation and suppression.We introduce a mixture Gaussian model constrained under a joint spatialtemporal-transform domain Dirichlet process,combined with total variation regularization to achieve disturbance signal suppression.Experimental results demonstrate that the proposed disturbance suppression method can be integrated with certain conventional motion target detection tasks,enabling adaptation to real-world data to a certain extent.Moreover,we provide a specific implementation of this process,which achieves a detection rate close to 100%with an approximate 0%false alarm rate in multiple sets of real target field test data.This research effectively advances the development of the field of damage parameter testing.
文摘Target-based and phenotype-based methods are the two main approaches for drug screening.Target-based drug screening focuses on specific targets CPA highly correlated with disease mechanisms,by detecting protein-ligand binding structure,dynamics and affinity.Currently,the four mainstream drug targets are G protein-coupled receptors(GPCRs),kinases,ion channels,and nuclear receptors,accounting for over 70%of effective drug targets,most of which are membrane proteins and enzymes.In recent years,various new drug targets have been continuously discovered,and the research focus has shifted from simple affinity analysis to high-throughput and high-content screening,as well as exploring drug-target interaction modes.These deepen reliance on the analytical techniques to have higher sensitivity,recognition specificity,and applicability to diversified target structures,which promoting the rapid development of novel screening methods.
基金funding via EUROfusion Enabling research Project No.AWP21-ENR-01-CEA-02“Advancing Shock Ignition for Direct-Drive Inertial Fusion,”the framework of the EUROfusion Consortium,funded by the European Union via the Euratom Research and Training Programme (Grant Agreement No.101052200-EUROfusion)+2 种基金the Czech Ministry of Education,Youth and Sports (CMEYS) for funding the operation of the PALS facility (Grant No.LM2023068)the EuroHPC Joint Undertaking for awarding access to Karolina at IT4Innovations (VSB-TU),Czechia under Project No.EHPC-REG-2023R02-006(DD-23-157)the Ministry of Education,Youth and Sports of the Czech Republic through e-INFRA CZ (Grant No.ID:90140)
文摘We investigate the spatial and temporal correlations of hot-electron generation in high-intensity laser interaction with massive and thin copper targets under conditions relevant to inertial confinement fusion.Using Ka time-resolved imaging,it is found that in the case of massive targets,the hot-electron generation follows the laser pulse intensity with a short delay needed for favorable plasma formation.Conversely,a significant delay in the x-ray emission compared with the laser pulse intensity profile is observed in the case of thin targets.Theoretical analysis and numerical simulations suggest that this is related to radiation preheating of the foil and the increase in hot-electron lifetime in a hot expanding plasma.
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.
文摘The application of deep learning for target detection in aerial images captured by Unmanned Aerial Vehicles(UAV)has emerged as a prominent research focus.Due to the considerable distance between UAVs and the photographed objects,coupled with complex shooting environments,existing models often struggle to achieve accurate real-time target detection.In this paper,a You Only Look Once v8(YOLOv8)model is modified from four aspects:the detection head,the up-sampling module,the feature extraction module,and the parameter optimization of positive sample screening,and the YOLO-S3DT model is proposed to improve the performance of the model for detecting small targets in aerial images.Experimental results show that all detection indexes of the proposed model are significantly improved without increasing the number of model parameters and with the limited growth of computation.Moreover,this model also has the best performance compared to other detecting models,demonstrating its advancement within this category of tasks.
基金supported by Natural Science Basic Research Plan in Shaanxi Province of China(No.2023-JC-QN-0733)Guangdong Basic and Applied Basic Research Foundation,China(No.2022A1515110753)+2 种基金China Postdoctoral Science Foundation(No.2022M722583)China Industry-UniversityResearch Innovation Foundation(No.2022IT188)National Key Laboratory of Air-based Information Perception and Fusion and the Aeronautic Science Foundation of China(No.20220001068001)。
文摘The paper presents a two-layer,disturbance-resistant,and fault-tolerant affine formation maneuver control scheme that accomplishes the surrounding of a dynamic target with multiple underactuated Quadrotor Unmanned Aerial Vehicles(QUAVs).This scheme mainly consists of predefinedtime estimators and fixed-time tracking controllers,with a hybrid Laplacian matrix describing the communication among these QUAVs.At the first layer,we devise predefined time estimators for leading and following QUAVs,enabling accurate estimation of desired information.In the second layer,we initially devise a fixed-time hybrid observer to estimate unknown disturbances and actuator faults.Fixedtime translational tracking controllers are then proposed,and the intermediary control input from these controllers is used to extract the desired attitude and angular velocities for the fixed-time rotational tracking controllers.We employ an exact tracking differentiator to handle variables that are challenging to differentiate directly.The paper includes a demonstration of the control system stability through mathematical proof,as well as the presentation of simulation results and comparative simulations.
