bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Situ Assembly of Choline Acetyltransferase Ligands by a Hydrothiolation Reaction Reveals Key Determinants for Inhibitor Design
Authors: Wiktelius Daniel , Allgardsson Anders , Bergström Tomas , Hoster Norman , Akfur Christine , Forsgren Nina , Lejon Christian , Hedenström Mattias , Linusson Anna , Ekström Fredrik 
Published: October 2020

AbstractThe potential drug target choline acetyltransferase (ChAT) catalyses the production of the neurotransmitter acetylcholine in cholinergic neurons, T‐cells, and B‐cells. Herein, we show that arylvinylpyridiniums (AVPs), the most widely studied class of ChAT inhibitors, act as substrate in an unusual coenzyme A‐dependent hydrothiolation reaction. This in situ synthesis yields an adduct that is the actual enzyme inhibitor. The adduct is deeply buried in the active site tunnel of ChAT and interactions with a hydrophobic pocket near the choline binding site have major implications for the molecular recognition of inhibitors. Our findings clarify the inhibition mechanism of AVPs, establish a drug modality that exploits a target‐catalysed reaction between exogenous and endogenous precursors, and provide new directions for the development of ChAT inhibitors with improved potency and bioactivity.
Highly Efficient and Stable Perovskite Solar Cells Enabled by Low‐Cost Industrial Organic Pigment Coating
Authors: He Qingquan , Worku Michael , Liu He , Lochner Eric , Robb Alex J. , Lteif Sandrine , Vellore Winfred J. S. Raaj , Hanson Kenneth , Schlenoff Joseph B. , Kim Bumjoon J. , Ma Biwu 
Published: October 2020

AbstractSurface passivation of perovskite solar cells (PSCs) using a low‐cost industrial organic pigment quinacridone (QA) is presented. The procedure involves solution processing a soluble derivative of QA, N,N‐bis(tert‐butyloxycarbonyl)‐quinacridone (TBOC‐QA), followed by thermal annealing to convert TBOC‐QA into insoluble QA. With halide perovskite thin films coated by QA, PSCs based on methylammonium lead iodide (MAPbI3) showed significantly improved performance with remarkable stability. A PCE of 21.1 % was achieved, which is much higher than 18.9 % recorded for the unmodified devices. The QA coating with exceptional insolubility and hydrophobicity also led to greatly enhanced contact angle from 35.6° for the pristine MAPbI3 thin films to 77.2° for QA coated MAPbI3 thin films. The stability of QA passivated MAPbI3 perovskite thin films and PSCs were significantly enhanced, retaining about 90 % of the initial efficiencies after more than 1000 hours storage under ambient conditions.
Regioselektiver Brom/Magnesium‐Austausch für die selektive Funktionalisierung von polyhalogenierten Arenen und Heterozyklen
Authors: Desaintjean Alexandre , Haupt Tobias , Bole Leonie J. , Judge Neil R. , Hevia Eva , Knochel Paul 
Published: October 2020

AbstractDie Verwendung der bimetallischen Kombination sBu2Mg⋅2 LiOR (R=2‐Ethylhexyl) in Toluol ermöglicht einen effizienten und regioselektiven Br/Mg‐Austausch mit verschiedenen Dibromarenen und ‐heteroarenen unter milden Reaktionsbedingungen und stellt Brom‐substituierte Magnesium‐Reagenzien bereit. Eine Untersuchung der Rolle von Lewis‐Donor‐Additiven in diesen Reaktionen offenbarte, dass N,N,N′,N′′,N′′‐Pentamethyldiethylenetriamin (PMDTA) die Regioselektivität des Br/Mg‐Austauschs an Dibrompyridinen und ‐chinolinen beeinflusst. Eine Kombination aus spektroskopischen mit röntgenkristallographischen Studien ermöglichte es, die gemischte Li/Mg‐Zusammensetzung der organometallischen Intermediate aufzuklären, welche diese Transformationen eingingen. Diese Systeme reagierten effektiv mit einer breiten Auswahl an Elektrophilen, inklusive Allylbromiden, Ketonen, Aldehyden und Weinrebamiden, in guten Ausbeuten.
Polyphenol‐Based Nanomedicine Evokes Immune Activation for Combination Cancer Treatment
Authors: Zhang Zhan , Sang Wei , Xie Lisi , Li Wenxi , Li Bei , Li Jie , Tian Hao , Yuan Zhen , Zhao Qi , Dai Yunlu 
Published: October 2020

