bluuebunny/crossref_metadata_2025 huggingface dataset:
Metal–organic frameworks as efficient materials for drug delivery: Synthesis, characterization, antioxidant, anticancer, antibacterial and molecular docking investigation
Authors: El‐Bindary Ashraf A. , Toson Elshahat A. , Shoueir Kamel R. , Aljohani Hind A. , Abo‐Ser Magy M.
Published: June 2020

Metal–organic framework (MOF) nano particles are a class of promising porous nano materials for biomedical applications. Owing to its high loading potential and pH‐sensitive degradation, most promising of the MOFs is the zeolitic imidazolate crystal framework (ZIF‐8), a progressive useful material for small molecule distribution. Doxorubicin (DOX), designated as a classical drug, was jobwise entrapped in ZIF‐8 nano particles. ZIF‐8 nano particles, as a novel carrier, were used to monitor the release of the anticancer drug DOX and prevent it from dissipating before reaching its goal. ZIF‐8 nano particles with encapsulated DOX (DOX@ZIF‐8) can be synthesized in a single pot by incorporation of DOX into the reaction mixture. MOFs and the designed drug delivery (DOX@ZIF‐8) system were characterized by Fourier transfer infrared, scanning electron microscopy, N2sorption isotherm and X‐ray diffraction. The impact of MOFs and the engineered drug delivery system on the viability of human breast and liver cancer cell lines was evaluated. The loaded drug was released at pH 5 faster than at pH 7.4. The nano particles of ZIF‐8 showed low cytotoxicity, while DOX@ZIF‐8 showed high cytotoxicity to HepG‐2 and MCF‐7 cells compared with free DOX at the equivalent concentration of DOX of >12.5 μg/ml. These findings indicate that DOX@ZIF‐8 nano particles are a promising method for the delivery of cancer cells to drugs. Furthermore, ZIF‐8, DOX and encapsulated DOX@ZIF‐8 compounds were screened for their potential antibacterial activities against pathogenic bacteria compared with standard antibiotics by the agar well diffusion technique. The results demonstrate that the DOX@ZIF‐8 exhibits a strong inhibition zone against Gram‐negative strains (Escherichia coli) in comparison with the reference drug gentamycin. The docking active site interactions were evaluated to predict the binding between DOX with the receptor of breast cancer 3hb5‐oxidoreductase and liver cancer 2h80‐lipid binding protein for anticancer activity.
Additive and free‐volume effects on the refractive index of a thiol‐ene polymer network
Authors: Filho Edmundo B. D. S. , Su Yue , Takashina Mamoru , Fowler Gary , Chien Po‐Hsiu , Stiegman Albert E.
Published: June 2020

A series of hard, transparent, thermoset polymer samples containing tetravinylsilane (TVS) and 1,3‐benzenedithiol (BDT) with varying loadings of zirconium oxide clusters Zr6(OH)4O4(OMc)12 (ZOC) were synthesized. Resulting polymers exhibited a higher refractive index (n) than the parent polymer containing only the monomers TVS and BDT. The refractive index reached a maximum value of 1.711 at a ZOC loading of 3 wt% and then decreased as the ZOC concentration in the polymer matrix increased. The refractive index of ZOC was determined to be 1.540 using the Becke line method. Because the refractive index of ZOC is lower than that of the TVS–BDT polymer matrix, the finding that the incorporation of small quantities of ZOC can increase the refractive index of the TVS–BDT polymer composite was unexpected and is accounted for by the effects of ZOC on the packing efficiency of the composite.
Enhanced dispersibility and uniform distribution of iron phosphonate to intensify its synergistic effect on polypropylene‐based intumescent flame‐retardant system
Authors: Liu Weifeng , Nie Ling , Luo Liehong , Yue Junfeng , Gan Lin , Lu Jun , Huang Jin , Liu Changhua
Published: June 2020

Good dispersion and distributed nanoscaled synergists are expected to greatly enhance the performance of flame retardants. Here, a new type of iron organic‐phosphonate (FeP) nanoparticles was synthesized and utilized as the synergist for polypropylene‐based intumescent flame‐retardant system (IFR/PP). To improve the dispersion of the FeP in the IFR/PP system, a master‐batch method was used to achieve separation between the FeP particles, which included hydrogen bonding with ammonium polyphosphate (APP). To improve its compatibility with PP, the hybrid synergist FeP@APP@CS was produced by electrostatic interaction with chitosan (CS). The results showed that the FeP@APP@CS nanoparticles were homogeneously dispersed in the PP matrix and selectively located on the IFR particles, achieving compatibility between the PP and IFR. The FeP@APP@CS/IFR/PP system exhibited an enhanced limiting oxygen index (LOI) of up to 28.5%, and achieved an improved vertical burning rating of V‐0 (UL‐94), compared to the IFR/PP system. The improved flame‐retardant properties, even at low levels of IFR loading, were attributed to the homogeneous dispersion of the FeP@APP@CS throughout the IFR system and the fine synergistic effect between the FeP@APP@CS and IFR.
Exploring in situ integration of pongamia oil to improve barrier properties of polyurethane coatings
Authors: Ranade Shyama , Neelakantan Lakshman
Published: June 2020

