bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biopharmaceutical characterization of a novel sustained‐release formulation of allopurinol with reduced nephrotoxicity
Authors: Nihei Takuya , Sato Hideyuki , Onoue Satomi 
Published: January 2021

AbstractThe present study was aimed to develop a novel sustained‐release formulation for allopurinol (ALP/SR) with the use of a pH‐sensitive polymer, hydroxypropyl methylcellulose acetate succinate, to reduce nephrotoxicity. ALP/SR was evaluated in terms of crystallinity, the dissolution profile, pharmacokinetic behavior, and nephrotoxicity in a rat model of nephropathy. Under acidic conditions (pH1.2), sustained release behavior was seen for ALP/SR, although both crystalline ALP and ALP/SR exhibited rapid dissolution at neutral condition. After multiple oral administrations of ALP samples (10 mg‐ALP/kg) for 4 days in a rat model of nephropathy, ALP/SR led to a low and sustained plasma concentration of ALP, as evidenced by half the maximum concentration of ALP and a 2.5‐fold increase in the half‐life of ALP compared with crystalline ALP, possibly due to suppressed dissolution behavior under acidic conditions. Repeated‐dosing of ALP/SR resulted in significant reductions in plasma creatinine and blood urea nitrogen levels by 73% and 69%, respectively, in comparison with crystalline ALP, suggesting the low nephrotoxic risk of ALP/SR. From these findings, a strategic SR formulation approach might be an efficacious dosage option for ALP to avoid severe nephrotoxicity in patients with nephropathy.
Incorporating RNA‐Seq transcriptomics into glycosylation‐integrating metabolic network modelling kinetics: Multiomic Chinese hamster ovary (CHO) cell bioreactors
Authors: Bezjak Lara , Erklavec Zajec Vivian , Baebler Špela , Stare Tjaša , Gruden Kristina , Pohar Andrej , Novak Uroš , Likozar Blaž 
Published: January 2021

AbstractIn this work, the kinetic model based on the previously developed metabolic and glycan reaction networks of the ovarian cells of the Chinese hamster ovary (CHO) cell line was improved by the inclusion of transcriptomic data that took into account the values of the RPKM gene (Reads per Kilobase of Exon per Million Reads Mapped). The transcriptomic (RNASeq) data were obtained together with metabolic and glycan data from the literature, and the concentrations with RPKM values were collected at several points in time from two fed‐batch processes. First, the fluxes were determined by regression analysis of the metabolic data, then these fluxes were corrected by using the fold change in gene expression as a measure of enzyme concentrations. Next, the corrected fluxes in the kinetic model were used to calculate the concentration profiles of the metabolites, and literature data were used to evaluate the predicted results of the model. Compared to other studies where the concentration profiles of CHO cell metabolites were described using a kinetic model without consideration of RNA‐Seq data to correct the fluxes, this model is unique. The additional integration of transcriptomic data led to better predictions of metabolic concentrations in the fed‐batch process, which is a significant improvement of the modelling technique used.
Flux redistribution of central carbon metabolism for efficient production of l‐tryptophan in Escherichia coli
Authors: Xiong Bo , Zhu Yongduo , Tian Daoguang , Jiang Shuai , Fan Xiaoguang , Ma Qian , Wu Heyun , Xie Xixian 
Published: January 2021

AbstractMicrobial production of l‐tryptophan (l‐trp) has received considerable attention because of its diverse applications in food additives and pharmaceuticals. Overexpression of rate‐limiting enzymes and blockage of competing pathways can effectively promote microbial production of l‐trp. However, the biosynthetic process remains suboptimal due to imbalanced flux distribution between central carbon and tryptophan metabolism, presenting a major challenge to further improvement of l‐trp yield. In this study, we redistributed central carbon metabolism to improve phosphoenolpyruvate (PEP) and erythrose‐4‐phosphate (E4P) pools in an l‐trp producing strain of Escherichia coli for efficient l‐trp synthesis. To do this, a phosphoketolase from Bifidobacterium adolescentis was introduced to strengthen E4P formation, and the l‐trp titer and yield increased to 10.8 g/L and 0.148 g/g glucose, respectively. Next, the phosphotransferase system was substituted with PEP‐independent glucose transport, meditated by a glucose facilitator from Zymomonas mobilis and native glucokinase. This modification improved l‐trp yield to 0.164 g/g glucose, concomitant with 58% and 40% decreases of acetate and lactate accumulation, respectively. Then, to channel more central carbon flux to the tryptophan biosynthetic pathway, several metabolic engineering strategies were applied to rewire the PEP‐pyruvate‐oxaloacetate node. Finally, the constructed strain SX11 produced 41.7 g/L l‐trp with an overall yield of 0.227 g/g glucose after 40 h fed‐batch fermentation in 5‐L bioreactor. This is the highest overall yield of l‐trp ever reported from a rationally engineered strain. Our results suggest the flux redistribution of central carbon metabolism to maintain sufficient supply of PEP and E4P is a promising strategy for efficient l‐trp biosynthesis, and this strategy would likely also increase the production of other aromatic amino acids and derivatives.
Sensitive and Visual Detection of Phosgene by a TICT‐Based BODIPY Dye with 8‐(o‐Hydroxy)aniline as the Active Site
Authors: Fu Ying‐Long , Chong Yuan‐Yuan , Li Hao , Feng Wei , Song Qin‐Hua 
Published: January 2021