AbstractEngineering multifunctional nanoplatforms with high therapeutic benefits has become a promising strategy for intractable cancer treatment. A novel polyphenol‐based nanocomplex was designed to evoke highly efficacious cancer immunosurveillance while localizing therapy on the primary tumor and to minimize systemic side effects. This nanocomplex is prepared via metal–polyphenol coordination by encapsulating a natural polyphenol, gossypol, and a newly synthesized polyphenol derivative, polyethylene glycol‐Chlorin e6 (Ce6). The combination of gossypol from cotton and the photosensitizer Ce6 can induce chemotherapeutic/photodynamic immunogenic cancer cell death upon laser irradiation, which is supported by a rich maturation of dendritic cells, concentrated secretion of inflammatory cytokines, and significant inhibition of distant untreated tumors. Finally, an assistance of the programmed‐cell‐death ligand‐1 checkpoint‐blockade immunotherapy can enhance the anti‐tumor immune stimulation of our nanoplatform to a higher level.
Photochemical Radical C–H Halogenation of Benzyl N‐Methyliminodiacetyl (MIDA) Boronates: Synthesis of α‐Functionalized Alkyl Boronates
Authors: Yang Ling , Tan Dong‐Hang , Fan Wen‐Xin , Liu Xu‐Ge , Wu Jia‐Qiang , Huang Zhi‐Shu , Li Qingjiang , Wang Honggen 
Published: October 2020

Abstractα‐Haloboronates are useful organic synthons that can be converted to a diverse array of α‐substituted alkyl borons. Methods to α‐haloboronates are limiting and often suffer from harsh reaction conditions. Reported herein is a photochemical radical C‐H halogenation of benzyl N‐methyliminodiacetyl (MIDA) boronates. Fluorination, chlorination, and bromination reactions were effective by using this protocol. Upon reaction with different nucleophiles, the C−Br bond in the brominated product could be readily transformed to a series of C−C, C−O, C−N, C−S, C−P, and C−I bonds, some of which are difficult to forge with α‐halo sp2‐B boronate esters. An activation effect of B(MIDA) moiety was found.
Managing Locally Excited and Charge‐Transfer Triplet States to Facilitate Up‐Conversion in Red TADF Emitters That Are Available for Both Vacuum‐ and Solution‐Processes
Authors: Chen Jia‐Xiong , Xiao Ya‐Fang , Wang Kai , Sun Dianming , Fan Xiao‐Chun , Zhang Xiang , Zhang Ming , Shi Yi‐Zhong , Yu Jia , Geng Feng‐Xia , Lee Chun‐Sing , Zhang Xiao‐Hong 
Published: October 2020

AbstractDeveloping red thermally activated delayed fluorescence (TADF) emitters for high‐performance OLEDs is still facing great challenge. Herein, three red TADF emitters, pDBBPZ‐DPXZ, pDTBPZ‐DPXZ, and oDTBPZ‐DPXZ, are designed and synthesized with same donor–acceptor (D‐A) backbone with different peripheral groups attaching on the A moieties. Their lowest triplet states change from locally excited to charge transfer character leading to significantly enhance reverse intersystem crossing process. In particular, oDTBPZ‐DPXZ exhibits efficient TADF feature and exciton utilization. It not only achieves an external quantum efficiency (EQE) of 20.1 % in red vacuum‐processed OLED, but also realize a high EQE of 18.5 % in a solution‐processed OLED, which is among the best results in solution‐processed red TADF OLEDs. This work provides an effective strategy for designing red TADF molecules by managing energy level alignments to facilitate the up‐conversion process and thus enhance exciton harvesting.
Molecularly Imprinted Polymer‐Based Smart Prodrug Delivery System for Specific Targeting, Prolonged Retention, and Tumor Microenvironment‐Triggered Release
Authors: Gu Zikuan , Dong Yueru , Xu Shuxin , Wang Lisheng , Liu Zhen 
Published: October 2020

