The human retina,a complex and highly specialized structure,includes multiple cell types that work synergistically to generate and transmit visual signals.However,genetic predisposition or age-related degeneration can...The human retina,a complex and highly specialized structure,includes multiple cell types that work synergistically to generate and transmit visual signals.However,genetic predisposition or age-related degeneration can lead to retinal damage that severely impairs vision or causes blindness.Treatment options for retinal diseases are limited,and there is an urgent need for innovative therapeutic strategies.Cell and gene therapies are promising because of the efficacy of delivery systems that transport therapeutic genes to targeted retinal cells.Gene delivery systems hold great promise for treating retinal diseases by enabling the targeted delivery of therapeutic genes to affected cells or by converting endogenous cells into functional ones to facilitate nerve regeneration,potentially restoring vision.This review focuses on two principal categories of gene delivery vectors used in the treatment of retinal diseases:viral and non-viral systems.Viral vectors,including lentiviruses and adeno-associated viruses,exploit the innate ability of viruses to infiltrate cells,which is followed by the introduction of therapeutic genetic material into target cells for gene correction.Lentiviruses can accommodate exogenous genes up to 8 kb in length,but their mechanism of integration into the host genome presents insertion mutation risks.Conversely,adeno-associated viruses are safer,as they exist as episomes in the nucleus,yet their limited packaging capacity constrains their application to a narrower spectrum of diseases,which necessitates the exploration of alternative delivery methods.In parallel,progress has also occurred in the development of novel non-viral delivery systems,particularly those based on liposomal technology.Manipulation of the ratios of hydrophilic and hydrophobic molecules within liposomes and the development of new lipid formulations have led to the creation of advanced non-viral vectors.These innovative systems include solid lipid nanoparticles,polymer nanoparticles,dendrimers,polymeric micelles,and polymeric nanoparticles.Compared with their viral counterparts,non-viral delivery systems offer markedly enhanced loading capacities that enable the direct delivery of nucleic acids,mRNA,or protein molecules into cells.This bypasses the need for DNA transcription and processing,which significantly enhances therapeutic efficiency.Nevertheless,the immunogenic potential and accumulation toxicity associated with non-viral particulate systems necessitates continued optimization to reduce adverse effects in vivo.This review explores the various delivery systems for retinal therapies and retinal nerve regeneration,and details the characteristics,advantages,limitations,and clinical applications of each vector type.By systematically outlining these factors,our goal is to guide the selection of the optimal delivery tool for a specific retinal disease,which will enhance treatment efficacy and improve patient outcomes while paving the way for more effective and targeted therapeutic interventions.展开更多
The mechanisms underlying the pathophysiology of ischemic stroke are complex and multifactorial and include excitotoxicity,oxidative stress,inflammatory responses,and blood–brain barrier disruption.While vascular rec...The mechanisms underlying the pathophysiology of ischemic stroke are complex and multifactorial and include excitotoxicity,oxidative stress,inflammatory responses,and blood–brain barrier disruption.While vascular recanalization treatments such as thrombolysis and mechanical thrombectomy have achieved some success,reperfusion injury remains a significant contributor to the exacerbation of brain injury.This emphasizes the need for developing neuroprotective strategies to mitigate this type of injury.The purpose of this review was to examine the application of nanotechnology in the treatment of ischemic stroke,covering research progress in nanoparticlebased drug delivery,targeted therapy,and antioxidant and anti-inflammatory applications.Nanobased drug delivery systems offer several advantages compared to traditional therapies,including enhanced blood–brain barrier penetration,prolonged drug circulation time,improved drug stability,and targeted delivery.For example,inorganic nanoparticles,such as those based on CeO_(2),have been widely studied for their strong antioxidant capabilities.Biomimetic nanoparticles,such as those coated with cell membranes,have garnered significant attention owing to their excellent biocompatibility and targeting abilities.Nanoparticles can be used to deliver a wide range of neuroprotective agents,such as antioxidants(e.g.,edaravone),anti-inflammatory drugs(e.g.,curcumin),and neurotrophic factors.Nanotechnology significantly enhances the efficacy of these drugs while minimizing adverse reactions.Although nanotechnology has demonstrated great potential in animal studies,its clinical application still faces several challenges,including the long-term safety of nanoparticles,the feasibility of large-scale production,quality control,and the ability to predict therapeutic effects in humans.In summary,nanotechnology holds significant promise for the treatment of ischemic stroke.Future research should focus on further exploring the mechanisms of action of nanoparticles,developing multifunctional nanoparticles,and validating their safety and efficacy through rigorous clinical trials.Moreover,interdisciplinary collaboration is essential for advancing the use of nanotechnology in stroke treatment.展开更多
Abstract ： Interlibrary Loan and Document Delivery Service is the major form for libraries to share resources.The librairies of universities or colleges can better guarantee the supply of document information ,accomm...Abstract ： Interlibrary Loan and Document Delivery Service is the major form for libraries to share resources.The librairies of universities or colleges can better guarantee the supply of document information ,accommodating to users＇ need for documents to the greatest extent.This article elaborates on the definition of Interlibrary Loan and Document Delivery as well as their significance with a key focus on the Interlibrary Loan and Document Delivery practice of Oriental Vocational and Technical College in Zhejiang, meanwhile it also puts forward some suggestions on how to better practisee the service of lnterlibrary Loan and Document Delivery.展开更多
In Chinese language studies, both “The Textual Research on Historical Documents” and “The Comparative Study of Historical Data” are traditional in methodology and they both deserve being treasured, passed on, and ...In Chinese language studies, both “The Textual Research on Historical Documents” and “The Comparative Study of Historical Data” are traditional in methodology and they both deserve being treasured, passed on, and further developed. It will certainly do harm to the development of academic research if any of the two methods is given unreasonable priority. The author claims that the best or one of the best methodologies of the historical study of Chinese language is the combination of the two, hence a new interpretation of “The Double-proof Method”. Meanwhile, this essay is also an attempt to put forward “The Law of Quan-ma and Gui-mei” in Chinese language studies, in which the author believes that it is not advisable to either treat Gui-mei as Quan-ma or vice versa in linguistic research. It is crucial for us to respect always the language facts first, which is considered the very soul of linguistics.展开更多