Polyurethane coatings have been the focus of continuous innovation, such as bio‐based coatings and self‐healing coatings. This study investigates the route achieving superior coatings by in situ integration of pongamia oil during the curing process. Stronger urethane and carbonyl bonds for these oil‐modified coatings are observed using Fourier transform infra‐red spectroscopy. Thermogravimetric analysis reveals an increase in their thermal stability. A sustained high coating resistance and an increased Bode impedance (by ∼102 Ω cm2) for the oil‐modified coatings is observed using electrochemical impedance spectroscopy, which is corroborated by the cyclic corrosion test. Scanning electron microscopy depicts a roughened coating morphology with an increased water contact angle due to the integrated oil‐polyurethane polymer chains. Further, a preliminary computational fluid dynamics confirms this inhibited electrolyte mass flow through an oil‐modified coating with denser regions as compared to a clear coating. A consolidated schematic model incorporating the experimental and simulation results is proposed.
Fire resistance performance of composite coating with geopolymer‐based bio‐fillers for lightweight panel application
Authors: Abdul Rashid Muhammad Khairi , Ramli Sulong Nor Hafizah , Alengaram Ubagaram Johnson
Published: June 2020

Structural insulated panel (SIP) requires fire‐resistant coating due to its substrate having low melting point. This article presents the effect of filler and binder on fire resistance, thermal stability, and surface morphology of composite coating. Palm oil clinker filler‐type coatings made using ordinary Portland cement (OPC:POC), calcium aluminate cement (CAC:POC), and alkali‐activated geopolymer (GP:POC) binders were analyzed. GP:POC was then compared to other geopolymer‐binder type coating with different fillers such as rice husk ash (GP:RHA), metakaolin (GP:MK), and hybrid filler of POC and RHA (GP:POC‐RHA). It was found that geopolymer binder‐type specimens have better fire‐resistance due to low thermal conductivity caused by their porous microstructure and intumescence behavior. Then, the coating formulation was optimized in terms of thickness, alkaline activator ratio and curing regime which produced GP:RHA' that lasted almost 2 hours during flame exposure test. This article concludes that geopolymer‐binder type composite is a plausible fire‐resistant coating for SIP.
Preparation of cellulose triacetate aerogel via non‐solvent impacted thermally induced phase separation for oil absorption
Authors: Wang Cheng , Okubayashi Satoko
Published: June 2020

The oil spill has caused significant attention on a global scale due to its damage to the environment and the economy. The development of economically and ecologically friendly oil sorbent materials has important meaning for the oil spill concern. In this work, we explored the non‐solvent impacted thermally induced phase separation (NITIPS) method to prepare the cellulose triacetate aerogel (CA) with low density (6.4–40.5 mg/cm3), high porosity (96.9–99.5%), large water contact angle (>129°) and high specific surface area (193–573 m2/g) as the oil sorbent material. The oil absorption capacity of CA with vegetable oil and vacuum pump oil reached 80.8 g/g and 38.9 g/g, respectively, consistent with Fick's law of diffusion. Moreover, the NITIPS method provided simpler process and controlled the shape of CA compared with the traditional thermally induced phase separation method. This study proved that the CA prepared by NITIPS methods played an important role as a potential oil absorption solids in the field of oil spill and organic chemical leakage.
Significantly high electromagnetic shielding effectiveness in polypyrrole synthesized by eco‐friendly and cost‐effective technique
Authors: Agrawal Rekha , Shah Jyoti , Gupta Govind , Srivastava Ritu , Sharma Chhemendra , Kotnala Ravinder
Published: June 2020

A facile and eco‐friendly synthesis of polypyrrole from monomer pyrrole using nominal amount of ferric chloride hexahydrate (FeCl3.6H2O) oxidant in aqueous solution by chemically oxidative polymerization method has been reported. The use of aqueous solvent and ferric chloride hexahydrate salt in polypyrrole synthesis have an eco‐friendly route favorable for the production of polypyrrole in large quantities. The synthesized polypyrrole samples exhibit good electrical conductivity (2 S/cm) and yield of 80% for reaction time of 8 hr at 5°C. Quality and properties of polypyrrole samples have been thoroughly investigated with varying reaction time and temperature while other synthesis parameters like molar ratio of oxidant to monomer, oxidant concentration, and solvent were kept constant. X‐ray diffraction analysis of polypyrrole with a shorter reaction time shows the presence of iron oxide (Fe2O3) peaks. The complete reaction may not occur at shorter reaction times due to which residual ferric ions converted into Fe2O3. X‐ray photoelectron spectroscopy measurement of polypyrrole also confirms the formation of Fe2O3. Appropriate selection of reaction time and temperature produced pure phase polypyrrole with high yield and good conductivity. Synthesized polypyrrole by our eco‐friendly and cost‐effective technique exhibits prominent electromagnetic shielding effectiveness value of 30 dB in the X‐band (8–12 GHz).
High‐yield water‐phase exfoliated few‐defect graphene for high performance polymer nanocomposites
Authors: Wang Peng , Li Mengxing , Zhang Jiajia , Dong Lei , Lu Hongbin
Published: June 2020

Application of graphene requires a high‐yield, low‐cost, scalable production method, but it remains highly challenging. We here report a water‐phase technique to produce few‐defect graphene nanosheets (FGS) with a high exfoliation yield (92%), based on the chemically expanded graphite with ultrahigh specific surface areas, and demonstrate the application in graphene‐polymer nanocomposites. The exfoliated FGS has low degree of oxidation and preserves good mechanical and electrical properties, revealing promising potential for improving comprehensive properties of polymer composites. When 0.5 wt% FGS was incorporated to poly(methyl methacrylate) (PMMA), the 5% weight loss temperature and storage modulus increase by 87°C and 21%, respectively, relative to the neat polymer. With increasing the content of FGS to 4.6 wt%, the glass transition temperature of the composite increases by 25°C. In addition, the composites show a percolation threshold as low as 0.25 vol% and excellent electrical conductivity (50 S/m for 2.7 vol% FGS‐PMMA composite).
Energy dissipation in natural rubber latex films: The effect of stabilizers, leaching and acetone‐treatment
Authors: Shakun Alexandra , Sarlin Essi , Vuorinen Jyrki
Published: June 2020

