Recent advances in zwitterionic nanoscale drug delivery systems to overcome biological barriers

Nanoscale drug delivery systems(nDDS)have been employed widely in enhancing the therapeutic efficacy of drugs against diseases with reduced side effects.Although several nDDS have been successfully approved for clinical use up to now,biological barriers between the administration site and the target site hinder the wider clinical adoption of nDDS in disease treatment.Polyethylene glycol(PEG)-modification(or PEGylation)has been regarded as the gold standard for stabilising nDDS in complex biological environment.However,the accelerated blood clearance(ABC)of PEGylated nDDS after repeated injections becomes great challenges for their clinical applications.Zwitterionic polymer,a novel family of antifouling materials,have evolved as an alternative to PEG due to their super-hydrophilicity and biocompatibility.Zwitterionic nDDS could avoid the generation of ABC phenomenon and exhibit longer blood circulation time than the PEGylated analogues.More impressively,zwitterionic nDDS have recently been shown to overcome multiple biological barriers such as nonspecific organ distribution,pressure gradients,impermeable cell membranes and lysosomal degradation without the need of any complex chemical modifications.The realization of overcoming multiple biological barriers by zwitterionic nDDS may simplify the current overly complex design of nDDS,which could facilitate their better clinical translation.Herein,we summarise the recent progress of zwitterionic nDDS at overcoming various biological barriers and analyse their underlyingmechanisms.Finally,prospects and challenges are introduced to guide the rational design of zwitterionic nDDS for disease treatment.

Utilizing engineered extracellular vesicles as delivery vectors in the management of ischemic stroke:a special outlook on mitochondrial delivery

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.

Microgels for Cell Delivery in Tissue Engineering and Regenerative Medicine

Microgels prepared from natural or synthetic hydrogel materials have aroused extensive attention as multifunctional cells or drug carriers,that are promising for tissue engineering and regenerative medicine.Microgels can also be aggregated into microporous scaffolds,promoting cell infiltration and proliferation for tissue repair.This review gives an overview of recent developments in the fabrication techniques and applications of microgels.A series of conventional and novel strategies including emulsification,microfluidic,lithography,electrospray,centrifugation,gas-shearing,three-dimensional bioprinting,etc.are discussed in depth.The characteristics and applications of microgels and microgel-based scaffolds for cell culture and delivery are elaborated with an emphasis on the advantages of these carriers in cell therapy.Additionally,we expound on the ongoing and foreseeable applications and current limitations of microgels and their aggregate in the field of biomedical engineering.Through stimulating innovative ideas,the present review paves new avenues for expanding the application of microgels in cell delivery techniques.

Digital twin driven and intelligence enabled content delivery in end-edge-cloud collaborative 5G networks

The rapid development of 5G/6G and AI enables an environment of Internet of Everything(IoE)which can support millions of connected mobile devices and applications to operate smoothly at high speed and low delay.However,these massive devices will lead to explosive traffic growth,which in turn cause great burden for the data transmission and content delivery.This challenge can be eased by sinking some critical content from cloud to edge.In this case,how to determine the critical content,where to sink and how to access the content correctly and efficiently become new challenges.This work focuses on establishing a highly efficient content delivery framework in the IoE environment.In particular,the IoE environment is re-constructed as an end-edge-cloud collaborative system,in which the concept of digital twin is applied to promote the collaboration.Based on the digital asset obtained by digital twin from end users,a content popularity prediction scheme is firstly proposed to decide the critical content by using the Temporal Pattern Attention(TPA)enabled Long Short-Term Memory(LSTM)model.Then,the prediction results are input for the proposed caching scheme to decide where to sink the critical content by using the Reinforce Learning(RL)technology.Finally,a collaborative routing scheme is proposed to determine the way to access the content with the objective of minimizing overhead.The experimental results indicate that the proposed schemes outperform the state-of-the-art benchmarks in terms of the caching hit rate,the average throughput,the successful content delivery rate and the average routing overhead.

