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...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.展开更多
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 deliver...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.展开更多
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 pro...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.展开更多
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...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.展开更多
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 senescen...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.展开更多
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 system...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.展开更多
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...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.展开更多
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 th...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.展开更多
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...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.展开更多
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 decreas...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.展开更多
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 postpa...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.展开更多
Complications of the liver are amongst the world’s worst diseases.Liver fibrosis is the first stage of liver problems,while cirrhosis is the last stage,which can lead to death.The creation of effective anti-fibrotic ...Complications of the liver are amongst the world’s worst diseases.Liver fibrosis is the first stage of liver problems,while cirrhosis is the last stage,which can lead to death.The creation of effective anti-fibrotic drug delivery methods appears critical due to the liver’s metabolic capacity for drugs and the presence of insurmountable physiological impediments in the way of targeting.Recent breakthroughs in anti-fibrotic agents have substantially assisted in fibrosis;nevertheless,the working mechanism of anti-fibrotic medications is not fully understood,and there is a need to design delivery systems that are well-understood and can aid in cirrhosis.Nanotechnology-based delivery systems are regarded to be effective but they have not been adequately researched for liver delivery.As a result,the capability of nanoparticles in hepatic delivery was explored.Another approach is targeted drug delivery,which can considerably improve efficacy if delivery systems are designed to target hepatic stellate cells(HSCs).We have addressed numerous delivery strategies that target HSCs,which can eventually aid in fibrosis.Recently genetics have proved to be useful,and methods for delivering genetic material to the target place have also been investigated where different techniques are depicted.To summarize,this review paper sheds light on themost recent breakthroughs in drug and gene-based nano and targeted delivery systems that have lately shown useful for the treatment of liver fibrosis and cirrhosis.展开更多
Expanding in the oral care business, being passionately driven by innovative and scientific products, functional toothpaste has recently become more popular for functionality, variety, and efficacy. Many new types of ...Expanding in the oral care business, being passionately driven by innovative and scientific products, functional toothpaste has recently become more popular for functionality, variety, and efficacy. Many new types of toothpaste are commercially manufactured with diverse fragrances, colors, probiotics, and pharmaceutical ingredients to enhance the functionalities of toothpaste. Our study attempted to create a toothpaste formulation that might facilitate the intraoral delivery of vitamin D3 into the bloodstream. Simply brushing our teeth with toothpaste should be easy to take the essential vitamin regularly. In this study, an emulsion-based toothpaste mixed with an azone compound and sodium dodecyl sulfate as penetration enhancers blended thoroughly with other ingredients and then with vitamin D. Multiple toothpaste characteristic tests were performed, such as abrasiveness, scratchiness, spreadability, pH, foaming, cleaning, and antibacterial strength with our vitamin D toothpaste, and compared with those of other commercial brand toothpaste. To confirm the intraoral delivery of vitamin D through the oral cavity, an earthworm transport study and TEER value test were conducted using L. terrestris skin. Our data demonstrated the high feasibility of intraoral delivery of vitamin D based on those two skin studies with various experimental support;our vitamin D toothpaste had comparable characteristics with other commercial toothpaste for cleaning functionality.展开更多