In this article, the author introduces the basic information and the historical development of document delivery and interlibrary loan services conducted by Chinese libraries at different organizational levels and in ...In this article, the author introduces the basic information and the historical development of document delivery and interlibrary loan services conducted by Chinese libraries at different organizational levels and in different geographical areas. It compares and analyzes the commonalities, peculiarities and service-effectiveness of three most important systems of document delivery and interlibrary loan currently available in China. The author also discusses the developing trend of such services in the future.展开更多
In the recent informatization of Chinese courts, the huge amount of law cases and judgment documents, which were digital stored,has provided a good foundation for the research of judicial big data and machine learning...In the recent informatization of Chinese courts, the huge amount of law cases and judgment documents, which were digital stored,has provided a good foundation for the research of judicial big data and machine learning. In this situation, some ideas about Chinese courts can reach automation or get better result through the research of machine learning, such as similar documents recommendation, workload evaluation based on similarity of judgement documents and prediction of possible relevant statutes. In trying to achieve all above mentioned, and also in face of the characteristics of Chinese judgement document, we propose a topic model based approach to measure the text similarity of Chinese judgement document, which is based on TF-IDF, Latent Dirichlet Allocation (LDA), Labeled Latent Dirichlet Allocation (LLDA) and other treatments. Combining with the characteristics of Chinese judgment document,we focus on the specific steps of approach, the preprocessing of corpus, the parameters choices of training and the evaluation of similarity measure result. Besides, implementing the approach for prediction of possible statutes and regarding the prediction accuracy as the evaluation metric, we designed experiments to demonstrate the reasonability of decisions in the process of design and the high performance of our approach on text similarity measure. The experiments also show the restriction of our approach which need to be focused in future work.展开更多
Blood-brain barrier disruption and the neuroinflammatory response are significant pathological features that critically influence disease progression and treatment outcomes.This review systematically analyzes the curr...Blood-brain barrier disruption and the neuroinflammatory response are significant pathological features that critically influence disease progression and treatment outcomes.This review systematically analyzes the current understanding of the bidirectional relationship between blood-brain barrier disruption and neuroinflammation in traumatic brain injury,along with emerging combination therapeutic strategies.Literature review indicates that blood-brain barrier disruption and neuroinflammatory responses are key pathological features following traumatic brain injury.In the acute phase after traumatic brain injury,the pathological characteristics include primary blood-brain barrier disruption and the activation of inflammatory cascades.In the subacute phase,the pathological features are characterized by repair mechanisms and inflammatory modulation.In the chronic phase,the pathological features show persistent low-grade inflammation and incomplete recovery of the blood-brain barrier.Various physiological changes,such as structural alterations of the blood-brain barrier,inflammatory cascades,and extracellular matrix remodeling,interact with each other and are influenced by genetic,age,sex,and environmental factors.The dynamic balance between blood-brain barrier permeability and neuroinflammation is regulated by hormones,particularly sex hormones and stress-related hormones.Additionally,the role of gastrointestinal hormones is receiving increasing attention.Current treatment strategies for traumatic brain injury include various methods such as conventional drug combinations,multimodality neuromonitoring,hyperbaric oxygen therapy,and non-invasive brain stimulation.Artificial intelligence also shows potential in treatment decision-making and personalized therapy.Emerging sequential combination strategies and precision medicine approaches can help improve treatment outcomes;however,challenges remain,such as inadequate research on the mechanisms of the chronic phase traumatic brain injury and difficulties with technology integration.Future research on traumatic brain injury should focus on personalized treatment strategies,the standardization of techniques,costeffectiveness evaluations,and addressing the needs of patients with comorbidities.A multidisciplinary approach should be used to enhance treatment and improve patient outcomes.展开更多
Chinese authorities have introduced a speed limit for new electric mopeds and banned sales of older models in the name of safety.Delivery riders worry the changes will cut the number of orders they can complete each d...Chinese authorities have introduced a speed limit for new electric mopeds and banned sales of older models in the name of safety.Delivery riders worry the changes will cut the number of orders they can complete each day,and their incomes By Wahg Shihan and Xie Ying.展开更多
In an asynchronous cooperative editing workflow of a structured document, each of the co-authors receives in the different phases of the editing process, a copy of the document to insert its contribution. For confiden...In an asynchronous cooperative editing workflow of a structured document, each of the co-authors receives in the different phases of the editing process, a copy of the document to insert its contribution. For confidentiality reasons, this copy may be only a partial replica containing only parts of the (global) document which are of demonstrated interest for the considered co-author. Note that some parts may be a demonstrated interest over a co-author;they will therefore be accessible concurrently. When it’s synchronization time (e.g. at the end of an asynchronous editing phase of the process), we want to merge all contributions of all authors in a single document. Due to the asynchronism of edition and to the potential existence of the document parts offering concurrent access, conflicts may arise and make partial replicas unmergeable in their entirety: they are inconsistent, meaning that they contain conflictual parts. The purpose of this paper is to propose a merging approach said by consensus of such partial replicas using tree automata. Specifically, from the partial replicas updates, we build a tree automaton that accepts exactly the consensus documents. These documents are the maximum prefixes containing no conflict of partial replicas merged.展开更多