Molecular Mechanisms of Intracellular Delivery of Nanoparticles Monitored by an Enzyme‑Induced Proximity Labeling

Achieving increasingly finely targeted drug delivery to organs,tissues,cells,and even to intracellular biomacromolecules is one of the core goals of nanomedicines.As the delivery destination is refined to cellular and subcellular targets,it is essential to explore the delivery of nanomedicines at the molecular level.However,due to the lack of technical methods,the molecular mechanism of the intracellular delivery of nanomedicines remains unclear to date.Here,we develop an enzyme-induced proximity labeling technology in nanoparticles(nano-EPL)for the real-time monitoring of proteins that interact with intracellular nanomedicines.Poly(lactic-co-glycolic acid)nanoparticles coupled with horseradish peroxidase(HRP)were fabricated as a model(HRP(+)-PNPs)to evaluate the molecular mechanism of nano delivery in macrophages.By adding the labeling probe biotin-phenol and the catalytic substrate H_(2)O_(2)at different time points in cellular delivery,nano-EPL technology was validated for the real-time in situ labeling of proteins interacting with nanoparticles.Nano-EPL achieves the dynamic molecular profiling of 740 proteins to map the intracellular delivery of HRP(+)-PNPs in macrophages over time.Based on dynamic clustering analysis of these proteins,we further discovered that different organelles,including endosomes,lysosomes,the endoplasmic reticulum,and the Golgi apparatus,are involved in delivery with distinct participation timelines.More importantly,the engagement of these organelles differentially affects the drug delivery efficiency,reflecting the spatial–temporal heterogeneity of nano delivery in cells.In summary,these findings highlight a significant methodological advance toward understanding the molecular mechanisms involved in the intracellular delivery of nanomedicines.

Advancing ophthalmic delivery of flurbiprofen via synergistic chiral resolution and ion-pairing strategies

Flurbiprofen(FB),a nonsteroidal anti-inflammatory drug,is widely employed in treating ocular inflammation owing to its remarkable anti-inflammatory effects.However,the racemic nature of its commercially available formulation(Ocufen^(R))limits the full potential of its therapeutic activity,as the(S)-enantiomer is responsible for the desired antiinflammatory effects.Additionally,the limited corneal permeability of FB significantly restricts its bioavailability.In this study,we successfully separated the chiral isomers of FB to obtain the highly active(S)-FB.Subsequently,utilizing ion-pairing technology,we coupled(S)-FB with various counter-ions,such as sodium,diethylamine,trimethamine(TMA),and l-arginine,to enhance its ocular bioavailability.A comprehensive evaluation encompassed balanced solubility,octanol-water partition coefficient,corneal permeability,ocular pharmacokinetics,tissue distribution,and in vivo ocular anti-inflammatory activity of each chiral isomer salt.Among the various formulations,S-FBTMA exhibited superior water solubility(about 1–12 mg/ml),lipid solubility(1<lgP_(ow)<3)and corneal permeability.In comparison to Ocufen^(R),S-FBTMA demonstrated significantly higher in vivo antiinflammatory activity and lower ocular irritability(such as conjunctival congestion and tingling).The findings from this research highlight the potential of chiral separation and ion-pair enhanced permeation techniques in providing pharmaceutical enterprises focused on drug development with a valuable avenue for improving therapeutic outcomes.

Which Neighborhoods Have Easier Access to Online Home Delivery Services?A Spatiotemporal Accessibility Analysis in Nanjing,China

The rise in online home delivery services(OHDS)has had a significant impact on how urban services are supplied and used in recent years.Studies on the spatial accessibility of OHDS are emerging,but few is known about the temporal dimension of OHDS accessibility as well as the geographic and socioeconomic differences in the spatiotemporal accessibility of OHDS.This study measures the spatiotemporal accessibility of four types of OHDS,namely leisure,fresh and convenient,medical,and catering services.The geographic and socioeconomic disparities in the spatiotemporal accessibility of these four types of OHDS are then identified using spatial statistical methods and the Kruskal-Wallis test(K-W test).The case study in Nanjing,China,suggests that:1)spatiotemporal accessibility better reflects the temporal variation of OHDS accessibility and avoids overestimation of OHDS accessibility when only considering its spatial dimension.2)The spatiotemporal accessibility of OHDS varies geographically and socioeconomically.Neighborhoods located in the main city or neighborhoods with higher housing prices,higher population density,and higher point of interest(POI)mix have better OHDS spatiotemporal accessibility.Our study contributes to the understanding of OHDS accessibility from a spatiotemporal perspective,and the empirical insights can assist policymakers in creating intervention plans that take into account variations in OHDS spatiotemporal accessibility.

