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Yingpeng Li,1 Ting Zhu,2,3 Jingxian Liang,2 Yuanqun Wu,2 Xiantong Guan,2 Tingting Liu,2 Shaowa Lü,2 Yongji Li,2 Yanhong Wang,2 Yang Ping4 1College of Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, People’s Republic of China; 2Key Laboratory of Basic and Application Research of Beiyao (Heilongjiang University of Chinese Medicine), Ministry of Education, Harbin, 150040, People’s Republic of China; 3Center of Pharmaceutical Engineering and Technology, College of Pharmacy, Harbin University of Commerce, Harbin, 150076, People’s Republic of China; 4College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang, 154007, People’s Republic of ChinaCorrespondence: Yanhong Wang, Key Laboratory of Basic and Application Research of Beiyao (Heilongjiang University of Chinese Medicine), Ministry of Education, Harbin, 150040, People’s Republic of China, Tel +86 18845587616, Email wang.yanhong@163.com Yang Ping, College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang, 154007, People’s Republic of China, Tel +86 18245482328, Email 18245482328@163.comBackground: Black plaster is one of the classic dosage forms of traditional Chinese medicine for external use and has been widely utilized since the Tang and Song Dynasties. In this paper, we take Goupi Gao as the research object and discuss the scientific characteristics of the black plaster dosage form. Goupi Gao ointment is a plaster for external use of traditional Chinese medicine.Methods: Methods for the morphological and quantitative characterization of black plaster’s microstructure, based on FESEM-IPP (Field Emission Scanning Electron Microscope IPP Image Processing) technology, were established. According to the actual operating temperature of Goupi Gao, three temperatures were selected: 28°C, 35°C, and 45°C. A UPLC analysis method was applied to the cinnamaldehyde and eugenol in Goupi Gao, and the release behavior of Goupi Gao from three samples at three temperatures was investigated using the paddle over disk method. Preparation of rabbit model of knee osteoarthritis of cold blood stasis type by cold stimulation combined with drug induction.Results: In terms of morphology, Goupi Gao and the blank black plaster matrix both formed a double continuous phase system with a thicker vegetable oil phase and crossed “branched” soap crystal fibers. Based on the IPP image quantification parameters, the pore area (A) was highly positively correlated with temperature. After the 28 °C treatment, A1 = (216.8± 59.5) μm2; after the 35 °C treatment, A2 = (259.7± 52.8) μm2; after the 45 °C treatment, A3 = (408.0± 57.7) μm2, and there were no significant differences in other pore parameters.Conclusion: The black plaster matrix’s unique structure makes it highly applicable in numerous medications; it exhibits slow-release and performs well in extreme temperatures, with good adhesion and peeling properties.Keywords: black plaster, Goupi Gao, microstructure, quantitative characterization, release behavior, pharmacodynamics

Intense lasers can accelerate protons in sufficient numbers and energy that the resulting beam can heat materials to exotic warm (10 s of eV temperature) states. Here we show with experimental data that a laser-driven proton beam focused onto a target heated it in a localized spot with size strongly dependent upon material and as small as 35 μm radius. Simulations indicate that cold stopping power values cannot model the intense proton beam transport in solid targets well enough to match the large differences observed. In the experiment a 74 J, 670 fs laser drove a focusing proton beam that transported through different thicknesses of solid Mylar, Al, Cu or Au, eventually heating a rear, thin, Au witness layer. The XUV emission seen from the rear of the Au indicated a clear dependence of proton beam transport upon atomic number, Z, of the transport layer: a larger and brighter emission spot was measured after proton transport through the lower Z foils even with equal mass density for supposed equivalent proton stopping range. Beam transport dynamics pertaining to the observed heated spot were investigated numerically with a particle-in-cell (PIC) code. In simulations protons moving through an Al transport layer result in higher Au temperature responsible for higher Au radiant emittance compared to a Cu transport case. The inferred finding that proton stopping varies with temperature in different materials, considerably changing the beam heating profile, can guide applications seeking to controllably heat targets with intense proton beams.