Ischemic stroke is a secondary cause of mortality worldwide,imposing considerable medical and economic burdens on society.Extracellular vesicles,serving as natural nanocarriers for drug delivery,exhibit excellent bioc...Ischemic stroke is a secondary cause of mortality worldwide,imposing considerable medical and economic burdens on society.Extracellular vesicles,serving as natural nanocarriers for drug delivery,exhibit excellent biocompatibility in vivo and have significant advantages in the management of ischemic stroke.However,the uncertain distribution and rapid clearance of extracellular vesicles impede their delivery efficiency.By utilizing membrane decoration or by encapsulating therapeutic cargo within extracellular vesicles,their delivery efficacy may be greatly improved.Furthermore,previous studies have indicated that microvesicles,a subset of large-sized extracellular vesicles,can transport mitochondria to neighboring cells,thereby aiding in the restoration of mitochondrial function post-ischemic stroke.Small extracellular vesicles have also demonstrated the capability to transfer mitochondrial components,such as proteins or deoxyribonucleic acid,or their sub-components,for extracellular vesicle-based ischemic stroke therapy.In this review,we undertake a comparative analysis of the isolation techniques employed for extracellular vesicles and present an overview of the current dominant extracellular vesicle modification methodologies.Given the complex facets of treating ischemic stroke,we also delineate various extracellular vesicle modification approaches which are suited to different facets of the treatment process.Moreover,given the burgeoning interest in mitochondrial delivery,we delved into the feasibility and existing research findings on the transportation of mitochondrial fractions or intact mitochondria through small extracellular vesicles and microvesicles to offer a fresh perspective on ischemic stroke therapy.展开更多
Attended collection and delivery points are vital components of ‘last-mile logistics’.Based on point of interest(POI) data for Cainiao Stations and China Post stations in Changsha City, China, this paper provides a ...Attended collection and delivery points are vital components of ‘last-mile logistics’.Based on point of interest(POI) data for Cainiao Stations and China Post stations in Changsha City, China, this paper provides a detailed exploration of the basic features, spatial distribution, and location influencing factors of attended collection and delivery points.Specifically, analyses of the types, service objects and location distributions of the attended collection and delivery points alongside a discussion of their spatial pattern and influencing factors provides a reference for their general geographic layout and characteristics.The findings of this study indicate that: 1) The main mode of operation of attended collection and delivery points is franchises, with other modes of operation rely on supermarkets and other individual shop types.2) The main service targets of attended collection and delivery points are communities, schools, and businesses, followed by townships, enterprises, scenic spots, and administrative units.3) Approximately 77.44% of the attended collection and delivery points are located near the exits of service areas;others are situated in the centre of the service areas.For the Cainiao Stations, 80% are located within 125 m of the exit;for the China Post stations, 80% are located within 175 m of the exit.4) The spatial distribution of the attended collection and delivery points in Changsha is unbalanced, with ‘more centre and fewer surrounding’.The centre is an ‘inverted triangle’, and the edge is an ‘orphan’, showing a northwest-southeast orientation and symmetrical along the axis.The layout of the attended collection and delivery points forms three core areas, and the number of sites decreases with the distance from the core.5) The number and distribution of the attended collection and delivery points are strongly consistent with the regional economic development level, population, and roadway system traffic convenience.Most attended collection and delivery points are on residential, scientific and educational, and commercial and financial land.展开更多
Vascular endothelial growth factor receptor 2(VEGFR-2)and neuropilin-1(NRP-1)are two prominent antiangiogenic targets.They are highly expressed on vascular endothelial cells and some tumor cells.Therefore,targeting VE...Vascular endothelial growth factor receptor 2(VEGFR-2)and neuropilin-1(NRP-1)are two prominent antiangiogenic targets.They are highly expressed on vascular endothelial cells and some tumor cells.Therefore,targeting VEGFR-2 and NRP-1 may be a potential antiangiogenic and antitumor strategy.A7R,a peptide with sequence of Ala-Thr-Trp-Leu-Pro-Pro-Arg that was found by phage display of peptide libraries,can preferentially target VEGFR-2 and NRP-1 and destroy the binding between vascular endothelial growth factor 165(VEGF165)and VEGFR-2 or NRP-1.This peptide is a new potent inhibitor of tumor angiogenesis and a targeting ligand for cancer therapy.This review describes the discovery,function and mechanism of the action of A7R,and further introduces the applications of A7R in antitumor angiogenic treatments,tumor angiogenesis imaging and targeted drug delivery systems.In this review,strategies to deliver different drugs by A7R-modified liposomes and nanoparticles are highlighted.A7R,a new dual targeting ligand of VEGFR-2 and NRP-1,is expected to have efficient therapeutic or targeting roles in tumor drug delivery.展开更多
A contextual review of models for chronic care was done to develop a context-adapted chronic care model-based service delivery model for chronic conditions including diabetes.The Philippines was used as the setting of...A contextual review of models for chronic care was done to develop a context-adapted chronic care model-based service delivery model for chronic conditions including diabetes.The Philippines was used as the setting of a low-to-middle-income country.A context-based narrative review of existing models for chronic care was conducted.A situational analysis was done at thegrassroots level,involving the leaders and members of the community,the patients,the local health system and the healthcare providers.A second analysis making use of certain organizational theories was done to explore on improving feasibility and acceptability of organizing care for chronic conditions.The analyses indicated that care for chronic conditions may be introduced,considering the needs of people with diabetes in particular and the community in general as recipients of care,and the issues and factors that may affect the healthcare workers and the health system as providers of this care.The context-adapted chronic care model-based service delivery model was constructed accordingly.Key features are:incorporation of chronic care in the health system's services; assimilation of chronic care delivery with the other responsibilities of the healthcare workers but with redistribution of certain tasks; and ensuring that the recipients of care experience the whole spectrum of basic chronic care that includes education and promotion in the general population,risk identification,screening,counseling including self-care development,and clinical management of the chronic condition and any co-morbidities,regardless of level of control of the condition.This way,low-to-middle income countries can introduce and improve care for chronic conditions without entailing much additional demand on their limited resources.展开更多