AbstractPhosgene and its substitutes (diphosgene and triphosgene) are widely utilized as chemical industrial materials and chemical warfare agents and pose a threat to public health and environmental safety due to their extreme toxicity. Research efforts have been directed to develop selective and sensitive detection methods for phosgene and its substitutes. In this paper, we have prepared two BODIPY‐based fluorescent probes, o‐Pah and o‐Pha, which are two isomers with different active sites, ortho‐aminohydroxy (3′,4′ or 4′,3′) phenyls at meso position of BODIPY, and compared their sensing performance toward triphosgene. The probe with o‐(4′‐amino‐3′‐hydroxyl), o‐Pha, exhibits better sensing performance over the o‐(3′‐amino‐4′‐hydroxyl), o‐Pah, for instance, a lower limit of detection (LOD) (0.34 nm vs. 1.2 nm), and more rapid response (10 s vs. 200 s). Furthermore, based on the above comparative studies, a red‐fluorescence probe o‐Phae has been constructed through extending 3,5‐conjugation of o‐Pha. The probe o‐Phae displays rapid response (60 s), high sensitivity to triphosgene (LOD=0.88 nm), and high selectivity for triphosgene over relevant analytes including nitric oxide. Finally, a facile test strip for phosgene was fabricated by immobilizing o‐Phae in a polyethylene oxide membrane for sensitive (<2 ppm) and selective detection of phosgene in the gas phase.
Spin–Orbit Charge‐Transfer Intersystem Crossing in Anthracene–Perylenebisimide Compact Electron Donor–Acceptor Dyads and Triads and Photochemical Dianion Formation
Authors: Rehmat Noreen , Kurganskii Ivan V. , Mahmood Zafar , Guan Qing Lin , Zhao Jianzhang , Xing Yong Heng , Gurzadyan Gagik G. , Fedin Matvey V. 
Published: January 2021

AbstractPerylenebisimide (PBI)–anthracene (AN) donor–acceptor dyads/triad were prepared to investigate spin–orbit charge‐transfer intersystem crossing (SOCT‐ISC). Molecular conformation was controlled by connecting PBI units to the 2‐ or 9‐position of the AN moiety. Steady‐state, time‐resolved transient absorption and emission spectroscopy revealed that chromophore orientation, electronic coupling, and dihedral angle between donor and acceptor exert a significant effect on the photophysical property. The dyad PBI‐9‐AN with orthogonal geometry shows weak ground‐state coupling and efficient intersystem crossing (ISC, ΦΔ=86 %) as compared with PBI‐2‐AN (ΦΔ=57 %), which has a more coplanar geometry. By nanosecond transient absorption spectroscopy, a long‐lived PBI localized triplet state was observed (τT=139 μs). Time‐resolved EPR spectroscopy demonstrated that the electron spin polarization pattern of the triplet state is sensitive to the geometry and number of AN units attached to PBI. Reversible and stepwise generation of near‐IR‐absorbing PBI radical anion (PBI−⋅) and dianion (PBI2−) was observed on photoexcitation in the presence of triethanolamine, and it was confirmed that selective photoexcitation at the near‐IR absorption bands of PBI.− is unable to produce PBI2−.
Phosphorescent Zwitterionic Pt(II) N‐Heterocyclic Allenylidene Complexes: Metallophilicity and Ionic Self‐Assembly†
Authors: Gao Qin , Peng Fei , Wang Chuanfei , Lin Jinqiang , Chang Xiaoyong , Zou Chao , Lu Wei 
Published: January 2021