文摘Peripheral immunity forms the foundation of tumor immunity,while tumor immunity represents a more refined adaptation of peripheral immune responses.The tumor microenvironment(TME),a localized niche surrounding tumor cells,is inherently immunosuppressive(1,2).Effective tumor therapy necessitates the dismantling of this microenvironment,aiming to eradicate tumors from the host system.
基金supported by the National Natural Science Foundation of China(No.62241109)the Tianjin Science and Technology Commissioner Project(No.20YDTPJC01110)。
文摘An improved model based on you only look once version 8(YOLOv8)is proposed to solve the problem of low detection accuracy due to the diversity of object sizes in optical remote sensing images.Firstly,the feature pyramid network(FPN)structure of the original YOLOv8 mode is replaced by the generalized-FPN(GFPN)structure in GiraffeDet to realize the"cross-layer"and"cross-scale"adaptive feature fusion,to enrich the semantic information and spatial information on the feature map to improve the target detection ability of the model.Secondly,a pyramid-pool module of multi atrous spatial pyramid pooling(MASPP)is designed by using the idea of atrous convolution and feature pyramid structure to extract multi-scale features,so as to improve the processing ability of the model for multi-scale objects.The experimental results show that the detection accuracy of the improved YOLOv8 model on DIOR dataset is 92%and mean average precision(mAP)is 87.9%,respectively 3.5%and 1.7%higher than those of the original model.It is proved the detection and classification ability of the proposed model on multi-dimensional optical remote sensing target has been improved.
基金supported by grants from National Natural Science Foundation of China(32370892)Science and Technology Commission of Shanghai Municipality(23141901200)+3 种基金Shanghai Natural Science Foundation(24ZR1450100)Health Commission of Shanghai Municipality(2022JC029)Biomaterials and Regenerative Medicine Institute Cooperative Research Project,Shanghai Jiaotong University School of Medicine(2022LHA11)Talent-Introduction Program of Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine(2022YJRC05).
文摘Osteoarthritis(OA)is one of the most common degenerative and age-related diseases in joints,which affects 654 million people worldwide.Current therapies could not fundamentally reverse the pathologic process of OA due to the complex pathogenesis.Although OA mechanisms have been investigated on a large scale over the past decade,the OA pathology correlated with aging-associated changes is still largely unrevealed.Therefore,in-depth analysis of the aging microenvironment and aging-related molecular mechanisms in OA may offer additional strategies for clinical prevention and treatment.In this review,we discuss the potential pathogenesis of OA in light of aging-associated changes and summarize three main components of the aging microenvironment of the OA joint:immune homeostatic imbalance,cellular senescence,and stem cell exhaustion,which could be induced by aging and further exacerbate OA progression.Additionally,it is emphasized that immune homeostatic imbalance appears before established OA,which occurs in the early stage and is the therapeutic window of opportunity for better clinical outcomes.Importantly,we evaluate recent therapeutic targets and promising interventions against these components,as well as the challenges and prospects for precise and individualized therapies of OA patients,which we believe would guide the construction of novel combined strategies targeting aging-related factors against OA for better treatments in the future.
基金supported by the National Key Technologies Research and Development Plan(No.2021YFE0106900)the National Natural Science Foundation of China(No.82173769)+1 种基金the Basic Research Cooperation Project of Beijing,Tianjin,Hebei from the Natural Science Foundation of Tianjin(No.20JCZXJC00070)the Applied Basic Research Multi-investment Foundation of Tianjin(No.21JCYBJC01540)。
文摘Small interfering RNA(siRNA),a promising revolutionary therapy,faces delivery obstacles due to its poor targeting,strong charge negativity and macromolecular nature.Clinical-approved siRNAs can now only be delivered to the liver mediated by the chemically conjugated N-acetylgalactosamine(GalNAc)ligand,the conjugate can be effectively uptaken into cells through interaction with asialoglycoprotein receptor(ASGPR)highly expressed on liver hepatocytes.To further explore an efficient non-hepatic targeted delivery strategy,in this study,we designed a delivery system that chemically conjugated p53 siRNA to renal tubular cell-targeting peptides for targeting the kidney,which was suitable for industrial transformation.Results showed that peptide-siRNA conjugate could specifically enter renal tubular epithelial cells and silence target genes.In cisplatin-induced acute kidney injury(AKI)mice,peptide-siRNA conjugate blocked the p53-mediated apoptotic pathway and alleviated renal damage.The innovative proposed system to conjugate kidney-targeting peptides with siRNA achieved the efficient kidney-targeted delivery of si RNA and provided a prospective choice for treating AKI.