Often we encounter documents with text printed on complex color background. Readability of textual contents in such documents is very poor due to complexity of the background and mix up of color(s) of foreground text ...Often we encounter documents with text printed on complex color background. Readability of textual contents in such documents is very poor due to complexity of the background and mix up of color(s) of foreground text with colors of background. Automatic segmentation of foreground text in such document images is very much essential for smooth reading of the document contents either by human or by machine. In this paper we propose a novel approach to extract the foreground text in color document images having complex background. The proposed approach is a hybrid approach which combines connected component and texture feature analysis of potential text regions. The proposed approach utilizes Canny edge detector to detect all possible text edge pixels. Connected component analysis is performed on these edge pixels to identify candidate text regions. Because of background complexity it is also possible that a non-text region may be identified as a text region. This problem is overcome by analyzing the texture features of potential text region corresponding to each connected component. An unsupervised local thresholding is devised to perform foreground segmentation in detected text regions. Finally the text regions which are noisy are identified and reprocessed to further enhance the quality of retrieved foreground. The proposed approach can handle document images with varying background of multiple colors and texture;and foreground text in any color, font, size and orientation. Experimental results show that the proposed algorithm detects on an average 97.12% of text regions in the source document. Readability of the extracted foreground text is illustrated through Optical character recognition (OCR) in case the text is in English. The proposed approach is compared with some existing methods of foreground separation in document images. Experimental results show that our approach performs better.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
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
Background:This study focused on developing and optimizing a self-microemulsifying drug delivery system(SMEDDS)to improve Lafutidine’s solubility and bioavailability,thereby enhancing its effectiveness in treating ga...Background:This study focused on developing and optimizing a self-microemulsifying drug delivery system(SMEDDS)to improve Lafutidine’s solubility and bioavailability,thereby enhancing its effectiveness in treating gastric ulcers.Traditional formulations are less effective due to their limited water solubility and bioavailability.Methods:The study used solubility tests,pseudo-ternary phase diagrams,and central composite design(CCD)to optimize.The formulation was optimized by varying the oil concentration(10–40%)and surfactant/cosurfactant ratio(0.33–3.00),and then tested for droplet size,drug content,emulsification,phase stability,and in vitro dissolution.Results:The study found that the optimized formulation contained 14%Capmul PG 8NF oil,62%Labrasol surfactant,and 24%Tween 80 cosurfactant.This combination generated an average droplet size of 111.02 nm and improved drug release properties.Furthermore,the formulation was stable without phase separation,with a drug content of 88.2–99.8%.Conclusion:SMEDDS significantly improves lafutidine delivery by increasing solubility and absorption,thereby overcoming oral administration challenges.The system quickly formed small droplets in water and released the drug in 15 min.Enhancing lafutidine’s bioavailability may improve its efficacy in treating gastric ulcers,resulting in better patient outcomes and potentially lower dosing frequency.展开更多
Nowadays,tremendous researches have been focused on the core-shell lipid-polymer nanoparticles(LPNs) due to the advantages of both liposomes and polymer nanoparticles.In this work,LPNs were applied to encapsulate brin...Nowadays,tremendous researches have been focused on the core-shell lipid-polymer nanoparticles(LPNs) due to the advantages of both liposomes and polymer nanoparticles.In this work,LPNs were applied to encapsulate brinzolamide(Brz-LPNs) for achieving sustained drug release,improving drug corneal permeation and enhancing drug topical therapeutic effect.The structure of Brz-LPNs was composed of poly(lactic-co-glycolic) acid(PLGA) nanocore which encapsulated Brz(Brz-NPs) and lipid shell around the core.Brz-LPNs were prepared by a modified thin-film dispersion method.With the parameters optimization of Brz-LPNs,optimal Brz-LPNs showed an average particle size of151.23±1.64 nm with a high encapsulation efficiency(EE) of 86.7%±2.28%.The core-shell structure of Brz-LPNs were confirmed by transmission electronic microscopy(TEM).Fourier transformed infrared spectra(FTIR) analysis proved that Brz was successfully entrapped into Brz-LPNs.Brz-LPNs exhibited obvious sustained release of Brz,compared with AZOPT^■ and Brz-LPs.Furthermore,the corneal accumulative permeability of Brz-LPNs significantly increased compared to the commercial available formulation(AZOPT^■) in vitro.Moreover,Brz-LPNs(1 mg/mL Brz) showed a more sustained and effective intraocular pressure(IOP) reduction than Brz-LPs(1 mg/mL) and AZOPT^■(10 mg/mL Brz) in vivo.In conclusion,Brz-LPNs,as promising ocular drug delivery systems,are well worth developing in the future for glaucoma treatment.展开更多
In non-small cell lung cancer(NSCLC),poly(ADP-ribose)polymerase 1(PARP1)induces genomic instability and promotes tumor progression by impairing DNA repair pathways.Although PARP1-targeting proteolysis-targeting chimer...In non-small cell lung cancer(NSCLC),poly(ADP-ribose)polymerase 1(PARP1)induces genomic instability and promotes tumor progression by impairing DNA repair pathways.Although PARP1-targeting proteolysis-targeting chimeras(PROTACs)offer a promising strategy for selective protein degradation,their clinical application remains limited by poor water solubility and insufficient tumor selectivity.Here,we report a pHresponsive magnetic nanoparticle system co-delivering β-lapachone(β-lap)and a PARP1-targeted PROTAC(PRO)for synergistic and tumor-targeting therapy.Designed with a hydrophobic self-assembled core and a magnetic coating,the nanoparticle(NP_(β-lap+PRO))enables pHresponsive drug release and magnetic resonance imaging(MRI)monitoring.β-Lap is a bioactivated drug that relies on NAD(P)H:quinone oxidoreductase 1(NQO1),which is overexpressed in NSCLC cells.It has the potential to deliver tumor-selective DNA damage and induce cell death.The NP_(β-lap+PRO) exploits elevated NQO1 levels in NSCLC to initiate β-lap-driven oxidative stress and DNA damage,while simultaneously enhancing PROTAC-mediated PARP1 degradation within the acidic tumor microenvironment synergistically induces apoptosis.In A549 NSCLC tumor models,this system effectively induces PARP1 degradation,blocks DNA repair,and preserves NAD(P)H pools,thereby amplifying β-lapinduced reactive oxygen species production,leading to enhanced DNA double-strand breaks and apoptosis.This study presents a biomarker-driven nanotherapeutic strategy that integrates PROTAC technology with redox-targeted combination therapy,offering a promising approach for precision treatment of NSCLC.展开更多
