bluuebunny/crossref_metadata_2025_split huggingface dataset:
Silver/Rhodium Relay Catalysis Enables C−H Functionalization of In Situ Generated Isoquinolines with Sulfoxonium Ylides: Construction of Hexahydrodibenzo[a,g]quinolizine Scaffolds
Authors: Li Quanzhe , Liu Ruixing , Wei Yin , Shi Min 
Published: March 2021

AbstractEmploying silver/rhodium relay catalysis strategy, an intramolecular electrophilic cyclization and C−H activation followed by cascade hydrogenation and reductive amination has been developed. The acylmethylated isoquinoline derivatives could be afforded with broad substrate scope in 23–88% yields, which could be further transformed to the core skeleton of hexahydrodibenzo[a,g]quinolizine as drug‐candidates. Moreover, this reaction was achieved in a gram‐scale. A reasonable reaction mechanism has been proposed based on a series of control and KIE experiments.magnified image
Chemoenzymatic Production of Enantiocomplementary 2‐Substituted 3‐Hydroxycarboxylic Acids from l‐α‐Amino Acids
Authors: Pickl Mathias , Marín‐Valls Roser , Joglar Jesús , Bujons Jordi , Clapés Pere 
Published: March 2021

AbstractA two‐enzyme cascade reaction plus in situ oxidative decarboxylation for the transformation of readily available canonical and non‐canonical l‐α‐amino acids into 2‐substituted 3‐hydroxycarboxylic acid derivatives is described. The biocatalytic cascade consisted of an oxidative deamination of l‐α‐amino acids by an l‐α‐amino acid deaminase from Cosenzaea myxofaciens, rendering 2‐oxoacid intermediates, with an ensuing aldol addition reaction to formaldehyde, catalyzed by metal‐dependent (R)‐ or (S)‐selective carboligases namely 2‐oxo‐3‐deoxy‐l‐rhamnonate aldolase (YfaU) and ketopantoate hydroxymethyltransferase (KPHMT), respectively, furnishing 3‐substituted 4‐hydroxy‐2‐oxoacids. The overall substrate conversion was optimized by balancing biocatalyst loading and amino acid and formaldehyde concentrations, yielding 36–98% aldol adduct formation and 91–98% ee for each enantiomer. Subsequent in situ follow‐up chemistry via hydrogen peroxide‐driven oxidative decarboxylation afforded the corresponding 2‐substituted 3‐hydroxycarboxylic acid derivatives.magnified image
Mesenteric traction syndrome in pigs: A single‐blinded, randomized controlled trial
Authors: Strandby Rune B. , Osterkamp Jens T. F. , Ambrus Rikard , Henriksen Amelie , Goetze Jens P. , Secher Niels H. , Achiam Michael P. , Svendsen Lars‐Bo 
Published: March 2021

AbstractBackgroundMesenteric traction syndrome is commonly observed in patients undergoing upper abdominal surgery and is associated with severe postoperative complications. A triad of hypotension, tachycardia, and facial flushing seems provoked by prostacyclin (PGI2) release from the gut in response to mesenteric traction. The administration of nonsteroidal anti‐inflammatory drugs (NSAID) inhibits PGI2 release, stabilizing the hemodynamic response. Here, we examined the effect of mesenteric traction on splanchnic blood flow in pigs randomized to NSAID or placebo treatment.Materials and MethodsTwenty pigs were allocated to either ketorolac or placebo treatment. Five minutes of manual mesenteric traction was applied. Plasma 6‐keto‐PGF1α, a stable metabolite of PGI2, hemodynamic variables, and regional blood flow (laser speckle contrast imaging) to the liver, stomach, small intestine, upper lip, and snout (laser Doppler flowmetry) were recorded prior to traction and 5 and 30 minutes thereafter.ResultsBoth groups of pigs presented a decrease in systemic vascular resistance (P = .01), mean arterial blood pressure (P = .001), and blood flow in the gastric antrum (P = .002). Plasma 6‐keto‐PGF1α did not increase in either group (P = .195), and cardiac output, heart rate, central venous pressure, and blood flow to the liver, small intestine, upper lip, and snout remained unchanged.ConclusionMesenteric traction resulted in cardiovascular depression, including reduced blood flow in the gastric antrum. Plasma 6‐keto‐PGF1α did not increase, and ketorolac administration did not alter the response to mesenteric traction. Furthers studies are needed to identify which substance is responsible for eliciting the cardiovascular response to mesenteric traction in pigs.
Deleterious effects of whole‐body vibration on the spine: A review of in vivo, ex vivo, and in vitro models
Authors: Patterson Folly , Miralami Raheleh , Tansey Keith E. , Prabhu Raj K. , Priddy Lauren B. 
Published: March 2021