Introduction: Multiple pregnancies have a higher risk of premature delivery and a weakened cervix has been associated with it. In most cases, emergency cerclage has proved to be beneficial as the birth of the first tw...Introduction: Multiple pregnancies have a higher risk of premature delivery and a weakened cervix has been associated with it. In most cases, emergency cerclage has proved to be beneficial as the birth of the first twin is usually followed by the unavoidable delivery of the second twin and most fetus dies shortly after delivery. Studies have noted that delayed delivery of the second fetus in a twin pregnancy is an effective management choice and the use of cervical cerclage after the first delivery is associated with a longer inter-delivery interval. We present a case of previable premature rupture of membrane of a dichorionic diamniotic twin gestation leading to the loss of the leading twin and subsequently having emergency cervical cerclage for the second twin and caesarean delivery at term. Case Presentation: She was a case of a 29 years old, G<sub>6</sub>P<sub>1</sub><sup>+4</sup> with 1 living child at a gestational age of 17 weeks plus 5 days who initially was diagnosed with dichorionic diamniotic twin gestation following an early ultrasound but presented with a history of bleeding and passage of liquor per vaginam. Ultrasound done on admission showed cervical funneling and a stable state of the second twin. She subsequently had emergency cervical cerclage after stabilization on account of previable premature rupture of membrane of a dichorionic diamniotic twin gestation with the loss of the leading twin. A repeat ultrasound done prior to discharge showed closed cervical os and a good state of the fetus. She then had elective caesarean delivery at term with a good feto-maternal outcome. Conclusion: Emergency cervical cerclage should be part of the options of management after stabilization in cases of previable premature rupture of membrane in a dichorionic or multichoronic gestation so as to save the viable once.展开更多
Previous studies have confirmed the relationship between iron-dependent ferroptosis and a peripheral nerve injury-induced neuropathic pain model.However,the role of fe rroptosis in inflammatory pain remains inconclusi...Previous studies have confirmed the relationship between iron-dependent ferroptosis and a peripheral nerve injury-induced neuropathic pain model.However,the role of fe rroptosis in inflammatory pain remains inconclusive.Therefore,we aimed to explore whether ferroptosis in the spinal cord and do rsal root ganglion contributes to complete Freund's adjuvant(CFA)-induced painful behaviors in rats.Our results revealed that various biochemical and morphological changes were associated with ferroptosis in the spinal cord and dorsal root ganglion tissues of CFA rats.These changes included iron overload,enhanced lipid peroxidation,disorders of anti-acyl-coenzyme A synthetase long-chain family member 4 and glutathione peroxidase 4 levels,and abnormal morphological changes in mitochondria.Intrathecal treatment of liproxstatin-1(a ferroptosis inhibitor)reve rsed these ferroptosis-related changes and alleviated mechanical and thermal hype rsensitivities in CFA rats.Our study demonstrated the occurrence of fe rroptosis in the spinal cord and do rsal root ganglion tissues in a rodent model of inflammatory pain and indicated that intrathecal administration of fe rroptosis inhibitors,such as liproxstatin-1,is a potential therapeutic strategy for treating inflammatory pain.展开更多
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 nov...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.展开更多
Cancer immunotherapy,a therapeutic approach that inhibits tumors by activating or strengthening anti-tumor immunity,is currently an important clinical strategy for cancer treatment;however,tumors can develop drug resi...Cancer immunotherapy,a therapeutic approach that inhibits tumors by activating or strengthening anti-tumor immunity,is currently an important clinical strategy for cancer treatment;however,tumors can develop drug resistance to immune surveillance,resulting in poor response rates and low therapeutic efficacy.In addition,changes in genes and signaling pathways in tumor cells prevent susceptibility to immunotherapeutic agents.Furthermore,tumors create an immunosuppressive microenvironment via immunosuppressive cells and secrete molecules that hinder immune cell and immune modulator infiltration or induce immune cell malfunction.To address these challenges,smart drug delivery systems(SDDSs)have been developed to overcome tumor cell resistance to immunomodulators,restore or boost immune cell activity,and magnify immune responses.To combat resistance to small molecules and monoclonal antibodies,SDDSs are used to co-deliver numerous therapeutic agents to tumor cells or immunosuppressive cells,thus increasing the drug concentration at the target site and improving efficacy.Herein,we discuss how SDDSs overcome drug resistance during cancer immunotherapy,with a focus on recent SDDS advances in thwarting drug resistance in immunotherapy by combining immunogenic cell death with immunotherapy and reversing the tumor immunosuppressive microenvironment.SDDSs that modulate the interferon signaling pathway and improve the efficacy of cell therapies are also presented.Finally,we discuss potential future SDDS perspectives in overcoming drug resistance in cancer immunotherapy.We believe that this review will contribute to the rational design of SDDSs and development of novel techniques to overcome immunotherapy resistance.展开更多
