bluuebunny/crossref_metadata_2025_split huggingface dataset:
Zielgerichtete Wirkstoffe für die Krebstherapie: Aktuelle Entwicklungen und Perspektiven
Authors: Chen Weihua , Sun Zhen , Lu Lehui 
Published: February 2020

AbstractSchwerwiegende Nebenwirkungen und mangelhafte therapeutische Wirksamkeit sind die primären Nachteile der derzeitigen Krebsmedikamente. Diese Problematik kann durch gezielte Ansteuerung, das sogenannte Targeting, minimiert werden, jedoch ist die zielgerichtete Wirksamkeit gegenwärtiger Medikamente noch dürftig und benötigt dringend Verbesserungen. Vor diesem Hintergrund fasst dieser Aufsatz zunächst die aktuellen Targetingstrategien in der Krebstherapie hinsichtlich Krebsgewebe und Organellen zusammen. Anschließend analysieren wir das systematische Targeting mit Krebsmedikamenten und schlussfolgern, dass der typische Verlauf eines zielgerichteten Medikaments, das durch intravenöse Injektion verabreicht wurde, eine CTIO‐Kaskade von mindestens vier Schritten durchläuft. Des Weiteren werden zur Sicherstellung einer hohen Gesamt‐Targetingeffizienz die in jedem Schritt benötigten Eigenschaften eines zielgerichteten Wirkstoffs weiter untersucht sowie einige Richtlinien für die Strukturoptimierung zur Gewinnung effektiver Targetingmedikamente offeriert. Zum Schluss beleuchten wir die wesentlichen Probleme und potenziellen Herausforderungen für die künftige Erforschung zielgerichteter Krebstherapien. Ziel dieses Aufsatzes ist es, die Entwicklung von Arzneimitteln für die Hochtechnologiemedizin gegen Krebs aktiv voranzutreiben.
Bacterial Autoimmune Drug Metabolism Transforms an Immunomodulator into Structurally and Functionally Divergent Antibiotics
Authors: Park Hyun Bong , Goddard Tyler N. , Oh Joonseok , Patel Jaymin , Wei Zheng , Perez Corey E. , Mercado Brandon Q. , Wang Rurun , Wyche Thomas P. , Piizzi Grazia , Flavell Richard A. , Crawford Jason M. 
Published: February 2020

AbstractTapinarof is a stilbene drug that is used to treat psoriasis and atopic dermatitis, and is thought to function through regulation of the AhR and Nrf2 signaling pathways, which have also been linked to inflammatory bowel diseases. It is produced by the gammaproteobacterial Photorhabdus genus, which thus represents a model to probe tapinarof structural and functional transformations. We show that Photorhabdus transforms tapinarof into novel drug metabolism products that kill inflammatory bacteria, and that a cupin enzyme contributes to the conversion of tapinarof and related dietary stilbenes into novel dimers. One dimer has activity against methicillin‐resistant Staphylococcus aureus (MRSA) and vancomycin‐resistant Enterococcus faecalis (VRE), and another undergoes spontaneous cyclizations to a cyclopropane‐bridge‐containing hexacyclic framework that exhibits activity against Mycobacterium. These dimers lack efficacy in a colitis mouse model, whereas the monomer reduces disease symptoms.
Toughening a Self‐Healable Supramolecular Polymer by Ionic Cluster‐Enhanced Iron‐Carboxylate Complexes
Authors: Deng Yuanxin , Zhang Qi , Feringa Ben L. , Tian He , Qu Da‐Hui 
Published: February 2020

AbstractSupramolecular polymers that can heal themselves automatically usually exhibit weakness in mechanical toughness and stretchability. Here we exploit a toughening strategy for a dynamic dry supramolecular network by introducing ionic cluster‐enhanced iron‐carboxylate complexes. The resulting dry supramolecular network simultaneous exhibits tough mechanical strength, high stretchability, self‐healing ability, and processability at room temperature. The excellent performance of these distinct supramolecular polymers is attributed to the hierarchical existence of four types of dynamic combinations in the high‐density dry network, including dynamic covalent disulfide bonds, noncovalent H‐bonds, iron‐carboxylate complexes and ionic clustering interactions. The extremely facile preparation method of this self‐healing polymer offers prospects for high‐performance low‐cost material among others for coatings and wearable devices.
Sequence‐Dependent DNA Functionalization of Upconversion Nanoparticles and Their Programmable Assemblies
Authors: Ge Huan , Wang Dongya , Pan Yue , Guo Yuanyuan , Li Hongyu , Zhang Fan , Zhu Xinyuan , Li Yuehua , Zhang Chuan , Huang Ling 
Published: February 2020