基金Hongguang Wu,Both authors contributed equally to this work and share first authorshipLing Dong,Both authors contributed equally to this work and share first authorship。
文摘The human retina,a complex and highly specialized structure,includes multiple cell types that work synergistically to generate and transmit visual signals.However,genetic predisposition or age-related degeneration can lead to retinal damage that severely impairs vision or causes blindness.Treatment options for retinal diseases are limited,and there is an urgent need for innovative therapeutic strategies.Cell and gene therapies are promising because of the efficacy of delivery systems that transport therapeutic genes to targeted retinal cells.Gene delivery systems hold great promise for treating retinal diseases by enabling the targeted delivery of therapeutic genes to affected cells or by converting endogenous cells into functional ones to facilitate nerve regeneration,potentially restoring vision.This review focuses on two principal categories of gene delivery vectors used in the treatment of retinal diseases:viral and non-viral systems.Viral vectors,including lentiviruses and adeno-associated viruses,exploit the innate ability of viruses to infiltrate cells,which is followed by the introduction of therapeutic genetic material into target cells for gene correction.Lentiviruses can accommodate exogenous genes up to 8 kb in length,but their mechanism of integration into the host genome presents insertion mutation risks.Conversely,adeno-associated viruses are safer,as they exist as episomes in the nucleus,yet their limited packaging capacity constrains their application to a narrower spectrum of diseases,which necessitates the exploration of alternative delivery methods.In parallel,progress has also occurred in the development of novel non-viral delivery systems,particularly those based on liposomal technology.Manipulation of the ratios of hydrophilic and hydrophobic molecules within liposomes and the development of new lipid formulations have led to the creation of advanced non-viral vectors.These innovative systems include solid lipid nanoparticles,polymer nanoparticles,dendrimers,polymeric micelles,and polymeric nanoparticles.Compared with their viral counterparts,non-viral delivery systems offer markedly enhanced loading capacities that enable the direct delivery of nucleic acids,mRNA,or protein molecules into cells.This bypasses the need for DNA transcription and processing,which significantly enhances therapeutic efficiency.Nevertheless,the immunogenic potential and accumulation toxicity associated with non-viral particulate systems necessitates continued optimization to reduce adverse effects in vivo.This review explores the various delivery systems for retinal therapies and retinal nerve regeneration,and details the characteristics,advantages,limitations,and clinical applications of each vector type.By systematically outlining these factors,our goal is to guide the selection of the optimal delivery tool for a specific retinal disease,which will enhance treatment efficacy and improve patient outcomes while paving the way for more effective and targeted therapeutic interventions.
基金supported by the National Natural Science Foundation of China,Nos.82301093(to QC)and 22334004(to HY)the Fuzhou University Fund for Testing Precious Equipment,No.2025T038(to QC)。
文摘The mechanisms underlying the pathophysiology of ischemic stroke are complex and multifactorial and include excitotoxicity,oxidative stress,inflammatory responses,and blood–brain barrier disruption.While vascular recanalization treatments such as thrombolysis and mechanical thrombectomy have achieved some success,reperfusion injury remains a significant contributor to the exacerbation of brain injury.This emphasizes the need for developing neuroprotective strategies to mitigate this type of injury.The purpose of this review was to examine the application of nanotechnology in the treatment of ischemic stroke,covering research progress in nanoparticlebased drug delivery,targeted therapy,and antioxidant and anti-inflammatory applications.Nanobased drug delivery systems offer several advantages compared to traditional therapies,including enhanced blood–brain barrier penetration,prolonged drug circulation time,improved drug stability,and targeted delivery.For example,inorganic nanoparticles,such as those based on CeO_(2),have been widely studied for their strong antioxidant capabilities.Biomimetic nanoparticles,such as those coated with cell membranes,have garnered significant attention owing to their excellent biocompatibility and targeting abilities.Nanoparticles can be used to deliver a wide range of neuroprotective agents,such as antioxidants(e.g.,edaravone),anti-inflammatory drugs(e.g.,curcumin),and neurotrophic factors.Nanotechnology significantly enhances the efficacy of these drugs while minimizing adverse reactions.Although nanotechnology has demonstrated great potential in animal studies,its clinical application still faces several challenges,including the long-term safety of nanoparticles,the feasibility of large-scale production,quality control,and the ability to predict therapeutic effects in humans.In summary,nanotechnology holds significant promise for the treatment of ischemic stroke.Future research should focus on further exploring the mechanisms of action of nanoparticles,developing multifunctional nanoparticles,and validating their safety and efficacy through rigorous clinical trials.Moreover,interdisciplinary collaboration is essential for advancing the use of nanotechnology in stroke treatment.
文摘Abstract ： Interlibrary Loan and Document Delivery Service is the major form for libraries to share resources.The librairies of universities or colleges can better guarantee the supply of document information ,accommodating to users＇ need for documents to the greatest extent.This article elaborates on the definition of Interlibrary Loan and Document Delivery as well as their significance with a key focus on the Interlibrary Loan and Document Delivery practice of Oriental Vocational and Technical College in Zhejiang, meanwhile it also puts forward some suggestions on how to better practisee the service of lnterlibrary Loan and Document Delivery.