文摘Conventional nutritional supplements frequently demonstrate limited clinical effectiveness due to the harsh milieu of the gastrointestinal tract,inefficient transepithelial transport,and rapid systemic clearance.Nanoliposomal delivery platforms-lipid bilayer vesicles on the nanometer scale-have attracted attention as an adaptive strategy to shield sensitive nutrients,navigate biological barriers,and deliver payloads directly to target tissues or even sub-cellular organelles.Despite a growing body of literature,a consolidated appraisal of design principles,targeting modalities,and translational hurdles is still needed to guide future nutraceutical innovation.We aim to:(1)Summarize the physicochemical foundations of nanoliposomal nutrient carriers;(2)Delineate state-of-the-art approaches for organ-specific and organelle-specific targeting,with particular emphasis on renal and mitochondrial delivery;(3)Evaluate current evidence supporting therapeutic benefits in cardiometabolic,neuroprotective,and renal-repair contexts;and(4)Map unresolved challenges-including manufacturing scale-up,cost,and regulatory oversight-to inform a roadmap for clinical translation.A systematic literature search was performed across PubMed,Web of Science,and Scopus through May 2025 using Boolean combinations of“nanoliposome”,“nutrient”,“targeted delivery”,“bioavailability”,and organ-specific terms(e.g.,“kidney”,“mitochondria”).Primary research articles,systematic reviews,and relevant meta-analyses written in English were included.Data were extracted on liposomal composition,particle size,surface modifications(e.g.,polyethylene glycol,ligand conjugation),in vitro and in vivo bio-distribution,efficacy outcomes,and safety profiles.Key design variables were mapped against reported biological performance to identify convergent principles.Sixty-four original studies and twenty-one reviews met inclusion criteria.Encapsulation within phosphatidylcholine-rich bilayers consistently enhanced nutrient stability in simulated gastric fluid and improved Caco-2 trans-epithelial transport two-fold to ten-fold compared with free compound controls.Ligand-mediated strategies-such as folate,lactoferrin,or peptide conjugation-achieved organ-specific accumulation,with kidney-directed liposomes demonstrating up to a four-fold increase in renal cortex uptake.Mitochondrial targeting using amphipathic peptides(e.g.,SS-31)or triphenylphosphonium moieties delivered antioxidant nutrients to the organelle,restoring mitochondrial membrane potential and reducing reactive oxygen species(ROS)in preclinical cardiomyopathy and neurodegeneration models.Endosomal escape was most effectively triggered by fusogenic lipids(e.g.,dioleoylphosphatidylethanolamine)or pH-responsive polymers.PEGylation prolonged circulation half-life by 3-6 hours but elicited anti-polyethylene glycol antibodies in approximately one-quarter of recipients;emerging natural sterol-mimetic or collagen-mimetic coatings showed comparable stealth behavior with superior biodegradability.Scalability remains limited:Only three studies reported pilot-scale(>10 L)batches with Good Manufacturing Practice-compliant reproducibility.Targeted nanoliposomal systems substantially improve nutrient stability,absorption,and tissue specificity,offering a credible route to transform supplement efficacy for cardiometabolic,renal,and neuroprotective indications.Optimization of lipid composition,escape mechanisms,and biocompatible surface chemistries can further enhance therapeutic indices.Nonetheless,industrial-scale manufacturing,cost containment,and immunogenicity mitigation remain critical obstacles.Addressing these gaps through standardized characterization protocols,head-to-head clinical trials,and biomaterial innovation will be essential to unlock the full potential of nanoliposomal nutraceuticals in routine healthcare practice.
基金supported by the National Natural Science Foundation of China(32072428)。
文摘Adelphocoris suturalis is a polyphagous pest that is increasingly causing severe economic damage due to more frequent outbreaks.The development of non-target resistance to commercial Bacillus thuringiensis(Bt)cotton has further exacerbated its pest status and amplified the need for more sustainable methods of control.RNA interference(RNAi)-based pest management strategies,such as root soaking and transgenic plants that express dsRNAs,have proven to be reliable,eco-friendly pest control strategies.To identify new RNAi targets for potential A.suturalis population control,we investigated the target of rapamycin(TOR)signaling pathway.A critical role for this pathway in A.suturalis reproductive regulation was suggested by pharmacological analyses.Subsequent RNAi-mediated knockdown of the A.suturalis TOR pathway genes TOR,Ras homolog enriched in the brain(Rheb),and ribosomal S6 kinase(S6K)reduced fertility.Moreover,a spray-induced and nanocarrier-delivered gene silencing(SI-NDGS)system targeting TOR successfully suppressed ovarian development,which demonstrates its effectiveness as a pest control target.These results provide a critical foundation for understanding reproductive regulation in A.suturalis and introduce new candidates for RNAi-based A.suturalis management.