AbstractDNA‐modified lanthanide‐doped upconversion nanoparticles (DNA‐UCNPs) that combine the functions of DNA and the optical features of UCNPs have shown great promise in a wide range of fields. However, challenges remain in precisely tethering and orienting the DNA strands on the UCNP surface. Herein, we systematically investigate the sequence dependence of DNAs in their interactions with UCNPs, and reveal that poly‐cytosine (poly‐C) has high affinity for the UCNP surface. A general approach to synthesize monodispersed DNA‐UCNP conjugates is developed using poly‐C‐containing diblock DNA strands. The poly‐C segment of the DNA strand binds to the surfaces of UCNPs and the second segment is oriented perpendicularly on the UCNP surface, making the DNA‐UCNPs highly stable and monodispersed in aqueous solution. The dense layer of DNA on the UCNP surface enables the programmable assembly of UCNPs with other DNA‐functionalized nanoparticles or DNA origamis through hybridization, resulting in the formation of well‐organized complex structures.
Modification of the Ferrous Oxidation‐Xylenol Orange Method for Determination of Peroxide Value in Highly Pigmented Sea Cucumber Viscera Lipid
Authors: Abuzaytoun Reem , Budge Suzanne , Hansen Lisbeth Truelstrup , MacKinnon Shawna 
Published: February 2020

AbstractA ferrous oxidation‐xylenol orange (FOX) method was modified to measure the levels of hydroperoxides in highly pigmented sea cucumber (Cucumaria frondosa) viscera lipid. With the FOX method, oil hydroperoxides oxidize Fe(II) to Fe(III) ions, which in turn bind to xylenol orange (XO) to form a complex that has a maximum absorbance at 560 nm. When applied to lipid extracts containing high levels of carotenoid pigments, the carotenoids interfere in the absorbance measurement because the XO‐complex and carotenoids absorb at the same wavelength. To avoid this, an approach was developed where carotenoids were removed from the solution containing the XO‐complex before absorbance measurements were made. This was accomplished by aqueous extraction of the reaction solution, leaving an organic layer containing the carotenoid pigment. The absorbance of the aqueous layer was subsequently measured at 560 nm allowing for determination of the lipid hydroperoxide content (mmol kg−1) using a cumene hydroperoxide calibration curve. The method was validated using oxidized, unpigmented fish oils. The modified FOX method described herein was linear, accurate, and precise, and was validated over a hydroperoxide concentration range of 5–35 meq kg−1 lipid. This modified FOX method for hydroperoxide determination of highly pigmented lipids is a valuable alternative to the methods presently available for determination of peroxide values.
Engineering protonation conformation of l‐aspartate‐α‐decarboxylase to relieve mechanism‐based inactivation
Authors: Qian Yuanyuan , Lu Cui , Liu Jia , Song Wei , Chen Xiulai , Luo Qiuling , Liu Liming , Wu Jing 
Published: February 2020

AbstractMechanism‐based inactivation of l‐aspartate‐α‐decarboxylase (PanD), which leads to irreversible modification of active site, is a major challenge in the efficient production of β‐alanine from L‐aspartic acid. In this study, a semi‐rational strategy that combined conformational dynamics and structural alignment was applied to increase the catalytic stability of Bacillus subtilis PanD (BsPanD). Using site‐saturation and C‐terminal deletion, the variant Q5 (BsPanDI46V/I88M/K104S/I126*) was generated. The catalytic half‐life and the total turnover number (TTN) of Q5 were 3.48‐fold and 2.52‐fold higher, respectively, compared with that of the parent Q0. The reasons for the differences were the prolonged distance d1 between the phenolic group of Tyr58 and pyruvoyl group of Ser25 (4.9 Å in Q0 vs. 5.5 Å in Q5), an increased difficulty for incorrect protonation to occur, and the decreased flexibility of residues in regions A, B, and C, thereby enhancing the probability of correct protonation. Variant Q5, coupled with l‐aspartase (AspA) in a 15‐L bioreactor, generated a linear cascade system using fumaric acid as a substrate, yielding 118.6 g/L β‐alanine with a product/catalyst (P/C) ratio of 5.9 g/g and a conversion > 99%. These results showed that reshaping the protonation conformation of PanD can efficiently relieve mechanism‐based inactivation and boost catalytic stability.
The course of recovery of locomotor function over a 10‐week observation period in a rat model of femoral nerve resection and autograft repair
Authors: Heinzel Johannes Christoph , Hercher David , Redl Heinz 
Published: February 2020