Ying Cao,1,* Yibei Dai,1,* Lingyu Zhang,1 Danhua Wang,1 Wen Hu,2 Qiao Yu,3 Xuchu Wang,1 Pan Yu,1 Weiwei Liu,1 Ying Ping,1 Tao Sun,1 Yiwen Sang,1 Zhenping Liu,4 Yan Chen,3 Zhihua Tao1 1Department of Laboratory Medicine, Zhejiang University School of Medicine Second Affiliated Hospital, Hangzhou, People’s Republic of China; 2National Clinical Research Center for Infectious Diseases, Zhejiang University School of Medicine First Affiliated Hospital, Hangzhou, People’s Republic of China; 3Center for Inflammatory Bowel Diseases, Department of Gastroenterology, Zhejiang University School of Medicine Second Affiliated Hospital, Hangzhou, People’s Republic of China; 4Department of Laboratory Medicine, the First People’s Hospital of Yuhang District, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan Chen; Zhihua Tao Tel +86 571 8778 3752Fax +86 571 8689 8730Email chenyan72_72@zju.edu.cn; zrtzh@zju.edu.cnBackground: Fecal biomarkers have emerged as one of the most useful tools for clinical management of inflammatory bowel disease (IBD). Oncostatin M (OSM), like fecal calprotectin (FC), is highly expressed in the inflamed intestinal mucosa which may have potential usefulness. We aimed to evaluate the additional utility of these two fecal biomarkers for IBD diagnosis, activity, and prediction of infliximab response over FC alone.Methods: In group 1, 236 IBD patients (145 Crohn’s disease, 91 ulcerative colitis), 50 disease controls, and 32 healthy controls were recruited for IBD diagnosis and activity. In group 2, baseline stool samples were collected from 62 patients to predict infliximab response at week 28 and 52. The performance of fecal biomarkers for IBD management was assessed by the area under the receiver operating characteristic curve (AUC).Results: Fecal OSM and FC levels were increased in IBD patients and were positively correlated with clinical and endoscopic activity. Their combination showed a better ability for disease diagnosis (AUC = 0.93) and slightly improved the capability to identify mucosal healing (AUC = 0.923). Baseline OSM and FC levels were elevated in non-responders at week 28 and 52. The AUCs of OSM, FC, and their combination to predict therapeutic response were 0.763, 0.834, and 0.859 at week 28, 0.638, 0.661, and 0.704 at week 52, respectively. Combined use of fecal and blood biomarkers improved predictive accuracy with an AUC of 0.919 at week 28 and 0.887 at week 52.Conclusion: In addition to FC, OSM is a novel fecal biomarker, and their combination is more beneficial for disease diagnosis and prediction of infliximab response but not for disease activity in IBD patients. Further larger-scale studies are required to confirm our findings.Keywords: inflammatory bowel disease, fecal biomarkers, oncostatin M, calprotectin, diagnosis, activity, infliximab response

Thermal conductivity is one of the most crucial physical properties of matter when it comes to understanding heat transport, hydrodynamic evolution, and energy balance in systems ranging from astrophysical objects to fusion plasmas. In the warm dense matter regime, experimental data are very scarce so that many theoretical models remain untested. Here we present the first thermal conductivity measurements of aluminum at 0.5-2.7 g/cc and 2-10 eV, using a recently developed platform of differential heating. A temperature gradient is induced in a Au/Al dual-layer target by proton heating, and subsequent heat flow from the hotter Au to the Al rear surface is detected by two simultaneous time-resolved diagnostics. A systematic data set allows for constraining both thermal conductivity and equation-of-state models. Simulations using Purgatorio model or Sesame S27314 for Al thermal conductivity and LEOS for Au/Al release equation-of-state show good agreement with data after 15 ps. Discrepancy still exists at early time 0-15 ps, likely due to non-equilibrium conditions.