AbstractProdrug and drug delivery systems are two effective strategies for improving the selectivity of chemotherapeutics. Molecularly imprinted polymers (MIPs) have emerged as promising carriers in targeted drug delivery for cancer treatment, but they have not yet been integrated with the prodrug strategy. Reported here is an MIP‐based smart prodrug delivery system for specific targeting, prolonged retention time, and tumor microenvironment‐triggered release. 5′‐Deoxy‐5‐fluorocytidine (DFCR) and sialic acid (SA) were used as a prodrug and a marker for tumor targeting, respectively. Their co‐imprinted nanoparticles were prepared as a smart carrier. Prodrug‐loaded MIP specifically and sustainably accumulated at the tumor site and then gradually released. Unlike conventional prodrug designs, which often require in‐liver bioconversion, this MIP‐based prodrug delivery is liver‐independent but tumor‐dependent. Thus, this study opens new access to the development of smart prodrug delivery nanoplatforms.
Diels–Alder Conversion of Acrylic Acid and 2,5‐Dimethylfuran to para‐Xylene Over Heterogeneous Bi‐BTC Metal‐Organic Framework Catalysts Under Mild Conditions
Authors: Yeh Jyun‐Yi , Chen Season S. , Li Shih‐Cheng , Chen Celine H. , Shishido Tetsuya , Tsang Daniel C. W. , Yamauchi Yusuke , Li Yi‐Pei , Wu Kevin C.‐W. 
Published: October 2020

AbstractThe heterogeneous metal‐organic framework Bi‐BTC successfully catalyzed the synthesis of para‐xylene from bio‐based 2,5‐dimethylfuran and acrylic acid in a promising yield (92 %), under relatively mild conditions (160 °C, 10 bar), and with a low reaction‐energy barrier (47.3 kJ mol−1). The proposed reaction strategy also demonstrates a remarkable versatility for furan derivatives such as furan and 2‐methylfuran.
Isomerization Reactions in Anionic Mesoionic Carbene‐Borates and Control of Properties and Reactivities in the Resulting CoII Complexes through Agostic Interactions
Authors: Stubbe Jessica , Neuman Nicolás I. , McLellan Ross , Sommer Michael G. , Nößler Maite , Beerhues Julia , Mulvey Robert E. , Sarkar Biprajit 
Published: October 2020

AbstractWe present herein anionic borate‐based bi‐mesoionic carbene compounds of the 1,2,3‐triazol‐4‐ylidene type that undergo C−N isomerization reactions. The isomerized compounds are excellent ligands for CoII centers. Strong agostic interactions with the “C−H”‐groups of the cyclohexyl substituents result in an unusual low‐spin square planar CoII complex, which is unreactive towards external substrates. Such agostic interactions are absent in the complex with phenyl substituents on the borate backbone. This complex displays a high‐spin tetrahedral CoII center, which is reactive towards external substrates including dioxygen. To the best of our knowledge, this is also the first investigation of agostic interactions through single‐crystal EPR spectroscopy. We conclusively show here that the structure and properties of these CoII complexes can be strongly influenced through interactions in the secondary coordination sphere. Additionally, we unravel a unique ligand rearrangement for these classes of anionic mesoionic carbene‐based ligands.
Carbenaporphyrins: No Longer Missing Ligands in N‐Heterocyclic Carbene Chemistry
Authors: Maulbetsch Theo , Kunz Doris 
Published: October 2020