AbstractOccupational exposure to whole‐body vibration is associated with the development of musculoskeletal, neurological, and other ailments. Low back pain and other spine disorders are prevalent among those exposed to whole‐body vibration in occupational and military settings. Although standards for limiting exposure to whole‐body vibration have been in place for decades, there is a lack of understanding of whole‐body vibration‐associated risks among safety and healthcare professionals. Consequently, disorders associated with whole‐body vibration exposure remain prevalent in the workforce and military. The relationship between whole‐body vibration and low back pain in humans has been established largely through cohort studies, for which vibration inputs that lead to symptoms are rarely, if ever, quantified. This gap in knowledge highlights the need for the development of relevant in vivo, ex vivo, and in vitro models to study such pathologies. The parameters of vibrational stimuli (eg, frequency and direction) play critical roles in such pathologies, but the specific cause‐and‐effect relationships between whole‐body vibration and spinal pathologies remain mostly unknown. This paper provides a summary of whole‐body vibration parameters; reviews in vivo, ex vivo, and in vitro models for spinal pathologies resulting from whole‐body vibration; and offers suggestions to address the gaps in translating injury biomechanics data to inform clinical practice.
Crystal Packing‐Guided Construction of Hetero‐Oligomeric Peptidic Ensembles as Synthetic 3‐in‐1 Transporters
Authors: Shen Jie , Ye Ruijuan , Zeng Huaqiang 
Published: March 2021

AbstractStrategies to generate heteromeric peptidic ensembles via a social self‐sorting process are limited. Herein, we report a crystal packing‐inspired social self‐sorting strategy broadly applicable to diverse types of H‐bonded peptidic frameworks. Specifically, a crystal structure of H‐bonded alkyl chain‐appended monopeptides reveals an inter‐chain separation distance of 4.8 Å dictated by the H‐bonded amide groups, which is larger than 4.1 Å separation distance desired by the tightly packed straight alkyl chains. This incompatibility results in loosely packed alkyl chains, prompting us to investigate and validate the feasibility of applying bulky tert‐butyl groups, modified with an anion‐binding group, to alternatively interpenetrate the straight alkyl chains, modified with a crown ether group. Structurally, this social self‐sorting approach generates highly stable hetero‐oligomeric ensembles, having alternated anion‐ and cation‐binding units vertically aligned to the same side. Functionally, these hetero‐oligomeric ensembles promote transmembrane transport of cations, anions and more interestingly zwitterionic species such as amino acids.
Drivers for spatial modelling of a critically endangered seabird on a dynamic ocean area: Balearic shearwaters are non‐vegetarian
Authors: de la Cruz Andrés , Ramos Fernando , Navarro Gabriel , Cózar Andrés , Bécares Juan , Arroyo Gonzalo Muñoz 
Published: March 2021

AbstractSpatial modelling is an important research tool to improve our knowledge about the distribution of wildlife in the ocean. Using different modelling techniques (MaxEnt and a generalized linear mixed model), a predictive habitat suitability model was developed for one of the most threatened seabirds in the world: the Balearic shearwater,Puffinus mauretanicus.Models were developed using a 10‐year dataset from the Gulf of Cádiz (on the south‐western Iberian Peninsula), a key foraging area for Balearic shearwaters during migration and the non‐breeding season.Predictive habitat maps strongly matched the observed distribution patterns, pointing to bathymetric features as the main modelling drivers. The species was concentrated on shallow areas (up to approximately 100 m in depth) of the continental shelf, very close to the mouth of the Guadalquivir River. In contrast with previous studies, Balearic shearwater distribution in the highly dynamic Gulf of Cádiz was not correlated with areas of high chlorophyllaconcentration.This lack of spatial correlation probably arises from the delay between the phytoplankton bloom and the response of the zooplankton and small fish that are preyed upon by Balearic shearwaters, which may result in important displacements of this trophic chain across the Gulf of Cádiz.The analysis presented contributes to a better understanding of the spatial distribution and ecology of the critically endangered top predator in the Gulf of Cádiz and offers important information to improve management plans.
Controlling the exponentially weighted moving average S2 control chart false alarm behavior when the in‐control variance level must be estimated
Authors: Knoth Sven 
Published: March 2021