We describe a 2 h general-chemistry experiment that introduces college students not only to the concepts, synthesis, and applications of nanomaterials at an early stage but also the use of a spectrophotometer for quantification and unknown determination based on Beer's Law. The procedure involves students (1) preparing a nanocomposite by chemically incorporating magnetite nanoparticles into activated carbon (AC), (2) using the as-prepared nanocomposite to treat an aspirin "metabolite" solution for 5 min, and (3) spectroscopically evaluating the nanocomposite's removal efficiency for this "pollutant". The spectroscopic measurement is based on a colored complex the pollutant forms with an acidified iron(III)-ion solution. The nanocomposite is magnetically recovered from treated water and is found to remove 90--130 mg of equivalent aspirin mass per gram of AC. The experiment, using commonly available chemicals and equipment, has been performed by 190 students in groups of two to three and is well-received and enjoyed by these students.

Experiments today can compress solids near isentropically to pressures approaching 100 × 106 atmospheres; however, determining the temperature of such matter remains a major challenge. Extended x-ray absorption fine-structure (EXAFS) spectroscopy is one of the few techniques sensitive to the bulk temperature of highly compressed solid matter, and the validity of this temperature measurement relies on constraining the local ion structure from the EXAFS spectrum. At high-energy-density (HED) conditions, the local ion structure often becomes distorted, which must be accounted for during the EXAFS analysis. Described here is a technique, using a parametrized ion-distribution model to directly analyze EXAFS spectra that provides a better constraint on the local structure than traditional second- or third-order cumulant expansion techniques at HED conditions. The parametrized ion-distribution model is benchmarked by analyzing EXAFS spectra from nickel molecular-dynamics simulations at ∼100 GPa and shown to provide a 10%–20% improvement in constraining the cumulants of the true ion distribution. [ABSTRACT FROM AUTHOR]

Inertial confinement fusion (ICF) with the laser-indirect-drive scheme has recently made a tremendous breakthrough recently after decades of intensive research effort. Taking this success to the next step, the ICF community is coming to a general consensus that laser direct-drive (LDD) fusion might be the viable way for enabling inertial fusion energy (IFE) and high-gain targets for other applications. Designing and understanding LDD fusion targets heavily rely on radiation-hydrodynamic code simulations, in which charged-particle transport plays an essential role in modeling laser-target energy coupling and bootstrap heating of fusion-produced α-particles. To better simulate charged-particle transport in LDD targets, over the past four decades the plasma physics community has advanced transport calculations from simple plasma physics models to sophisticated computations based on first-principles methods. In this review, we give an overview of the current status of charged-particle transport modeling for LDD fusion, including what challenges we still face and the possible paths moving forward to advance transport modeling for ICF simulations. We hope this review will provide a summary of exciting challenges to stimulate young minds to enter the field, facilitate further progress in understanding warm-dense matter physics, and ultimately bridge toward the success of reliable LDD fusion designs for IFE and other high-gain ICF applications. [ABSTRACT FROM AUTHOR]

Experimental investigation of electron-ion coupling and electron heat capacity of copper in warm and dense states are presented. From time-resolved x-ray absorption spectroscopy, the temporal evolution of electron temperature is obtained for non-equilibrium warm dense copper heated by an intense femtosecond laser pulse. Electron heat capacity and electron-ion coupling are inferred from the initial electron temperature and its decrease over 10 ps. Data are compared with various theoretical models.

