bluuebunny/crossref_metadata_2025 huggingface dataset:
TGFBI modulates tumour hypoxia and promotes breast cancer metastasis
Authors: Fico Flavia , Santamaria‐Martínez Albert
Published: October 2020

Breast cancer metastasis is a complex process that depends not only on intrinsic characteristics of metastatic stem cells, but also on the particular microenvironment that supports their growth and modulates the plasticity of the system. In search for microenvironmental factors supporting cancer stem cell (CSC) growth and tumour progression to metastasis, we here investigated the role of the matricellular protein transforming growth factor beta induced (TGFBI) in breast cancer. We crossed the MMTV‐PyMT model of mammary gland tumorigenesis with a TgfbiΔ/Δ mouse and studied the CSC content of the tumours. We performed RNAseq on wt and ko tumours, and analysed the tumour vasculature and the immune compartment by IHC and FACS. The source of TGFBI expression was determined by qPCR and by bone marrow transplantation experiments. Finally, we performed in silico analyses using the METABRIC cohort to assess the potential prognostic value of TGFBI. We observed that deletion of Tgfbi led to a dramatic decrease in CSC content and lung metastasis. Our results show that lack of TGFBI resulted in tumour vessel normalisation, with improved vessel perfusion and decreased hypoxia, a major factor controlling CSCs and metastasis. Furthermore, human data mining in a cohort of breast cancer patients showed that higher expression of TGFBI correlates with poor prognosis and is associated with the more aggressive subtypes of breast cancer. Overall, these data reveal a novel biological mechanism controlling metastasis that could potentially be exploited to improve the efficacy and delivery of chemotherapeutic agents in breast cancer.
Topological Interlocking and Geometric Stiffening as Complementary Strategies for Strong Plant Shells
Authors: Huss Jessica C. , Antreich Sebastian J. , Bachmayr Jakob , Xiao Nannan , Eder Michaela , Konnerth Johannes , Gierlinger Notburga
Published: October 2020

Many organisms encapsulate their embryos in hard, protective shells. While birds and reptiles largely rely on mineralized shells, plants often develop highly robust lignocellulosic shells. Despite the abundance of hard plant shells, particularly nutshells, it remains unclear which fundamental properties drive their mechanical stability. This multiscale analysis of six prominent (nut)shells (pine, pistachio, walnut, pecan, hazelnut, and macadamia) reveals geometric and structural strengthening mechanisms on the cellular and macroscopic length scales. The strongest tissues, found in walnut and pistachio, exploit the topological interlocking of 3D‐puzzle cells and thereby outperform the fiber‐reinforced structure of macadamia under tensile and compressive loading. On the macroscopic scale, strengthening occurs via an increased shell thickness, spherical shape, small size, and a lack of extended sutures. These functional interrelations suggest that simple geometric modifications are a powerful and resource‐efficient strategy for plants to enhance the fracture resistance of entire shells and their tissues. Understanding the interplay between structure, geometry, and mechanics in hard plant shells provides new perspectives on the evolutionary diversification of hard seed coats, as well as insights for nutshell‐based material applications.
Examining Food Purchase Behavior and Food Values During the COVID‐19 Pandemic
Authors: Ellison Brenna , McFadden Brandon , Rickard Bradley J. , Wilson Norbert L. W.
Published: October 2020

The COVID‐19 pandemic has altered conceptions of “normal” globally, including food purchasing and acquisition decisions. In this paper, we surveyed a panel of 1,370 U.S. households four times during the COVID‐19 pandemic from mid‐March to late April 2020. With this unique panel, we observe changes in food expenditures, shopping behaviors, and food values as the pandemic evolved. Our results reveal reductions in food‐away‐from‐home expenditures and increases in online grocery shopping. Food values appear to be fairly stable in the early stages of the pandemic; however, decreases in the importance of price and nutrition reveal tradeoffs households make during the pandemic.
Carnosine attenuates vascular smooth muscle cells calcification through mTOR signaling pathway
Authors: Huang Yi , Wang Jinli , Luo Mandi , Yan Dan , Zhang Cuntai
Published: October 2020

Objective

Vascular calcification is prevalent in the aging population, as we know that arterial calcification is associated with aging. Recent studies have demonstrated that carnosine, a naturally occurring dipeptide, performs the treatment of aging‐related diseases, such as atherosclerosis and type 2 diabetes. Here, we investigated the role of carnosine in a calcification model of vascular smooth muscle cells (VSMCs).