AbstractInvestigating the problem of setting control limits for an exponentially weighted moving average (EWMA) chart in the case of parameter uncertainty is more accessible when monitoring the variance because only one parameter has to be estimated. Simply ignoring the induced uncertainty frequently leads to control charts with poor false alarm performances. Adjusting the unconditional in‐control (IC) average run length (ARL) makes the situation even worse. Guaranteeing a minimum conditional IC ARL with some given probability is another very popular approach to solving these difficulties. However, it is very conservative as well as more complex and more difficult to communicate. We utilize the probability of a false alarm within the planned number of points to be plotted on the control chart. It turns out that adjusting this probability produces notably different limit adjustments compared to controlling the unconditional IC ARL. We then develop numerical algorithms to determine the respective modifications of the upper and two‐sided EWMA charts based on the sample variance for normally distributed data. These algorithms are made available within an R package. Finally, the impacts of the EWMA smoothing constant and the size of the preliminary sample on the control chart design and its performance are studied.
Powerful anti‐inflammatory action of luteolin: Potential increase with IL‐38
Authors: Conti Pio , Caraffa Alessandro , Gallenga Carla E. , Ross Rhiannon , Kritas Spyros K. , Frydas Ilyas , Younes Alì , Di Emidio Paolo , Ronconi Gianpaolo , Pandolfi Franco 
Published: March 2021

AbstractLuteolin belongs to the flavone family originally present in some fruits and vegetables, including olives, which decrease intracellular levels of reactive oxygen species (ROS) following the activation of various stimuli. Luteolin inhibits inflammation, a complex process involving immune cells that accumulate at the site of infectious or non‐infectious injury, with alteration of the endothelium leading to recruitment of leukocytes. Cytokines have been widely reported to act as immune system mediators, and IL‐1 family members evolved to assist in host defense against infections. Interleukin (IL)‐1 and Toll‐like receptor (TLR) are involved in the innate immunity in almost all living organisms. After being synthesized, IL‐1 induces numerous inflammatory mediators including itself, other pro‐inflammatory cytokines/chemokines, and arachidonic acid products, which contribute to the pathogenesis of immune diseases. Among the 11 members of the IL‐1 family, there are two new cytokines that suppress inflammation, IL‐37 and IL‐38. IL‐38 binds IL‐36 receptor (IL‐1R6) and inhibits several pro‐inflammatory cytokines, including IL‐6, through c‐Jun N‐terminal kinase (JNK) induction and reducing AP1 and nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NFκB) activity, alleviating inflammatory diseases. Therefore, since luteolin, IL‐37 and IL‐38 are all anti‐inflammatory molecules with different signaling pathways, it is pertinent to recommend the combination of luteolin with these anti‐inflammatory cytokines in inflammation.
Evaluating the effects of microparticle addition on mycelial morphology, natural yellow pigments productivity, and key genes regulation in submerged fermentation of Monascus purpureus
Authors: Huang Jing , Guan Hong‐Wei , Huang Yue‐Ying , Lai Ke‐Sheng , Chen Hui‐Ying , Xue Han , Zhang Bo‐Bo 
Published: March 2021

AbstractMorphology plays an important role in fungal fermentation and secondary metabolites biosynthesis. One novel technique, microparticle‐enhanced cultivation was successfully utilized to control the morphology of Monascus purpureus precisely and enhance the yield of yellow pigments. The production of yellow pigments increased to 554.2 U/ml when 4 g/L 5000 mesh talc added at 24 h. Field emission scanning electron microscope observation indicated that the actual effect depends on the properties of microparticle. Sharp‐edged microparticles showed better stimulatory effects than smooth, round‐shaped ones. Particle size analysis, scanning electron microscope, and cell integrity evaluation proved obvious morphological changes were induced by talc addition, including smaller mycelial size, rougher hyphae, and decreased cell integrity. Furthermore, the expression levels of MrpigG, MrpigD, MrpigE, and MrpigH were significantly upregulated by the addition of talc. It indicated that the microparticle could not only affect the mycelial morphology, but also influence the expression levels of key genes in biosynthetic pathway of Monascus yellow pigments.
Analysis and optimal design of batch and two‐column continuous chromatographic frontal processes for monoclonal antibody purification
Authors: Shi Ce , Vogg Sebastian , Lin Dong‐Qiang , Sponchioni Mattia , Morbidelli Massimo 
Published: March 2021