Main observation and conclusionThree zwitterionic and one cationic N‐heterocyclic allenylidene (NHA) platinum(II) complexes were prepared and characterized via NMR, HR‐MS, and FT‐IR, etc. Single crystal structure analyses revealed the various intermolecular packing modes via multiple noncovalent interactions (short Pt···Pt contacts, π‐π interactions). The spectroscopic data demonstrated stability of the allenylidene metal complexes is largely ascribed to the resonance structures of zwitterionic acetylide. The zwitterionic and analogue cationic NHA Pt(II) monomers showed similar steady‐state photoluminescent properties in dilute fluid solution. Highly efficient solid‐state phosphorescent emissions (quantum yield up to 20%) of these NHA Pt(II) complexes are correlated with their dispersive metallophilic Pt···Pt interactions. HR‐MS spectrum indicated zwitterionic monomers can self‐assemble into oligomers, such as dimer, trimer and even hexamer in a mixed H2O/MeOH solvent. Meanwhile, molecular aggregates showed variable red‐shifted phosphorescence by manipulating the concentration, temperature, time and solvent in the self‐assembly of zwitterionic NHA platinum(II) complex.
Predictors of treatment benefits after enhanced external counterpulsation in patients with refractory angina pectoris
Authors: Wu Eline , Mårtensson Jan , Desta Liyew , Broström Anders 
Published: January 2021

AbstractBackgroundEnhanced external counterpulsation (EECP) is a noninvasive treatment that can decrease limiting symptoms in patients with refractory angina pectoris (RAP). Identifying responders to EECP is important as EECP is not widely available and relatively time intensive.HypothesisThe effect of EECP treatment on physical capacity in patients with RAP can be predicted from baseline patient characteristics and clinical factors.MethodsThis explorative study includes all patients from a cardiology clinic who had finished one EECP treatment and a 6 min walk test pre and post EECP. Clinical data, including Canadian Cardiovascular Society (CCS) classification and left ventricular ejection fraction (LVEF), were assessed before treatment. If patients increased their 6 min walking distance (6MWD) by 10% post EECP, they were considered responders.ResultsOf the 119 patients (men = 97, 40–91 years), 49 (41.2%) were responders. Multinomial regression analysis showed that functional status (i.e., CCS class ≥3) (OR 3.10, 95% CI 1.12–8.57), LVEF <50% (OR 2.82, 95% CI 1.02–7.80), and prior performed revascularization (i.e., ≤ 1 type of intervention) (OR 2.77, 95% CI 1.06–7.20) were predictors of response to EECP (p < .05, Accuracy 63.6%). Traditional risk factors (e.g., gender, smoking, and comorbidities) did not predict response.ConclusionsEECP treatment should be considered preferentially for patients that have a greater functional impairment, evidence of systolic left ventricular dysfunction, and exposure to fewer types of revascularization, either PCI or CABG. Improvement in 6MWD post EECP could imply improvement in physical capacity, which is a likely contributor to improved well‐being among patients with RAP.
Characterizing the growth and winter survival of commercially available and experimental genotypes of St. Augustinegrass
Authors: Moseley David O. , Trappe Jon M. , Milla‐Lewis Susana R. , Chandra Ambika , Kenworthy Kevin E. , Liu Wenwen , Patton Aaron J. 
Published: January 2021

AbstractSt. Augustinegrass [Stenotaphrum secundatum (Walter) Kuntze] is a commonly used warm‐season turfgrass for lawns in warm‐humid to tropical climates. Efforts to breed improved cultivars with enhanced abiotic and biotic stress tolerance are ongoing, but additional data on their growth and adaptation are needed. Twenty‐one commercially available St. Augustinegrass cultivars and eight experimental genotypes were planted in the field in Fayetteville, AR, in both 2009 and 2010 to study their stolon, leaf, and establishment characteristics, as well as winter survival. ‘Floratam’, ‘Floralawn’, ‘FX‐10’, ‘FA‐40’ (Mercedes™), ‘B12’ (Sapphire®), and WS had the highest stolon growth rate (>8.9 mm d−1), whereas ‘TR 6‐10’ (Amerishade®), ‘6‐72‐99’ (Delmar™), ‘6‐72‐182’ (Jade™), ‘6‐72‐130’ (Sunclipse™), 106G3, 106T3, and SV27 had the lowest stolon growth rate (<5.1 mm d−1). Cultivars ‘Floraverde’, Floralawn, Floratam, B12 (Sapphire), and ‘Texas Common’ were the quickest to establish. Principal component analysis (PCA) identified that cultivars with similar ploidy levels had similar growth characteristics as increasing ploidy resulted in wider and longer leaves, as well as larger stolon diameter and internode length. Cultivars considered dwarf types with short stolons or narrow‐short leaves grouped separately from cultivars with long stolons or wide‐long leaves. Genotypes VNS (Classic™), GF, VNS (Majestic™), ‘SS‐100’ (Palmetto®), ‘Raleigh’, TAES 5714, and Texas Common showed the highest winter survival and associated coverage after winter in both years. Results from this study are intended to help turfgrass breeders, turf producers, practitioners, and homeowners make informed cultivar selection decisions. Planting well‐adapted cultivars will reduce reestablishment costs from winter‐kill and ultimately increase sustainability.
Modification of ventriculo–arterial coupling by spironolactone in nonischemic dilated cardiomyopathy
Authors: Lawson Mark A. , Hansen David E. , Gupta Deepak K. , Bell Susan P. , Adkisson Douglas W. , Mallugari Ravinder R. , Sawyer Douglas B. , Ooi Henry , Kronenberg Marvin W. 
Published: January 2021