Methods

In this research, we used an in vitro model of VSMC calcification to investigate the role of carnosine in the progression of rat VSMC calcification.

Results

Carnosine treatment attenuated calcium deposition in a dose‐dependent manner, detected by Alizarin Red S staining and calcium content assay. Carnosine also reduced the protein level of Runx2, bone morphogenetic protein 2 (BMP‐2), and cellular reactive oxygen species (ROS) production. Further, carnosine inhibited the activation of the mammalian target of rapamycin (mTOR) pathway.

Conclusion

Carnosine attenuated the VSMC calcification via inhibition of osteoblastic transdifferentiation and the mTOR signaling pathway.
The role of novel COQ8B mutations in glomerulopathy and related kidney defects
Authors: AbuMaziad Asmaa S. , Thaker Tarjani M. , Tomasiak Thomas M. , Chong Chyi Chyi , Galindo Maureen K. , Hoyme H. Eugene
Published: October 2020

Background and Objectives

Glomerulopathies affect kidney glomeruli and can lead to end‐stage renal disease if untreated. Clinical and experimental evidence have identified numerous (>20) genetic mutations in the mitochondrial coenzyme Q8B protein (COQ8B) primarily associated with nephrotic syndrome. Yet, little else is understood about COQ8B activity in renal pathogenesis and its role in mitochondrial dysfunction. We identified additional novel COQ8B mutations in a glomerulopathy patient and aimed to define the potential structural and functional defects of COQ8B mutations.

Design, Setting, Participants, and Measurements

Whole exome sequencing was performed on a Hispanic female presenting with proteinuria. Novel mutations in the COQ8B gene were identified. The effects of mutation on protein function, mitochondrial morphology, and disease progression were investigated by histopathology, transmission electron microscopy, homology modeling, and in silico structural analysis.

Results

We have characterized the pathophysiology of novel COQ8B mutations, compound heterozygous for two alterations c.1037T>G (p.I346S), and c.1560G>A (p.W520X), in the progression of proteinuria in a Hispanic female. Histopathology revealed defects in podocyte structure and mitochondrial morphology. In silico and computation analyses highlight possible structural origins of COQ8B dysfunction in the presence of mutations.

Conclusions

Novel mutations in COQ8B present promising biomarkers for the early detection and therapeutic targeting of mitochondrial glomerulopathy. Insights from structural modeling suggest roles of mutation‐dependent alterations in COQ8B allosteric regulation, protein folding, or stability in renal pathogenesis.
Moyamoya syndrome in a child with Legius syndrome: Introducing a cerebral vasculopathy to the SPRED1 phenotype?
Authors: Pabst Lisa , Carroll Jennifer , Lo Warren , Truxal Kristen V.
Published: October 2020

Legius syndrome is a disorder of the RAS and mitogen‐activated protein kinase (MAPK) pathway first described in 2007 by Eric Legius, et al., that has been considered a milder phenotype than reported in the RASopathy neurofibromatosis type 1 (NF1). However, with approximately 200 cases reported in the literature, the Legius syndrome phenotype remains to be fully characterized. We report a child who presented with moyamoya syndrome and who has Legius syndrome due to a pathogenic variant in SPRED1. Vascular complications such as moyamoya syndrome have been reported in NF1. However, this association has not been reported in Legius syndrome. This child’s case may represent an expansion of the clinical phenotype of Legius syndrome, and further study is needed. We emphasize the importance of obtaining neuroimaging studies in patients with Legius syndrome who present with new neurologic deficits.
Electrochemical 1,2‐Diarylation of Alkenes Enabled by Direct Dual C–H Functionalizations of Electron‐Rich Aromatic Hydrocarbons
Authors: Qin Jing‐Hao , Luo Mu‐Jia , An De‐Lie , Li Jin‐Heng
Published: October 2020