AbstractThe synthesis of an NHC‐containing porphyrinoid ligand is presented. The formally antiaromatic 20 πe− macrocyclic framework can be obtained via a 1,3‐dipolar cycloaddition (“click‐reaction”) to form two triazole moieties which were alkylated to the respective triazolium macrocycle. Deprotonation of the ligand precursor with lithium bases to the respective dilithio carbenaporphyrin complex and transmetallation to scandium lead to complexes that exhibit orange fluorescence. Optical property combined with TD‐DFT studies verify an aromatic character for each heterocyclic moiety rather than an antiaromatic macrocycle in the ligand precursor as well as in the complexes. While the geometric features of the carbenaporphyrin ligand strongly resemble those of porphyrin, DFT calculations reveal a stronger electron‐donating ability of the new ligand.
Synthesis, biological evaluation, and in silico study of pyrazoline‐conjugated 2,4‐dimethyl‐1H‐pyrrole‐3‐carboxylic acid derivatives
Authors: Rasal Nishant K. , Sonawane Rahul B. , Jagtap Sangeeta V. 
Published: October 2020

AbstractA potential molecular hybridization strategy was used to develop 24 novel pyrazoline‐conjugated 2,4‐dimethyl‐1H‐pyrrole‐3‐carboxylic acid and amide derivatives. The preliminary in vitro antimicrobial assay delivered four potential derivatives with growth inhibition in the range of 50.87–56.60% at the concentration of 32 µg/ml. In the search of an anticancer candidate, all derivatives were screened by NCI‐60 at 10 µM concentration, revealing that 12 derivatives were potential agents against the various types of cancer cell lines, with growth inhibition in the range of 50.21–108.37%. The in vitro cytotoxicity assay against the cell line HEK293 (human embryonic kidney cells) and the hemolysis assay of the representative potent compounds propose their potential for a good therapeutic index. In silico studies of the most potent derivatives qualified their significant pharmacokinetic properties with good predicted oral bioavailability and their adherence to Lipinski's rule of five for druglikeness. A molecular docking study against VEGFR‐2 with the best‐scored conformations reinforced their anticancer potency. The docking study of the most potent compound against VEGFR‐2 with the best‐scored conformations displayed a binding affinity (−9.5 kcal/mol) comparable with the drug sunitinib (−9.9 kcal/mol) and exhibited that tighter interactions at the active adenosine triphosphate site might be responsible for anticancer potency.
Synthesis, antimicrobial evaluation, DNA gyrase inhibition, and in silico pharmacokinetic studies of novel quinoline derivatives
Authors: El‐Shershaby Mohamed H. , El‐Gamal Kamal M. , Bayoumi Ashraf H. , El‐Adl Khaled , Ahmed Hany E. A. , Abulkhair Hamada S. 
Published: October 2020

AbstractHerein, we report the synthesis and in vitro antimicrobial evaluation of novel quinoline derivatives as DNA gyrase inhibitors. The preliminary antimicrobial activity was assessed against a panel of pathogenic microbes including Gram‐positive bacteria (Streptococcus pneumoniae and Bacillus subtilis), Gram‐negative bacteria (Pseudomonas aeruginosa and Escherichia coli), and fungal strains (Aspergillus fumigatus, Syncephalastrum racemosum, Geotrichum candidum, and Candida albicans). Compounds that revealed the best activity were subjected to further biological studies to determine their minimum inhibitory concentrations (MICs) against the selected pathogens as well as their in vitro activity against the E. coli DNA gyrase, to realize whether their antimicrobial action is mediated via inhibition of this enzyme. Four of the new derivatives (14, 17, 20, and 23) demonstrated a relatively potent antimicrobial activity with MIC values in the range of 0.66–5.29 μg/ml. Among them, compound 14 exhibited a particularly potent broad‐spectrum antimicrobial activity against most of the tested strains of bacteria and fungi, with MIC values in the range of 0.66–3.98 μg/ml. A subsequent in vitro investigation against the bacterial DNA gyrase target enzyme revealed a significant potent inhibitory activity of quinoline derivative 14, which can be observed from its IC50 value (3.39 μM). Also, a molecular docking study of the most active compounds was carried out to explore the binding affinity of the new ligands toward the active site of DNA gyrase enzyme as a proposed target of their activity. Furthermore, the ADMET profiles of the most highly effective derivatives were analyzed to evaluate their potentials to be developed as good drug candidates.
Platelet Glycoprotein Ib α‐Chain as a Putative Therapeutic Target for Juvenile Idiopathic Arthritis: A Mendelian Randomization Study
Authors: Luo Shan , Clarke Sarah L. N. , Ramanan Athimalaipet V. , Thompson Susan D. , Langefeld Carl D. , Marion Miranda C. , Grom Alexei A. , Schooling C. Mary , Gaunt Tom R. , Yeung Shiu Lun Au , Zheng Jie 
Published: October 2020