Natural rubber (NR) is a versatile material possessing outstanding mechanical properties, which can be used in multiple applications including the rapidly developing dielectric elastomer generators (DEGs). One of the drawbacks of the existing DEGs is their low efficiency, which can be improved by lowering the dielectric and mechanical losses originating from the material. Therefore, the present research was focusing on assessing the ways to minimize the dielectric and mechanical losses of NR films rather than developing a DEG. In this article, the effect of natural proteins and the rubber stabilizers on energy dissipation of NR films was evaluated. Moreover, the effect of sample posttreatment (with water and acetone), curing and time after cure was discussed. As a result, deproteinized NR stabilized by ammonium caseinate outperformed unmodified NR due to reduced dielectric losses, mechanical hysteresis and stress relaxation. Moreover, the posttreatment methods were found to moderately reduce the material‐relates losses.
GinJinn: An object‐detection pipeline for automated feature extraction from herbarium specimens
Authors: Ott Tankred , Palm Christoph , Vogt Robert , Oberprieler Christoph
Published: June 2020

Premise

The generation of morphological data in evolutionary, taxonomic, and ecological studies of plants using herbarium material has traditionally been a labor‐intensive task. Recent progress in machine learning using deep artificial neural networks (deep learning) for image classification and object detection has facilitated the establishment of a pipeline for the automatic recognition and extraction of relevant structures in images of herbarium specimens.

Methods and Results

We implemented an extendable pipeline based on state‐of‐the‐art deep‐learning object‐detection methods to collect leaf images from herbarium specimens of two species of the genus Leucanthemum. Using 183 specimens as the training data set, our pipeline extracted one or more intact leaves in 95% of the 61 test images.

Conclusions

We establish GinJinn as a deep‐learning object‐detection tool for the automatic recognition and extraction of individual leaves or other structures from herbarium specimens. Our pipeline offers greater flexibility and a lower entrance barrier than previous image‐processing approaches based on hand‐crafted features.
Omics technologies for kidney disease research
Authors: Wang Dan , Yang Jiayi , Fan Jinjin , Chen Wei , Nikolic‐Paterson David J. , Li Jinhua
Published: June 2020

Omics‐based technologies in the areas of genomics, transcriptomics, and proteomics are revolutionizing research into many types of human and experimental disease. This review focuses on the potential of omics technologies to identify pathogenic mechanisms and biomarkers of disease in order to improve the diagnosis, prognosis, monitoring, and treatment of kidney disease.
miR‐203a‐3p promotes loureirin A‐induced hair follicle stem cells differentiation by targeting Smad1
Authors: Luo Ziwei , Dou Jianping , Xie Fangfang , Lu Jianghua , Han Qianting , Zhou Xianxi , Kong Jiechen , Chen Dongfeng , Liu Aijun
Published: June 2020

MicroRNAs (miRNAs) participate in the repair of skin trauma. Our previous study indicated that loureirin A promoted hair follicle stem cells (HFSCs) to repair skin epidermis. However, the mechanism of miRNA‐mediated regulation of loureirin A‐induced HFSC differentiation remained to be explored. In the present study, HFSCs from rat vibrissa were identified by immunofluorescence in vitro. Microarray and quantitative real time polymerase chain reaction analyses demonstrated that miR‐203a‐3p was upregulated in differentiated HFSCs induced by loureirin A. The expression of cytoskeletal keratin (CK) 5 and involucrin was promoted by miR‐203a‐3p mimics while repressed by a miR‐203a‐3p inhibitor. Smad1 was identified as a key target of miR‐203a‐3p using target prediction tools. Luciferase reporter gene test confirmed a special target association between miR‐203a‐3p and Smad1. Short interfering Smad1 was transfected into HFSCs, and the expression levels of CK5 and involucrin were upregulated. Thus, it can be inferred that miR‐203a‐3p negatively regulated the expression of Smad1 and promoted the differentiation of loureirin A‐induced HFSCs. Bone morphogenetic protein (BMP) signal inhibition and Wnt activation coregulate skin injury repair. BMP/Smad1 signaling is involved in maintaining the characteristics of HFSCs and inhibiting their differentiation. Our results showed that miR‐203a‐3p reduces Smad1 to release BMP inhibition. Taken together, miR‐203a‐3p/Smad1 is a potential therapeutic molecular target in skin wound healing, and may play an active role in wound repair and regenerative medicine.
Rebamipide potentially mitigates methotrexate‐induced nephrotoxicity via inhibition of oxidative stress and inflammation: A molecular and histochemical study
Authors: Elmansy Rasha A. , Seleem Hanan S. , Mahmoud Amany R. , Hassanein Emad H. M. , Ali Fares E. M.
Published: June 2020

