Targeted anti-cancer therapy: Co-delivery of VEGF siRNA and Phenethyl isothiocyanate (PEITC) via cRGD-modified lipid nanoparticles for enhanced anti-angiogenic efficacy

Anti-tumor angiogenesis therapy, targeting the suppression of blood vessel growth in tumors, presents a potent approach in the battle against cancer. Traditional therapies have primarily concentrated on single-target techniques, with a specific emphasis on targeting the vascular endothelial growth factor, but have not reached ideal therapeutic efficacy. In response to this issue, our study introduced a novel nanoparticle system known as CS-siRNA/PEITC&L-cRGD NPs. These chitosan-based nanoparticles have been recognized for their excellent biocompatibility and ability to deliver genes. To enhance their targeted delivery capability, they were combined with a cyclic RGD peptide (cRGD). Targeted co-delivery of gene and chemotherapeutic agents was achieved through the use of a negatively charged lipid shell and cRGD, which possesses high affinity for integrin αvβ3 overexpressed in tumor cells and neovasculature. In this multifaceted approach, co-delivery of VEGF siRNA and phenethyl isothiocyanate (PEITC) was employed to target both tumor vascular endothelial cells and tumor cells simultaneously. The co-delivery of VEGF siRNA and PEITC could achieve precise silencing of VEGF, inhibit the accumulation of HIF-1α under hypoxic conditions, and induce apoptosis in tumor cells. In summary, we have successfully developed a nanoparticle delivery platform that utilizes a dual mechanism of action of anti-tumor angiogenesis and pro-tumor apoptosis, which provides a robust and potent strategy for the delivery of anti-cancer therapeutics.

Bone site-specific delivery of siRNA

Small interfering RNAs （siRNA） have enormous potential as therapeutics to target and treat various bone disor- ders such as osteoporosis and cancer bone metastases. However, effective and specific delivery of siRNA therapeu- tics to bone and bone-specific cells in vivo is very challenging. To realize the full therapeutic potential of siRNA in treating bone disorders, a safe and efficient, tissue- and cell-specific delivery system must be developed. This review focuses on recent advances in bone site-specific delivery of siRNA at the tissue or cellular level. Bone-targeted nanoparticulate siRNA carriers and various bone-targeted moieties such as bisphosphonates, oligopeptides （Asp）8 and （AspSerSer）6, and aptamers are highlighted. Incorporation of these bone-seeking targeting moieties into siRNA carriers allows for recognition of different sub-tissue functional domains of bone and also specific cell types residing in bone tissue. It also provides a means for bone-formation surface-, bone-resorption surface-, or osteoblast- specific targeting and transportation of siRNA therapeutics. The discussion mainly focuses on systemic and local bone-specific delivery of siRNA in osteoporosis and bone metastasis preclinical models.

Design and preparation of a new multi-targeted drug delivery system using multifunctional nanoparticles for co-delivery of siRNA and paclitaxel

Drug resistance is a great challenge in cancer therapy using chemotherapeutic agents. Administration of these drugs with siRNA is an efficacious strategy in this battle. Here, the present study tried to incorporate siRNA and paclitaxel(PTX) simultaneously into a novel nanocarrier. The selectivity of carrier to target cancer tissues was optimized through conjugation of folic acid(FA) and glucose(Glu) onto its surface. The structure of nanocarrier was formed from ternary magnetic copolymers based on FeCopolyethyleneimine(FeCo-PEI) nanoparticles and polylactic acid-polyethylene glycol(PLA-PEG) gene delivery system. Biocompatibility of FeCo-PEI-PLA-PEG-FA(NPsA), FeCo-PEI-PLA-PEG-Glu(NPsB) and FeCo-PEI-PLA-PEG-FA/Glu(NPsAB) nanoparticles and also influence of PTX-loaded nanoparticles on in vitro cytotoxicity were examined using MTT assay. Besides, siRNA-FAM internalization was investigated by fluorescence microscopy. The results showed the blank nanoparticles were significantly less cytotoxic at various concentrations. Meanwhile, siRNA-FAM/PTX encapsulated nanoparticles exhibited significant anticancer activity against MCF-7 and BT-474 cell lines. NPsAB/siRNA/PTX nanoparticles showed greater effects on MCF-7 and BT-474 cells viability than NPsA/siRNA/PTX and NPsB/siRNA/PTX.Also, they induced significantly higher anticancer effects on cancer cells compared with NPsA/siRNA/PTX and NPsB/siRNA/PTX due to their multi-targeted properties using FA and Glu. We concluded that NPsAB nanoparticles have a great potential for co-delivery of both drugs and genes for use in gene therapy and chemotherapy.