A cobalt‐promoted electrochemical 1,2‐diarylation of alkenes with electron‐rich aromatic hydrocarbons via direct dual C−H functionalizations is described, which employs a radical relay strategy to produce polyaryl‐functionalized alkanes. Simply by using graphite rod cathode instead of platinum plate cathode, chemoselectivity of this radical relay strategy is shifted to the dehydrogenative [2+2+2] cycloaddition via 1,2‐diarylation, annulation, and dehydrogenation cascades leading to complex 11,12‐dihydroindolo[2,3‐a]carbazoles. Mechanistical studies indicate that a key step for the radical relay processes is transformations of the aromatic hydrocarbons to the aryl sp2‐hybridized carbon‐centered radicals via deprotonation of the corresponding aryl radical cation intermediates with bases.
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

The 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

Surface 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

Die 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

Engineering 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

α‐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

Developing 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

Prodrug 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

The 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

We 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

The 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.
Functionalization of superparamagnetic Fe3O4@SiO2nanoparticles with a Cu(II) binuclear Schiff base complex as an efficient and reusable nanomagnetic catalyst forN‐arylation of α‐amino acids and nitrogen‐containing heterocycles with aryl halides
Authors: Sardarian A. R. , Kazemnejadi M. , Esmaeilpour M.
Published: October 2020

Fe3O4@SiO2nanoparticles was functionalized with a binuclear Schiff base Cu(II)‐complex (Fe3O4@SiO2/Schiff base‐Cu(II) NPs) and used as an effective magnetic hetereogeneous nanocatalyst for theN‐arylation of α‐amino acids and nitrogen‐containig heterocycles. The catalyst, Fe3O4@SiO2/Schiff base‐Cu(II) NPs, was characterized by Fourier transform infrared (FTIR) and ultraviolet‐visible (UV‐vis) analyses step by step. Size, morphology, and size distribution of the nanocatalyst were studied by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and dynamic light scatterings (DLS) analyses, respectively. The structure of Fe3O4nanoparticles was checked by X‐ray diffraction (XRD) technique. Furthermore, the magnetic properties of the nanocatalyst were investigated by vibrating sample magnetometer (VSM) analysis. Loading content as well as leaching amounts of copper supported by the catalyst was measured by inductive coupled plasma (ICP) analysis. Also, thermal studies of the nanocatalyst was studied by thermal gravimetric analysis (TGA) instrument. X‐ray photoelectron spectroscopy (XPS) analysis of the catalyst revealed that the copper sites are in +2 oxidation state. The Fe3O4@SiO2/Schiff base‐Cu(II) complex was found to be an effective catalyst for C–N cross‐coupling reactions, which high to excellent yields were achieved for α‐amino acids as well asN‐hetereocyclic compounds. Easy recoverability of the catalyst by an external magnet, reusability up to eight runs without significant loss of activity, and its well stability during the reaction are among the other highlights of this catalyst.
Preparation of mesoporous CexCoO as highly effective catalysts for toluene combustion: The synergetic effects of structural template and Ce doping
Authors: Liu Wei , Fan Jiaying , Song Zhongxian , Zhang Xuejun
Published: October 2020

