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Stroma-targeting strategies in pancreatic cancer:Past lessons,challenges and prospects

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World Journal of Gastroenterology 2021年第18期27卷 2105-2121页

作者： Faran Polani patrick m Grierson Kian-Huat Lim Division of Oncology Department of Internal MedicineBarnes-Jewish Hospital and The Alvin J.Siteman Comprehensive Cancer CenterWashington University School of MedicineSaint LouisMO 63110United States

Pancreatic ductal adenocarcinoma(PDAC)is projected to emerge as the second leading cause of cancer-related death after *** treatment resistance is perhaps the most significant factor that underlies the poor prognosis of *** date,combination chemotherapy remains the mainstay of treatment for most PDAC *** to other cancer types,treatment response of PDAC tumors to similar chemotherapy regimens is clearly much lower and *** from typically harboring genetic alterations that to date remain undruggable and are drivers of treatment resistance,PDAC tumors are uniquely characterized by a densely fibrotic stroma that has well-established roles in promoting cancer progression and treatment ***,emerging evidence also suggests that indiscriminate targeting and near complete depletion of stroma may promote PDAC aggressiveness and lead to detrimental *** conflicting results undoubtedly warrant the need for a more in-depth understanding of the heterogeneity of tumor stroma in order to develop modulatory strategies in favor of tumor *** advent of novel techniques including single cell RNA sequencing and multiplex immunohistochemistry have further illuminated the complex heterogeneity of tumor cells,stromal fibroblasts,and immune *** new knowledge is instrumental for development of more refined therapeutic strategies that can ultimately defeat this ***,we provide a concise review on lessons learned from past stromatargeting strategies,new challenges revealed from recent preclinical and clinical studies,as well as new prospects in the treatment of PDAC.

关键词： Stroma Pancreatic cancer Treatment resistance Cancer-associated fibroblasts Clinical trials

Crystallization kinetics of Sn_(40)Se_(60) thin films for phase change memory applications

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Journal of Semiconductors 2015年第6期36卷 17-20页

作者： Joshua m.Kundu patrick m.Karimi Walter K.Njoroge Department of Physics Kenyatta University

The crystallization kinetics of Sn4oSe6o thin films has been successfully investigated using sheet resis- tance versus temperature measurements. Thermal evaporation was used to deposit the films on ordinary glass sub- strates. The crystallization temperature for Sn4oSe60 thin film was found to be 156.6 -t- 0.3 ~C. In the as-deposited state, the sheet resistance was found to be 195 mf2/[2, this value declined to 1560 f2/[2] upon annealing. The value of activation energy obtained from the Kissinger plot was 0.62 ＋ 0.07 eV. From the results obtained, SnaoSe60 is a promising alloy for PCm application because of its high electrical contrast, high crystallization temperature, and relatively high activation energy.

关键词： crystallization temperature activation energy electrical contrast phase change memory

Non-thermal plasma enhances performances of biochar in wastewater treatment and energy storage applications

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Frontiers of Chemical Science and Engineering 2022年第4期16卷 475-483页

作者： Rusen Zhou Xiaoxiang Wang Renwu Zhou Janith Weerasinghe Tianqi Zhang Yanbin Xin Hao Wang patrick Cullen Hongxia Wang Kostya(Ken)Ostrikov College of Environmental Science and Engineering Dalian Maritime UniversityDalian 116026China School of Chemistry and Physics and QUT Centre for materials Science Queensland University of TechnologyQLD 4000Australia School of Chemical and Biomolecular Engineering The University of SydneyNSW 2006Australia Centre for Future materials University of Southern QueenslandQLD 4350Australia

Surface functionalization or modification to introduce more oxygen-containing functional groups to biochar is an effective strategy for tuning the physicochemical properties and promoting follow-up *** this study,non-thermal plasma was applied for biochar surface carving before being used in contaminant removal and energy storage *** results showed that even a low dose of plasma exposure could introduce a high number density of oxygen-functional groups and enhance the hydrophilicity and metal affinity of the pristine *** plasma-treated biochar enabled a faster metal-adsorption rate and a 40%higher maximum adsorption capacity of heavy metal ion Pb^(2+).moreover,to add more functionality to biochar surface,biochar with and without plasma pre-treatment was activated by KOH at a temperature of 800℃.Using the same amount of KOH,the plasma treatment resulted in an activated carbon product with the larger BET surface area and pore *** performance of the treated activated carbon as a supercapacitor electrode was also substantially improved by>30%.This study may provide guidelines for enhancing the surface functionality and application performances of biochar using non-thermal-based techniques.