Dual-targeted lung cancer therapy via inhalation delivery of UCNP-siRNA-AS1411 nanocages

Objective:Although great progress has been made in the field of siRNA gene therapy,safe,efficient,and targeted delivery of siRNA are still major challenges in siRNA therapeutics.Methods:We developed an up-conversion nanoparticle-based nanocage system.This system protected the siRNA from being degraded by nucleases in organisms and selectively delivered the siRNAs to the tumor sites,due to modifications of targeted molecules on the surfaces of nanocages and local inhalation.Results:The siRNAs delivered by the up-conversion nanoparticle nanocages were protected from degradation in transit to the tumor sites,where they accumulated.Compared with the passive target and control groups,the up-conversion nanoparticles based on the nanocage system showed a tumor suppressive effect after approximately 3 weeks of treatment.Conclusions:The up-conversion nanoparticle nanocages efficiently delivered vascular endothelial growth factor siRNAs to tumor sites.Mice with lung tumors treated with tumors targeting up-conversion nanoparticle nanocages showed steady body weight changes,high tumor inhibition ratios,and longer survival times.

Delivery systems for siRNA drug development in cancer therapy

Since the discovery of the Nobel prize-winning mechanism of RNA interference(RNAi)ten years ago,it has become a promising drug target for the treatment of multiple diseases,including cancer.There have already been some successful applications of siRNA drugs in the treatment of age-related macular degeneration and respiratory syncytial virus infection.However,significant barriers still exist on the road to clinical applications of siRNA drugs,including poor cellular uptake,instability under physiological conditions,off-target effects and possible immunogenicity.The successful application of siRNA for cancer therapy requires the development of clinically suitable,safe and effective drug delivery systems.Herein,we review the design criteria for siRNA delivery systems and potential siRNA drug delivery systems for cancer therapy,including chemical modifications,lipidbased nanovectors,polymer-mediated delivery systems,conjugate delivery systems,and others.

Anti-EpCAM functionalized graphene oxide vector for tumor targeted siRNA delivery and cancer therapy

Graphene oxide(GO) has emerged as a potential drug delivery vector. For siRNA delivery, GO should be modified to endow it with gene delivery ability and targeting effect. However, the cationic materials used previously usually had greater toxicity. In this study, GO was modified with a non-toxicity cationic material(chitosan) and a tumor specific monoclonal antibody(anti-EpCAM) for the delivery of survivin-siRNA(GCE/siRNA). And the vector(GCE) prepared was proved with excellent biosafety and tumor targeting effect. The GCE exhibited superior performance in loading si RNA, maintained stability in different solutions and showed excellent protection effect for survivin-siRNA in vitro. The gene silencing results in vitro showed that the m RNA level and protein level were down-regulated by 48.24% ± 2.50% and 44.12% ± 3.03%, respectively, which was equal with positive control( P > 0.05). It was also demonstrated that GCE/siRNA had a strong antitumor effect in vitro, which was attributed to the efficient antiproliferation, and migration and invasion inhibition effect of GCE/siRNA. The results in vivo indicated that GCE could accumulate siRNA in tumor tissues. The tumor inhibition rate of GCE/siRNA 54.74% ± 5.51% was significantly higher than control 4.87% ±8.49%. Moreover, GCE/siRNA showed no toxicity for blood and main organs, suggesting that it is a biosafety carrier for gene delivery. Taken together, this study provides a novel design strategy for gene delivery system and siRNA formulation.