Chaojun Liu,1,* Zhen Zhang,1,* Yu Ping,1 Guohui Qin,1– 3 Kai Zhang,1 Nomathamsanqa Resegofetse Maimela,1 Lan Huang,1 Shengli Yang,1 Yi Zhang1– 3 1Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, People’s Republic of China; 2Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, People’s Republic of China; 3Henan Key Laboratory for Tumor Immunology and Biotherapy, Zhengzhou, Henan 450052, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yi Zhang; Shengli YangBiotherapy Center, The First Affiliated Hospital of Zhengzhou University, 1th Jianshe Road, Zhengzhou, Henan 450052, People’s Republic of China+86-371-6691-5320; +86-371-6691-2993Email yizhang@zzu.edu.cn; slyang@sibs.ac.cnBackground: Programmed cell death protein-1 (PD-1) blockade therapy is one of the most remarkable immunotherapy strategies in many solid tumors, excluding glioma. The PD-1 expression, immune characteristics, and prognosis relevance in glioma remain poorly understood.Patients and Methods: RNA sequencing (RNA-seq) and mRNA microarray data were obtained for 325 and 301 glioma patients, respectively, from the Chinese Glioma Genome Atlas (CGGA) database. We analyzed the expression profile of PDCD1 (encoding PD-1) according to the different grade, isocitrate dehydrogenase (IDH) mutation status, and molecular subtype of glioblastoma. Gene ontology (GO) analyses were performed to explore biological processes of PD-1-related genes. Survival analysis was conducted using the Kaplan–Meier method. The findings were validated using The Cancer Genome Atlas (TCGA) RNA-seq data from 697 glioma samples. We also confirmed the PDCD1 gene expression feature and survival relevance in our own cohort of 73 glioma patients. R language was used for statistical analysis and generating figures.Results: PDCD1 was enriched in glioblastoma (WHO, grade IV), IDH wild-type glioma and mesenchymal glioblastoma in CGGA and TCGA datasets; similar results were validated in our own patient cohort. GO analysis revealed that PDCD1-related genes were involved in inflammation immune responses and T cell-mediated immune responses in glioma. Circos plots indicated that PDCD1 was positively associated with CD28, ICOS, and the inhibitory checkpoint molecules CTLA4, HAVCR2, TIGIT, and LAG3. Patients with PDCD1 upregulation had much shorter overall survival.Conclusion: PDCD1 upregulation was found in more malignant phenotypes of glioma and indicated a worse prognosis. Immunotherapy of targeting PD-1 or combined with other checkpoint molecules (eg, TIM-3, LAG-3, or TIGIT) blockade may represent a promising treatment strategy for glioma.Keywords: programmed cell death 1, glioma, The Cancer Genome Atlas, survival analysis, immunotherapy, costimulatory, inhibitory T-cell receptors

Recent experiments of laser-driven ejecta microjets performed at OMEGA 60 reveal tortuous jets whereby the jets appear to deviate from their initial trajectory as they travel in vacuum. To understand these data, we perform two dimensional numerical simulations, considering different target thicknesses, pressures, and models of the drive conditions. In particular, modeling the finite laser spot size appears essential in reproducing qualitatively the non-planar shock observed in the experiment. Simulations capture jet deflection by accounting for a slight misalignment of the laser pointing with respect to the groove axis along with spatial variation of the laser pulse intensity. The principal physical mechanism appears to be that lateral momentum is imparted by release waves arising from the non-planar drive. The induced off-axis velocity is small in comparison to the jet axial velocity but integrates into a pronounced deflection over the course of the experiment. The analysis of jet axial and lateral mass distributions is found to be reproduced reasonably by the simulations. Simulated radiographs are in qualitative agreement with the experiments, though their differences point to potential shortcomings in modeling strictly three-dimensional experiments using two-dimensional hydrodynamic simulations. The simple analysis is able to explain part of the observed discrepancy in simulated vs experimental jet masses. [ABSTRACT FROM AUTHOR]

