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The natural evolution of urban forms over time is a key issue in urban morphology. With the rapid development of 7quantitative analytical tools and new urban data, new research potential has emerged. This study attempts to develop an analytical framework for evaluating the urban maturation process. Using street blocks as the analytical unit, this study integrates the spatial design network analysis (sDNA), Spacematrix, Points-of-Interests (POIs), and Open Street Map (OSM) in the geographical information system (GIS) to calculate the urban maturation index in the context of big data. Shanghai, a metropolitan city with a long urbanisation history and a series of new towns, was selected as the case study. The validation of this new index was first achieved by comparing this maturation index between several districts located in the city centre and suburban new towns. Insights in this direction would help generate new urban design guidance for creating vibrant urban places. This study also aimed to introduce new quantitative thinking into the previously qualitative and intuition-based fields of urban morphology and urban design.

Additional file 1: Table S1. Encapsulation efficiency stability of the drug in 4 liposomes at 3 months (n = 3). Fig. S1. Diameter and ζ-potential of Tf-ELE/CTX@BLIP, Tf-ELE/CTX@LIP, ELE/CTX@BLIP and ELE/CTX@LIP. Fig. S2. 7-days stability of TF-ELE/CTX@BLIP diameter in different medium. Fig. S3. Flow cytometry analysis of RG2 glioma cells after incubation with Tf-ELE/CTX@BLIP, Tf-ELE/CTX@LIP, ELE/CTX@BLIP and ELE/CTX@LIP for 2 h. Rho B = 20 μg/mL. Fig. S4. CLSM images of RG2, U251 and C6 glioma cells treated with Tf-ELE/CTX@BLIP for 2 h. Scale bar = 50 μm. Fig. S5. Flow cytometry analysis of RAW264.7 cells treated with Tf-ELE/CTX@BLIP, Tf-ELE/CTX@LIP, ELE/CTX@BLIP and ELE/CTX@LIP for 2 h. Rho B = 20 μg/mL. Fig. S6. WB analysis of P-gp in bEnd.3 cells. Relative protein expression was calculated. Cells preconditioned with (1) control; (2) verapamil; (3) ELE/CTX@LIP; (4) ELE/CTX@BLIP; (5) Tf-ELE/CTX@LIP; (6) Tf-ELE/CTX@BLIP. (*P < 0.05, n=3). Fig. S7. Corresponding quantitative fluorescent analysis of brain, liver, heart, spleen, lung and kidney at 48 h post-injection in glioma-beard mice. *p < 0.05. Fig. S8. In vivo fluorescence imaging of Tf-Cypate@BLIP, Tf-Cypate@LIP, Cypate@BLIP and Cypate@LIP in normal mice. Cypate = 0.5 mg/kg. Fig. S9. Averaged fluorescent intensity of saline, free CTX, free ELE, ELE/CTX@LIP, ELE/CTX@BLIP, Tf-ELE/CTX@LIP and Tf-ELE/CTX@BLIP in nude mice bearing orthotopic glioma brain within 15 days of treatments. Fig. S10. H&E staining of brain sections of orthotopic glioma-bearing mice in different formulation groups. Fig. S11. Biochemical parameter analysis after treated with saline, free CTX, free ELE, ELE/CTX@LIP, ELE/CTX@BLIP, Tf-ELE/CTX@LIP and Tf-ELE/CTX@BLIP. (A) BLI-T: total bilirubin, (B) BUN: blood urea nitrogen, (C) URIC: uric acid, (D) ALT: alanine transaminase, (E) CRE: creatinine, (F) AST: aspartate transaminase.