关键词： non-thermal plasma surface functionalization biochar modification wastewater treatment supercapacitor

mathematical model Development and 3D Printing of Cylindrically Shaped Biofilm Carrier media from Recycled Plastic Waste for Wastewater Treatment

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Journal of Environmental Protection 2022年第1期13卷 15-31页

作者： Selamo Basile Nyuysoni James m. mutua patrick G. Home Department of mechanical Engineering Pan African University Institute for Basic Sciences Technology and Innovation Nairobi Kenya Department of mechanical Engineering Jomo Kenyatta University of Agriculture and Technology Nairobi Kenya Department of Soil Water and Environmental Engineering Jomo Kenyatta University of Agriculture and Technology Nairobi Kenya

Wastewater management and purification remain one of the greatest problems of mankind. The biological wastewater treatment technique uses a biofilm media carrier where microorganisms attach themselves to the surface. This biofilter is usually made from virgin plastic pellets and can also be produced from recycled waste plastic and used in wastewater treatment. The need to treat water using low-cost carrier media has led to finding alternative sources of materials for biofilter manufacturing. Therefore, this work is centered on the recycling of waste plastic to make filaments which are then used for 3D printing of a high specific surface area (SSA) less clogging biofilm carrier through the parametric redesign. In the current study, the polypropylene material was recycled to make a 2.85 mm diameter filament compatible with the Ultimaker S3. moreover, analytical models and governing equations were developed for the design of the K3 Kaldnes and mB3 media. Empirical surface area (SA), specific surface area, and volume of the respective carriers were determined using the model developed. SolidWorks was used to design and evaluate the same parameters which were then compared to model results. The errors in SSA obtained from the model with respect to the SolidWorks results for both the K3 Kaldnes and mB3 media were 0.34% and 0.76% respectively. With these small error margins, the model can serve as a tool and guideline for the designing of cylindrically shaped carriers. By transforming plastics into biofilters, waste plastics are mopped up reducing pollutions. Consequently, the deployment of such biofilters will enhance efficient wastewater treatment for a cleaner environment and the wellbeing of human race.

关键词： Specific Surface Area Recycling Cylindrically Shaped Carriers Clogging Passage Diameter

Chronic peripheral inflammation: a possible contributor to neurodegenerative diseases

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Neural Regeneration Research 2021年第9期16卷 1711-1714页

作者： patrick Süβ Addison J.Lana Johannes C.m.Schlachetzki Department of molecular Neurology Friedrich-Alexander-University Erlangen-NürnbergUniversity Hospital ErlangenErlangenGermany Department of Cellular and molecular medicine University of California San DiegoLa JollaCAUSA

The contribution of chronic peripheral inflammation to the pathogenesis of neurodegenerative diseases is an outstanding question. Sustained activation of the peripheral innate and adaptive immune systems occurs in the context of a broad array of disorders ranging from chronic infectious diseases to autoimmune and metabolic diseases. In addition, progressive systemic inflammation is increasingly recognized during aging. Peripheral immune cells could potentially modulate the cellular brain environment via the secretion of soluble molecules. There is an ongoing debate whether peripheral immune cells have the potential to migrate into the brain under certain permissive circumstances. In this perspective, we discuss the possible contribution of chronic peripheral inflammation to the pathogenesis of age-related neurodegenerative diseases with a focus on microglia, the resident immune cells of the brain parenchyma.

关键词： aging Alzheimer's disease inflammation innate immune system microglia neurodegeneration Parkinson's disease

Revisiting the dissolution of biogenic Si in marine sediments： a key term in the ocean Si budget

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Acta Geochimica 2017年第3期36卷 429-432页

作者： patrick Frings Department of Geoscience Swedish Museum of Natural History 10405 Stockholm Sweden Earth Surface Geochemistry GFZ German Research Centre for Geosciences 14473 Telegrafenberg Potsdam Germany

Of the　~240*10^(12)mol year^(-1)of biogenic silica(bSi)produced by diatoms and other silicifying organisms,only roughly 3%–4%escapes dissolution to be permanently *** the global scale,how,where and why b Si is preserved in sediment is not well *** help address this,I compile 6245 porewater dissolved Si concentrations from 453 sediment cores,to derive the concentration gradient at the sediment–water interface and thus diffusive fluxes out of the *** range from\0.002 to 3.4 mol m^(-2)year^(-1),and are independent of temperature,depth and *** classified by sediment lithology,predominantly siliceous sediments unsurprisingly have higher mean diffusive fluxes than predominantly calcareous or clay-rich *** with the areal extent of these lithologies,the‘best-guess’global sedimentary b Si recycling flux is69 9 10^(12)mol year^(-1).

