Enzyme-Activated Prodrug-Based Smart Liposomes Specifically Enhance Tumor Hemoperfusion with Efficient Drug Delivery to Pancreatic Cancer Cells and Stellate Cells

Tumor-specific enhanced delivery of chemotherapeutics and modulators to tumor cells and activated pancreatic stellate cells (aPSCs), respectively, represents safer and more effective therapy for pancreatic cancer. Herein, a membrane type 1-matrix metalloproteinase (MT1-MMP)-cleavable spacer is used to assemble low-density cRGDfK onto thermosensitive liposomes loaded with phosphorylated calcipotriol (PCAL) and doxorubicin (DOX), yielding MR-T-PD. The liposome-linked cRGDfK prodrug on MR-T-PD surface is first activated by MT1-MMP, which is selectively expressed on tumor endothelial cells, to release cRGDfK. The free cRGDfK specifically promotes tumor angiogenesis, leading to 3.4-fold higher accumulation and a wider distribution of MR-T-PD in tumors. Furthermore, MR-T-PD rapidly releases PCAL and DOX into the interstitium under heat treatment. The released DOX enters tumor cells to induce apoptosis, whereas the PCAL prodrug is converted to CAL by alkaline phosphatase on the surface of aPSCs; CAL can then enter aPSCs to induce quiescence and promote the antitumor effect of DOX. Finally, by enhancing the exposure of DOX and CAL to tumor cells and aPSCs, respectively, in a tumor-specific manner, MR-T-PD exerts superior efficacy (a 5.9-fold decrease in tumor weight) without causing additional side effects. Overall, this prodrug-based smart liposome system represents a promising paradigm for pancreatic cancer therapy.     

Nanovaccine-Mediated Cell Selective Delivery of Neoantigens Potentiating Adoptive Dendritic Cell Transfer for Personalized Immunization

Neoantigen vaccines and adoptive dendritic cell (DC) transfer are major clinical approaches to initiate personalized immunity in cancer patients. However, the immunization efficacy is largely limited by the in vivo trajectory including neoantigens’ access to resident DCs and DCs’ access to lymph nodes (LNs). Herein, an innovative strategy is proposed to improve personalized immunization through neoantigen-loaded nanovaccines synergized with adoptive DC transfer. It is found that it enables selective delivery of neoantigens to resident DCs and macrophages by coating cancer cell membranes onto neoantigen-loaded nanoparticles. In addition, the nanovaccines promote the secretion of chemokine C-C motif ligand 2 (CCL2), CCL3, and C-X-C motif ligand 10 from macrophages, thus potentiating the access of transferred DCs to LNs. This immunization strategy enables coordinated delivery of identified neoantigens and autologous tumor lysate-derived undefined antigens, leading to initiation of antitumor T cell immunity in a personalized manner. It significantly inhibits tumor growth in prophylactic and established mouse tumor models. The findings provide a new vision for potentiating adoptive cell transfer by nanovaccines, which may open the door to a transformative possibility for improving personalized immunization.     

医院耗材智能柜在科室耗材精细化管理中的应用研究

为了解决医院耗材数量多、种类复杂导致的科室耗材管理琐碎繁杂问题。本文提出基于人工智能调度及智能柜分类管理的医院科室耗材精细化管理方法。利用大数据方法建立医院科室耗材数据库,分段拟合控制数据库信息,通过空间资源优化分配方法重组数据,构造医院科室耗材的智能柜,智能分类识别医院科室耗材,提取医院科室耗材信息的统计特征量,规则化调度和自动更新医院科室耗材管理信息,实现医院科室耗材的精细化管理和评估。仿真结果表明,本文方法可实现医院科室耗材精细化管理,分类性能较好,精细化水平较高。     

纳米药物非临床药代动力学的研究策略及关注要点

随着纳米技术的迅速发展，纳米药物的研发已成为目前药物创新的发展方向之一。纳米药物具有基于纳米结构的尺度效应，其药代动力学特征与普通药物相比存在明显差异，其药代动力学研究与普通药物相比也有其特殊性。本文着重探讨纳米药物的非临床药代动力学的研究策略及关注要点，包括受试物、体内/外试验、生物样本分析、数据评价分析等，期望为研发者提供参考。     

Engineering Nanorobots for Tumor-Targeting Drug Delivery: From Dynamic Control to Stimuli-Responsive Strategy

Nanotechnology has been widely applied to the fabrication of drug delivery systems in the past decades. Recently, with the progress made in microfabrication approaches, nanorobots are steadily becoming a promising means for tumor-targeting drug delivery. In general, nanorobots can be divided into two categories: nanomotors and stimuli-responsive nanorobots. Nanomotors are nanoscale systems with the ability to convert surrounding energies into mechanical motion, whereas stimuli-responsive nanorobots are featured with activatable capacity in response to various endogenous and exogenous stimulations. In this minireview, the dynamic control of nanomotors and the rational design of stimuli-responsive nanorobots are overviewed, with particular emphasis on their contribution to tumor-targeting therapy. Moreover, challenges and perspectives associated with the future development of nanorobots are presented.     