AbstractThe increasing demand for efficient and robust processes in the purification of monoclonal antibodies (mAbs) has recently brought frontal chromatography to the forefront. Applied during the polishing step, it enables the removal of high molecular weight aggregates from the target product, achieving high purities. Typically, this process is operated in batch using a single column, which makes it intrinsically subjected to a purity‐yield tradeoff. This means that high purities can only be achieved at the cost of lowering the product yield and vice versa. Recently, a two‐column continuous implementation of frontal chromatography, referred to as Flow2, was developed. Despite being able of alleviating the purity‐yield tradeoff typical of batch operations, the increase in the number of process parameters complicates its optimal design, with the risk of not exploiting its full potential. In this study, we developed an ad hoc design procedure (DP) suitable for the optimization of both batch frontal chromatography and Flow2 in terms of purity, yield, and productivity. This procedure provided similar results as a multiobjective optimization based on genetic algorithm but with lower computational effort. Then, batch and Flow2 operated at their optimal conditions were compared. Besides showing a more favorable Pareto front of yield and productivity at a specified purity, the Flow2 process demonstrated improved robustness compared to the batch process with respect to modifications in the loading linear velocity, washing buffer ionic strength and loading time, thus providing an appealing operation for integrated processes.
Antibacterial and Anti‐biofilm Activity of the Human Breast Milk Glycoprotein Lactoferrin against Group B Streptococcus
Authors: Lu Jacky , Francis Jamisha D. , Guevara Miriam A. , Moore Rebecca E. , Chambers Schuyler A. , Doster Ryan S. , Eastman Alison J. , Rogers Lisa M. , Noble Kristen N. , Manning Shannon D. , Damo Steven M. , Aronoff David M. , Townsend Steven D. , Gaddy Jennifer A. 
Published: March 2021

AbstractGroup B Streptococcus (GBS) is an encapsulated Gram‐positive human pathogen that causes invasive infections in pregnant hosts and neonates, as well as immunocompromised individuals. Colonization of the human host requires the ability to adhere to mucosal surfaces and circumnavigate the nutritional challenges and antimicrobial defenses associated with the innate immune response. Biofilm formation is a critical process to facilitate GBS survival and establishment of a replicative niche in the vertebrate host. Previous work has shown that the host responds to GBS infection by producing the innate antimicrobial glycoprotein lactoferrin, which has been implicated in repressing bacterial growth and biofilm formation. Additionally, lactoferrin is highly abundant in human breast milk and could serve a protective role against invasive microbial pathogens. This study demonstrates that human breast milk lactoferrin has antimicrobial and anti‐biofilm activity against GBS and inhibits its adherence to human gestational membranes. Together, these results indicate that human milk lactoferrin could be used as a prebiotic chemotherapeutic strategy to limit the impact of bacterial adherence and biofilm formation on GBS‐associated disease outcomes.
Single antiplatelet therapy with use of prasugrel in patients undergoing percutaneous coronary intervention
Authors: Otsuka Tatsuhiko , Ueki Yasushi , Kavaliauskaite Raminta , Zanchin Thomas , Bär Sarah , Stortecky Stefan , Pilgrim Thomas , Valgimigli Marco , Meier Bernhard , Heg Dik , Windecker Stephan , Räber Lorenz 
Published: March 2021