Yanping Lu,1 Shunping Han,1 Hongyue Zheng,1 Rui Ma,1 Yuting Ping,1 Jiafeng Zou,1 Hongxia Tang,1 Yongping Zhang,2 Xiuling Xu,1 Fanzhu Li1 1College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China; 2College of Pharmaceutical Sciences, Guiyang University of Chinese Medicine, Guiyang, Guizhou, China Background: The Traditional Chinese Medicine, arsenic trioxide (ATO, As2O3) could inhibit growth and induce apoptosis in a variety of solid tumor cells, but it is severely limited in the treatment of glioma due to its poor BBB penetration and nonspecifcity distribution in vivo. Purpose: The objective of this study was encapsulating ATO in the modified PAMAM dendrimers to solve the problem that the poor antitumor effect of ATO to glioma, which provide a novel angle for the study of glioma treatment. Methods: The targeting drug carrier (RGDyC-mPEG-PAMAM) was synthesized based on Arg-Gly-Asp (RGDyC) and αvβ3 integrin targeting ligand, and conjugated to PEGylated fifth generation polyamidoamine dendrimer (mPEG-PAMAM). It was characterized by nuclear magnetic resonance, fourier transform infrared spectra, Nano-particle size-zeta potential analyzer,etc. The in vitro release characteristics were studied by dialysis bag method. MTT assay was used to investigate the cytotoxicity of carriers and the antitumor effect of ATO formulation. In vitro blood-brain barrier (BBB) and C6 cell co-culture models were established to investigate the inhibitory effect of different ATO formulation after transporting across BBB. Pharmacokinetic and antitumor efficacy studies were investigated in an orthotopic murine model of C6 glioma. Results: The prepared RGDyC-mPEG-PAMAM was characterized for spherical dendrites, comparable size (21.60±6.81 nm), and zeta potential (5.36±0.22 mV). In vitro release showed that more ATO was released from RGDyC-mPEG-PAMAM/ATO (79.5%) at pH 5.5 than that of pH 7.4, during 48 hours. The cytotoxicity of PEG-modified carriers was lower than that of the naked PAMAM on both human brain microvascular endothelial cells and C6 cells. In in vitro BBB model, modification of RGDyC heightened the cytotoxicity of ATO loaded on PAMAM, due to an increased uptake by C6 cells. The results of cell cycle and apoptosis analysis revealed that RGDyC-mPEG-PAMAM/ATO arrested the cell cycle in G2-M and exhibited threefold increase in percentage of apoptosis to that in the PEG-PAMAM/ATO group. Compared with ATO-sol group, both RGDyC-mPEG-PAMAM/ATO and mPEG-PAMAM/ATO groups prolonged the half-life time, increased area under the curve, and improved antitumor effect, significantly. While the tumor volume inhibitory of RGDyC-mPEG-PAMAM/ATO was 61.46±12.26%, it was approximately fourfold higher than the ATO-sol group, and twofold to the mPEG-PAMAM/ATO group. Conclusion: In this report, RGDyC-mPEG-PAMAM could enhance the antitumor of ATO to glioma, it provides a desirable strategy for targeted therapy of glioma. Keywords: arsenic trioxide, blood-brain barrier, RGDyC, PEG co-modified, glioma targeting delivery, PAMAM dendrimer

We describe a 2 h introductory laboratory procedure that prepares a novel magnetic antimicrobial activated carbon nanocomposite in which nanoscale sized magnetite and silver particles are incorporated (MACAg). The MACAg nanocomposite has achieved the synergistic properties derived from its components and demonstrated its applicability as an effective and recoverable antimicrobial agent for water disinfection. The principle is successfully illustrated by a significant reduction in the number of microbes in an "Escherichia coli" ("E. coli") solution of 2 × 10[superscript 6] colony forming units following its treatment with MACAg for 10 min. The exercise allows the college students to (1) be introduced to an exciting class of advanced materials, known as nanocomposites, at an early stage, (2) gain working experiences at nanochemistry-microbiology interface, and (3) see the use and experience the fun of chemistry. The experiment uses readily available materials, can be run in a general or introductory chemistry laboratory environment, and is well received and enjoyed by the students. The experiment is also suitable for advanced high school students.