Layered Coded Cache Placement and Cooperative Delivery with Sharing Links in Satellite-Terrestrial Integrated Networks

Cooperative utilization of multidimensional resources including cache, power and spectrum in satellite-terrestrial integrated networks(STINs) can provide a feasible approach for massive streaming media content delivery over the seamless global coverage area. However, the on-board supportable resources of a single satellite are extremely limited and lack of interaction with others. In this paper, we design a network model with two-layered cache deployment, i.e., satellite layer and ground base station layer, and two types of sharing links, i.e., terrestrial-satellite sharing(TSS) links and inter-satellite sharing(ISS) links, to enhance the capability of cooperative delivery over STINs. Thus, we use rateless codes for the content divided-packet transmission, and derive the total energy efficiency(EE) in the whole transmission procedure, which is defined as the ratio of traffic offloading and energy consumption. We formulate two optimization problems about maximizing EE in different sharing scenarios(only TSS and TSS-ISS),and propose two optimized algorithms to obtain the optimal content placement matrixes, respectively.Simulation results demonstrate that, enabling sharing links with optimized cache placement have more than 2 times improvement of EE performance than other traditional placement schemes. Particularly, TSS-ISS schemes have the higher EE performance than only TSS schemes under the conditions of enough number of satellites and smaller inter-satellite distances.

Oral administration microrobots for drug delivery

Oral administration is the most simple, noninvasive, convenient treatment. With the increasing demands on thetargeted drug delivery, the traditional oral treatment now is facing some challenges: 1) biologics how toimplement the oral treatment and ensure the bioavailability is not lower than the subcutaneous injections;2)How to achieve targeted therapy of some drugs in the gastrointestinal tract? Based on these two issues, drugdelivery microrobots have shown great application prospect in oral drug delivery due to their characteristics offlexible locomotion or driven ability. Therefore, this paper summarizes various drug delivery microrobotsdeveloped in recent years and divides them into four categories according to different driving modes: magneticcontrolleddrug delivery microrobots, anchored drug delivery microrobots, self-propelled drug delivery microrobotsand biohybrid drug delivery microrobots. As oral drug delivery microrobots involve disciplines such asmaterials science, mechanical engineering, medicine, and control systems, this paper begins by introducing thegastrointestinal barriers that oral drug delivery must overcome. Subsequently, it provides an overview of typicalmaterials involved in the design process of oral drug delivery microrobots. To enhance readers’ understanding ofthe working principles and design process of oral drug delivery microrobots, we present a guideline for designingsuch microrobots. Furthermore, the current development status of various types of oral drug delivery microrobotsis reviewed, summarizing their respective advantages and limitations. Finally, considering the significantconcerns regarding safety and clinical translation, we discuss the challenges and prospections of clinical translationfor various oral drug delivery microrobots presented in this paper, providing corresponding suggestions foraddressing some existing challenges.

Spatiotemporal transformable nano-assembly for on-demand drug delivery to enhance anti-tumor immunotherapy

Induction of tumor cell senescence has become a promising strategy for anti-tumor immunotherapy,but fibrotic matrix severely blocks senescence inducers penetration and immune cells infiltration.Herein,we designed a cancer-associated fibroblasts(CAFs)triggered structure-transformable nano-assembly(HSD-P@V),which can directionally deliver valsartan(Val,CAFs regulator)and doxorubicin(DOX,senescence inducer)to the specific targets.In detail,DOX is conjugated with hyaluronic acid(HA)via diselenide bonds(Se-Se)to form HSD micelles,while CAFs-sensitive peptide is grafted onto the HSD to form a hydrophilic polymer,which is coated on Val nanocrystals(VNs)surface for improving the stability and achieving responsive release.Once arriving at tumor microenvironment and touching CAFs,HSD-P@V disintegrates into VNs and HSD micelles due to sensitive peptide detachment.VNs can degrade the extracellularmatrix,leading to the enhanced penetration of HSD.HSD targets tumor cells,releases DOX to induce senescence,and recruits effector immune cells.Furthermore,senescent cells are cleared by the recruited immune cells to finish the integrated anti-tumor therapy.In vitro and in vivo results show that the nanoassembly remarkably inhibits tumor growth as well as lungmetastasis,and extends tumorbearing mice survival.This work provides a promising paradigm of programmed delivering multi-site nanomedicine for cancer immunotherapy.