Characterization of modified mesoporous silica nanoparticles as vectors for siRNA delivery

Gene therapy using siRNA molecules is nowadays considered as a promising approach. For successful therapy, development of a stable and reliable vector for siRNA is crucial. Non-viral and non-organic vectors like mesoporous silica nanoparticles(MSN) are associated with lack of most viral vector drawbacks, such as toxicity, immunogenicity, but also generally a low nucleic acid carrying capacity. To overcome this hurdle, we here modified the pore walls of MSNs with surface-hyperbranching polymerized poly(ethyleneimine)(hbPEI), which provides an abundance of amino-groups for loading of a larger amount of siRNA molecules via electrostatic adsorption. After loading, the particles were covered with a second layer of pre-polymerized PEI to provide better protection of siRNA inside the pores, more effective cellular uptake and endosomal escape. To test the transfection efficiency of PEI covered si RNA/MSNs, MDA-MB 231 breast cancer cells stably expressing GFP were used. We demonstrate that PEI-coated si RNA/MSN complexes provide more effective delivery of si RNAs compared to unmodified MSNs. Thus, it can be concluded that appropriately surface-modified MSNs can be considered as prospective vectors for therapeutic siRNA delivery.

Optimization of siRNA Delivery Method into the Liver by Sequential Injection of Polyglutamic Acid and Cationic Lipoplex

Previously, we developed a novel siRNA transfer method to the liver by sequential intravenous injection of poly-L-glutamic acid (PGA) and cationic liposome/siRNA complex (cationic lipoplex). In this study, we examined the effects of the charge ratio (+/-) of cationic liposome/siRNA, molecular weight of PGA and cationic lipid of cationic liposome on the biodistribution of siRNA after sequential injection of PGA plus cationic lipoplex. When 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)/cholesterol (Chol) lipoplex was intravenously injected into mice, the accumulation of siRNA was mainly observed in the lungs. In contrast, when DOTAP/Chol lipoplex was intravenously injected at 1 min after intravenous injection of PGA, siRNA was largely accumulated in the liver. The charge ratio (+/-) of DOTAP/Chol liposome/siRNA did not affect the biodistribution of siRNA after sequential injection. As regards the molecular weight of PGA, the accumulation of siRNA was observed mainly in the liver after the sequential injection of PGA of 20.5, 38, 64 or 200 kDa plus DOTAP/Chol lipoplex. Furthermore, to examine the effect of cationic lipid of cationic liposome on the biodistribution of siRNA, we prepared other cationic liposomes composed of 1,2-di-O-octadecenyl-3-trimethylammonium propane chloride (DOTMA)/Chol, dimethyldioctade-cylammonium bromide (DDAB)/Chol and O,O’-ditetradecanoyl-N-(α-trimethylammonioacetyl)di-ethanolamine chloride (DC-6-14)/Chol. For the cationic liposomes, the accumulation of siRNA was observed mainly in the liver when their cationic lipoplexes were sequentially injected after injection of PGA into mice. From these findings, sequential injection of PGA plus cationic lipoplex could deliver siRNA efficiently into the liver regardless of the charge ratio (+/-) of lipoplex, lengths of PGA and cationic lipid of liposome.

Design, mechanism, delivery and therapeutics of canonical and Dicer-substrate siRNA

Upon the discovery of RNA interference(RNAi),canonical small interfering RNA(si RNA) has been recognized to trigger sequence-specific gene silencing. Despite the benefits of si RNAs as potential new drugs,there are obstacles still to be overcome,including off-target effects and immune stimulation. More recently,Dicer substrate si RNA(Dsi RNA) has been introduced as an alternative to si RNA. Similarly,it also is proving to be potent and target-specific,while rendering less immune stimulation. Dsi RNA is 25–30 nucleotides in length,and is further cleaved and processed by the Dicer enzyme. As with si RNA,it is crucial to design and develop a stable,safe,and efficient system for the delivery of Dsi RNA into the cytoplasm of targeted cells. Several polymeric nanoparticle systems have been well established to load Dsi RNA for in vitro and in vivo delivery,thereby overcoming a major hurdle in the therapeutic uses of Dsi RNA. The present review focuses on a comparison of si RNA and Dsi RNA on the basis of their design,mechanism,in vitro and in vivo delivery,and therapeutics.