AbstractBackgroundA great extent of knowledge on peripheral nerve regeneration has been gathered using the rat sciatic nerve model. The femoral nerve model of the rat offers an interesting alternative, as it lacks disadvantageous features such as automutilation. For the analysis of locomotor behavior in rats after sciatic nerve injury, the CatWalk™ XT Gait Analysis System is often used. However, lesions of the femoral nerve in the rat have yet remained unstudied with this method.Material and MethodsTen male Sprague Dawley rats were evaluated with the CatWalk XT to study their gait after a 6‐mm resection of the right femoral nerve and reconstruction with an autologous nerve graft. Animals were observed for 10 weeks after surgery.ResultsPrint Area, Print Length, Swing Speed, and Duty Cycle decreased to a minimum of 40% of baseline 2 weeks after surgery. Swing Time was elevated more than twofold at this time point. However, all these parameters recovered back to >90% of baseline values at 10 weeks after surgery. This degree of functional recovery has not been reported after sciatic nerve resection and autograft repair. Base of support varied minimally postoperatively in contrast to a strong decrement after sciatic nerve resection and repair.ConclusionWe hereby provide a comprehensive in‐depth analysis of how to study functional recovery after injury of the femoral nerve in the rat via the CatWalk XT. We place special emphasis on highlighting the differences between the femoral nerve and sciatic nerve injury model in this context.
In Situ Spectroscopic Studies on the Redox Cycle of NH3−SCR over Cu−CHA Zeolites
Authors: Liu Chong , Kubota Hiroe , Amada Takehiro , Kon Kenichi , Toyao Takashi , Maeno Zen , Ueda Kakuya , Ohyama Junya , Satsuma Atsushi , Tanigawa Takuya , Tsunoji Nao , Sano Tsuneji , Shimizu Ken‐ichi 
Published: February 2020

AbstractThe selective catalytic reduction of NO with ammonia (NH3−SCR) catalyzed by Cu−CHA zeolites is thoroughly investigated using in situ spectroscopic experiments combined with on‐line mass spectroscopy (MS) under steady‐state NH3−SCR conditions and transient conditions for Cu(II)/Cu(I) redox cycles. Quantitative analysis of the in situ XANES spectra of Cu−CHA under steady‐state conditions of NH3−SCR show that NH3‐coordinated Cu(II) species is the dominant Cu species at low temperatures (100–150 °C). At higher temperatures, Cu(II) species and [Cu(NH3)2]+ complex coexist, possibly because the rate of the Cu(II)→Cu(I) reduction step is comparable to that of the Cu(I)→Cu(II) oxidation step. In situ XANES, IR/MS, and UV‐vis/MS experiments on the reduction half cycle demonstrate that the reduction of Cu(II) species occurs via the reaction of NH3‐liganded Cu(II) with NO to yield N2 and H2O. For the oxidation half cycle, in situ XANES experiments of Cu(I) oxidation in 10 % O2 at 200 °C indicate that an increased density in CHA zeolite exhibits a higher oxidation rate. In situ UV‐vis experiments of Cu(I) reoxidation using different mixtures of oxidant feed gas demonstrate the key role of O2 in the oxidation cycle. It is suggested that the reoxidation of Cu(I) to Cu(II) species occurs with only O2 as the oxidant, and a high Cu density in CHA zeolite promotes SCR activity by enhancing the oxidative activation of Cu(I) to Cu(II) during the catalytic cycle.
Characterization of Lyophilization of Frozen Bulky Solids
Authors: Foerst Petra , Gruber Sebastian , Schulz Michael , Vorhauer Nicole , Tsotsas Evangelos 
Published: February 2020

AbstractTwo methods to study the primary freeze‐drying behavior of bulky solids are presented, namely, lyomicroscopy and neutron imaging. The applicability of both methods to visualize the evolution of the sublimation front is tested for maltodextrin particles with different sizes and solid concentrations. Exemplary results for both methods are reported and the applicability of both methods to study freeze‐drying behavior of bulk solids is described. To estimate the impact of particle size and bed height for the freeze‐drying of bulky solids, a modified Biot number is introduced to estimate the optimum particle size for a given bed height and formulation. The applicability of the two methods with regard to the modified Biot numbers is discussed.
The Thioredoxin System: A Promising Target for Cancer Drug Development
Authors: Ghareeb Hiba , Metanis Norman 
Published: February 2020