Preparation and Characterization of pH-Responsive Charge Reversal Nanocomposite for miRNA Delivery

pH-responsive charge reversal loaded miRNA nanocomposite was prepared by electrostatic self-assembly.The morphology,particle size and zeta potential of the nanocomposites were analyzed by transmission electron microscopy and dynamic light scattering.The synthesis of the polymer was analyzed by^(1)H-NMR.The zeta-potential changes and cellular uptake effects of the nanocomplexes under different pH environments were investigated.The experimental results show that the surface morphology of the nanocomposite is spherical,and the average particle size is about 135 nm.As the pH value of the solution gradually decreases,the surface charge of the nanocomposite reverses from negative charge to positive charge(from-9.4 to+17.1 mV).Cellular uptake mediated by pH-responsive nanocomposite is selective for tumor cells,and the cellular uptake effect in tumor cells at pH 6.5 was approximately 3 times higher than that at pH 7.4.This pH responsive charge reversal nanocomposite has promising application prospects for gene delivery in the weak acid environment of tumors.

The state-of-the-art of atmospheric pressure plasma for transdermal drug delivery

Plasma-enhanced transdermal drug delivery(TDD) presents advantages over traditional methods,including painless application, minimal skin damage, and rapid recovery of permeability. To harness its clinical potential, factors related to plasma’s unique properties, such as reactive species and electric fields, must be carefully considered.This review provides a concise summary of conventional TDD methods and subsequently offers a comprehensive examination of the current state-of-the-art in plasma-enhanced TDD. This includes an analysis of the impact of plasma on HaCaT human keratinocyte cells, ex vivo/in vivo studies, and clinical research on plasma-assisted TDD. Moreover, the review explores the effects of plasma on skin physical characteristics such as microhole formation, transepidermal water loss(TEWL), molecular structure of the stratum corneum(SC), and skin resistance. Additionally, it discusses the involvement of various reactive agents in plasma-enhanced TDD, encompassing electric fields,charged particles, UV/VUV radiation, heat, and reactive species. Lastly, the review briefly addresses the temporal behavior of the skin after plasma treatment, safety considerations, and potential risks associated with plasma-enhanced TDD.

Uncertainty quantification of mechanism motion based on coupled mechanism—motor dynamic model for ammunition delivery system

In this paper,a dynamic modeling method of motor driven electromechanical system is presented,and the uncertainty quantification of mechanism motion is investigated based on this method.The main contribution is to propose a novel mechanism-motor coupling dynamic modeling method,in which the relationship between mechanism motion and motor rotation is established according to the geometric coordination of the system.The advantages of this include establishing intuitive coupling between the mechanism and motor,facilitating the discussion for the influence of both mechanical and electrical parameters on the mechanism,and enabling dynamic simulation with controller to take the randomness of the electric load into account.Dynamic simulation considering feedback control of ammunition delivery system is carried out,and the feasibility of the model is verified experimentally.Based on probability density evolution theory,we comprehensively discuss the effects of system parameters on mechanism motion from the perspective of uncertainty quantization.Our work can not only provide guidance for engineering design of ammunition delivery mechanism,but also provide theoretical support for modeling and uncertainty quantification research of mechatronics system.

A food-grade and senescent cell-targeted fisetin delivery system based on whey protein isolate-galactooligosaccharides Maillard conjugate

Cellular senescence is the results of aging and age-related diseases,and the development of anti-aging methods may improve health and extend longevity.The natural flavonol fisetin has been shown to antagonize senescence in vitro and increases longevity in vivo,but has poor water solubility and limited bioavailability.In this study,a food-grade and senescent cell-targeted delivery system for fisetin was developed based on whey protein isolate-galactooligosaccharides(WPI-GOS)Maillard conjugate,which could recognize senescence associatedβ-galactosidase in senescent cells.The fisetin nanoparticles possessed a high encapsulation efficiency,excellent dispersibility in water,good storage stability and well biocompatibility.Moreover,they could effectively accumulate and retain in senescent cells with excellent senescent cell-targeting efficacy,and inhibit the oxidative stress-induced cellular senescence in vitro.Thus,this novel nanoparticle system based on WPI-GOS Maillard conjugate showed promise to deliver hydrophobic bioactive ingredients like fisetin to senescent cells to improve their bioavailability and anti-senescence effect.