AbstractAimsWe sought to clarify the role of ventriculo–arterial (V–A) coupling in the treatment of nonischemic dilated cardiomyopathy (NIDCM) by adding a mineralocorticoid receptor antagonist (MRA) to conventional anti‐failure therapy.Methods and resultsWe employed cardiac magnetic resonance imaging to quantify left ventricular (LV) contractility and V–A coupling in normal subjects at rest (n = 11) and in patients with NIDCM (n = 12) before and after long term anti‐failure therapy, in which MRA was added to conventional anti‐failure therapy. After ≥6 months' treatment in NIDCM patients, LV volumes and mass decreased, and the LV ejection fraction increased from a median of 24% (17, 27) (interquartile range IQR) to 47 (42, 52) (P < 0.002), with a marked reduction in arterial elastance (Ea) from 2.89 mmHg/mL (2.34, 4.0) to 1.50 (1.29, 1.95) (P < 0.002), similar to Ea of normal subjects, 1.53 (1.34, 1.67) (P > 0.05). The V–A coupling ratio, Ea/end‐systolic elastance (single‐beat method), decreased by −1.08 (−1.96, −0.55), (P = 0.003), as did Ea/end‐systolic pressure/end‐systolic pressure ratio, −0.54 (0.35, 0.87), (P = 0.002). The preload recruitable stroke work (PRSW) increased as did PRSW indexed for Ea (both P = 0.002), which reflected ‘total circulatory performance’.ConclusionsIn NIDCM, adding MRA to conventional anti‐failure therapy markedly improved LV ejection fraction and reduced peripheral vascular resistance, due to both improved LV contractility and especially to enhanced V–A coupling, as Ea decreased to normal. Total circulatory performance was a sensitive indicator of both LV pump performance and the arterial loading conditions.
Predictive value of H2FPEF score in patients with heart failure with preserved ejection fraction
Authors: Sun Yuxi , Wang Niuniu , Li Xiao , Zhang Yanli , Yang Jie , Tse Gary , Liu Ying 
Published: January 2021

AbstractAimsThe H2FPEF score is a convenient risk stratification tool for diagnosing heart failure with preserved ejection fraction (HFpEF). This study examined the value of the H2FPEF score for predicting all‐cause mortality and rehospitalization in HFpEF patients.Methods and resultsThis was a retrospective cohort study of patients diagnosed with HFpEF by echocardiography at a single tertiary centre between 1 January 2015 and 30 April 2018. According to the H2FPEF score, the subjects were divided into low (0–1 points), intermediate (2–5 points), and high (6–9 points) score groups. The primary outcomes were all‐cause mortality and rehospitalization. A total of 476 patients (mean age: 70.5 ± 8.4 years, 60.7% female) were included. Of these, 47 (9.9%), 262 (55.0%), and 167 (35.1%) were classified into the low, intermediate, and high score groups, respectively. Over a mean follow‐up of 27.5 months, 63 patients (13.2%) died, and 311 patients (65.3%) were rehospitalized. The mortality rates were 3 (6.4%), 29 (11.1%), and 31 (18.6%), and the number of patients with rehospitalization was 28 (59.6%), 159 (60.7%), and 124 (74.3%) for the low, intermediate, and high score groups, respectively. Multivariate Cox regression identified H2FPEF score as an independent predictor of all‐cause mortality (hazard ratio [HR]: 1.46, 95% CI: 1.23–1.73, P < 0.0001) and rehospitalization (HR: 1.15, 95% CI: 1.08–1.22, P < 0.0001). Receiver operating characteristic (ROC) analysis demonstrated the H2FPEF score can effectively predict all‐cause mortality (AUC 0.67, 95% CI: 0.60–0.73, P < 0.0001) and rehospitalization (AUC 0.59, 95% CI: 0.54–0.65, P = 0.001) after adjusting for age and NYHA class. With a cut‐off value of 5.5, the sensitivity and specificity were 68.3% and 55.4% for all‐cause mortality and 50.5% and 66.7% for rehospitalization.ConclusionsThe H2FPEF score can be used to predict prognosis in HFpEF patients. Higher scores are associated with higher all‐cause mortality and rehospitalization.
Hydrolysis of B2pin2 over Pd/C Catalyst: High Efficiency, Mechanism, and in situ Tandem Reaction
Authors: Li Ning , Shen Jialu , Liu Xiang 
Published: January 2021