Elaborately engineering of lipid nanoparticle for targeting delivery of siRNA and suppressing acute liver injury

Small interfering RNA(siRNA)-based gene silencing has been considered as a potential therapy modality against inflammatory diseases.Nevertheless,the effective delivery of siRNA to desired destination still remains challenging due to poor stability,high molecular weight and negative charge.Currently,ionizable lipid nanoparticle(LNP)has been extensively used as vector for effective delivery of siRNA.Herein,we report a mannose-modified LNP(M-MC_(3) LNP@TNFα)loading tumor necrosis factorα(TNFα)siRNA for targeting liver macrophages,achieving effectively inhibit acute liver injury.The M-MC_(3) LNP@TNFαnot only increases the internalization of LNP by macrophages,but also enhances the gene silencing efficiency of TNFαin vitro.Additionally,the M-MC_(3) LNP@TNFαexhibits higher accumulation in liver of healthy mice than that of MC_(3) LNP@TNFα(un-modified LNP)owing to the targeting effect of mannose.As expected,the M-MC_(3) LNP@TNFαsignificantly suppresses the expression of TNFαand ameliorates liver damage in acute liver injury model.Such a LNP targeting siRNA delivery holds great potential for the treatment of diseases associated with liver in the future.

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.

纳米凝胶搭载的siRNA通过靶向抑制施万细胞铁死亡促进周围神经损伤修复

目的:探究周围神经损伤(PNI)后施万细胞的死亡机制,使用纳米凝胶搭载的siRNA靶向抑制施万细胞死亡。方法:下载GEO数据库中PNI的转录组数据,依次进行数据处理、差异分析、GO功能富集分析、铁死亡通路鉴定以及靶基因的筛选。通过蛋白印记和qPCR实验验证靶基因的差异性。自组装单宁酸(TA)-siRNA纳米凝胶,通过丁达尔效应实验、粒径和电位测量、细胞吞噬实验、细胞骨架染色和CCK-8细胞活力实验鉴定纳米凝胶的物理学和生物学特性。通过划痕实验、免疫荧光染色实验、蛋白印记和qPCR实验验证TA-siRNA纳米凝胶抑制施万细胞铁死亡的有效性。结果:PNI后施万细胞出现明显的铁死亡现象,Bex1是调控施万细胞铁死亡的关键基因。TA-siRNA纳米凝胶具有优良的物理学和生物学特性,能够将siRNA成功地携带到损伤的施万细胞中并沉默靶基因,从而有效地抑制施万细胞损伤后的铁死亡。结论:纳米凝胶搭载的siRNA可以靶向抑制施万细胞铁死亡,为临床治疗PNI提供新的方向。

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.

靶向端粒酶逆转录酶基因siRNA抑制兔早期后发性白内障的实验研究

目的观察靶向端粒酶逆转录酶(TERT)基因小干扰RNA(siRNA)对兔眼白内障术后早期晶状体后囊膜混浊的抑制作用。方法选取20只新西兰大白兔(40眼)纳入研究,采用自身对照法,分为2组:右眼为靶向TERT基因siRNA重组腺病毒TERT-siRNA-Adv组(实验组),左眼为阴性对照重组腺病毒Adv组(对照组),每组20眼;均实施超声乳化晶状体吸除术,术后前房内分别注入0.1 mL滴度为10^(9) PFU/mL的TERT-siRNA-Adv和阴性对照腺病毒;术后第1天、1周、2周、4周观察眼压、角膜水肿、前房闪辉及后发性白内障(PCO)分级情况,术后4周对术眼各组织行病理学检查及采用Western印迹法检测后囊膜细胞内α-平滑肌肌动蛋白(α-SMA)表达变化。结果实验组后囊膜混浊较对照组明显减轻(P<0.05);术后早期存在轻度眼压升高以及眼前节炎症反应(角膜水肿、前房闪辉),但于术后1周恢复,2组间差异无统计学意义(P>0.05)。与对照组相比,实验组后囊膜细胞内α-SMA相对表达量明显下降(P<0.05);组织病理学结果显示,实验组后囊膜下少量成纤维细胞增殖,对照组后囊膜下多层成纤维细胞增殖,囊膜结构紊乱;2组角膜、虹膜各层组织细胞排列整齐,结构完整,无明显炎性细胞浸润。结论靶向TERT基因siRNA可有效抑制晶状体上皮细胞增殖以及兔早期PCO的发生,且对眼前段各组织无明显毒性作用。

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.

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.