Medical image detection and azithromycin in the treatment of pelvic inflammation based on intelligent hospital system

The pelvic infection and people genital tract inflammation, infertility, chronic pain, and reasons for detecting ectopic pregnancy. Diagnostic and management challenges, from different signs and symptoms and a variety of microbial etiology is not fully delineated largely responsible. Because of the potential for serious things of the network, it is recommended for the diagnosis and treatment of low barriers to entry. One of pelvic inflammatory infection of pregnant woman of childbearing age is not the most testing an important public pelvic problem remains. This is the main long-term internet of things, such as tubal factor infertility, ectopic pregnancy and chronic pelvic pain. Also, acute care and its complications lead to significant pelvic care costs. These long-term preventions of the internet of things depend on the microbial cause of acute knowledge of strategies based on treatment. All aware that it is a polymicrobic acute infection. Organisms, Chlamydia trachomatis and Neisseria gonorrhoeae sexually transmit presence, in many cases, including the endogenous vaginal and cervical flora often associated with microorganisms. It contains anaerobic and facultative bacteria similar to those associated with bacterial most importantly mycoplasma has also recently been involved in acute reasons. Therefore, a therapeutic regimen for acute should provide a wide spectral range that is effective against these microorganisms.     

Carbonation of Chrysotile under Subduction Conditions

In order to understand the role of serpentine minerals in the global carbon cycle, high-pressure X-ray diffraction (XRD) experiments were performed on chrysotile (Mg₃Si₂O₅(OH)₄) using carbon dioxide (CO₂) as a pressure medium. Synchrotron XRD patterns revealed the formation of magnesite and high-pressure chrysotile after heating at 170 °C for 1 h at 2.5(1) GPa. The Rietveld refinement suggests that the unit cell composition of the original chrysotile changes to Mg_2.4(1)Si₂O₅(OH)_2.4(1) upon the formation of magnesite, which appears to be driven by the dehydrogenation of the innermost hydroxyl group, OH3, and the rearrangement of magnesium (Mg) at the M1 site, leading to the formation of metastable monodehydroxylated chrysotile. Metastable chrysotile is observed up to 5.0(1) GPa and 500 °C, which corresponds to the slab Moho geotherms for the South Sumatra and Ryukyu subduction zone. After recovery to ambient conditions, the characteristic fibrous morphology of the original chrysotile was found to have changed to an earthy form. These results can help us to understand deep carbon cycling along the subduction zones, and may prompt the design of a novel method of asbestos detoxification using pressure and temperature.     

富硒长双歧杆菌DD98菌株对伊立替康所致小鼠腹泻及肠道菌群的影响

本研究建立伊立替康所致腹泻小鼠模型,通过长期灌胃富硒DD98(Selenium-enriched Bifidobacterium longum Se-DD98)菌株(一株新的长双歧杆菌菌株),评价其对伊立替康所致腹泻及肠道菌群的影响。正常对照组和伊立替康组小鼠每天灌胃无菌蒸馏水,实验组小鼠每天灌胃低剂量(活菌数1×108 CFU/kg)、高剂量(活菌数1×109 CFU/kg)Se-DD98菌液,除正常对照组外其他各组在第17 d腹腔注射伊立替康,实验周期为24 d。测定小鼠体重,小鼠腹泻等级,免疫指标,肠道菌群以及回肠组织结构。结果表明:与伊立替康组比较,Se-DD98低、高剂量组小鼠体重显著增加(P<0.05);腹泻等级显著降低(P<0.05);高剂量组白细胞数目显著增加(P<0.05),低、高剂量组脾脏指数和中性粒细胞数目均显著增加(P<0.05),说明Se-DD98具有调节免疫功能的作用。同时,低、高剂量组大肠杆菌、梭菌和拟杆菌含量均比正常组和伊立替康组显著减少(P<0.05),而双歧杆菌含量显著增加(P<0.01)。此外Se-DD98低、高剂量均能减轻伊立替康导致的肠道粘膜、细胞和腺体损伤。上述结果表明Se-DD98可能通过调节肠道菌群和保护肠道粘膜发挥缓解伊立替康导致的腹泻的作用。提示Se-DD98在辅助治疗伊立替康所致的腹泻等方面具有潜在应用前景。     

Detecting Cysteine in Bioimaging with a Near-Infrared Probe Based on a Novel Fluorescence Quenching Mechanism

Near-infrared (NIR) fluorescent probes are very significant for detecting cysteine in biological systems. Herein, we report a highly selective and sensitive NIR turn-on fluorescent probe (BDP-NIR) based on BODIPY with large Stokes shift (105 nm) for detecting Cys. We clarified the sensing mechanism based on the different thiol-induced S_NAr substitution/rearrangement reaction of the probe with cysteine and homocysteine/glutathione, which leads to the corresponding amino- and thiol-BODIPY dyes with distinct photophysical properties. Moreover, a novel mechanism of fluorescence quenching was demonstrated by density functional theory calculation. The reason for the fluorescence quenching of the probe might be intersystem crossing (from singlet to triplet excited state). Moreover, BDP-NIR had a high linear dynamic range of 0–500 μM, which was promising for detecting cysteine quantificationally. Significantly, BDP-NIR was capable of sensing endogenous cysteine in living cells and in vivo.     

高温固定流化床费托合成技术及其产物加工路线

与采用低温费托合成主产油品技术相比，产品更为多元化和高值化的高温费托合成技术在目前市场环境下显示出非常明显的优势。本文综述了高温费托合成技术的发展历程及其最新进展，重点介绍了高温费托合成过程中的核心问题，主要包括高温费托合成工艺、固定流化床反应器、费托合成催化剂；介绍了高温费托合成产物分布与特性，讨论了高温费托合成产物的加工路线，并对高温费托合成煤间接液化的工业应用前景和产业化方向进行了展望。结果表明：高温费托合成技术具有产物附加值高、兼顾油品和化学品、技术发展成熟等优势，产物中轻组分含量高、碳数分布较窄、高附加值的α-烯烃含量高；精细化、高端化、差异化加工是实现高温费托合成产物高值化利用的关键。