Cobalt‐based catalyst, as a typical catalyst for volatile organic compounds (VOCs) combustion, has attracted extensive attention. However, the catalytic activity of pure Co3O4 is difficult to meet the requirements of practical application especially at low temperatures. Therefore, it is key to find an effective way to improve the catalytic performance of Co3O4. In this paper, Co3O4 is modified by engineering a combination of structural template and Ce dopant. The various characterization results verify that the template agent and the doping of appropriate Ce lead to great changes in the texture property and low temperature reducibility of Co3O4, thus resulting in superior catalytic performances of obtained mesoporous CexCoO catalysts. In particular, the best catalyst, Ce0.05CoO, achieves a toluene conversion of T90% at 238°C, which is significantly lower than many of the Co‐based catalysts reported in previous literatures. Furthermore, the toluene conversion rate maintains above 90% during 100 h at 238°C. The excellent catalytic performance of Ce0.05CoO can be attributed to its large specific surface area, uniform pore structure, good low temperature reducibility, and abundant surface oxygen species.
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

A 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

Herein, 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

Objective

To 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.

Methods

We 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.

Results

After 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.

Conclusion

The 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

We 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

Venturi 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 study

Gestational 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

As 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

Pleural 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.
Dithieno[a,e]pentalenes: Highly Antiaromatic Yet Stable π‐Electron Systems without Bulky Substituents
Authors: Usuba Junichi , Hayakawa Masahiro , Yamaguchi Shigehiro , Fukazawa Aiko
Published: October 2020

Dithieno[a,e]penalenes (DTPs) with various substituents were synthesized as a class of antiaromatic compounds. Annulation of thiophene rings imparts the pentalene moiety with high thermal stability even without bulky substituents, while retaining antiaromaticity. The higher magnitude of antiaromaticity in DTPs, in addition to the differences in the electronic structures of the fused aromatic rings, resulted in a narrower HOMO–LUMO gap than that of the corresponding dibenzo[a,e]pentalene analog, giving rise to red‐shifted electronic absorption that reaches the near‐infrared region. Moreover, systematic investigations on the solid‐state packing structure revealed that DTPs prefer offset face‐to‐face packing motifs rather than face‐centered π–π stacking. In particular, the thienyl‐substituted DTP bearing hydrophilic side chains exhibited thermochromic behavior in polar solvents, which was ascribed to the formation of aggregates.
Circularly Polarized Luminescence of a Stereogenic Curved Paraphenylene Anchoring a Chiral Binaphthyl in Solution and Solid State
Authors: Sato Kenta , Hasegawa Masashi , Nojima Yuki , Hara Nobuyuki , Nishiuchi Tomohiko , Imai Yoshitane , Mazaki Yasuhiro
Published: October 2020

A curved stereogenic [6]paraphenylene ([6]PP), anchoring a chiral binaphthyl scaffold at 7,7’‐positions, was prepared and investigated for its properties as a solid‐state circularly polarized luminescence (CPL) dye. X‐ray analysis revealed a helically twisted structure of PP units induced by axial chirality of binaphthyl framework. The curved [6]PP exhibits fluorescence in powder and polymethyl methacrylate (PMMA) film as well as solution. A significant increase in quantum yield was observed for a non‐fluid PMMA film owing the suppression of the molecular motion. The gCPL values of the dye in solution and as PMMA film were almost the same (4.3–4.4×10−3) and lager than that in powder. TD‐DFT calculations in the excited state suggest that the exciton can be delocalized into a twisted PP unit to produce a larger magnetic transition dipole moment.
Health‐related quality of life outcomes for the LEAP study—CALGB 70305 (Alliance): A lymphedema prevention intervention trial for newly diagnosed breast cancer patients
Authors: Naughton Michelle J. , Liu Heshan , Seisler Drew K. , Le‐Rademacher Jennifer , Armer Jane M. , Oliveri Jill M. , Sloan Jeffrey A. , Hock Karen , Schwartz Michael , Unzeitig Gary , Melnik Marianne , Yee Lisa D. , Fleming Gini F. , Taylor John R. , Loprinzi Charles , Paskett Electra D.
Published: October 2020

Background

Lymphedema is an adverse effect of breast cancer treatment that causes swelling and pain in the arm and hand. We tested 2 lymphedema prevention interventions and their impact on health‐related quality of life (HRQOL) in a group‐randomized trial at 38 cooperative group sites within the United States.