Massive content delivery will become one of the most prominent tasks of future B5G/6G communication.However,various multimedia applications possess huge differences in terms of object oriented(i.e.,machine or user)and...Massive content delivery will become one of the most prominent tasks of future B5G/6G communication.However,various multimedia applications possess huge differences in terms of object oriented(i.e.,machine or user)and corresponding quality evaluation metric,which will significantly impact the design of encoding or decoding within content delivery strategy.To get over this dilemma,we firstly integrate the digital twin into the edge networks to accurately and timely capture Quality-of-Decision(QoD)or Quality-of-Experience(QoE)for the guidance of content delivery.Then,in terms of machinecentric communication,a QoD-driven compression mechanism is designed for video analytics via temporally lightweight frame classification and spatially uneven quality assignment,which can achieve a balance among decision-making,delivered content,and encoding latency.Finally,in terms of user-centric communication,by fully leveraging haptic physical properties and semantic correlations of heterogeneous streams,we develop a QoE-driven video enhancement scheme to supply high data fidelity.Numerical results demonstrate the remarkable performance improvement of massive content delivery.展开更多
Exosomes,as promising vehicles,have been widely used in the research of oral drug delivery,but the generally low drug loading efficiency of exosomes seriously limits its application and transformation.In this study,we...Exosomes,as promising vehicles,have been widely used in the research of oral drug delivery,but the generally low drug loading efficiency of exosomes seriously limits its application and transformation.In this study,we systematically investigated the effects of drug loading methods and physicochemical properties(lipophilicity and molecular weight)on drug loading efficiency of milk-derived exosomes to explore the most appropriate loading conditions.Our finding revealed that the drug loading efficiency of exosomes was closely related to the drug loading method,drug lipophilicity,drug molecular weight and exosome/drug proportions.Of note,we demonstrated the universality that hydrophilic biomacromolecule drugs were the most appropriate loading drugs for milk-derived exosomes,which was attributed to the efficient loading capacity and sustained release behavior.Furthermore,milk-derived exosomes could significantly improve the transepithelial transport and oral bioavailability of model hydrophilic biomacromolecule drugs(octreotide,exendin-4 and salmon calcitonin).Collectively,our results suggested that the encapsulation of hydrophilic biomacromolecule drugs might be the most promising direction for milk exosomes as oral drug delivery vehicles.展开更多
Current treatments for advanced hepatocellular carcinoma(HCC)have limited success in improving patients’quality of life and prolonging life expectancy.The clinical need for more efficient and safe therapies has contr...Current treatments for advanced hepatocellular carcinoma(HCC)have limited success in improving patients’quality of life and prolonging life expectancy.The clinical need for more efficient and safe therapies has contributed to the exploration of emerging strategies.Recently,there has been increased interest in oncolytic viruses(OVs)as a therapeutic modality for HCC.OVs undergo selective replication in cancerous tissues and kill tumor cells.Strikingly,pexastimogene devacirepvec(Pexa-Vec)was granted an orphan drug status in HCC by the U.S.Food and Drug Administration(FDA)in 2013.Meanwhile,dozens of OVs are being tested in HCC-directed clinical and preclinical trials.In this review,the pathogenesis and current therapies of HCC are outlined.Next,we summarize multiple OVs as single therapeutic agents for the treatment of HCC,which have demonstrated certain efficacy and lowtoxicity.Emerging carrier cell-,bioengineered cell mimetic-or nonbiological vehicle-mediated OV intravenous delivery systems in HCC therapy are described.In addition,we highlight the combination treatments between oncolytic virotherapy and other modalities.Finally,the clinical challenges and prospects of OV-based biotherapy are discussed,with the aim of continuing to develop a fascinating approach in HCC patients.展开更多
基金supported by Natural Science Foundation of Beijing Municipality(L212013)National Key Research and Development Program of China(No.2022YFA1206104)+2 种基金AI+Health Collaborative Innovation Cultivation Project(Z211100003521002)National Natural Science Foundation of China(81971718,82073786,81872809,U20A20412,81821004)Beijing Natural Science Foundation(7222020).