ObjectiveTo ascertain the role of platelet glycoprotein Ib α‐chain (GPIbα) plasma protein levels in cardiovascular, autoimmune, and autoinflammatory diseases and whether its effects are mediated by platelet count.MethodsWe performed a two‐sample Mendelian randomization (MR) study, using both a cis‐acting protein quantitative trait locus (cis‐pQTL) and trans‐pQTL near the GP1BA and BRAP genes as instruments. To assess if platelet count mediated the effect, we then performed a two‐step MR study. Putative associations (GPIbα/platelet count/disease) detected by MR analyses were subsequently assessed using multiple‐trait colocalization analyses.ResultsAfter correction for multiple testing (Bonferroni‐corrected threshold P ≤ 2 × 10−3), GPIbα, instrumented by either cis‐pQTL or trans‐pQTL, was causally implicated with an increased risk of oligoarticular and rheumatoid factor (RF)–negative polyarticular juvenile idiopathic arthritis (JIA). These effects of GPIbα appeared to be mediated by platelet count and were supported by strong evidence of colocalization (probability of all 3 traits sharing a common causal variant ≥0.80). GPIbα instrumented by cis‐pQTL did not appear to affect cardiovascular risk, although the GPIbα trans‐pQTL was associated with an increased risk of cardiovascular diseases and autoimmune diseases but a decreased risk of autoinflammatory diseases, suggesting that this trans‐acting instrument operates through other pathways.ConclusionThe role of platelets in thrombosis is well‐established; however, our findings provide some novel genetic evidence that platelets may be causally implicated in the development of oligoarticular and RF‐negative polyarticular JIA, and indicate that GPIbα may serve as a putative therapeutic target for these JIA subtypes.
Authors' noninstitutional emails and their correlation with retraction
Authors: Liu Xiaomei , Chen Xiaotian 
Published: October 2020

AbstractWe collected research articles from Retraction Watch database, Scopus, and a major retraction announcement by Springer, to identify emails used by authors. Authors' emails can be institutional emails and noninstitutional emails. Data suggest that retracted articles are more likely to use noninstitutional emails, but it is difficult to generalize. The study put some focus on authors from China.
Venturi flowmeter performance installed downstream of the branch of a tee junction
Authors: Sandberg Benjamin G. , Johnson Michael C. , Sharp Zachary B. 
Published: October 2020

AbstractVenturi flowmeters are robust and can function in many different and difficult installations. One such installation is downstream on the branch of a tee junction. For the most accurate flow measurement, a Venturi in this installation needs a laboratory calibration. Laboratory calibration adds cost to a project, may not be feasible, and in some circumstances, the Venturi has already been installed and cannot be taken out for calibration. For these reasons, this research used computational fluid dynamics (CFD) to determine the percent difference from the manufacturer's straight‐line calibrated or expected discharge coefficient, C, and adjust for it in tee installations. Laboratory data were collected to validate CFD models. The Cs from tee installations, of different distances downstream of the tee branch, were divided by a corresponding straight‐line C at the same Reynolds number to create a ratio to adjust the straight‐line C for a more accurate determination of the flow rate.
The role of Smad4 in the regulation of insulin resistance, inflammation and cell proliferation in HTR8‐Svneo cells
Authors: Li Ling , Bai Yu , Du Runyu , Tang Lei , Li Ling 
Published: October 2020

