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Moisture was frequently used as dielectric heating source in classical microwave-able systems to facilitate microwave-induced in situ amorphization, however such systems may face the potential of drug hydrolysis. In this study, solid thermolytic salts were proposed to function as moisture substitutes and their feasibility and impacts on microwave-induced in situ amorphization were investigated. It was found that NH4HCO3 was a promising solid alkaline salt to facilitate both microwave-induced in situ amorphization and in situ salt formation of acidic indomethacin (IND). Moreover, it could improve the chemical stability of the drug and the dissolution performance of compacts relative to classical moisture-based compacts upon microwaving. Further mechanistic study suggested that the in situ amorphization occurred prior to the in situ salt formation, especially in formulations with low drug loadings and high solid salt mass ratios. For compacts with low polymer ratios, in situ salt formation took place subsequently, where the previously amorphized IND within compacts could interact with the NH3 gas produced in situ by the decomposition of NH4HCO3 and form the ammonium IND salt. Microwaving time showed great impacts on the decomposition of NH4HCO3 and the in situ generation of water and NH3, which indirectly affected the amorphization and salt formation of IND. In comparison to the moisture-based systems, the NH4HCO3-based system showed a number of advantages, including the reduced potential of IND hydrolysis due to the absence of absorbed moisture, a wider category of applicable polymeric carriers other than hygroscopic polymers, and an increase in drug loading up to 50% (w/w).

Microwave-induced in situ amorphization is a novel technology for preparing amorphous solid dispersions (ASDs) to address the challenges of their long-term physical stability and downstream processing. To date, only few types of dielectric materials have been reported for microwave-induced in situ amorphization, which restricted the extensive research of this technology. This study aimed to investigate the feasibility and mechanisms of utilizing the non-ionic surfactants, i.e. Kollisolv P124, Kolliphor RH40, D-ɑ-tocopheryl polyethylene glycol succinate (TPGS), Tween (T) 60 (T60), T65, T80 and T85, as plasticizers to facilitate microwave-induced in situ amorphization. It was found that the successful application of surfactants could be related with their low Tm, low Mw and high HLB. Kolliphor RH40 was selected as a typical surfactant due to its excellent dielectric heating ability, plasticizing effect and solubilizing effect when facilitating amorphization. Then, the dissolution-mediated in situ amorphization mechanism was investigated and intuitively demonstrated. For the most promising formulation, i.e. microwaved systems with Korlliphor RH40 at 1.5 (w/w) plasticizer/polymer ratio, a complete and fast in vitro dissolution was observed relative to the untreated systems. In conclusion, non-ionic surfactants had the potential to facilitate microwave-induced in situ amorphization, which provided a new direction in the formulation designation for microwave-able systems.

In urban transportation systems, taxis are regarded as flexible, convenient, and time-saving. Taxi demand is affected by various built-environment factors and by the time of the day. Although many studies have investigated correlations between taxi demand and the built environment, the direct and spillover effects of built environment factors on taxi demand have not been examined at a fine spatial scale. To address this gap in the literature, this paper employs spatial econometric models using GPS-tracked taxi trips, mobile signaling data, and points of interest (POIs) to study taxi demand in Beijing at a 1-kilometer square grid resolution. The results show that, in the morning and evening peak hours, road network density has the strongest (positive) direct and indirect impact on taxi ridership. A relationship is also found between public transportation and taxi ridership: bus coverage has positive direct effects and insignificant indirect effects on taxi pick-ups and drop-offs, while subway coverage has negative indirect effects, suggesting that it may absorb taxi demand from surrounding grids. Results also indicate that various built-environment factors affect taxi demand differently at morning and evening peak times. This study reveals the complex nature of taxi ridership and has important implications for policymakers, transport planners, and other stakeholders in megacities around the world. © 2022 Elsevier Ltd

Although shrinking cities' socio-economic sustainability has been focused in academia, the diffusing nature of shrinking cities’ environmental impact has rarely been systematically investigated. It remains uncertain the spatial extent of the effect of shrinking cities has on the environment. In this study, we address this issue by calculating the concentration of PM2.5 in the built-up area of 640 prefecture-level and county-level cities in China, and applying the Spatial Dubin Model (SDM) to analyze the spatial relationship between shrinking cities, built-up area expansion, and air pollution in China between 2000 and 2016. Our statistical findings indicate a negative relationship between shrinking cities and increased air pollution, both directly and indirectly. When cities contract, the growth of air pollution in local and surrounding areas decreases by 0.143% and 0.635%, respectively. However, shrinking cities associated with urban built-up area expansion have relatively higher air pollution growth. They contribute 0.598% and 4.968%, respectively, to the increase in air pollution in the local and surrounding areas. Besides, local economic development in mitigating air pollution has a positive spatial spillover effect on air quality in the neighboring cities. In contrast, local population size has a negative spatial spillover effect. The above findings contribute knowledge to the convoluted spatial dynamics between urban decline and air pollution in China. The associated policy implications are also discussed. © 2021 Elsevier Ltd