Stem cell technology for antitumor drug loading and delivery in oncology

The main aim of antineoplastic treatment is to maximize patient benefit by augmenting the drug accumulation within affected organs and tissues,thus incrementing drug effects and,at the same time,reducing the damage of non-involved tissues to cytotoxic agents.Mesenchymal stromal cells(MSC)represent a group of undifferentiated multipotent cells presenting wide self-renewal features and the capacity to differentiate into an assortment of mesenchymal family cells.During the last year,they have been proposed as natural carriers for the selective release of antitumor drugs to malignant cll,s thus optimizing cytotoxic action on cancer cll,while significantly reducing adverse side efect on healthy cells.MSC chemotherapeutic drug loading and delivery is an encouraging new area of cell therapy for several tumors,especially for those with unsatisfactory prognosis and limited treatment options available.Although some experim ental models have been sucesfuly developed,phase I dinical studies are needed to confirm this potential application of cell therapy,in particular in the case of primary and secondary lung cancers.

Ionic liquids as the effective technology for enhancing transdermal drug delivery: Design principles, roles, mechanisms, and future challenges

Ionic liquids (ILs) have been proven to be an effective technology for enhancing drug transdermal absorption. However, due to the unique structural components of ILs, the design of efficient ILs and elucidation of action mechanisms remain to be explored. In this review, basic design principles of ideal ILs for transdermal drug delivery system (TDDS) are discussed considering melting point, skin permeability, and toxicity, which depend on the molar ratios, types, functional groups of ions and inter-ionic interactions. Secondly, the contributions of ILs to the development of TDDS through different roles are described: as novel skin penetration enhancers for enhancing transdermal absorption of drugs;as novel solvents for improving the solubility of drugs in carriers;as novel active pharmaceutical ingredients (API-ILs) for regulating skin permeability, solubility, release, and pharmacokinetic behaviors of drugs;and as novel polymers for the development of smart medical materials. Moreover, diverse action mechanisms, mainly including the interactions among ILs, drugs, polymers, and skin components, are summarized. Finally, future challenges related to ILs are discussed, including underlying quantitative structure-activity relationships, complex interaction forces between anions, drugs, polymers and skin microenvironment, long-term stability, and in vivo safety issues. In summary, this article will promote the development of TDDS based on ILs.

Vehicle-oriented ridesharing package delivery in blockchain system

Package delivery via ridesharing provides appealing benefits of lower delivery cost and efficient vehicle usage.Most existing ridesharing systems operate the matching of ridesharing in a centralized manner,which may result in the single point of failure once the controller breaks down or is under attack.To tackle such problems,our goal in this paper is to develop a blockchain-based package delivery ridesharing system,where decentralization is adopted to remove intermediaries and direct transactions between the providers and the requestors are allowed.To complete the matching process under decentralized structure,an Event-Triggered Distributed Deep Reinforcement Learning(ETDDRL)algorithm is proposed to generate/update the real-time ridesharing orders for the new coming ridesharing requests from a local view.Simulation results reveal the vast potential of the ETDDRL matching algorithm under the blockchain framework for the promotion of the ridesharing profits.Finally,we develop an application for Android-based terminals to verify the ETDDRL matching algorithm.

Ultrasound combined blood-brain barrier targeting brain delivery of four-in-one molecular aggregates for the enhancement of anesthetic efficacy and toxicity reduction via propofol-etomidate synergistically inhibition GABA receptor