Gestational diabetes mellitus (GDM) is a metabolic disorder whose major pathophysiological basis is demonstrated as placental insulin resistance (IR), while Smad4 always functions in the signal transduction of transforming growth factor beta (TGF‐β) pathway. Our study aims to figure out the role of Smad4 in an insulin resistance (IR) cellular model using placental trophoblast cell line. Importantly, HTR8‐Svneo cells, in the status of IR, indicated a significant increase in the expression of Smad4. Subsequently, the HTR8‐Svneo cell line with up‐regulated or depleted Smad4 was respectively achieved by the effective over‐expressed plasmid or siRNA of Smad4. We found out that the deficiency of Smad4 could promote the insulin sensitivity and restrict the inflammatory response in IR group of cells with significant augment in glucose uptake, up‐regulation of insulin signalling‐related molecules and attenuation in inflammatory biomarker expressions. On the contrary, the over‐expression of Smad4 showed a reversal effect on these alterations in IR group of cells. Besides, the positive effect of Smad4 on cell viability was also observed in our study.Significance of the studyGestational diabetes mellitus (GDM) is a metabolic disorder whose major pathophysiological basis is demonstrated as insulin resistance (IR). Importantly, our findings indicate that the deficiency of Smad4 significantly improves the insulin sensitivity and relieves the inflammation in the cellular model of IR. Besides, the positive effect of Smad4 on cell viability was also observed in our study. Our present findings provide novel insights for the investigation on molecular details about the GDM pathogenesis.
Fat mass and obesity‐associated protein regulates lipogenesis via m6A modification in fatty acid synthase mRNA
Authors: Sun Donglei , Zhao Tianhe , Zhang Qian , Wu Mei , Zhang Zunzhen 
Published: October 2020

AbstractAs the first identified N6‐methyladenosine (m6A) demethylase, fat mass and obesity‐associated (FTO) protein is associated with fatty acid synthase (FASN) and lipid accumulation. However, little is known about the regulatory role of FTO in the expression of FASN and de novo lipogenesis through m6A modification. In this study, we used FTO small interfering RNA to explore the effects of FTO knockdown on hepatic lipogenesis and its underlying epigenetic mechanism in HepG2 cells. We found that knockdown of FTO increased m6A levels in total RNA and enhanced the expression of YTH domain family member 2 which serves as the m6A‐binding protein. The de novo lipogenic enzymes and intracellular lipid content were significantly decreased under FTO knockdown. Mechanistically, knockdown of FTO dramatically enhanced m6A levels in FASN messenger RNA (mRNA), leading to the reduced expression of FASN mRNA through m6A‐mediated mRNA decay. The protein expressions of FASN along with acetyl CoA carboxylase and ATP‐citrate lyase were further decreased, which inhibited de novo lipogenesis, thereby resulting in the deficiency of lipid accumulation in HepG2 cells and the induction of cellular apoptosis. The results reveal that FTO regulates hepatic lipogenesis via FTO‐dependent m6A demethylation in FASN mRNA and indicate the critical role of FTO‐mediated lipid metabolism in the survival of HepG2 cells. This study provides novel insights into a unique RNA epigenetic mechanism by which FTO mediates hepatic lipid accumulation through m6A modification and indicates that FTO could be a potential target for obesity‐related diseases and cancer.
Bilateral pleural empyema by Enterobacter infection secondary to pancreaticopleural fistula
Authors: Hasegawa Koichi , Toriyama Ayano , Nomizo Takashi , Fukata Hiroko , Goto Kenichi , Nakamura Yasukiyo , Hamada Tatsuo , Kanda Naoki , Kita Hideo 
Published: October 2020

AbstractPleural empyema secondary to pancreaticopleural fistula can be caused by ascending infection of enteric organisms from infected pancreatic pseudocysts. This unique route of infection should be noted for appropriate empirical antibiotic therapy.