p53 exerts anticancer effects by regulating enhancer formation and activity

The abnormality of the p53 tumor suppressor is crucial in lung cancer development,because p53 regulates target gene promoters to combat cancer.Recent studies have shown extensive p53 binding to enhancer elements.However,whether p53 exerts a tumor suppressor role by shaping the enhancer landscape remains poorly understood.In the current study,we employed several functional genomics approaches to assess the enhancer activity at p53 binding sites throughout the genome based on our established TP53 knockout(KO)human bronchial epithelial cells(BEAS-2B).A total of 943 active regular enhancers and 370 super-enhancers(SEs)disappeared upon the deletion of p53,indicating that p53 modulates the activity of hundreds of enhancer elements.We found that one p53-dependent SE,located on chromosome 9 and designated as KLF4-SE,regulated the expression of the Krüppel-like factor 4(KLF4)gene.Furthermore,the deletion of p53 significantly decreased the KLF4-SE enhancer activity and the KLF4 expression,but increased colony formation ability in the nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced cell transformation model.Subsequently,in TP53 KO cells,the overexpression of KLF4 partially reversed the increased clonogenic capacity caused by p53 deficiency.Consistently,KLF4 expression also decreased in lung cancer tissues and cell lines.It appeared that overexpression of KLF4 significantly suppressed the proliferation and migration of lung cancer cells.Collectively,our results suggest that the regulation of enhancer formation and activity by p53 is an integral component of the p53 tumor suppressor function.Therefore,our findings offer some novel insights into the regulation mechanism of p53 in lung oncogenesis and introduce a new strategy for screening therapeutic targets.

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

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

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.

Ginger oil-loaded transdermal adhesive patch treats post-traumatic stress disorder

Objective To find a viable alternative to reduce the number of doses required for the patients with post-traumatic stress disorder(PTSD),and to improve efficacy and patient compliance.Methods In this study,we used ginger oil,a phytochemical with potential therapeutic properties,to prepare ginger oil patches.High-performance liquid chromatography(HPLC)was used to quantify the main active component of ginger oil,6-gingerol.Transdermal absorption experiments were conducted to optimize the various pressure-sensitive adhesives and permeation enhancers,including their type and concentration.Subsequently,the ginger oil patches were optimized and subjected to content determination and property evaluations.A PTSD mouse model was established using the foot-shock method.The therapeutic effect of ginger oil patches on PTSD was assessed through pathological sections,behavioral tests,and the evaluation of biomarkers such as tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),brain-derived neurotrophic factor(BDNF),and melatonin(MT).Results The results demonstrated that ginger oil patches exerted therapeutic effects against PTSD by inhibiting inflammatory responses and modulating MT and BDNF levels.Pharmacokinetic experiments revealed that ginger oil patches maintained a stable blood drug concentration for at least one day,addressing the rapid metabolism drawback of 6-gingerol and enhancing its therapeutic efficacy.Conclusions Ginger oil can be prepared as a transdermal drug patch that meets these requirements,and the bioavailability of the prepared patch is better than that of oral administration.It can improve PTSD with good patient compliance and ease of administration.Therefore,it is a promising therapeutic formulation for the treatment of PTSD.

Exploring the limited use of transdermal medications in psychiatry:Challenges and potential solutions

Transdermal medications are an useful yet underutilized tool in the field of psychiatry.Despite numerous advantages of using this route of medication delivery,transdermal medications remain less popular compared to other routes of medication administration such as oral and intramuscular routes in the management of various psychiatric conditions.In this editorial,we examine the advantages of transdermal medications with a brief overview of transdermal being used in psychiatry and other medical specialties.We discuss the factors that play a role in their limited usage in psychiatry.We highlight certain patient categories who can specifically benefit from them and discuss potential solutions that can broaden the perspective of treating clinicians making this an intriguing avenue in the field of psychiatry.

Research Progress on Application of Borneol As Permeation Enhancer in Functional Cosmetics

Borneol, as a traditional natural permeation enhancer, has been widely used to promote the transdermal absorption of active ingredients. In this review, the mechanism of borneol in promoting permeation by destroying the highly ordered lipid structure of the lipid layer and by destroying the hydrogen-bond network was described. The application of borneol in promoting the transdermal absorption of the active ingredients of traditional Chinese medicine and chemical drugs was introduced. The application of borneol as a natural ingredient added to functional cosmetics was summarized, and its effects on skin-spot treatment, acne skin care, eczema skin care, skin repair and anti-oxidation were introduced. Finally, the possible problems in the application of borneol in cosmetics were put forward, and the application prospect of borneol in the development of cosmetics was given.