Methotrexate (MTX) is a widely used chemotherapeutic agent; nevertheless, the nephrotoxicity associated with its use has limited its clinical use. Rebamipide (REB) is a gastro‐protective agent with diverse promising biological activities. Here, we investigated the renoprotective effects of REB against MTX‐induced nephrotoxicity in rats. Male Wistar rats were allocated into four groups: the normal control group, the REB group (100 mg kg−1 day−1, PO, for 12 days), the MTX group (which received a single injection of 20 mg/kg, ip), and the REB + MTX group (which received 100 mg kg−1 day−1 REB for 7 days before and 5 days after being injected with 20 mg/kg MTX). Interestingly, MTX triggered kidney injury, characterized by renal dysfunction along with histopathological alterations. Moreover, increased reactive oxygen species level and inflammatory response were detected in the kidney of MTX‐treated rats. However, REB prevented MTX‐induced oxidative kidney injury and boosted an antioxidant balance. Mechanistically, REB markedly activated the NRF‐2 protein and upregulated the expression of both SIRT‐1 and FOXO‐3 genes. Additionally, REB administration strongly inhibited the inflammatory response by downregulating both NF‐κB‐p65 and TLR‐4. Finally, the coadministration of REB and MTX activated the mTOR/PI3K/AKT signaling pathway. Simultaneously, REB treatment attenuated the reduction in glomerular size, the widening of the capsular spaces, and the tubular cell damage due to MTX administration. Taken together, these results indicate the potential of REB as adjuvant therapy to prevent nephrotoxicity in patients receiving MTX treatment.
Solvent Vapor Annealing Upgraded Orderly Intermolecular Stacking and Crystallinity to Enhance Memory Device Performance
Authors: Guo Chunxiu , Zhang Qijian , Li Hua , Lu Jianmei
Published: June 2020

Molecular stacking and crystallinity in a film can effectively affect the charge‐carrier mobility of semiconductor materials and corresponding device performance. Currently, solvent vapor annealing (SVA), as an effective thin‐film optimization strategy, which can select the appropriate solvent according to the characteristics of the molecular structure to optimize the intermolecular orderly arrangement, is often adopted. Thus, a small conjugated molecule C20‐ID(TPCN)2 with flexible alkyl side chains was synthesized and applied as active layer of sandwich memory devices. The active layer film has been annealed with different polar solvent vapors to evaluate the relationship among the molecular structure, solvent selection, annealing parameters and intermolecular stacking. Compared to un‐annealed devices, the memory devices based on the films through CH2Cl2‐annealing show better performance with a lower threshold voltage due to developed ordered molecular aggregation and better crystallinity, while a hydrophilic solvent vapor will weaken the device performance. This work not only reveals that selecting an appropriate solvent vapor for the molecular structure could be of vital importance in inducing the desired intermolecular stacking mode, but also provides a novel insight for the realization of organic semiconductor devices with excellent performance.
Light‐driven catalysis with engineered enzymes and biomimetic systems
Authors: Edwards Emily H. , Bren Kara L.
Published: June 2020

Efforts to drive catalytic reactions with light, inspired by natural processes like photosynthesis, have a long history and have seen significant recent growth. Successfully engineering systems using biomolecular and bioinspired catalysts to carry out light‐driven chemical reactions capitalizes on advantages offered from the fields of biocatalysis and photocatalysis. In particular, driving reactions under mild conditions and in water, in which enzymes are operative, using sunlight as a renewable energy source yield environmentally friendly systems. Furthermore, using enzymes and bioinspired systems can take advantage of the high efficiency and specificity of biocatalysts. There are many challenges to overcome to fully capitalize on the potential of light‐driven biocatalysis. In this mini‐review, we discuss examples of enzymes and engineered biomolecular catalysts that are activated via electron transfer from a photosensitizer in a photocatalytic system. We place an emphasis on selected forefront chemical reactions of high interest, including CH oxidation, proton reduction, water oxidation, CO2 reduction, and N2 reduction.
Progress and barriers in understanding and preventing indirect land‐use change
Authors: Daioglou Vassilis , Woltjer Geert , Strengers Bart , Elbersen Berien , Barberena Ibañez Goizeder , Sánchez Gonzalez David , Gil Barno Javier , van Vuuren Detlef P.
Published: June 2020

Climate change mitigation pathways have highlighted both the critical role of land‐use emissions, and the potential use of biofuels as a low‐emission energy carrier. This has led to concerns about the emission mitigation potential of biofuels, particularly related to indirect land‐use change (ILUC). This arises when the production of biofuels displaces the production of land‐based products elsewhere, either directly or via changes in crop prices, leading to indirect greenhouse gas (GHG) emissions. We review a large body of literature that has emerged on ILUC assessment and quantification, highlighting the methodologies employed, the resultant emission factors, modeled dynamics driving ILUC, and the uncertainty therein. Our review reveals that improvements in ILUC assessment methods have failed to reduce uncertainty and increase confidence in ILUC factors, instead making marginal improvements to economic models. Thus, while assessments have highlighted measures that could reduce ILUC, it is impossible to control or determine the actual ILUC resulting from biofuel production. This makes ILUC a poor guiding principle for land‐use and climate policy, and does not help with the determination of the GHG performance of biofuels. Instead climate and land‐use policy should focus on more integrated protection of terrestrial resources, covering all land‐use‐related products. © 2020 The Authors. Biofuels, Bioproducts, and Biorefining published by Society of Chemical Industry and John Wiley & Sons, Ltd
From industrial by‐products to value‐added compounds: the design of efficient microbial cell factories by coupling systems metabolic engineering and bioprocesses
Authors: Rangel Albert E. T. , Gómez Ramírez Jorge Mario , González Barrios Andrés Fernando
Published: June 2020