Microwave-induced in situ amorphization is an emerging technology to tackle the persistent stability issue of amorphous solid dispersions (ASDs) during manufacture and storage. The aim of this study was to introduce new effective polymeric carriers with diverse properties to microwave-induced in situ amorphization and to better understand their functions in relation to the final dissolution performance of microwaved tablets. Tablets composed of indomethacin (IND) and different polymers were compacted, stored at 75% relative humidity for at least 1 week and microwaved at 1000 W to induce amorphization. A series of polymers, polyvinylpyrrolidone/vinyl acetate copolymers (PVP/VA) of different monomer weight ratios displaying varying properties in functional group ratio, hygroscopicity, molecular weight (Mw), and glass transition temperature (Tg) of the polymer were used as model carriers. The results suggested that more than 90% of IND was amorphized after 20 mins microwaving in all 20% (w/w) drug loaded tablets except for IND:PVAc tablets presenting approx. 36% residual crystallinity. Among them, tablets composed of PVP/VA I-335 and PVP K30 achieved complete in situ amorphization upon microwaving. Further analysis indicated that the influencing factors, polymer Mw and Tg of moisture-plasticized polymer, played a major role in microwave-induced in situ amorphization. In in vitro dissolution study, ASDs containing PVP/VA I-535 with moderate hydrophilicity and 0.96 ± 1.92% IND residual crystallinity showed the most rapid and complete drug release among all formulations, presenting the most promising dissolution performance. Further study on the chemical stability of such formulation showed a statistically insignificant decrease of drug content after pre-conditioning and microwaving (P = 0.288 > 0.05).

Zircaloy coating is one of the crucial technical ways to improve the accident tolerance of nuclear fuel cladding, which enables the zirconium-water reaction problems to be solved. Zr2Al3C4 coating is one type of candidate solutions to improve the high-temperature oxidation resistance of zirconium claddings. However, little study has been performed on the synthesis of Zr2Al3C4 coatings on zirconium alloy substrates due to the inter-diffusion, as well as the difference of the thermal expansion coefficients between the Zr2Al3C4 coating and the substrates. In this study, Zr2Al3C4 coatings were prepared through room-temperature magnetron sputtering and post annealing on zirconium alloy (ZIRLO) substrates with magnetron-sputtered Al/Mo-C interlayers. The effects of Al/Mo-C interlayers on phases and microstructures of Zr-Al-C coatings after annealing were studied by different methods. It is found that the coatings without interlayer are broken and no Zr2Al3C4 phase is formed due to significant interdiffusion between the Zr-Al-C coating and the substrate during annealing at 800 degrees C for 3 h. The Al/Mo-C interlayers prevented elemental diffusion between Zr-Al-C coatings and substrates during the post-annealing process. The Al/Mo-C interlayers act as diffusion barriers and greatly reduce the stoichiometric deviations from Zr2Al3C4 phase, which facilitates the formation of the Zr2Al3C4 phase in the final coating. Moreover, this diffusion-barrier layers contribute to eliminating cracks induced by the difference of the thermal expansion coefficients between the Zr2Al3C4 coatings and substrates. At the same time, the adhesions between Zr-Al-C coatings with Al/Mo-C interlayers and substrates were improved after annealing, with their strength exceeding 30 N., Funding Agencies|National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [51873146]; Ningbo Municipal Natural Science Foundation [2018A610005]; Major Project of the Ministry of Science and Technology of China [2015ZX06004-001]; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University (Faculty Grant SFO-Mat-LiU) [2009 00971]

In order to reduce the tunnel construction accidents and ensure the safety of personnel, a comprehensive assessment method of tunnel construction risk based on combination weighting and cloud model is constructed according to the characteristics of tunnel construction. The risk assessment index system is established based on researches on engineering geological condition, natural environmental condition, Tunnel engineering design scheme and construction management. On this basis, the tunnel risk is divided into 4 levels and the index risk level standard is proposed. In order to improve the rationality of weighting, a weight calculation method based on AHP, entropy method and Lagrange multiplier method is constructed. Finally, the normal cloud generator is used to form comparison pictures of risk clouds and standard clouds, which demonstrates the risk status of the evaluation indexes at all levels. With reference to Deda Tunnel of Sichuan-Tibet Railway engineering of high integrated risk level, management decision-making is required. The evaluation results are basically consistent with engineering practices, proving that the method has good feasibility and applicability.