Advances in Transdermal Drug Delivery for Cancer Therapy

Transdermal drug delivery offers a promising alternative to traditional cancer therapies by providing a non-invasive,controlled,and targeted delivery of therapeutic agents.This paper explores the advancements,benefits,and challenges associated with transdermal drug delivery systems(TDDS)in cancer treatment.It highlights the mechanisms of action,key technologies,and the potential impact on patient outcomes.By examining recent studies and clinical trials,this paper aims to provide a comprehensive overview of the efficacy,safety,and prospects of transdermal drug delivery in oncology.

The Effects of Some Penetration Enhancers on the Transdermal Iontophoretic Delivery of Insulin in Vitro *

The effects of some commonly used penetration enhancers such as laurocapram (AZ), oleic acid (OA), poloxamer (POL) and propylene glycol (PG) on the in vitro transdermal iontophoretic delivery of insulin through full-thickness mouse skin were investigated. The results showed that AZ had a synergistic effect on iontophoretic ability to enhance skin permeation of insulin, and PG could further increase this effect. 5% AZ / PG increased the iontophoretic steady state flux of insulin by a factor of 2.75 compared to that treated with iontophoresis alone. OA did not further enhance iontophoretic effect to increase skin permeation of insulin. The combination of iontophoresis and some enhancer provided a novel idea and possibility for transdermal delivery of insulin.

Novel chemical permeation enhancers for transdermal drug delivery

Transdermal drug delivery has been accepted as a potential non-invasive route of drug administration,with advantages of prolonged therapeutic action,decreased side effect,easy use and better patient compliance.However,development of transdermal products is primarily hindered by the low permeability of the skin.To overcome this barrier effect,numerous new chemicals have been synthesized as potential permeation enhancers for transdermal drug delivery.In this review,we presented an overview of the investigations in this field,and further implications on selection or design of suitable permeation enhancers for transdermal drug delivery were also discussed.

Investigating the potential of essential oils as penetration enhancer for transdermal losartan delivery: Effectiveness and mechanism of action

The effect of tea tree oil(TTO),cumin oil(CO),rose oil(RO)and aloe vera oil(AVO)on the skin permeation of losartan potassium(LP)was investigated.In vitro skin permeation studies were carried out using rat skin.The mechanism of skin permeation enhancement of LP by essential oils treatment was evaluated by FTIR,DSC,activation energy measurement and histopathological examination.Both concurrent ethanol/enhancer treatment and neat enhancer pretreatment of rat SC with all the oils produced significance increase in the LP flux over the control.The effectiveness of the oils as the penetration enhancers was found to be in the following descending order:AVO>RO>CO>TTO.However,only AVO was the only enhancer to provide target flux required to deliver the therapeutic transdermal dose of LP.FTIR and DSC spectra of the enhancer treated SC indicated that TTO,CO,RO and AVO increased the LP permeation by extraction of SC lipids.The results of thermodynamic studies and histopathological examination of AVO treated SC suggested additional mechanisms for AVO facilitated permeation i.e.transient reduction in barrier resistance of SC and intracellular transport by dekeratinization of corneocytes which may be attributed to the presence of triglycerides as constituents of AVO.It is feasible to deliver therapeutically effective dose of LP via transdermal route using AVO as penetration enhancer.

Nano transdermal system combining mitochondria-targeting cerium oxide nanoparticles with all-trans retinoic acid for psoriasis

Psoriasis is an inflammatory skin disease that is intricately linked to oxidative stress.Antioxidation and inhibition of abnormal proliferation of keratinocytes are pivotal strategies for psoriasis.Delivering drugs with these effects to the site of skin lesions is a challenge that needs to be solved.Herein,we reported a nanotransdermal delivery system composed of all-trans retinoic acid(TRA),triphenylphosphine(TPP)-modified cerium oxide(CeO2)nanoparticles,flexible nanoliposomes and gels(TCeO_(2)-TRA-FNL-Gel).The results revealed that TCeO_(2)synthesized by the anti-micelle method,with a size of approximately 5 nm,possessed excellent mitochondrial targeting ability and valence conversion capability related to scavenging reactive oxygen species(ROS).TCeO_(2)-TRA-FNL prepared by the film dispersion method,with a size of approximately 70 nm,showed high drug encapsulation efficiency(>96%).TCeO_(2)-TRA-FNL-Gel further showed sustained drug release behaviors,great transdermal permeation ability,and greater skin retention than the free TRA.The results of in vitro EGF-induced and H2O2-induced models suggested that TCeO_(2)-TRA-FNL effectively reduced the level of inflammation and alleviated oxidative stress in HaCat cells.The results of in vivo imiquimod(IMQ)-induced model indicated that TCeO_(2)-TRA-FNL-Gel could greatly alleviate the psoriasis symptoms.In summary,the transdermal drug delivery system designed in this study has shown excellent therapeutic effects on psoriasis and is prospective for the safe and accurate therapy of psoriasis.