文摘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.
基金supported by National Natural Sciences Foundation of China(No.62271165,62027802,61831008)the Guangdong Basic and Applied Basic Research Foundation(No.2023A1515030297,2021A1515011572)Shenzhen Science and Technology Program ZDSYS20210623091808025,Stable Support Plan Program GXWD20231129102638002.
文摘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.
基金supported by the National Natural Science Foundation of China(Grant Nos.11472137 and U2141246)。
文摘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.
文摘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.
基金supported by Dalian Youth Science and Technology Star Project(2020RQ121)the National Science Fund for Distinguished Young Scholars of China(31925031)+1 种基金Doctoral Scientific Research Foundation of Liaoning Province(2020-BS-211)Liaoning Province Education Administration(J2020101)。
文摘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.
文摘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.
文摘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.
基金supported by the National Key Research and Development Program of China(2021YFB2600405).
文摘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.
文摘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.
文摘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.
文摘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.
文摘Complications of the liver are amongst the world’s worst diseases.Liver fibrosis is the first stage of liver problems,while cirrhosis is the last stage,which can lead to death.The creation of effective anti-fibrotic drug delivery methods appears critical due to the liver’s metabolic capacity for drugs and the presence of insurmountable physiological impediments in the way of targeting.Recent breakthroughs in anti-fibrotic agents have substantially assisted in fibrosis;nevertheless,the working mechanism of anti-fibrotic medications is not fully understood,and there is a need to design delivery systems that are well-understood and can aid in cirrhosis.Nanotechnology-based delivery systems are regarded to be effective but they have not been adequately researched for liver delivery.As a result,the capability of nanoparticles in hepatic delivery was explored.Another approach is targeted drug delivery,which can considerably improve efficacy if delivery systems are designed to target hepatic stellate cells(HSCs).We have addressed numerous delivery strategies that target HSCs,which can eventually aid in fibrosis.Recently genetics have proved to be useful,and methods for delivering genetic material to the target place have also been investigated where different techniques are depicted.To summarize,this review paper sheds light on themost recent breakthroughs in drug and gene-based nano and targeted delivery systems that have lately shown useful for the treatment of liver fibrosis and cirrhosis.
文摘Expanding in the oral care business, being passionately driven by innovative and scientific products, functional toothpaste has recently become more popular for functionality, variety, and efficacy. Many new types of toothpaste are commercially manufactured with diverse fragrances, colors, probiotics, and pharmaceutical ingredients to enhance the functionalities of toothpaste. Our study attempted to create a toothpaste formulation that might facilitate the intraoral delivery of vitamin D3 into the bloodstream. Simply brushing our teeth with toothpaste should be easy to take the essential vitamin regularly. In this study, an emulsion-based toothpaste mixed with an azone compound and sodium dodecyl sulfate as penetration enhancers blended thoroughly with other ingredients and then with vitamin D. Multiple toothpaste characteristic tests were performed, such as abrasiveness, scratchiness, spreadability, pH, foaming, cleaning, and antibacterial strength with our vitamin D toothpaste, and compared with those of other commercial brand toothpaste. To confirm the intraoral delivery of vitamin D through the oral cavity, an earthworm transport study and TEER value test were conducted using L. terrestris skin. Our data demonstrated the high feasibility of intraoral delivery of vitamin D based on those two skin studies with various experimental support;our vitamin D toothpaste had comparable characteristics with other commercial toothpaste for cleaning functionality.