AbstractA facile and effective synthesis of H2 or D2 from Pd/C catalyzed hydrolysis of B2pin2 has first been developed. Among them, B2pin2 is frequently used for borylation reaction, and has rarely been used for hydrogen evolution. The kinetic isotope effects (KIEs) and tandem reaction for diphenylacetylene and norbornene hydrogenation have confirmed both two H atoms of H2 gas are provided from H2O. This is contrary to other boron compounds hydrolysis (including NH3BH3, NaBH4), which generates H2 with only one H atom provided by water and the other one by boron compounds. Note that the hydrolysis of B2pin2 in D2O also provides an easy and useful synthesis of D2.
Modulating Prins Cyclization versus Tandem Prins Processes for the Synthesis of Hexahydro‐1H‐pyrano[3,4‐c]chromenes
Authors: Satteyyanaidu Vallabhareddy , Chandrashekhar Rapelli , Reddy B. V. Subba , Lalli Claudia 
Published: January 2021

AbstractWe propose the synthesis of biologically relevant hexahydro‐1H‐pyrano[3,4‐c]chromenes, via a tandem Prins/Friedels‐Crafts process, catalyzed by BF3.Et2O, starting from (E)‐ and (Z)‐5‐phenoxypent‐3‐en‐1‐ol. The diastereoselectivity of the process is controlled by the geometry of the homoallylic alcohol. We also point out that the Prins product can be obtained in high yields and good diastereoselectivity when the reaction is promoted by AlCl3 as Lewis acid in the presence of an external nucleophile.
Diastereoselective Synthesis of γ‐Lactones through Reaction of Sulfoxonium Ylides, Aldehydes, and Ketenes: Substrate Scope and Mechanistic Studies
Authors: Peraino Nicholas J. , Mondal Mukulesh , Ho Han‐Jen , Beuque Antoine , Viola Evan , Gary Melanie , Wheeler Kraig A. , Kerrigan Nessan J. 
Published: January 2021

AbstractIn this article, we describe the synthesis of γ‐lactones through the reaction of sulfoxonium ylides, aldehydes, and disubstituted ketenes. The one‐pot sequential method provides access to γ‐lactones from disubstituted ketenes, in moderate to excellent yields, and with good diastereoselectivity favoring the trans‐diastereomer (dr up to 92 : 8). The reaction mechanism was investigated by performing labeling, crossover, and various control experiments. The results of those experiments support the reaction mechanism involving betaine formation, reaction of the betaine with a ketene to form an enolate intermediate, [3,3]‐sigmatropic rearrangement of an enolate intermediate, and finally, 5‐exo‐tet cyclization to afford the γ‐lactone product.
Allosteric Guest Binding in Chiral Zirconium(IV) Double Decker Porphyrin Cages
Authors: Bruekers Jeroen P. J. , Hellinghuizen Matthijs A. , Vanthuyne Nicolas , Tinnemans Paul , Gilissen Pieter J. , Buma Wybren Jan , Naubron Jean‐Valère , Crassous Jeanne , Elemans Johannes A. A. W. , Nolte Roeland J. M. 
Published: January 2021

AbstractChiral zirconium(IV) double cage sandwich complex Zr(1)2 has been synthesized in one step from porphyrin cage H21. Zr(1)2 was obtained as a racemate, which was resolved by HPLC and the enantiomers were isolated in >99.5 % ee. Their absolute configurations were assigned on the basis of X‐ray crystallography and circular dichroism spectroscopy. Vibrational circular dichroism (VCD) experiments on the enantiomers of Zr(1)2 revealed that the chirality around the zirconium center is propagated throughout the whole cage structure. The axial conformational chirality of the double cage complex displayed a VCD fingerprint similar to the one observed previously for a related chiral cage compound with planar and point chirality. Zr(1)2 shows fluorescence, which is quenched when viologen guests bind in its cavities. The binding of viologen and dihydroxybenzene derivatives in the two cavities of Zr(1)2 occurs with negative allostery, the cooperativity factors α (=4 K2/K1) being as low as 0.0076 for the binding of N,N’‐dimethylviologen. These allosteric effects are attributed to a pinching of the second cavity as a result of guest binding in the first cavity.