Investigating a Vitamin D Delivery Toothpaste Using a Penetration Enhancer Compound

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.

Low-Light Enhancer for UAV Night Tracking Based on Zero-DCE++

Unmanned aerial vehicle (UAV) target tracking tasks can currently be successfully completed in daytime situations with enough lighting, but they are unable to do so in nighttime scenes with inadequate lighting, poor contrast, and low signal-to-noise ratio. This letter presents an enhanced low-light enhancer for UAV nighttime tracking based on Zero-DCE++ due to its ad-vantages of low processing cost and quick inference. We developed a light-weight UCBAM capable of integrating channel information and spatial features and offered a fully considered curve projection model in light of the low signal-to-noise ratio of night scenes. This method significantly improved the tracking performance of the UAV tracker in night situations when tested on the public UAVDark135 and compared to other cutting-edge low-light enhancers. By applying our work to different trackers, this search shows how broadly applicable it is.

Research Progress on Application of Borneol as Permeation Enhancer in Functional Cosmetics

Borneol,as a traditional natural permeation enhancer,has been widely used to promote the transdermal absorption of active ingredients.The mechanism of borneol in promoting permeation by destroying the highly ordered lipid structure of the lipid layer and by destroying the hydrogen-bond network was described.The application of borneol in promoting the transdermal absorption of the active ingredients of traditional Chinese medicine and chemical drugs was introduced.The application of borneol as a natural ingredient added to functional cosmetics was summarized,and its effects on skin-spot treatment,acne skin care,eczema skin care,skin repair and anti-oxidation were introduced.Finally,the possible problems in the application of borneol in cosmetics were put forward,and the application prospect of borneol in the development of cosmetics was given。

基于特征强化U⁃Net的地震速度反演方法

基于深度神经网络的地震速度反演方法面临的挑战是:时间域地震数据与空间域模型信息间语义映射的弱对应关系导致多解性;神经网络将地震数据映射到速度模型过程中缺少有效引导,易受噪声干扰,影响反演精度。为此,提出一种基于特征强化U‑Net的地震速度反演方法。首先,通过多炮地震数据特征叠加使输入网络的地震时间序列信号与对应速度模型之间的空间关系更加明确;其次,基于多尺度特征融合的思想设计具有不同尺寸卷积核的模块,以增强网络对有效特征的学习能力;然后,利用注意力门引导网络,增强网络重点关注的特征;最后,结合瓶颈残差和预激活的思想,在网络中加入预激活瓶颈残差,避免梯度消失和网络退化。实验表明,该方法在地震速度反演方面具有更高的精度,并在抗噪声测试中效果较好,具有一定的泛化能力。

基于加速康复外科理念的集束化护理措施在老年胰十二指肠切除术患者中的应用

目的:评价实施基于加速康复外科理念的集束化护理措施对老年胰十二指肠切除术后患者的效果,以期促进患者术后早期康复。方法:选取北京市某三级甲等医院肝胆外科2019年8月至2023年3月收治的老年胰十二指肠切除术患者,依据是否采用基于加速康复外科理念的集束化护理措施将患者分为观察组和对照组,依据患者的基线资料采用1∶1倾向性配比分析将两组患者进行匹配,比较两组患者术后恢复情况。结果:观察组患者术后胃肠道功能恢复情况优于对照组,术后住院时间比对照组短,术后胃瘫和下肢静脉血栓的发生率低于对照组(P<0.05)。结论:基于加速康复外科理念的集束化护理措施有助于促进老年胰十二指肠切除术后患者的胃肠道功能的恢复,减少了部分并发症的发生率,缩短了患者术后住院时间,值得进一步推广。