文摘Introduction: Multiple pregnancies have a higher risk of premature delivery and a weakened cervix has been associated with it. In most cases, emergency cerclage has proved to be beneficial as the birth of the first twin is usually followed by the unavoidable delivery of the second twin and most fetus dies shortly after delivery. Studies have noted that delayed delivery of the second fetus in a twin pregnancy is an effective management choice and the use of cervical cerclage after the first delivery is associated with a longer inter-delivery interval. We present a case of previable premature rupture of membrane of a dichorionic diamniotic twin gestation leading to the loss of the leading twin and subsequently having emergency cervical cerclage for the second twin and caesarean delivery at term. Case Presentation: She was a case of a 29 years old, G<sub>6</sub>P<sub>1</sub><sup>+4</sup> with 1 living child at a gestational age of 17 weeks plus 5 days who initially was diagnosed with dichorionic diamniotic twin gestation following an early ultrasound but presented with a history of bleeding and passage of liquor per vaginam. Ultrasound done on admission showed cervical funneling and a stable state of the second twin. She subsequently had emergency cervical cerclage after stabilization on account of previable premature rupture of membrane of a dichorionic diamniotic twin gestation with the loss of the leading twin. A repeat ultrasound done prior to discharge showed closed cervical os and a good state of the fetus. She then had elective caesarean delivery at term with a good feto-maternal outcome. Conclusion: Emergency cervical cerclage should be part of the options of management after stabilization in cases of previable premature rupture of membrane in a dichorionic or multichoronic gestation so as to save the viable once.
基金supported by the Basic and Applied Basic Research Foundation of Guangdong Province,No.2021A1515220081(to XL)。
文摘Previous studies have confirmed the relationship between iron-dependent ferroptosis and a peripheral nerve injury-induced neuropathic pain model.However,the role of fe rroptosis in inflammatory pain remains inconclusive.Therefore,we aimed to explore whether ferroptosis in the spinal cord and do rsal root ganglion contributes to complete Freund's adjuvant(CFA)-induced painful behaviors in rats.Our results revealed that various biochemical and morphological changes were associated with ferroptosis in the spinal cord and dorsal root ganglion tissues of CFA rats.These changes included iron overload,enhanced lipid peroxidation,disorders of anti-acyl-coenzyme A synthetase long-chain family member 4 and glutathione peroxidase 4 levels,and abnormal morphological changes in mitochondria.Intrathecal treatment of liproxstatin-1(a ferroptosis inhibitor)reve rsed these ferroptosis-related changes and alleviated mechanical and thermal hype rsensitivities in CFA rats.Our study demonstrated the occurrence of fe rroptosis in the spinal cord and do rsal root ganglion tissues in a rodent model of inflammatory pain and indicated that intrathecal administration of fe rroptosis inhibitors,such as liproxstatin-1,is a potential therapeutic strategy for treating inflammatory pain.
基金the financial support of the National Natural Science Foundation of China(No.52102453)。
文摘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.
基金supported by the National Key R&D Program of China(Grant No.2022YFC3401404)the National Natural Science Foundation of China(Grant Nos.32170935 and 31930066).
文摘Cancer immunotherapy,a therapeutic approach that inhibits tumors by activating or strengthening anti-tumor immunity,is currently an important clinical strategy for cancer treatment;however,tumors can develop drug resistance to immune surveillance,resulting in poor response rates and low therapeutic efficacy.In addition,changes in genes and signaling pathways in tumor cells prevent susceptibility to immunotherapeutic agents.Furthermore,tumors create an immunosuppressive microenvironment via immunosuppressive cells and secrete molecules that hinder immune cell and immune modulator infiltration or induce immune cell malfunction.To address these challenges,smart drug delivery systems(SDDSs)have been developed to overcome tumor cell resistance to immunomodulators,restore or boost immune cell activity,and magnify immune responses.To combat resistance to small molecules and monoclonal antibodies,SDDSs are used to co-deliver numerous therapeutic agents to tumor cells or immunosuppressive cells,thus increasing the drug concentration at the target site and improving efficacy.Herein,we discuss how SDDSs overcome drug resistance during cancer immunotherapy,with a focus on recent SDDS advances in thwarting drug resistance in immunotherapy by combining immunogenic cell death with immunotherapy and reversing the tumor immunosuppressive microenvironment.SDDSs that modulate the interferon signaling pathway and improve the efficacy of cell therapies are also presented.Finally,we discuss potential future SDDS perspectives in overcoming drug resistance in cancer immunotherapy.We believe that this review will contribute to the rational design of SDDSs and development of novel techniques to overcome immunotherapy resistance.