Methods

Patients were recruited before breast surgery. Sites were randomly assigned to education‐only (EO) lymphedema prevention or education plus exercise and physical therapy (LEAP). Lymphedema was defined as a ≥10% difference in arm volume at any time from baseline to 18 months postsurgery. HRQOL was assessed using the Functional Assessment of Cancer Therapy–Breast plus 4 lymphedema items (FACT‐B+4). Longitudinal mixed model regression analysis, adjusting for key demographic and clinical variables, examined participants' HRQOL by intervention group and lymphedema status.

Results

A total of 547 patients (56% LEAP) were enrolled and completed HRQOL assessments. The results revealed no differences between the interventions in preventing lymphedema (P = .37) or HRQOL (FACT‐B+4 total score; P = .8777). At 18 months, the presence of lymphedema was associated with HRQOL at borderline significance (P = .0825). However, African American patients reported greater lymphedema symptoms (P = .0002) and better emotional functioning (P = .0335) than patients of other races or ethnicities. Lower HRQOL during the intervention was associated with younger age (P ≤ .0001), Eastern Cooperative Oncology Group performance status >0 (P = .0002), ≥1 positive lymph nodes (P = .0009), having no education beyond high school (P < .0001), having undergone chemotherapy (P = .0242), and having had only axillary node dissection or sentinel node biopsy versus both (P = .0007).

Conclusion

The tested interventions did not differ in preventing lymphedema or in HRQOL outcomes. African American women reported greater HRQOL impacts due to lymphedema symptoms than women of other races or ethnicities.
Benefit of delayed primary excision in rhabdomyosarcoma: A report from the Children's Oncology Group
Authors: Lautz Timothy B. , Chi Yueh‐Yun , Li Minjie , Wolden Suzanne L. , Casey Dana L. , Routh Jonathan C. , Granberg Candace F. , Binite Odion , Rudzinski Erin R. , Hawkins Douglas S. , Venkatramani Rajkumar , Rodeberg David A.
Published: October 2020

Background

Most children with intermediate‐risk rhabdomyosarcoma (RMS) have gross disease (group III) at the initiation of chemotherapy. Delayed primary excision (DPE) after induction chemotherapy allows for a reduction in adjuvant radiation dose, but with the risk of potential surgical morbidity. The objectives of this study were to compare outcomes in children with group III RMS who did and did not undergo DPE and to assess surgical morbidity.

Methods

The study included 369 patients who had clinical group III RMS at sites amenable to DPE from intermediate‐risk Children's Oncology Group studies D9803 (encouraged DPE) and ARST0531 (discouraged DPE).

Results

The primary tumor site was bladder/prostate (136 patients; 37%), extremity (97 patients; 26%), trunk (24 patients; 7%), retroperitoneum (91 patients; 25%), or intrathoracic/perineum/perianal (21 patients; 6%). In total, 112 patients (53.9%) underwent DPE in D9803, and 26 patients (16.2%) underwent DPE in ARST0531 (P < .001), with loss of vital organ or function in 30 of 138 patients (22%). DPE allowed for a reduced radiation dose in 110 of 135 patients (81%; 51% were reduced to 36 Gy, and 30% were reduced to 42 Gy). Patients who underwent DPE had improved unadjusted overall survival (P = .013). In adjusted regression analysis, the risk of death (hazard ratio, 0.71; 95% CI 0.43‐1.16) was similar for patients who did and did not undergo DPE and was improved for the subset of patients who had tumors of the trunk and retroperitoneum (hazard ratio, 0.44; 95% CI, 0.20‐0.97).