Jie Li,1– 4 Jiaqian Zhao,2– 5 Tiantian Tan,2– 4 Mengmeng Liu,2– 4 Zhaowu Zeng,2– 4 Yiying Zeng,2– 4 Lele Zhang,6 Chaomei Fu,1 Dajing Chen,2– 4 Tian Xie2– 4 1College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China; 2Holistic Integrative Pharmacy Institutes, Hangzhou Normal University, Hangzhou, Zhejiang, People’s Republic of China; 3Key Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province, Hangzhou, Zhejiang, People’s Republic of China; 4Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou, Zhejiang, People’s Republic of China; 5College of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 6School of Medicine, Chengdu University, Chengdu, People’s Republic of ChinaCorrespondence: Tian Xie; Zhaowu ZengHolistic Integrative Pharmacy Institutes, Hangzhou Normal University, 1378 Wenyixi Road, Hangzhou, Zhejiang 311121, People’s Republic of ChinaTel +86 5 712 886 8269Email xbs@dljg.sina.net; artgreenking@126.comAbstract: Gliomas are the most common tumor of the central nervous system. However, the presence of the brain barrier blocks the effective delivery of drugs and leads to the treatment failure of various drugs. The development of a nanoparticle drug delivery system (NDDS) can solve this problem. In this review, we summarized the brain barrier (including blood–brain barrier (BBB), blood–brain tumor barriers (BBTB), brain–cerebrospinal fluid barrier (BCB), and nose-to-brain barrier), NDDS of glioma (such as passive targeting systems, active targeting systems, and environmental responsive targeting systems), and NDDS efficacy improvement strategies and deficiencies. The research prospect of drug-targeted delivery systems for glioma is also discussed.Keywords: glioma, brain barrier, nanoparticle drug delivery system, efficacy improvement strategies, deficiencies of NDDS

Paclitaxel is highly effective at killing many malignant tumors, however, the development of drug resistance is common in clinical applications. The issue of overcoming paclitaxel resistance is a difficult challenge at present. In this study, we developed nano drugs to treat paclitaxel-resistant lung adenocarcinoma. We selected cabazitaxel and &beta, elemene, which have fewer issues with drug resistance, and successfully prepared cabazitaxel liposome, &beta, elemene liposome and cabazitaxel-&beta, elemene complex liposome with good flexibility. The encapsulation efficiencies of cabazitaxel and &beta, elemene in these liposomes were detected by precipitation microfiltration and microfiltration centrifugation methods, respectively. Their encapsulation efficiencies were all above 95%. The release rates were detected by a dialysis method. The release profiles of cabazitaxel and &beta, elemene in these liposomes conformed to the Weibull equation. The release of cabazitaxel and &beta, elemene in the complex liposome were almost synchronous. The pharmacodynamics study showed that cabazitaxel flexible liposome and &beta, elemene flexible liposome were relatively good at overcoming paclitaxel resistance on paclitaxel-resistant lung adenocarcinoma. As the flexible complex liposome, the dosage of cabazitaxel could be reduced to 25% that of the cabazitaxel injection while retaining a similar therapeutic effect. It showed that &beta, elemene can replace some of the cabazitaxel, allowing the dosage of cabazitaxel to be reduced, thereby reducing the drug toxicity.

Bingtao Zhai,1 Yiying Zeng,2–5 Zhaowu Zeng,2–4 Nana Zhang,2–4 Chenxi Li,2–4 Yijun Zeng,2–4 Yu You,1 Shuling Wang,2–4 Xiabin Chen,2–4 Xinbing Sui,2–4 Tian Xie2–4 1College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China; 2Holistic Integrative Pharmacy Institutes, Hangzhou Normal University, Hangzhou, Zhejiang, China; 3Key Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province, Hangzhou, Zhejiang, China; 4Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou, Zhejiang, China; 5College of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China Abstract: β-elemene is a noncytotoxic Class II antitumor drug extracted from the traditional Chinese medicine Curcuma wenyujin Y. H. Chen et C. Ling. β-elemene exerts its effects by inhibiting cell proliferation, arresting the cell cycle, inducing cell apoptosis, exerting antiangiogenesis and antimetastasis effects, reversing multiple-drug resistance (MDR), and enhancing the immune system. Elemene injection and oral emulsion have been used to treat various tumors, including cancer of the lung, liver, brain, breast, ovary, gastric, prostate, and other tissues, for >20years. The safety of both elemene injection and oral emulsion in the clinic has been discussed. Recently, the secondary development of β-elemene has attracted the attention of researchers and made great progress. On the one hand, studies have been carried out on liposome-based systems (including solid lipid nanoparticles [SLNs], nanostructured lipid carriers [NLCs], long-circulating liposomes, active targeting liposomes, and multidrug-loaded liposomes) and emulsion systems (including microemulsions, self-emulsion drug delivery systems [SEDDSs], and active targeting microemulsion) to solve the issues of poor solubility in water, low bioavailability, and severe phlebitis, as well as to improve antitumor efficacy. The pharmacokinetics of different drug delivery systems of β-elemene are also summarized. On the other hand, a number of highly active anticancer β-elemene derivatives have been obtained through modification of the structure of β-elemene. This review focuses on the two drug delivery systems and derivatives of β-elemene for cancer therapy. Keywords: β-elemene, pharmacokinetics, drug delivery system, derivative, safety