文摘In Chinese language studies, both “The Textual Research on Historical Documents” and “The Comparative Study of Historical Data” are traditional in methodology and they both deserve being treasured, passed on, and further developed. It will certainly do harm to the development of academic research if any of the two methods is given unreasonable priority. The author claims that the best or one of the best methodologies of the historical study of Chinese language is the combination of the two, hence a new interpretation of “The Double-proof Method”. Meanwhile, this essay is also an attempt to put forward “The Law of Quan-ma and Gui-mei” in Chinese language studies, in which the author believes that it is not advisable to either treat Gui-mei as Quan-ma or vice versa in linguistic research. It is crucial for us to respect always the language facts first, which is considered the very soul of linguistics.
文摘In this article, the author introduces the basic information and the historical development of document delivery and interlibrary loan services conducted by Chinese libraries at different organizational levels and in different geographical areas. It compares and analyzes the commonalities, peculiarities and service-effectiveness of three most important systems of document delivery and interlibrary loan currently available in China. The author also discusses the developing trend of such services in the future.
文摘In the recent informatization of Chinese courts, the huge amount of law cases and judgment documents, which were digital stored,has provided a good foundation for the research of judicial big data and machine learning. In this situation, some ideas about Chinese courts can reach automation or get better result through the research of machine learning, such as similar documents recommendation, workload evaluation based on similarity of judgement documents and prediction of possible relevant statutes. In trying to achieve all above mentioned, and also in face of the characteristics of Chinese judgement document, we propose a topic model based approach to measure the text similarity of Chinese judgement document, which is based on TF-IDF, Latent Dirichlet Allocation (LDA), Labeled Latent Dirichlet Allocation (LLDA) and other treatments. Combining with the characteristics of Chinese judgment document,we focus on the specific steps of approach, the preprocessing of corpus, the parameters choices of training and the evaluation of similarity measure result. Besides, implementing the approach for prediction of possible statutes and regarding the prediction accuracy as the evaluation metric, we designed experiments to demonstrate the reasonability of decisions in the process of design and the high performance of our approach on text similarity measure. The experiments also show the restriction of our approach which need to be focused in future work.
基金supported by Open Scientific Research Program of Military Logistics,No.BLB20J009(to YZhao).
文摘Blood-brain barrier disruption and the neuroinflammatory response are significant pathological features that critically influence disease progression and treatment outcomes.This review systematically analyzes the current understanding of the bidirectional relationship between blood-brain barrier disruption and neuroinflammation in traumatic brain injury,along with emerging combination therapeutic strategies.Literature review indicates that blood-brain barrier disruption and neuroinflammatory responses are key pathological features following traumatic brain injury.In the acute phase after traumatic brain injury,the pathological characteristics include primary blood-brain barrier disruption and the activation of inflammatory cascades.In the subacute phase,the pathological features are characterized by repair mechanisms and inflammatory modulation.In the chronic phase,the pathological features show persistent low-grade inflammation and incomplete recovery of the blood-brain barrier.Various physiological changes,such as structural alterations of the blood-brain barrier,inflammatory cascades,and extracellular matrix remodeling,interact with each other and are influenced by genetic,age,sex,and environmental factors.The dynamic balance between blood-brain barrier permeability and neuroinflammation is regulated by hormones,particularly sex hormones and stress-related hormones.Additionally,the role of gastrointestinal hormones is receiving increasing attention.Current treatment strategies for traumatic brain injury include various methods such as conventional drug combinations,multimodality neuromonitoring,hyperbaric oxygen therapy,and non-invasive brain stimulation.Artificial intelligence also shows potential in treatment decision-making and personalized therapy.Emerging sequential combination strategies and precision medicine approaches can help improve treatment outcomes;however,challenges remain,such as inadequate research on the mechanisms of the chronic phase traumatic brain injury and difficulties with technology integration.Future research on traumatic brain injury should focus on personalized treatment strategies,the standardization of techniques,costeffectiveness evaluations,and addressing the needs of patients with comorbidities.A multidisciplinary approach should be used to enhance treatment and improve patient outcomes.
文摘Chinese authorities have introduced a speed limit for new electric mopeds and banned sales of older models in the name of safety.Delivery riders worry the changes will cut the number of orders they can complete each day,and their incomes By Wahg Shihan and Xie Ying.
文摘In an asynchronous cooperative editing workflow of a structured document, each of the co-authors receives in the different phases of the editing process, a copy of the document to insert its contribution. For confidentiality reasons, this copy may be only a partial replica containing only parts of the (global) document which are of demonstrated interest for the considered co-author. Note that some parts may be a demonstrated interest over a co-author;they will therefore be accessible concurrently. When it’s synchronization time (e.g. at the end of an asynchronous editing phase of the process), we want to merge all contributions of all authors in a single document. Due to the asynchronism of edition and to the potential existence of the document parts offering concurrent access, conflicts may arise and make partial replicas unmergeable in their entirety: they are inconsistent, meaning that they contain conflictual parts. The purpose of this paper is to propose a merging approach said by consensus of such partial replicas using tree automata. Specifically, from the partial replicas updates, we build a tree automaton that accepts exactly the consensus documents. These documents are the maximum prefixes containing no conflict of partial replicas merged.