Microbial cell factories have been used for the production of valuable chemical compounds using a classical metabolic engineering approach, but this requires much time and cost, and labor‐intensive processes to make cell factories industrially competitive. Systems metabolic engineering is an upgraded version, which understands the cell as a complex system in which networks of genes, transcripts, proteins, and metabolites are connected, facilitating the analysis of potential cell factories. However, efficient cell factory design, which aims for industrial‐scale production, requires a comprehensive system, which goes beyond metabolism and considers industrial production challenges. A review is provided here of the developments and challenges in the application of systems biology for metabolic engineering and in recovery and purification processes for scaling up bio‐based chemical production. Then, a new design, build, test, and learn prediction cycle for metabolic engineering is proposed, for the design of efficient cell factories. This considers system‐wide characteristics and relies upon the integration of upstream (strain development), midstream (fermentation), and downstream (recovery and purification) analysis for strain design. In addition to this cycle, three issues should be taken into consideration: (i) The use of simple, available, and inexpensive materials; (ii) the identification and elimination of bottlenecks using non‐complex recovery and purification processes; (iii) the assessment of commercial and chemical industry requirements from the perspective of system efficiency. In this context, highly efficient microbial cell factories should be developed to produce compounds with improved production performance to meet industrial application requirements. © 2020 Society of Chemical Industry and John Wiley & Sons, Ltd
Moral tribalism and its discontents: How intuitive theories of ethics shape consumers' deference to experts
Authors: Johnson Samuel G.B. , Rodrigues Max , Tuckett David
Published: June 2020

We study the psychology at the intersection of two social trends. First, as markets become increasingly specialized, consumers must increasingly defer to outside experts to decide among complex products. Second, people divide themselves increasingly into moral tribes, defining themselves in terms of shared values with their group and often seeing these values as being objectively right or wrong. We tested how and why these tribalistic tendencies affect consumers' willingness to defer to experts. We find that consumers are indeed tribalistic in which experts they find convincing, preferring products advocated by experts who share their moral values (Study 1), with this effect generalizing across product categories (books and electronics) and measures (purchase intentions, information‐seeking, willingness‐to‐pay, product attitudes, and consequential choices). We also establish the mechanisms underlying these effects: because many consumers believe moral matters to be objective facts, experts who disagree with those values are seen as less competent and therefore less believable (Studies 2 and 3), with this effect strongest among consumers who are high in their belief in objective moral truth (Study 4). Overall, these studies seek not only to establish dynamics of tribalistic deference to experts but also to identify which consumers are more or less likely to fall prey to these tribalistic tendencies.
Selective reaction of homocysteine with o‐phthalaldehyde under flow conditions in highly alkaline medium: fluorimetric determination using zone fluidics
Authors: Tsiasioti Apostolia , Andreou Aikaterini , Tzanavaras Paraskevas D.
Published: June 2020

In the present study we report the reaction between homocysteine and o‐phthalaldehyde under flow conditions. Homocysteine reacts on‐line with the derivatization reagent in a strong alkaline medium and in the absence of nucleophilic reagents to yield a fluorescent derivative (λex/λem = 370/480 nm). The reaction variables were investigated using the concept of zone fluidics. Selectivity factors against other compounds were calculated at 10‐fold excess. The findings formed the basis of an automated proposed method that was found to be linear in the range 0.1–1.5 μmol L−1, with a limit of detection of 20 nmol L−1 and relative standard deviation < 0.5% (within‐day) and 3.2% (between‐day). The method proved to be rapid, offering a practical sampling rate of 24 h−1 and accurate following application to an artificial urine matrix with minimum dilution.
Technoeconomic analysis of semicontinuous bioreactor production of biopharmaceuticals in transgenic rice cell suspension cultures
Authors: Corbin Jasmine M. , McNulty Matthew J. , Macharoen Kantharakorn , McDonald Karen A. , Nandi Somen
Published: June 2020

Biopharmaceutical protein production using transgenic plant cell bioreactor processes offers advantages over microbial and mammalian cell culture platforms in its ability to produce complex biologics with simple chemically defined media and reduced biosafety concerns. A disadvantage of plant cells from a traditional batch bioprocessing perspective is their slow growth rate which has motivated us to develop semicontinuous and/or perfusion processes. Although the economic benefits of plant cell culture bioprocesses are often mentioned in the literature, to our knowledge no rigorous technoeconomic models or analyses have been published. Here we present technoeconomic models in SuperPro Designer® for the large‐scale production of recombinant butyrylcholinesterase (BChE), a prophylactic/therapeutic bioscavenger against organophosphate nerve agent poisoning, in inducible transgenic rice cell suspension cultures. The base facility designed to produce 25 kg BChE per year utilizing two‐stage semicontinuous bioreactor operation manufactures a single 400 mg dose of BChE for $263. Semicontinuous operation scenarios result in 4–11% reduction over traditional two‐stage batch operation scenarios. In addition to providing a simulation tool that will be useful to the plant‐made pharmaceutical community, the model also provides a computational framework that can be used for other semicontinuous or batch bioreactor‐based processes.
Human trabecular meshwork cell behavior is influenced by collagen scaffold pore architecture and glycosaminoglycan composition
Authors: Osmond Matthew J. , Krebs Melissa D. , Pantcheva Mina B.
Published: June 2020