Ying Li,1,2 Meng Wang,1,2 Bu-Wei Huang,1,2 Yuan Ping,3 Jian You,1 Jian-Qing Gao1,2 1Institute of Pharmaceutics, College of Pharmaceutical Sciences, 2Zhejiang Province Key Laboratory of Anticancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People’s Republic of China; 3School of Materials Science and Engineering, Nanyang Technological University, Singapore Abstract: Although widely used in chemotherapy, free doxorubicin (Dox) might enhance cell malignancy undesirably. Liposomal Dox (Doxlipo) has been clinically approved for the treatment of breast cancer due to reduced systematical toxicity and increased tumor targeting, yet the transcriptome-wide elucidation of the Doxlipo formulations remains elusive. To this end, we explored the impact of two Dox liposomal formulations, Doxlipo mainly containing hydrogenated soy phosphatidylcholine or 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, on the transcriptional pattern of MCF-7 cells. The two types of Dox liposomal formulations with different drug release kinetics were investigated to reveal the relationship between the formulation and tumor malignancy. Interestingly, we found that liposomal formulation significantly altered the transcriptional pattern of a wide range of genes. Under equivalent dosage of Dox, free Dox substantially changed the expression of ANK1, ACTA2, GPR87, GDF15, FZD6, and WNT4 in MCF-7 cells. Notably, free Dox induced much higher expression of ABCB1 and significantly enhanced the cell migration behavior in comparison with HSPC Doxlipo under a similar level of cytotoxicity. Finally, siRNA targeting GPR87 was codelivered with cationic Doxlipo to reduce the expression of malignancy-related genes. Our study, for the first time, provides an overview of the influence of formulation on the malignancy at transcriptional level and reveals the relationship between cytotoxicity and cell malignancy from the formulation aspect, offering valuable reference for the future formulation design for anticancer drug delivery. Keywords: liposomes, doxorubicin, cellular uptake, cell malignancy, transcriptional profiling

A bifunctional magnetic Fe3O4@SiO2@TiO2 or MS-TiO2 antimicrobial nanocomposite was prepared based on simple sol-gel methods with common equipment and chemicals. Reaction pH was found to influence the TiO2 upload in the nanocomposite. The alkaline condition produced the greatest TiO2 upload, while the acidic condition the least. Annealing at 300 °C turned the as-synthesized amorphous TiO2 into one with high content of anatase, the most photoactive form of TiO2. Irradiated by 365 nm UV light, a sample of 30 mg/mL of annealed nanocomposite containing 12.6 wt.% Ti was shown to be able to completely eradicate 104 CFU/mL of the laboratory-grown E. coli within 25 min, 25 min faster than the control when the 365 nm UV light was employed alone. The nanocomposite demonstrated consistent antimicrobial performance over repeated uses and was easily recoverable magnetically due to its high magnetization value (33 emu/g). Additionally, it was shown to reduce the bacterial count in a real surface water sample containing 500–5000 CFU/mL of different microbes by 62 ± 3% within 30 min. The irradiating 365 nm UV light alone was found to have generated little biocidal effect on this surface water sample. The nanocomposite is promising to serve as an effective, safe, and eco-friendly antimicrobial agent, especially for surface water disinfection.

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A general chemistry laboratory experiment using readily available chemicals is described to introduce college students to an exciting class of nanocomposite materials. In a one-step room temperature synthetic process, magnetite nanoparticles are embedded onto activated carbon matrix. The resultant nanocomposite has been shown to combine the adsorption ability of the activated carbon and the magnetic properties of the magnetite nanoparticles, enabling its application as a fast, effective, low-cost, and recyclable aromatic water pollutant adsorbent. This quality is illustrated by its rapid removal of the surrogate "pollutants", made of several dyes in the Fisher universal indicator, within 2-3 min. A successful "pollutant" removal is indicated by the absence of the rainbow colors because of the presence of the "pollutants" in the "polluted" water when different quantities of an acid or a base are added. The nanocomposite's reusability as the "pollutant" adsorbent is demonstrated after its used surface is regenerated using ethanol as the extracting solvent. The exercise allows students to (i) gain awareness of timely environmental issues; (ii) be exposed to the modern field of nanoscience; and (iii) appreciate the roles new and advanced materials play in keeping our water clean. Students have fun working in the lab and find the experience interesting and motivating. The experiment is also suitable for advanced high school students.