基金supported by the grants from University of Macao,China,Nos.MYRG2022-00221-ICMS(to YZ)and MYRG-CRG2022-00011-ICMS(to RW)the Natural Science Foundation of Guangdong Province,No.2023A1515010034(to YZ)。
文摘Ischemic stroke is a secondary cause of mortality worldwide,imposing considerable medical and economic burdens on society.Extracellular vesicles,serving as natural nanocarriers for drug delivery,exhibit excellent biocompatibility in vivo and have significant advantages in the management of ischemic stroke.However,the uncertain distribution and rapid clearance of extracellular vesicles impede their delivery efficiency.By utilizing membrane decoration or by encapsulating therapeutic cargo within extracellular vesicles,their delivery efficacy may be greatly improved.Furthermore,previous studies have indicated that microvesicles,a subset of large-sized extracellular vesicles,can transport mitochondria to neighboring cells,thereby aiding in the restoration of mitochondrial function post-ischemic stroke.Small extracellular vesicles have also demonstrated the capability to transfer mitochondrial components,such as proteins or deoxyribonucleic acid,or their sub-components,for extracellular vesicle-based ischemic stroke therapy.In this review,we undertake a comparative analysis of the isolation techniques employed for extracellular vesicles and present an overview of the current dominant extracellular vesicle modification methodologies.Given the complex facets of treating ischemic stroke,we also delineate various extracellular vesicle modification approaches which are suited to different facets of the treatment process.Moreover,given the burgeoning interest in mitochondrial delivery,we delved into the feasibility and existing research findings on the transportation of mitochondrial fractions or intact mitochondria through small extracellular vesicles and microvesicles to offer a fresh perspective on ischemic stroke therapy.
基金Under the auspices of the Tang Scholar Program of Northwest University(No.2016)
文摘Attended collection and delivery points are vital components of ‘last-mile logistics’.Based on point of interest(POI) data for Cainiao Stations and China Post stations in Changsha City, China, this paper provides a detailed exploration of the basic features, spatial distribution, and location influencing factors of attended collection and delivery points.Specifically, analyses of the types, service objects and location distributions of the attended collection and delivery points alongside a discussion of their spatial pattern and influencing factors provides a reference for their general geographic layout and characteristics.The findings of this study indicate that: 1) The main mode of operation of attended collection and delivery points is franchises, with other modes of operation rely on supermarkets and other individual shop types.2) The main service targets of attended collection and delivery points are communities, schools, and businesses, followed by townships, enterprises, scenic spots, and administrative units.3) Approximately 77.44% of the attended collection and delivery points are located near the exits of service areas;others are situated in the centre of the service areas.For the Cainiao Stations, 80% are located within 125 m of the exit;for the China Post stations, 80% are located within 175 m of the exit.4) The spatial distribution of the attended collection and delivery points in Changsha is unbalanced, with ‘more centre and fewer surrounding’.The centre is an ‘inverted triangle’, and the edge is an ‘orphan’, showing a northwest-southeast orientation and symmetrical along the axis.The layout of the attended collection and delivery points forms three core areas, and the number of sites decreases with the distance from the core.5) The number and distribution of the attended collection and delivery points are strongly consistent with the regional economic development level, population, and roadway system traffic convenience.Most attended collection and delivery points are on residential, scientific and educational, and commercial and financial land.
基金funded by National Natural Science Foundation of China(No.81302686)Primary Research&Developement Plan of Shandong Province(No.2016GSF201083)
文摘Vascular endothelial growth factor receptor 2(VEGFR-2)and neuropilin-1(NRP-1)are two prominent antiangiogenic targets.They are highly expressed on vascular endothelial cells and some tumor cells.Therefore,targeting VEGFR-2 and NRP-1 may be a potential antiangiogenic and antitumor strategy.A7R,a peptide with sequence of Ala-Thr-Trp-Leu-Pro-Pro-Arg that was found by phage display of peptide libraries,can preferentially target VEGFR-2 and NRP-1 and destroy the binding between vascular endothelial growth factor 165(VEGF165)and VEGFR-2 or NRP-1.This peptide is a new potent inhibitor of tumor angiogenesis and a targeting ligand for cancer therapy.This review describes the discovery,function and mechanism of the action of A7R,and further introduces the applications of A7R in antitumor angiogenic treatments,tumor angiogenesis imaging and targeted drug delivery systems.In this review,strategies to deliver different drugs by A7R-modified liposomes and nanoparticles are highlighted.A7R,a new dual targeting ligand of VEGFR-2 and NRP-1,is expected to have efficient therapeutic or targeting roles in tumor drug delivery.
基金Supported by The Belgian Directorate for Development Cooperation through the Institute of Tropical Medicine,Antwerp
文摘A contextual review of models for chronic care was done to develop a context-adapted chronic care model-based service delivery model for chronic conditions including diabetes.The Philippines was used as the setting of a low-to-middle-income country.A context-based narrative review of existing models for chronic care was conducted.A situational analysis was done at thegrassroots level,involving the leaders and members of the community,the patients,the local health system and the healthcare providers.A second analysis making use of certain organizational theories was done to explore on improving feasibility and acceptability of organizing care for chronic conditions.The analyses indicated that care for chronic conditions may be introduced,considering the needs of people with diabetes in particular and the community in general as recipients of care,and the issues and factors that may affect the healthcare workers and the health system as providers of this care.The context-adapted chronic care model-based service delivery model was constructed accordingly.Key features are:incorporation of chronic care in the health system's services; assimilation of chronic care delivery with the other responsibilities of the healthcare workers but with redistribution of certain tasks; and ensuring that the recipients of care experience the whole spectrum of basic chronic care that includes education and promotion in the general population,risk identification,screening,counseling including self-care development,and clinical management of the chronic condition and any co-morbidities,regardless of level of control of the condition.This way,low-to-middle income countries can introduce and improve care for chronic conditions without entailing much additional demand on their limited resources.