Glaucoma is a degenerative eye disease in which damage to the optic nerve leads to a characteristic loss of vision. The primary risk factor for glaucoma is an increased intraocular pressure that is caused by an imbalance of aqueous humor generation and subsequent drainage through the trabecular meshwork (TM) drainage system. The small size, donor tissue limitations, and high complexity of the TM make it difficult to research the relationship between the TM cells and their immediate environment. Thus, a biomaterial‐based approach may be more appropriate for research manipulations and in vitro drug development platforms. In this work, human TM (hTM) cells were cultured on various collagen scaffolds containing different glycosaminoglycans (GAGs) and different pore architectures to better understand how hTM cells respond to changes in their extracellular environment. Cellular response was measured by quantifying cellular proliferation and expression of an important extracellular matrix protein, fibronectin. The pore architecture of the scaffolds was altered using freeze‐casting technique to make both large and small pores that were aligned or with a non‐aligned random structure. The composition of the scaffolds was altered with the addition of chondroitin sulfate and/or hyaluronic acid. It was found that the hTM cells grown on large pore scaffolds proliferate more than those grown on small pores. There was an increase in the fibronectin expression with the incorporation of GAGs, and its morphology was changed by the underlying pore architecture. This work will help provide an insight into the behavior of hTM cells when introducing changes in their microenvironment.
Immobilization rapidly selects for chemoresistant ovarian cancer cells with enhanced ability to enter dormancy
Authors: Lam Tiffany , Aguirre‐Ghiso Julio A. , Geller Melissa A. , Aksan Alptekin , Azarin Samira M.
Published: June 2020

Around 20–30% of ovarian cancer patients exhibit chemoresistance, but there are currently no methods to predict whether a patient will respond to chemotherapy. Here, we discovered that chemoresistant ovarian cancer cells exhibit enhanced survival in a quiescent state upon experiencing the stress of physical confinement. When immobilized in stiff silica gels, most ovarian cancer cells die within days, but surviving cells exhibit hallmarks of single‐cell dormancy. Upon extraction from gels, the cells resume proliferation but demonstrate enhanced viability upon reimmobilization, indicating that initial immobilization selects for cells with a higher propensity to enter dormancy. RNA‐seq analysis of the extracted cells shows they have signaling responses similar to cells surviving cisplatin treatment, and in comparison to chemoresistant patient cohorts, they share differentially expressed genes that are associated with platinum‐resistance pathways. Furthermore, these extracted cells demonstrate greater resistance to cisplatin and paclitaxel, despite being proliferative. In contrast, serum starvation and hypoxia could not effectively select for chemoresistant cells upon removal of the environmental stress. These findings demonstrate that ovarian cancer chemoresistance and the ability to enter dormancy are linked, and immobilization rapidly distinguishes chemoresistant cells. This platform could be suitable for mechanistic studies, drug development, or as a clinical diagnostic tool.
Biomass and pigment production for Arthrospira platensis via semi‐continuous cultivation in photobioreactors: Temperature effects
Authors: Karemore Ankush , Yuan Yanhui , Porubsky William , Chance Ronald
Published: June 2020

This study describes the response of Arthrospira platensis to a variety of temperature conditions as reflected in variations of photosynthetic parameters, pigmentation, and biomass productivity in indoor photobioreactor (PBR) cultivations. These experiments are designed to better understand the impact of temperature, seasonal variations, and acclimation effects on outdoor biomass production. The irradiance level and temperature range (20–39°C) are chosen to enable modeling of semi‐continuous operation of large‐scale outdoor PBR deployments. Overall, the cultivations are quite stable with some pigment‐related instabilities after prolonged high‐temperature exposure. Changes in productivity with temperature, as reflected in measured photosynthetic parameters, are immediate and mainly attributable to the temperature dependence of the photosaturation parameter, a secondary factor being variation in pigment content on a longer time scale corresponding to turnover of the culture population. Though pigment changes are not accompanied by significant changes in productivity, prolonged exposure at 35°C and above yields a clear degradation in performance. Productivities in a semi‐continuous operation are quantitatively reproduced with a productivity model incorporating photosynthetic parameters measured herein. This study confirms the importance of temperature for biomass and pigment production in Arthrospira cultivations and provides a basis for risk assessments related to temperature mitigation for large‐scale outdoor cultivations.
Simultaneous determination of VD2, VD3, 25(OH) D2, and 25(OH) D3 in human plasma using electrospray LC–MS/MS as well as its application to evaluate VD plasma levels in depressive, schizophrenic patients and healthy individuals
Authors: Lyu Haiyan , Wang Suping , Jin Ying , Shen Rong , Chen Jiayun , Zhu Chunyan , Chen Binbin , Wu Caisheng
Published: June 2020

Vitamin D measurements in biological fluids by liquid chromatography–tandem mass spectrometry (LC–MS/MS) have been widely used but remain challenging at very low concentration levels. Rapid, high recovery, sensitive and reliable measurements of vitamin D, as well as its primary metabolites using LC–MS/MS are urgently needed for a routine clinical laboratory. Herein, we reported a novel electrospray LC–MS/MS method for determining vitamin D and its primary metabolites using the supported liquid extraction method to achieve higher recoveries, with optimized pH values to achieve optimal derivatization efficiency for higher sensitivity and selected chromatographic conditions to shorten the separation time. The method has been validated with respect to selectivity, recovery, matrix effects, accuracy and precision, stabilities, carryover and dilution effects. The method has been successfully applied to quantify the VD plasma concentrations of depressive, schizophrenic patients and healthy individuals. The result showed that there were significant differences in plasma VD levels between mental disorder patients with healthy individuals, and the total VD levels in mental disorder patients were much higher than healthy individuals, which might require larger clinical samples for validation.
A qualitative exploration of the sociology of poststroke visual impairments and the associated health inequalities
Authors: Hanna Kerry , Mercer David , Rowe Fiona
Published: June 2020

Introduction

Inequalities have been found to exist within the visually impaired stroke population on an individual level, in relation to demographic differences, unequal access to vision services, transport, employment, and financial repercussions. The long‐term impact of living with poststroke visual impairments must be explored, in order to identify complications accessing NHS services and to inform possible changes to service planning and delivery in order to tackle such complications.

