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.

Development and Evaluation of 3D Delivery Animation Software Designed to Improve the Mother’s and Spouse’s Satisfaction with Delivery

Purpose: To clarify the effectiveness of 3-D delivery animation software for the mother’s and husband’s satisfaction with delivery. Subjects and Method: We independently developed a software application used to display the pelvic region and explain the labor process. The study involved a collaboration with hospital staff who recruited 18 primiparous and 18 multiparous mothers who were hospitalized for delivery at Facility A. The midwife explained the process of delivery using the “Delivery Animation Software”. A self-administered, anonymous questionnaire was distributed and analyzed separately for primiparous and multiparous mothers and their husbands. Results: 1) For both primiparous and multiparous couples, both mothers and their husbands gained a significantly higher level of understanding after delivery than during pregnancy. 2) The Self-Evaluation Scale for Experience of Delivery results were as follows: “I did my best for the baby even if it was painful” was selected more often for “birth coping skills”;“reliable medical staff” was selected more often for “physiological birth process”;“the birth progressed as I expected” was selected frequently by primiparous mothers;and “the birth progressed smoothly” was selected often by multiparous mothers. 3) In terms of husbands’ satisfaction with the delivery, “I was satisfied with the delivery”, “I was given an easy-to-understand explanation”, and “They explained the process to me” was selected of primiparous and multiparous fathers. 4) All primiparous and multiparous mothers positively evaluated whether the delivery animation was helpful in understanding the process of delivery. Conclusion: The delivery animation was effective in improving the understanding and satisfaction of both the mothers and their husbands.

Enhancing Private Healthcare Effectiveness in Lagos State, Nigeria: An Overview of the Effect of Quality Improvement Initiatives and Implications for Sustainable Healthcare Delivery

Background: Nigeria, a nation grappling with rapid population growth, economic intricacies, and complex healthcare challenges, particularly in Lagos State, the economic hub and most populous state, faces the challenge of ensuring quality healthcare access. The overview of the effect of quality improvement initiatives in this paper focuses on private healthcare providers in Lagos State, Nigeria. The study assesses the impact of donor-funded quality improvement projects on these private healthcare facilities. It explores the level of participation, perceived support, and tangible effects of the initiatives on healthcare delivery within private healthcare facilities. It also examines how these initiatives influence patient inflow and facility ratings, and bring about additional benefits and improvements, provides insights into the challenges faced by private healthcare providers in implementing quality improvement projects and elicits recommendations for improving the effectiveness of such initiatives. Methods: Qualitative research design was employed for in-depth exploration, utilizing semi-structured interviews. Private healthcare providers in Lagos involved in the SP4FP Quality Improvement Project were purposively sampled for diversity. Face-to-face interviews elicited insights into participation, perceived support, and project effects. Questions covered participation levels, support perception, changes observed, challenges faced, and recommendations. Thematic analysis identified recurring themes from interview transcripts. Adherence to ethical guidelines ensured participant confidentiality and informed consent. Results: Respondents affirmed active involvement in the SP4FP Quality Improvement Project, echoing literature emphasizing private-sector collaboration with the public sector. While acknowledging positive influences on facility ratings, respondents highlighted challenges within the broader Nigerian healthcare landscape affecting patient numbers. Respondents cited tangible improvements, particularly in staff management and patient care processes, validating the positive influence of quality improvement projects. Financial constraints emerged as a significant challenge, aligning with existing literature emphasizing the pragmatic difficulties faced by private healthcare providers. Conclusions: This study illuminates the complex landscape of private healthcare provision in Lagos State, emphasizing the positive impact of donor-funded quality improvement projects. The findings provide nuanced insights, guiding policymakers, healthcare managers, and practitioners toward collaborative, sustainable improvements. As Nigeria progresses, these lessons will be crucial in shaping healthcare policies prioritizing population well-being.

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.

A Proposed Approach for Measuring Maturity Level of Software Delivery

Software delivery is vital for modern organizations, driving innovation and competitiveness. Measuring an organization’s maturity in software delivery is crucial for efficiency and quality. The Capability Maturity Model (CMM) framework provides a roadmap for improvement but assessing an organization’s CMM Level is challenging. This paper offers a quantitative approach tailored to the CMM framework, using Goal-Question-Metric (GQM) frame-works for each key process area (KPA). These frameworks include metrics and questions to compute maturity scores effectively. The study also refines practices into questions for a thorough assessment. The result is an Analysis Matrix that calculates weighted scores and an overall maturity score. This approach helps organizations assess and enhance their software delivery processes systematically, aiming for improved practices and growth.

Targeting therapy for hepatocellular carcinoma by delivering microRNAs as exosomal cargo

Exosomes,the smallest extracellular vesicles,have gained significant attention as key mediators in intercellular communication,influencing both physiological and pathological processes,particularly in cancer progression.A recent review article by Wang et al was published in a timely manner to stimulate future research and facilitate practical developments for targeted treatment of hepatocellular carcinoma using exosomes,with a focus on the origin from which exosomes derive.If information about the mechanisms for delivering exosomes to specific cells is incorporated,the concept of targeted therapy for hepatocellular carcinoma using exosomes could be more comprehensively understood.