文摘Often we encounter documents with text printed on complex color background. Readability of textual contents in such documents is very poor due to complexity of the background and mix up of color(s) of foreground text with colors of background. Automatic segmentation of foreground text in such document images is very much essential for smooth reading of the document contents either by human or by machine. In this paper we propose a novel approach to extract the foreground text in color document images having complex background. The proposed approach is a hybrid approach which combines connected component and texture feature analysis of potential text regions. The proposed approach utilizes Canny edge detector to detect all possible text edge pixels. Connected component analysis is performed on these edge pixels to identify candidate text regions. Because of background complexity it is also possible that a non-text region may be identified as a text region. This problem is overcome by analyzing the texture features of potential text region corresponding to each connected component. An unsupervised local thresholding is devised to perform foreground segmentation in detected text regions. Finally the text regions which are noisy are identified and reprocessed to further enhance the quality of retrieved foreground. The proposed approach can handle document images with varying background of multiple colors and texture;and foreground text in any color, font, size and orientation. Experimental results show that the proposed algorithm detects on an average 97.12% of text regions in the source document. Readability of the extracted foreground text is illustrated through Optical character recognition (OCR) in case the text is in English. The proposed approach is compared with some existing methods of foreground separation in document images. Experimental results show that our approach performs better.
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.
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.
文摘Background:This study focused on developing and optimizing a self-microemulsifying drug delivery system(SMEDDS)to improve Lafutidine’s solubility and bioavailability,thereby enhancing its effectiveness in treating gastric ulcers.Traditional formulations are less effective due to their limited water solubility and bioavailability.Methods:The study used solubility tests,pseudo-ternary phase diagrams,and central composite design(CCD)to optimize.The formulation was optimized by varying the oil concentration(10–40%)and surfactant/cosurfactant ratio(0.33–3.00),and then tested for droplet size,drug content,emulsification,phase stability,and in vitro dissolution.Results:The study found that the optimized formulation contained 14%Capmul PG 8NF oil,62%Labrasol surfactant,and 24%Tween 80 cosurfactant.This combination generated an average droplet size of 111.02 nm and improved drug release properties.Furthermore,the formulation was stable without phase separation,with a drug content of 88.2–99.8%.Conclusion:SMEDDS significantly improves lafutidine delivery by increasing solubility and absorption,thereby overcoming oral administration challenges.The system quickly formed small droplets in water and released the drug in 15 min.Enhancing lafutidine’s bioavailability may improve its efficacy in treating gastric ulcers,resulting in better patient outcomes and potentially lower dosing frequency.
基金financially supported by Sichuan Province Science and Technology Support Program(Nos.16ZC2698 and 2018JY0582)the National Natural Science Foundation of China(No.81872821)。
文摘Nowadays,tremendous researches have been focused on the core-shell lipid-polymer nanoparticles(LPNs) due to the advantages of both liposomes and polymer nanoparticles.In this work,LPNs were applied to encapsulate brinzolamide(Brz-LPNs) for achieving sustained drug release,improving drug corneal permeation and enhancing drug topical therapeutic effect.The structure of Brz-LPNs was composed of poly(lactic-co-glycolic) acid(PLGA) nanocore which encapsulated Brz(Brz-NPs) and lipid shell around the core.Brz-LPNs were prepared by a modified thin-film dispersion method.With the parameters optimization of Brz-LPNs,optimal Brz-LPNs showed an average particle size of151.23±1.64 nm with a high encapsulation efficiency(EE) of 86.7%±2.28%.The core-shell structure of Brz-LPNs were confirmed by transmission electronic microscopy(TEM).Fourier transformed infrared spectra(FTIR) analysis proved that Brz was successfully entrapped into Brz-LPNs.Brz-LPNs exhibited obvious sustained release of Brz,compared with AZOPT^■ and Brz-LPs.Furthermore,the corneal accumulative permeability of Brz-LPNs significantly increased compared to the commercial available formulation(AZOPT^■) in vitro.Moreover,Brz-LPNs(1 mg/mL Brz) showed a more sustained and effective intraocular pressure(IOP) reduction than Brz-LPs(1 mg/mL) and AZOPT^■(10 mg/mL Brz) in vivo.In conclusion,Brz-LPNs,as promising ocular drug delivery systems,are well worth developing in the future for glaucoma treatment.
基金supported by the Key Laboratory of Advanced Interdisciplinary Studies,The First Affiliated Hospital of Guangzhou Medical University of China(No.2023A03J0355)OpenProject of State Key Laboratory of Respiratory Disease of China(No.SKIRD OP-202311)Guangdong Provincial Zhong Nanshan Medical Foundation of China(No.ZNS-XS-ZZ-202409-007).
文摘In non-small cell lung cancer(NSCLC),poly(ADP-ribose)polymerase 1(PARP1)induces genomic instability and promotes tumor progression by impairing DNA repair pathways.Although PARP1-targeting proteolysis-targeting chimeras(PROTACs)offer a promising strategy for selective protein degradation,their clinical application remains limited by poor water solubility and insufficient tumor selectivity.Here,we report a pHresponsive magnetic nanoparticle system co-delivering β-lapachone(β-lap)and a PARP1-targeted PROTAC(PRO)for synergistic and tumor-targeting therapy.Designed with a hydrophobic self-assembled core and a magnetic coating,the nanoparticle(NP_(β-lap+PRO))enables pHresponsive drug release and magnetic resonance imaging(MRI)monitoring.β-Lap is a bioactivated drug that relies on NAD(P)H:quinone oxidoreductase 1(NQO1),which is overexpressed in NSCLC cells.It has the potential to deliver tumor-selective DNA damage and induce cell death.The NP_(β-lap+PRO) exploits elevated NQO1 levels in NSCLC to initiate β-lap-driven oxidative stress and DNA damage,while simultaneously enhancing PROTAC-mediated PARP1 degradation within the acidic tumor microenvironment synergistically induces apoptosis.In A549 NSCLC tumor models,this system effectively induces PARP1 degradation,blocks DNA repair,and preserves NAD(P)H pools,thereby amplifying β-lapinduced reactive oxygen species production,leading to enhanced DNA double-strand breaks and apoptosis.This study presents a biomarker-driven nanotherapeutic strategy that integrates PROTAC technology with redox-targeted combination therapy,offering a promising approach for precision treatment of NSCLC.