Aim

To explore the extent of health inequalities within visually impaired stroke survivors in the northwest of England and discuss potential solutions to these.

Methods

Focus groups and individual interviews (n = 13 stroke survivors and n = 1 spouse) were conducted between October 2016 and January 2017. Transcription and thematic analysis of the transcripts was undertaken, using line‐by‐line coding, underpinned with social constructionism.

Results

The findings draw on lived experiences of stroke survivors across their journey from prestroke to life after stroke. The three overarching experiences of stroke and visual impairment that emerged in respondent accounts were constructed in terms of “loss,” concerning (a) the physical being, (b) the psychosocial being and, (c) the systematic organization of health care.

Conclusion

The stroke survivors frequently reported a complete lack of visual care, with many recounting apathetic experiences, often resonating power imbalance in the healthcare system. Where suitable care is being offered after stroke, a desire for a personalized approach to rehabilitation, with adapted communication methods specific to individual needs, featured strongly in many of the respondent accounts. The findings emphasize a need to ensure vision rehabilitation is offered to all stroke survivors suffering from poststroke visual impairment, and to educate stroke clinicians and patients of the bigger picture of life after stroke, highlighting all forms of available support.
High‐frequency transcranial magnetic stimulation protects APP/PS1 mice against Alzheimer’s disease progress by reducing APOE and enhancing autophagy
Authors: Chen Xia , Dong Guo‐Ying , Wang Lin‐Xiao
Published: June 2020

Introduction

The repetitive transcranial magnetic stimulation (rTMS) has clinically wide application prospect of psychiatry and neuroscience, for its painless, noninvasive, and high efficiency. So far, rTMS has been used in the treatment of Alzheimer's disease (AD) but the underlying mechanism is not clear.

Methods and Results

The APP/PS1 mice at 3‐month‐old were treated by 5 Hz high‐frequency (HF) rTMS for two weeks. After rTMS treatment, the AD‐like cognitive impairments of APP/PS1 mice were investigated subsequently, and molecular mechanisms underlying was further explored. The study showed that the 2‐week rTMS at 5Hz frequency improved cognitive impairments and AD‐like pathology (including a decrease in p‐Tau, APP, Aβ, and PP2A expression) of APP/PS1 mice. Although BDNF‐TrkB signaling was significantly enhanced, no differences of SYN, PSD95 and p‐AKT were observed in the brain of APP/PS1 mice. On the contrary, the LC3Ⅱ/LC3Ⅰ ratio was elevated with a significant reduction of ApoE and p62 in mice.

Conclusions

rTMS exerts a potentially protective role in the prevention and treatment of AD by reducing ApoE expression and promoting autophagic flux, which provides a new insight into the mechanism of rTMS.
Industry convergence as a strategy for achieving sustainable development of agricultural complex: The case of Sandun‐Lanli in China
Authors: Chen Xiaowei , Zhang Tianyu , Jia Fu
Published: June 2020

The purpose of the paper is to conceptualize and provide empirical evidence for the adoption of industry convergence strategy to sustainably develop the agricultural complex (AC) as a form of multifunctional agriculture in the Chinese context, which aims to achieve environmental sustainability in agricultural production and promotion of farmers' income and employment opportunities. A longitudinal single‐case study method was adopted. Thirty‐six face‐to‐face interviews were carried out with key respondents from various levels and types of government agencies, the Wu‐Sheng Company, and village collectives; participative observations were conducted during the fieldwork between 2016 and 2019. We found sustainability is embedded in and achieved through the industry convergence strategies of AC in the rural area of China. We are the first to formally define AC, propose the four‐stage industry convergence strategies of Wu‐Sheng in the process of developing the AC, and build connection between the AC and sustainable development. The case provides important, rich insights into the AC, industry convergence, and agricultural land use policy and therefore has enormous implications for agricultural companies as well as governments.
A phase I study of toripalimab, an anti‐PD‐1 antibody, in patients with refractory malignant solid tumors
Authors: Wei Xiao‐Li , Ren Chao , Wang Feng‐Hua , Zhang Yang , Zhao Hong‐Yun , Zou Ben‐Yan , Wang Zhi‐Qiang , Qiu Miao‐Zhen , Zhang Dong‐Sheng , Luo Hui‐Yan , Wang Feng , Yao Sheng , Xu Rui‐Hua
Published: June 2020

Background

Several programmed cell death ligand 1 (PD‐L1)/programmed cell death protein 1 (PD‐1) antibodies have been approved for cancer treatment worldwide. Their pharmacokinetic and pharmacodynamic characteristics have been reported mainly in western countries, but related data in Chinese patients are limited. This study was conducted to investigate the safety, efficacy, pharmacokinetics, and pharmacodynamics of an anti‐PD‐1 antibody, toripalimab, in Chinese patients.

Methods

A single‐center phase I study was conducted in Sun Yat‐sen University Cancer Center. Eligible patients were adults with histologically confirmed, treatment‐refractory, advanced, solitary malignant tumors. Toripalimab was intravenously infused every 2 weeks in dose‐escalating cohorts at 0.3 mg/kg, 1 mg/kg, 3 mg/kg, 10 mg/kg, and 240 mg. The study followed standard 3 + 3 design.