Epidemiological Aspects of Stillbirth and Neonatal Deaths in the Delivery Room at the Libreville Mother-Child University Hospital from 2019 to 2022

Introduction: Stillbirths are estimated at 2 million each year, of which more than 40% occur during labour. Our objective was to study the epidemiological aspects of stillbirth and neonatal deaths in the delivery room in our health facility. Patients and methods: Prospective, descriptive and analytical study, conducted at the Jeanne Ebori Foundation Mother-Child University Hospital over 4 years (January 2019-December 2022). All neonatal deaths in the delivery room or foetal death in utero, were included. Results: Among the 18,346 deliveries performed, 512 newborns were declared dead in the delivery room (27.9‰ live births), divided into in utero foetal death (19.0‰) and immediate neonatal death (8.9‰). The mean age was 34.3 weeks of amenorrhea. The rate of preterm birth was 60.4%. The sex ratio was 1.1. The average weight was 2186.6. The main causes were vascular (46.1%), foetal (20.2%), adnexal (17.1%) and asphyxia per partum (16.6%). Foetal causes were more likely to result in IUFD than other causes (OR = 6.4 [2.4 - 15.7], p < 0.001). After birth, partum asphyxia was more likely to lead to death before 15 minutes of life than other causes (OR = 11 [6.1 - 18.9], p Conclusion: The causes of stillbirth and early neonatal mortality are dominated by maternal vascular pathologies. However, the proportion of childbirth-related causes remains worrying. Better monitoring of pregnancy and labour will minimize this prevalence in our hospital.

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.

Factors Influencing Mode of Delivery: A Case-Control Study

The primary objective of this investigation was to scrutinize the prepregnancy conditions and lifestyles of 2046 women residing in Liuzhou City, with the aim of delineating the determinants of delivery methods. Evidently, the study unearthed substantial correlations between prepregnancy body mass index, educational attainment, exposure to passive smoking, medical history, and other variables with the mode of delivery. Furthermore, a predictive nomogram model was formulated to accurately forecast the likelihood of cesarean section. These discernments equip pertinent authorities with the means to institute targeted screening and supportive measures for women contemplating pregnancy based on these identified factors. Moreover, provision of services such as prepregnancy counseling and clinical risk assessments could be instrumental in curbing the incidence of cesarean section.

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.

Obstetric Anesthesia Practice Significantly Evolved: A Field for Cesarean Delivery Parturient for the Provision of Safe Anesthesia in Urgent Circumstances

General anesthesia and Obstetric Anesthesia is the gold standard for a cesarean section but there are some cases where general anesthesia is unavoidable. The use of general anesthesia for cesarean delivery has decreased in recent years due to the widespread use of neuraxial techniques. The choice of anesthesia techniques for cesarean delivery depends on several factors, including the patient’s psychology and the attending physician’s experience. It is chosen because of its safety profile and its benefits to the mother and fetus. It may be indicated due to emergency, maternal refusal of regional techniques, or regional contraindications. Major complications include failed intubation, gastric content aspiration, and increased bleeding risk. This study aims to evaluate the impact of a newly launched team on obstetric anesthesia practice.

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.

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.

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.

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.

Spontaneous Paravesical and Broad Ligament Hematoma after Vaginal Delivery Had Uterine Artery Embolization after Evacuating the Hematoma

Broad ligament hematoma is typically seen during cesarean section due to rupture of branches of uterine and vaginal vessels and it’s rare to be seen post-normal vaginal delivery. Addressing puerperal hematomas postpartum presents considerable challenges for obstetric care providers. While hematomas such as those affecting the vulva, vulvovaginal region, or paravaginal area are frequently encountered, retroperitoneal hematomas are rare and notably pose a greater risk to the life of the patient. The medical literature contains scant case reports on retroperitoneal hematomas, with no consensus on a definitive treatment approach. Pelvic arterial embolization has emerged as both a sensible and increasingly preferred method for treating these hematomas recently, but its application is contingent upon the patient maintaining hemodynamic stability and the availability of a specialized interventional embolization unit. In our case, we are presenting a very rare case of a 31-year-old primigravida female with a history of in vitro fertilization pregnancy. She delivered a normal vaginal delivery at 31 weeks gestation. Unfortunately, she experienced multiple complications intrapartum, including preeclampsia and placental abruption. These complications increased her risk of developing a broad ligament hematoma.

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.

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.

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.

A bi-population immune algorithm for weapon transportation support scheduling problem with pickup and delivery on aircraft carrier deck

The weapon transportation support scheduling problem on aircraft carrier deck is the key to restricting the sortie rate and combat capability of carrier-based aircraft.This paper studies the problem and presents a novel solution architecture.Taking the interference of the carrier-based aircraft deck layout on the weapon transportation route and precedence constraint into consideration,a mixed integer formulation is established to minimize the total objective,which is constituted of makespan,load variance and accumulative transfer time of support unit.Solution approach is developed for the model.Firstly,based on modeling the carrier aircraft parked on deck as convex obstacles,the path library of weapon transportation is constructed through visibility graph and Warshall-Floyd methods.We then propose a bi-population immune algorithm in which a population-based forward/backward scheduling technique,local search schemes and a chaotic catastrophe operator are embedded.Besides,the randomkey solution representation and serial scheduling generation scheme are adopted to conveniently obtain a better solution.The Taguchi method is additionally employed to determine key parameters of the algorithm.Finally,on a set of generated realistic instances,we demonstrate that the proposed algorithm outperforms all compared algorithms designed for similar optimization problems and can significantly improve the efficiency,and that the established model and the bi-population immune algorithm can effectively respond to the weapon support requirements of carrier-based aircraft under different sortie missions.