水凝胶微针在经皮给药系统中的研究进展

微针是一种微凸起阵列组成的微创装置,穿过皮肤角质层形成暂时性微通道,可实现对药物的经皮递送。对微针在经皮给药应用中的优缺点进行了简单阐述,重点介绍了水凝胶微针。综述了水凝胶微针的形成机制、基质材料及制备方法,并对水凝胶微针在疾病诊断和治疗方面的应用进行了介绍,指出了水凝胶微针在生物安全性、制定载药量标准等方面存在的问题,对未来的研究方向进行了展望。智能化、便携化是未来的微针发展趋势,若可以实现根据患者需求在给药时间、给药部位、给药剂量等方面的精准调控,水凝胶微针将在疾病诊断与治疗方面发挥更大的潜力。

心肌超声造影定量分析辅助诊断左心房非活动性黏液瘤一例

1病例资料患者女性,51岁,因“发现血压升高6年余,反复头晕1年余”于2022年1月25日入院。患者6年前诊断为“高血压1级,低危组”,规律服用硝苯地平缓释片,20 mg/d,血压控制平稳。近1年来反复出现头晕,无头疼、恶心呕吐,无视物旋转,无肢体麻木等。既往无特殊。查体:血压135/80 mmHg,体温36.5℃,神志清楚,步行入院,双肺未闻及干湿啰音;心界不大,心率76次/min,心律齐,未闻及病理性杂音;腹软,无压痛,肝脾肋下未触及;双下肢无水肿,生理反射正常,病理反射未引出。头部CT检查未见异常。

基于Transformer和自适应特征融合的矿井低照度图像亮度提升和细节增强方法

高质量矿井影像为矿山安全生产提供保障,也有利于提高后续图像分析技术的性能。矿井影像受低照度环境的影响,易出现亮度低,照度不均,颜色失真,细节信息丢失严重等问题。针对上述问题,提出一种基于Transformer和自适应特征融合的矿井低照度图像亮度提升和细节增强方法。基于生成对抗思想搭建生成对抗式主体模型框架,使用目标图像域而非单一参考图像驱动判别器监督生成器的训练,实现对低照度图像的充分增强;基于特征表示学习理论搭建特征编码器,将图像解耦为亮度分量和反射分量,避免图像增强过程中亮度与颜色特征相互影响从而导致颜色失真问题;设计CEM-Transformer Encoder通过捕获全局上下文关系和提取局部区域特征,能够充分提升整体图像亮度并消除局部区域照度不均;在反射分量增强过程中,使用结合CEM-Cross-Transformer Encoder的跳跃连接将低级特征与深层网络处特征进行自适应融合,能够有效避免细节特征丢失,并在编码网络中添加ECA-Net,提高浅层网络的特征提取效率。制作矿井低照度图像数据集为矿井低照度图像增强任务提供数据资源。试验显示,在矿井低照度图像数据集和公共数据集中,与5种先进的低照度图像增强算法相比,该算法增强图像的质量指标PSNR、SSIM、VIF平均提高了16.564%,10.998%,16.226%和14.438%,10.888%,14.948%,证明该算法能够有效提升整体图像亮度,消除照度不均,避免颜色失真和细节丢失,实现矿井低照度图像增强。

基于LMIENet图像增强的矿井下低光环境目标检测方法

煤矿井下工作环境复杂,存在人造光源亮度低、粉尘多和水气密度大等不利因素,导致现有的目标检测算法在应用到煤矿井下时,存在提取特征困难、目标识别和定位精度低等问题。提出一种煤矿井下低照度环境目标检测算法,由矿井低光图像增强模块LMIENet和目标检测模块组成,使用图像增强模块对原始图像进行画质提升,恢复各类图像信息,再使用目标检测网络对增强图像进行特定目标检测,有效提高检测的精确度。在图像增强模块中,改进Zero-DCE算法设计轻量级增强参数预测网络,计算像素级增强参数矩阵,用于低光照图像的亮度调整和画质增强,该网络通过设计的非参考损失函数隐性衡量图像的增强效果,引导网络进行无监督学习,使网络能够不依赖配对数据集对原始图像进行自适应的画质增强。目标检测模块中,采用YOLO v8n目标检测模型,其轻量化的模型尺寸和高灵活性可避免模型整体复杂度过高;采用Focal-EIoU Loss改进回归损失函数,有效加速模型收敛并提升模型检测精度。实验结果显示:与经典目标检测算法Faster R–CNN,SSD,RetinaNet,FCOS等相比,提出算法在自建矿井人员数据集上表现出色,低光照环境下目标检测的mAP@0.5达到98.0%,mAP@0.5∶0.95达64.8%,在实验环境中单帧图像推理时间仅11 ms,优于其他对比方法,证明提出算法能够有效实现在煤矿井下低照度复杂环境下的目标检测,且耗时短、计算效率高。