Results

Between 15th March 2016 and 27th September 2016, 25 patients were enrolled, of whom 3 (12.0%), 7 (28.0%), 6 (24.0%), 6 (24.0%), 3 (12.0%) received 0.3 mg/kg, 1 mg/kg, 3 mg/kg, 10 mg/kg, and 240 mg toripalimab, respectively. After a median follow‐up time of 5.0 months (range: 1.5‐19.8 months), we observed that the commonest treatment‐related adverse events (TRAEs) were fatigue (64.0%) and rash (24.0%). No grade 3 or higher TRAEs were observed. No dose‐limiting toxicity, treatment‐related serious adverse events (SAEs), or treatment‐related death occurred. Objective response rate was 12.5%. The half‐life of toripalimab was 150‐222 h after a single dose infusion. Most patients, including those from the 0.3 mg/kg group, maintained complete PD‐1 receptor occupancy (> 80%) on activated T cells since receiving the first dose of toripalimab.

Conclusions

Toripalimab is a promising anti‐PD‐1 antibody, which was well tolerated and demonstrated anti‐tumor activity in treatment‐refractory advanced solitary malignant tumors. Further exploration in various tumors and combination therapies is warranted.
Progesterone at high doses reduces the growth of U87 and A172 glioblastoma cells: Proteomic changes regarding metabolism and immunity
Authors: Altinoz Meric A. , Ucal Yasemin , Yilmaz Muazzez C. , Kiris İrem , Ozisik Ozan , Sezerman Ugur , Ozpinar Aysel , Elmaci İlhan
Published: June 2020

While pregnancy may accelerate glioblastoma multiforme (GBM) growth, parity and progesterone (P4) containing treatments (ie, hormone replacement therapy) reduce the risk of GBM development. In parallel, low and high doses of P4 exert stimulating and inhibitory actions on GBM growth, respectively. The mechanisms behind the high‐dose P4‐suppression of GBM growth is unknown. In the present study, we assessed the changes in growth and proteomic profiles when high‐dose P4 (100 and 300 µM) was administered in human U87 and A172 GBM cell lines. The xCELLigence system was used to examine cell growth when different concentrations of P4 (20, 50, 100, and 300 µM) was administered. The protein profiles were determined by two‐dimensional gel electrophoresis in both cell lines when 100 and 300 µM P4 were administered. Finally, the pathways enriched by the differentially expressed proteins were assessed using bioinformatic tools. Increasing doses of P4 blocked the growth of both GBM cells. We identified 26 and 51 differentially expressed proteins (fc > 2) in A172 and U87 cell lines treated with P4, respectively. Only the pro‐tumorigenic mitochondrial ornithine aminotransferase and anti‐apoptotic mitochondrial 60 kDa heat shock protein were downregulated in A172 cell line and U87 cell line when treated with P4, respectively. Detoxification of reactive oxygen species, cellular response to stress, glucose metabolism, and immunity‐related proteins were altered in P4‐treated GBM cell lines. The paradox on the effect of low and high doses of P4 on GBM growth is gaining attention. The mechanism related to the high dose of P4 on GBM growth can be explained by the alterations in detoxification mechanisms, stress, and immune response and glucose metabolism. P4 suppresses GBM growth and as it is nontoxic in comparison to classical chemotherapeutics, it can be used as a new strategy in GBM treatment in the future.
Assessment of somatic mutations in urine and plasma of Wilms tumor patients
Authors: Miguez Ana Carolina Kerekes , Barros Bruna D. de Figueiredo , de Souza Jorge E. S. , da Costa Cecília Maria L. , Cunha Isabela Werneck , Barbosa Paula Nicole Vieira P. , Apezzato Maria Lúcia P. , de Souza Sandro J. , Carraro Dirce Maria
Published: June 2020

Tumor DNA has been detected in body fluids of cancer patients. Somatic tumor mutations are being used as biomarkers in body fluids to monitor chemotherapy response as a minimally invasive tool. In this study, we evaluated the potential of tracking somatic mutations in free DNA of plasma and urine collected from Wilms tumor (WT) patients for monitoring treatment response. Wilms tumor is a pediatric renal tumor resulting from cell differentiation errors during nephrogenesis. Its mutational repertoire is not completely defined. Thus, for identifying somatic mutations from tumor tissue DNA, we screened matched tumor/leukocyte DNAs using either a panel containing 16 WT‐associated genes or whole‐exome sequencing (WES). The identified somatic tumor mutations were tracked in urine and plasma DNA collected before, during and after treatment. At least one somatic mutation was identified in five out of six WT tissue samples analyzed. Somatic mutations were detected in body fluids before treatment in all five patients (three patients in urine, three in plasma, and one in both body fluids). In all patients, a decrease of the variant allele fraction of somatic mutations was observed in body fluids during neoadjuvant chemotherapy. Interestingly, the persistence of somatic mutations in body fluids was in accordance with clinical parameters. For one patient who progressed to death, it persisted in high levels in serial body fluid samples during treatment. For three patients without disease progression, somatic mutations were not consistently detected in samples throughout monitoring. For one patient with bilateral disease, a somatic mutation was detected at low levels with no support of clinical manifestation. Our results demonstrated the potential of tracking somatic mutations in urine and plasma DNA as a minimally invasive tool for monitoring WT patients. Additional investigation is needed to check the clinical value of insistent somatic mutations in body fluids.