AbstractThe thioredoxin system is highly conserved system found in all living cells and comprises NADPH, thioredoxin, and thioredoxin reductase. This system plays a critical role in preserving a reduced intracellular environment, and its involvement in regulating a wide range of cellular functions makes it especially vital to cellular homeostasis. Its critical role is not limited to healthy cells, it is also involved in cancer development, and is overexpressed in many cancers. This makes the thioredoxin system a promising target for cancer drug development. As such, over the last decade, many inhibitors have been developed that target the thioredoxin system, most of which are small molecules targeting the thioredoxin reductase C‐terminal redox center. A few inhibitors of thioredoxin have also been developed. We believe that more efforts should be invested in developing protein/peptide‐based inhibitors against both thioredoxin reductase and/or thioredoxin.
Dietary advanced glycation end products and the risk of postmenopausal breast cancer in the National Institutes of Health‐AARP Diet and Health Study
Authors: Peterson Lindsay L. , Park Seho , Park Yikyung , Colditz Graham A. , Anbardar Narges , Turner David P. 
Published: February 2020

BackgroundAdvanced glycation end products (AGEs) are reactive metabolites produced as a by‐product of sugar metabolism and are consumed through the diet in high‐fat and highly processed foods. They are associated with chronic inflammatory diseases, and evidence suggests that they play a role in carcinogenesis. The authors evaluated the association of dietary AGE intake and the risk of postmenopausal invasive breast cancer.MethodsThis was a prospective cohort study of 183,548 postmenopausal women in the National Institutes of Health‐AARP Diet and Health Study. The main outcome was incident invasive breast cancer. AGE intake was estimated from food‐frequency questionnaires. Incident breast cancer cases were identified through state cancer registries. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals for developing breast cancer according to AGE intake quintiles. Multivariable regression models were adjusted for breast cancer risk factors.ResultsThe mean follow‐up was 12.8 years, and 9851 breast cancers (1978 advanced stage) were identified. The median AGE daily intake was 5932 kilo units per 100 kilocalories (KU/1000 kcal). Women with higher intake tended to have lower education levels, higher body mass index, less physical activity, were current smokers, and had higher fat and meat intake. The highest quintile of AGE intake (compared with the lowest) was associated with an increased risk of breast cancer (HR, 1.09; 95% CI, 1.02‐1.16; P = .03) after adjusting for breast cancer risk factors and particularly was associated with 37% of advanced‐stage tumors (HR, 1.37; 95% CI, 1.09‐1.74; P < .02) after adjusting for risk factors and fat and meat intake.ConclusionsDietary AGEs may play a role in the development of postmenopausal breast cancer.
Recent Achievements in Noble Metal Catalysts with Unique Nanostructures for Liquid Fuel Cells
Authors: Sun Qiwen , Xu Hui , Du Yukou 
Published: February 2020

AbstractIn recent years, research efforts have been focused on the design and fabrication of highly efficient catalysts for liquid fuel cells, because the use of these cells is an important approach for alleviating environmental pollution and energy crises. However, the limitations of the catalytic performance of industrial Pt/C have strongly hindered the development of these fuel cells. The catalyst morphology has a strong impact on its performance; nanostructured catalysts are preferred as they offer large specific surface area and more exposed active centers. In view of this, many catalysts with unique structures have been synthesized in recent years, all of which show excellent catalytic performance characteristics. Despite these achievements, few efforts have been made to survey this field comprehensively. Herein, the recent advances in catalysts for liquid fuel cells are summarized, with a focus on noble metal catalysts with unique morphologies such as nanowires, nanosheets, and assembly structures. Their formation mechanisms are discussed critically. The relationship between the unique morphologies and excellent performance of these catalysts is also explored. This work may provide guidelines for the further development of liquid fuel cells.
A Quinone Anode for Lithium‐Ion Batteries in Mild Aqueous Electrolytes
Authors: Jing Yan , Liang Yanliang , Gheytani Saman , Yao Yan 
Published: February 2020