AbstractObjectivesWe aimed to assess the ischemic and bleeding risks of single antiplatelet therapy (SAPT) with prasugrel compared with standard dual antiplatelet therapy (DAPT) (aspirin plus clopidogrel for 1 year) in patients with chronic coronary syndrome (CCS) treated with new generation drug‐eluting stents (DES).BackgroundTo date, data on SAPT with potent P2Y12 inhibitors in the absence of aspirin immediately after PCI are limited.MethodsBetween January 2009 and November 2019, all CCS patients undergoing percutaneous coronary intervention (PCI) enrolled to the Bern PCI registry were considered for analysis. We performed propensity score matching in a 1:4 fashion to compare patients who received SAPT with prasugrel versus standard DAPT. The primary ischemic endpoint was a composite of cardiovascular death, myocardial infarction, and stroke and the primary bleeding endpoint was BARC 3 or 5 bleeding, both assessed at 1 year.ResultsAfter propensity score matching, the final study population consisted of 225 patients with SAPT and 889 with DAPT. There was no significant difference in rates of the primary ischemic (5.2% vs. 4.2%, p = .50) or the primary bleeding (1.5% vs. 2.0%, p = .60) endpoints between groups. SAPT was not associated with an increased risk of definite stent thrombosis (0.9% vs. 0.8%, p = .83).ConclusionsAmong selected CCS patients undergoing PCI with DES, SAPT with prasugrel was not associated with an excess of ischemic events compared with standard DAPT. No difference in bleeding was observed either. The results may serve as the basis for larger trials assessing the potential benefits and risks of SAPT.
High Current Production of Shewanella Oneidensis with Electrospun Carbon Nanofiber Anodes is Directly Linked to Biofilm Formation**
Authors: Erben Johannes , Wang Xinyu , Kerzenmacher Sven 
Published: March 2021

AbstractWe study the current production of Shewanella oneidensis MR‐1 with electrospun carbon fiber anode materials and analyze the effect of the anode morphology on the micro‐, meso‐ and macroscale. The materials feature fiber diameters in the range between 108 nm and 623 nm, resulting in distinct macropore sizes and surface roughness factors. A maximum current density of (255
71) μA cm−2 was obtained with 286 nm fiber diameter material. Additionally, micro‐ and mesoporosity were introduced by CO2 and steam activation which did not improve the current production significantly. The current production is directly linked to the biofilm dry weight under anaerobic and micro‐aerobic conditions. Our findings suggest that either the surface area or the pore size related to the fiber diameter determines the attractiveness of the anodes as habitat and therefore biofilm formation and current production. Reanalysis of previous works supports these findings.
Unveiling Luminescent IrI and RhI N‐Heterocyclic Carbene Complexes: Structure, Photophysical Specifics, and Cellular Localization in the Endoplasmic Reticulum
Authors: Daubit Isabelle Marie , Wortmann Svenja , Siegmund Daniel , Hahn Stephan , Nuernberger Patrick , Metzler‐Nolte Nils 
Published: March 2021

AbstractComplexes of RhI and IrI of the [M(COD)(NHC)X] type (where M=Rh or Ir, COD=1,5‐cyclooctadiene, NHC=N‐heterocyclic carbene, and X=halide) have recently shown promising cytotoxic activities against several cancer cell lines. Initial mechanism of action studies provided some knowledge about their interaction with DNA and proteins. However, information about their cellular localization remains scarce owing to luminescence quenching within this complex type. Herein, the synthesis of two rare examples of luminescent RhI and IrI [M(COD)(NHC)I] complexes with 1,8‐naphthalimide‐based emitting ligands is reported. All new complexes are comprehensively characterized, including with single‐crystal X‐ray structures. Steric crowding in one derivative leads to two distinct rotamers in solution, which apparently can be distinguished both by pronounced NMR shifts and by their respective spectral and temporal emission signatures. When the photophysical properties of these new complexes are exploited for cellular imaging in HT‐29 and PT‐45 cancer cell lines, it is demonstrated that the complexes accumulate predominantly in the endoplasmic reticulum, which is an entirely new finding and provides the first insight into the cellular localization of such IrI(NHC) complexes.
An Efficient Synthesis of 3‐Alkylpyridine Alkaloids Enables Their Biological Evaluation
Authors: Kaplan Anna R. , Schrank Cassandra L. , Wuest William M. 
Published: March 2021

Abstract3‐Alkylpyridine alkaloids (3‐APAs) isolated from the arctic sponge Haliclona viscosa are a promising group of bioactive marine alkaloids. However, due to limited bioavailability, investigations of their bioactivity have been hampered. Additionally, synthesis of a common intermediate requires the use of protecting groups and harsh conditions. In this work, we developed a simple and concise two‐step route to nine different natural and synthetic haliclocyclins. These compounds displayed modest antibiotic activity against several Gram‐positive bacterial strains.