Conclusions

Children with group III RMS have equivalent or improved outcomes with DPE and can receive a decreased radiation dose for definitive local control. The choice of local control modality should weigh the potential morbidity of surgery versus that of higher dose irradiation.
Hypomagnesemia and survival in patients with head and neck cancers who received primary concurrent chemoradiation
Authors: Liu Wenli , Qdaisat Aiham , Ferrarotto Renata , Fuller Clifton D. , Guo Ming , Meyer Larissa A. , Narayanan Santhosshi , Lopez Gabriel , Cohen Lorenzo , Bruera Eduardo , Hanna Ehab Y. , Yeung Sai‐Ching J.
Published: October 2020

Background

Prior research has confirmed that persistent hypomagnesemia was predictive of shorter survival among patients with ovarian cancer who received carboplatin‐based chemotherapy. In the current retrospective study, the authors examined the association between hypomagnesemia and survival in patients with head and neck cancer who received concurrent chemoradiation with weekly infusions of cisplatin and/or carboplatin.

Methods

Patients with head and neck cancers who had undergone chemoradiation with cisplatin and/or carboplatin between January 1, 2010, and December 31, 2014, were included. Patients were aged ≥18 years with pathology of squamous cell carcinoma of the larynx, oral cavity, or oropharynx who had received at least 30 fractions of radiotherapy with concurrent weekly cisplatin and/or carboplatin. Pathology features, laboratory results, Eastern Cooperative Oncology Group performance status, social histories, and survival were recorded. The association between hypomagnesemia and survival was analyzed controlling for known prognostic factors.

Results

The final cohort consisted of 439 patients with a median age of 59 years. A greater frequency of hypomagnesemia during the treatment course was found to be significantly associated with shorter survival (hazard ratio [HR], 1.13; P = .033) independent of age (HR, 1.65; P = .042), cancer site (nonoropharynx vs oropharynx: HR, 2.15 [P = .003]), Eastern Cooperative Oncology Group performance status (>1 vs ≤1: HR, 2.64 [P < .001]), and smoking history (smoker vs nonsmoker: HR, 1.88 [P = .012]). In addition, more severe hypomagnesemia was associated with shorter survival compared with the milder form.

Conclusions

The frequency and severity of hypomagnesemia during treatment are prognostic of survival for patients with head and neck cancers who are receiving concurrent chemoradiation with cisplatin and/or carboplatin. A prospective study is needed to investigate the impact of the prevention of hypomagnesemia on survival in this patient population.
An integrated approach for the characterization of one‐ and two‐gene imazamox‐resistant wheat lines
Authors: Anastasini Valentina , Depetris Mara Belén , Ochogavía Ana Claudia , Nestares Graciela , Breccia Gabriela
Published: October 2020

In wheat (Triticum aestivum L.), cultivars resistant to imidazolinone herbicides are an important tool for weed management. The target site of imidazolinones is acetohydroxyacid synthase (AHAS), an enzyme coded by three homeologous genes (ahasL‐A1, ahasL‐B1, and ahasL‐D1). This study aimed to evaluate the effect of the imidazolinone herbicide imazamox on a single‐gene (AhasL‐D1) resistant line (R1) and a two‐gene (AhasL‐B1 and AhasL‐D1) resistant line (R2) at multiple biological levels. These lines showed variation in the transcriptional levels of ahasL homeologs, but no differences in total AHAS activity. The relative contribution of resistant alleles to the ahasL transcript pool accounted for 47% in the R1 line and 77% in the R2 line. The in vitro AHAS inhibition of the R1 line was intermediate between the R2 and the susceptible lines. At an anatomical level, high imazamox concentrations induced alterations in the root tip features of R1 plants but did not affect R2 plants, whereas at in vivo AHAS activity and whole‐plant levels, both resistant lines showed high resistance. The herbicide dose that reduced shoot biomass of resistant lines by 50% was 35‐fold higher than that of the susceptible line. We conclude that homeolog variation allows a higher contribution of resistance genes to the ahasL transcript pool in the R1 and R2 lines. Although both resistant lines showed high whole‐plant resistance, the differential root damage induced by imazamox between wheat lines suggests that two‐gene resistant cultivars could be an effective option to avoid the negative impacts caused by herbicide residues in the soil.