AbstractAqueous batteries could be potentially used for grid‐scale energy storage owing to the use of nonflammable electrolytes and long cycle life. Recently, quinones have shown examples as redox‐active materials in aqueous batteries under either strong acidic or basic conditions. However, a quinone‐based battery with a less corrosive electrolyte is still rare. Given that quinone‐based batteries are heavily influenced by the pH of electrolytes, we studied the influence of acid dissociation constants (pKa) of hydroquinones on their performance as solid electrode materials. We measured the pKa of anthracene‐9,10‐diol (AQH2) and benzo[1,2‐b:4,5‐b′]dithiophene‐4,8‐diol (BDTDH2) from the Pourbaix diagrams of two para‐quinone monomers [i.e., anthracene‐9,10‐dione (AQ) and benzo[1,2‐b:4,5‐b′]dithiophene‐4,8‐dione (BDTD)]. Subsequently, their polymeric forms [i.e., poly(anthraquinonyl sulfide) (PAQS) and poly(benzo[1,2‐b:4,5‐b′]dithiophene‐4,8‐dione‐2,6‐diyl sulfide) (PBDTDS)] were investigated as electrodes in aqueous lithium‐ion cells. At pH 13, PAQS demonstrates a low capacity and poor cycle life, whereas PBDTDS shows a capacity of 196 mAh g−1 and fade rates of 0.0038 % per cycle over 4200 cycles, 0.77 % per day over 21 days. The differences in capacity and cycle stability can be explained by the difference of corresponding pKa values. A full cell with the configuration of (−)PBDTDS|2.5 m Li2SO4 (pH 13)|LiCoO2(+) shows a voltage of 1.08 V, a capacity of 72 mAh g−1 and ≈99.9 % of Coulombic efficiency for 500 stable cycles.
Association between objectively measured physical behaviour and neck‐ and/or low back pain: A systematic review
Authors: Øverås Cecilie K. , Villumsen Morten , Axén Iben , Cabrita Miriam , Leboeuf‐Yde Charlotte , Hartvigsen Jan , Mork Paul J. 
Published: February 2020

AbstractBackground and objectiveClinical guidelines recommend physical activity to manage neck pain (NP) and low back pain (LBP). However, studies used to support these guidelines are based on self‐reports of physical behaviour, which are prone to bias and misclassification. This systematic review aimed to investigate associations between objectively measured physical behaviour and the risk or prognosis of NP and/or LBP.Databases and data treatmentLiterature searches were performed in MEDLINE, Embase and Scopus from their inception until 18 January 2019. We considered prospective cohort studies for eligibility. Article selection, data extraction and critical appraisal were carried out by independent reviewers. Results were stratified on activity/sedentariness.ResultsTen articles out of 897 unique records identified met the inclusion criteria, of which eight studied working populations with mainly blue‐collar workers. The overall results indicate that increased sitting time at work reduces the risk of NP and LBP while increased physical activity during work and/or leisure increases the risk of these conditions among blue‐collar workers; however, associations were weak. Physical activity was not associated with prognosis of LBP (no studies investigated prognosis of NP). Most of the included articles have methodological shortcomings.ConclusionsThis review indicates that, among blue‐collar workers, increased sitting at work may protect against NP and LBP while increased physical activity during work and/or leisure may increase this risk. There was no evidence supporting physical activity as a prognostic factor for LBP. Findings should be interpreted with caution due to the weak associations and few available studies with methodological shortcomings.SignificanceBased on prospective cohort studies with objectively measured physical behaviour, this review questions the common notion that increased physical activity is associated with reduced risk or better prognosis of NP and/or LBP. We found that, among blue‐collar workers, increased sitting time at work reduces the risk of NP and LBP, whereas physical activity somewhat increases the risk. Despite methodological shortcomings, there was consistency in the direction of the results, although high‐quality articles reported the weakest associations.Systematic review registration: PROSPERO CRD42018100765
Ageing Tests at Constant Currents and Associated Modeling of High Temperature PEMFC MEAs
Authors: Rigal S. , Turpin C. , Jaafar A. , Hordé T. , Jollys J.‐B. , Chadourne N. 
Published: February 2020

AbstractIn this work, seven commercially available high temperature (HT) membrane electrode assemblies (MEAs), using a phosphoric acid doped polybenzimidazole (PBI) membrane, were tested at six constant current densities during mostly around 540 h: 1, 0.6, 0.4, 0.2, 0.1, and 0 A cm−2. The MEA aged at 0.6 A cm−2 appears to be the less degraded one and the MEAs working at 0 and 1 A cm−2 seem to be the most degrading ones. Degradations are supposed to be mainly due to the carbon corrosion of electrodes and the loss of electrolyte with the MEA aged at 1 A cm−2. The characterization periods have a significant impact on cell ageing. The corrosion of carbon support is considered here to be the major degradation for the tests carried out between 0 and 0.6 A cm−2. A degradation rate was calculated using the voltage from the polarization curves and it appears to be more relevant compare to the degradation rate calculated using the voltage during endurance period. The modeling approach shows promising results and it seems that the electrochemical surface area, measured by cyclic voltammetry, can be included into the modeling in order to obtain higher parameter consistency.