基金partly supported by the National Natural Science Foundation of China (Grants No.62231017 and No.62071254)the Priority Academic Program Development of Jiangsu Higher Education Institutions。
文摘Massive content delivery will become one of the most prominent tasks of future B5G/6G communication.However,various multimedia applications possess huge differences in terms of object oriented(i.e.,machine or user)and corresponding quality evaluation metric,which will significantly impact the design of encoding or decoding within content delivery strategy.To get over this dilemma,we firstly integrate the digital twin into the edge networks to accurately and timely capture Quality-of-Decision(QoD)or Quality-of-Experience(QoE)for the guidance of content delivery.Then,in terms of machinecentric communication,a QoD-driven compression mechanism is designed for video analytics via temporally lightweight frame classification and spatially uneven quality assignment,which can achieve a balance among decision-making,delivered content,and encoding latency.Finally,in terms of user-centric communication,by fully leveraging haptic physical properties and semantic correlations of heterogeneous streams,we develop a QoE-driven video enhancement scheme to supply high data fidelity.Numerical results demonstrate the remarkable performance improvement of massive content delivery.
基金The authors gratefully acknowledge financial support from National Natural Science Foundation of China(81872818)National Key R&D Program of China(2021YFE0115200).
文摘Exosomes,as promising vehicles,have been widely used in the research of oral drug delivery,but the generally low drug loading efficiency of exosomes seriously limits its application and transformation.In this study,we systematically investigated the effects of drug loading methods and physicochemical properties(lipophilicity and molecular weight)on drug loading efficiency of milk-derived exosomes to explore the most appropriate loading conditions.Our finding revealed that the drug loading efficiency of exosomes was closely related to the drug loading method,drug lipophilicity,drug molecular weight and exosome/drug proportions.Of note,we demonstrated the universality that hydrophilic biomacromolecule drugs were the most appropriate loading drugs for milk-derived exosomes,which was attributed to the efficient loading capacity and sustained release behavior.Furthermore,milk-derived exosomes could significantly improve the transepithelial transport and oral bioavailability of model hydrophilic biomacromolecule drugs(octreotide,exendin-4 and salmon calcitonin).Collectively,our results suggested that the encapsulation of hydrophilic biomacromolecule drugs might be the most promising direction for milk exosomes as oral drug delivery vehicles.
基金by the National Natural Science Foundation of China(No.81700453).
文摘Current treatments for advanced hepatocellular carcinoma(HCC)have limited success in improving patients’quality of life and prolonging life expectancy.The clinical need for more efficient and safe therapies has contributed to the exploration of emerging strategies.Recently,there has been increased interest in oncolytic viruses(OVs)as a therapeutic modality for HCC.OVs undergo selective replication in cancerous tissues and kill tumor cells.Strikingly,pexastimogene devacirepvec(Pexa-Vec)was granted an orphan drug status in HCC by the U.S.Food and Drug Administration(FDA)in 2013.Meanwhile,dozens of OVs are being tested in HCC-directed clinical and preclinical trials.In this review,the pathogenesis and current therapies of HCC are outlined.Next,we summarize multiple OVs as single therapeutic agents for the treatment of HCC,which have demonstrated certain efficacy and lowtoxicity.Emerging carrier cell-,bioengineered cell mimetic-or nonbiological vehicle-mediated OV intravenous delivery systems in HCC therapy are described.In addition,we highlight the combination treatments between oncolytic virotherapy and other modalities.Finally,the clinical challenges and prospects of OV-based biotherapy are discussed,with the aim of continuing to develop a fascinating approach in HCC patients.