关键词：海洋沉积物生物硅溶解硅术语预算浓度梯度扩散通量岩性分类

Cathodic activated stainless steel mesh as a highly active electrocatalyst for the oxygen evolution reaction with self-healing possibility

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Journal of Energy Chemistry 2020年第10期29卷 153-160页

作者： Gui-Rong Zhang Liu-Liu Shen patrick Schmatz Konrad Krois Bastian J.m.Etzold Ernst-Berl-Institut für Technische und makromolekulare Chemie Technische Universit鋞Darmstadt64287 DarmstadtGermany

The oxygen evolution reaction(OER)represents one of the major bottlenecks for broad-based applications of many clean energy storage/conversion *** key to solving this problem lies in developing high-performing,cost effective and stable catalysts for the ***,we demonstrate that ubiquitous stainless steel mesh(SSm)materials activated by a facile cathodization treatment can be employed as a high performing OER catalyst,as showcased by the impressively low overpotentials of 275 and 319 mV to reach the benchmark current densities of 10 and 100 mA cm^−2(1.0 m KOH),*** SSm also exhibits excellent performance in a two-electrode water electrolyzer,which requires a low cell voltage of 1.58 at 10 mA cm^−2 and outperforms many of water electrolyzers using earth-abundant OER ***,cathodized SSm with minor performance degradation after the stability test can also be readily healed by subjecting it to an additional cathodization *** is disclosed that the superior performance of cathodized SSms stems from the surface enrichment of OER active Ni(oxy)hydroxide,facile gas-bubble removal and transportation over the unique mesh-structured surfaces,while the abundant reservoir of nickel in the bulk allows healing of the catalyst by a facile cathodization.

关键词： Oxygen evolution reaction Water splitting Stainless steel mesh Cathodization mass transfer limitation Self-healing

The emerging role and targetability of the TCA cycle in cancer metabolism

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Protein & Cell 2018年第2期9卷 216-237页

作者： Nicole m. Anderson patrick mucka Joseph G. Kern Hui Feng Abramson Family Cancer Research Institute University of Pennsylvania Philadelphia PA 19104-6160 USA Perelman School of medicine at the University of Pennsylvania Philadelphia PA 19104 USA Departments of Pharmacology and medicine The Center for Cancer Research Section of Hematology and Medical Oncology Boston University School of Medicine Boston MA 02118 USA Program in Biomedical Sciences Boston University School of Medicine Boston MA 02118 USA

The tricarboxylic acid （TCA） cycle is a central route for oxidative phosphorylation in cells, and fulfills their bioenergetic, biosynthetic, and redox balance require- ments. Despite early dogma that cancer cells bypass the TCA cycle and primarily utilize aerobic glycolysis, emerging evidence demonstrates that certain cancer cells, especially those with deregulated oncogene and tumor suppressor expression, rely heavily on the TCA cycle for energy production and macromolecule synthesis. As the field progresses, the importance of aberrant TCA cycle function in tumorigenesis and the potentials of applying small molecule inhibitors to perturb the enhanced cycle function for cancer treatment start to evolve. In this review, we summarize current knowledge about the fuels feeding the cycle, effects of oncogenes and tumor suppressors on fuel and cycle usage, common genetic alterations and deregulation of cycle enzymes, and potential therapeutic opportunities for targeting the TCA cycle in cancer cells. With the application of advanced technology and in vivo model organism studies, it is our hope that studies of this previously overlooked biochemical hub will provide fresh insights into cancer metabolism and tumorigenesis, subsequently revealing vulnerabilities for thera- peutic interventions in various cancer types.

关键词： glutaminolysis the TCA cycle cancer metabolism glycolysis

mechanistic considerations for the use of monoclonal antibodies for cancer therapy

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癌症生物学与医学：英文版 2014年第1期11卷 20-33页

作者： patrick m.Glassman Joseph P.Balthasar Department of Pharmaceutical Sciences School of Pharmacy and Pharmaceutical Sciences University at Buffalo The State University of New York

Since the approval of rituximab in 1997, monoclonal antibodies(mAbs) have become an increasingly important component of therapeutic regimens in oncology. The success of mAbs as a therapeutic class is a result of great strides that have been made in molecular biology and in biotechnology over the past several decades. Currently, there are 14 approved mAb products for oncology indications, and there are ten additional mAbs in late stages of clinical trials. Compared to traditional chemotherapeutic agents, mAbs have several advantages, including a long circulating half-life and high target specificity. Antibodies can serve as cytotoxic agents when administered alone, exerting a pharmacologic effect through several mechanisms involving the antigen binding(Fab) and/or Fc domains of the molecule, and mAbs may also be utilized as drug carriers, targeting a toxic payload to cancer cells. The extremely high affinity of mAbs for their targets, which is desirable with respect to pharmacodynamics(i.e., contributing to the high therapeutic selectivity of mAb), often leads to complex, non-linear, target-mediated pharmacokinetics. In this report, we summarize the pharmacokinetic and pharmacodynamics of mAbs that have been approved and of mAbs that are nearing approval for oncology indications, with particular focus on the molecular and cellular mechanisms responsible for their disposition and efficacy.

关键词：单克隆抗体治疗方案分子生物学药物代谢动力学癌症机械细胞毒性细胞机制