To enhance the anesthetic efficacy and reduce toxic side effects,a strategy is proposed involving the utilization of general anesthetics of Propofol(Pro)and Eto-midate(Eto)to synergistic inhibition GABA receptors simultaneously.Four-in-one molecular aggregates were prepared to implement this strategy,which comprised of Pro and Eto with the bridging molecule monoglyceride monooleate(GMO)and sur-factant F127 through intermolecular forces.The blood-brain barrier(BBB)targeted lactoferrin(LF)is affixed to their surface,obtaining thefinal molecular aggregates.By employing lactoferrin enrich aggregates to the BBB,followed by ultrasound combine microbubbles to open the BBB,a remarkable 4.5-fold enhancement in brain drug delivery was achieved.The molecular aggregates group maintained sta-ble parameters of heart rate,diastolic blood pressure,and systolic blood pressure.A notable increase of more than twice therapeutic index(TI)value was observed,implying their higher anesthesia efficiency and reduced toxicity.Electroencephalo-gram(EEG)experiments demonstrate a significant elevation in the proportion of θ waves from 28%to 80%for aggregates,accompanied by a nearlyfivefold reduc-tion in the proportion ofθwaves,meaning a significant improvement in synergistic anesthesia effectiveness(interaction index 0.289)with lower drug dosage.Further-more,mouse immunofluorescence brain slice experiments suggest Pro and Eto enter the GABA receptor simultaneously,resulting in synergistic inhibition of GABA receptors.

Evaluation of hybrid closed-loop insulin delivery system in type 1 diabetes in real-world clinical practice:One-year observational study

BACKGROUND In 2016,the Food and Drug Administration approved the first hybrid closed-loop(HCL)insulin delivery system for adults with type 1 diabetes(T1D).There is limited information on the impact of using HCL systems on patient-reported outcomes(PROs)in patients with T1D in real-world clinical practice.In this independent study,we evaluated glycemic parameters and PROs over one year of continuous use of Medtronic’s 670G HCL in real-world clinical practice.AIM To assess the effects of hybrid closed loop system on glycemic control and quality of life in adults with T1D.METHODS We evaluated 71 patients with T1D(mean age:45.5±12.1 years;59%females;body weight:83.8±18.7 kg,body mass index:28.7±5.6 kg/m2,A1C:7.6%±0.8%)who were treated with HCL at Joslin Clinic from 2017 to 2019.We measured A1C and percent of glucose time-in-range(%TIR)at baseline and 12 months.We measured percent time in auto mode(%TiAM)for the last two weeks preceding the final visit and assessed PROs through several validated quality-of-life surveys related to general health and diabetes management.RESULTS At 12 mo,A1C decreased by 0.3%±0.1%(P=0.001)and%TIR increased by 8.1%±2.5%(P=0.002).The average%TiAM was only 64.3%±32.8%and was not associated with A1C,%TIR or PROs.PROs,provided at baseline and at the end of the study,showed that the physical functioning submodule of 36Item Short-Form Health Survey increased significantly by 22.9%(P<0.001).Hypoglycemia fear survey/worry scale decreased significantly by 24.9%(P<0.000);Problem Areas In Diabetes reduced significantly by-17.2%(P=0.002).The emotional burden submodules of dietary diversity score reduced significantly by-44.7%(P=0.001).Furthermore,analysis of Clarke questionnaire showed no increase in awareness of hypoglycemic episodes.WHO-5 showed no improvements in subject’s wellbeing among participants after starting the 670G HCL system.Finally,analysis of Pittsburgh Sleep Quality Index showed no difference in sleep quality,sleep latency,or duration of sleep from baseline to 12 mo.CONCLUSION The use of HCL in real-world clinical practice for one year was associated with significant improvements in A1C,%TIR,physical functioning,hypoglycemia fear,emotional distress,and emotional burden related to diabetes management.However,these changes were not associated with time in auto mode.

Research and application of key technologies for data delivery in railway engineering design based on metadata

In view of the problems of inconsistent data semantics,inconsistent data formats,and difficult data quality assurance between the railway engineering design phase and the construction and operation phase,as well as the difficulty in fully realizing the value of design results,this paper proposes a design and implementation scheme for a railway engineering collaborative design platform.The railway engineering collaborative design platform mainly includes functional modules such as metadata management,design collaboration,design delivery management,model component library,model rendering services,and Building Information Modeling(BIM)application services.Based on this,research is conducted on multi-disciplinary parameterized collaborative design technology for railway engineering,infrastructure data management and delivery technology,and design multi-source data fusion and application technology.The railway engineering collaborative design platform is compared with other railway design software to further validate its advantages and advanced features.The platform has been widely applied in multiple railway construction projects,greatly improving the design and project management efficiency.