The thermodynamically unstable nature of amorphous drugs has led to a persistent stability issue of amorphous solid dispersions (ASDs). Lately, microwave-induced in situ amorphization has been proposed as a promising solution to this problem, where the originally loaded crystalline drug is in situ amorphized within the final dosage form using a household microwave oven prior to oral administration. In addition to circumventing issues with physical stability, it can also simplify the problematic downstream processing of ASDs. In this review paper, we address the significance of exploring and developing this novel technology with an emphasis on systemically reviewing the currently available literature in this pharmaceutical arena and highlighting the underlying mechanisms involved in inducing in situ amorphization. Specifically, in order to achieve a high drug amorphicity, formulations should be composed of drugs with high solubility in polymers, as well as polymers with high hygroscopicity and good post-plasticized flexibility of chains. Furthermore, high microwave energy input is considered to be a desirable factor. Lastly, this review discusses challenges in the development of this technology including chemical stability, selection criteria for excipients and the dissolution performance of the microwave-induced ASDs.

Qiang-Wei Wang,1,* Yi-Wen Wang,2,* Zhi-Liang Wang,1 Zhao-Shi Bao,3 Tao Jiang,3– 5 Zheng Wang,3 Gan You3 1Beijing Neurosurgical Institute, Capital Medical University, Beijing, People’s Republic of China; 2Huadong Medical Institute of Biotechniques, Nanjing, People’s Republic of China; 3Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 4China National Clinical Research Center for Neurological Diseases, Beijing, People’s Republic of China; 5Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Gan YouDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 119 South Fourth Ring West Road, Fengtai District, Beijing 100070, People’s Republic of ChinaTel/Fax +86-10-59976785Email Ganyou2016@126.comPurpose: Incidentally discovered diffusely infiltrating lower-grade gliomas (incidental LGGs, iLGGs) are defined as gliomas occasionally found in patients without tumor-related symptoms. At present, very few in-depth research studies on incidental LGGs were reported. We aimed to find out the inherent difference between iLGGs and LGGs with tumor-related symptoms.Patients and Methods: We enrolled 2486 all-grade gliomas and screened 1594 lower-grade gliomas for further analysis. Medical records were retrospectively reviewed for iLGGs. Clinical and mRNA sequencing data were collected for in-depth analysis.Results: We found that with increasing grade, the proportion of incidental glioma patients decreased obviously. In 1594 patients who underwent craniotomy for LGG, 80 (5%) patients were discovered incidentally. Grade II patients (88%) and patients bearing 1p/19q co-deletion in their tumors (23%) were more likely to be diagnosed as iLGGs. Regular radiological screening (48%) and trauma (24%) were the main complaint

Qiang-Wei Wang,1 Han-Jie Liu,1 Zheng Zhao,1 Ying Zhang,1 Zheng Wang,2 Tao Jiang,1,2 Zhao-Shi Bao2,3 1Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, People’s Republic of China; 2Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, People’s Republic of China; 3Division of Life Science, Hong Kong University of Science and Technology, Hong Kong, People’s Republic of ChinaCorrespondence: Zhao-Shi BaoDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 119 South Fourth Ring West Road, Fengtai District, Beijing 100070, People’s Republic of ChinaTel/Fax +86-10-59976785Email baozhaoshi@bjtth.orgPurpose: Autophagy plays a vital role in cancer initiation, malignant progression, and resistance to treatment; however, autophagy-related gene sets have rarely been analyzed in glioblastoma. The purpose of this study was to evaluate the prognostic significance of autophagy-related genes in patients with glioblastoma.Patients and methods: Here, we collected whole transcriptome expression data from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) datasets to explore the relationship between autophagy-related gene expression and glioblastoma prognosis. R language was the primary analysis and drawing tool.Results: We screened 531 autophagy-related genes and identified 14 associated with overall survival in data from 986 patients with glioblastoma. Patients could be clustered into two groups (high and low risk) using expression data from the 14 associated genes, based on significant differences in clinicopathology and prognosis. Next, we constructed a signature based on the 14 genes and found that most patients designated high risk using our gene signature were IDH wild-type, MGMT promoter non-methylated, and likely to have more malignant tumor subtypes (including classical and mesenchymal subtypes). Survival

Recently, great progress has been made in virtual reality(VR) research and application. However, virtual reality faces a big problem since its appearance, i.e. discomfort (nausea, stomach awareness, etc). Discomfort can be relieved by increasing hardware (sensor, cpu and display) speed. But this will increase cost. This paper gives another low cost solution. The phenomenon of cybersickness is explained with the control theory: discomfort arises if feedback scene differs from expectation, so it can be relieved by disturbing feedback loop in human brain. A hardware platform is build to test this explanation. The VR display on a Samsung S6 is blurred while head movement is detected. The effect is evaluated by comparing responses to the Simulated Sickness Questionnaire (SSQ) between a control and experimental condition. Experimental results show that the new method can ease discomfort remarkably with little extra cost. As a result, VR may be used more widely in teaching (like foreign language, medicine). It's also reasonable to expect likewise merits in other VR applications.