bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heavy‐Atom Tunneling Through Crossing Potential Energy Surfaces: Cyclization of a Triplet 2‐Formylarylnitrene to a Singlet 2,1‐Benzisoxazole
Authors: Nunes Cláudio M. , Viegas Luís P. , Wood Samuel A. , Roque José P. L. , McMahon Robert J. , Fausto Rui 
Published: June 2020

AbstractNot long ago, the occurrence of quantum mechanical tunneling (QMT) chemistry involving atoms heavier than hydrogen was considered unreasonable. Contributing to the shift of this paradigm, we present here the discovery of a new and distinct heavy‐atom QMT reaction. Triplet syn‐2‐formyl‐3‐fluorophenylnitrene, generated in argon matrices by UV‐irradiation of an azide precursor, was found to spontaneously cyclize to singlet 4‐fluoro‐2,1‐benzisoxazole. Monitoring the transformation by IR spectroscopy, temperature‐independent rate constants (k≈1.4×10−3 s−1; half‐life of ≈8 min) were measured from 10 to 20 K. Computational estimated rate constants are in fair agreement with experimental values, providing evidence for a mechanism involving heavy‐atom QMT through crossing triplet to singlet potential energy surfaces. Moreover, the heavy‐atom QMT takes place with considerable displacement of the oxygen atom, which establishes a new limit for the heavier atom involved in a QMT reaction in cryogenic matrices.
Tetrazine Carbon Nanotubes for Pretargeted In Vivo “Click‐to‐Release” Bioorthogonal Tumour Imaging
Authors: Li He , Conde João , Guerreiro Ana , Bernardes Gonçalo J. L. 
Published: June 2020

AbstractThe bioorthogonal inverse‐electron‐demand Diels–Alder (IEDDA) cleavage reaction between tetrazine and trans‐cyclooctene (TCO) is a powerful way to control the release of bioactive agents and imaging probes. In this study, a pretargeted activation strategy using single‐walled carbon nanotubes (SWCNTs) that bear tetrazines (TZ@SWCNTs) and a TCO‐caged molecule was used to deliver active effector molecules. To optimize a turn‐on signal by using in vivo fluorescence imaging, we developed a new fluorogenic near‐infrared probe that can be activated by bioorthogonal chemistry and image tumours in mice by caging hemicyanine with TCO (tHCA). With our pretargeting strategy, we have shown selective doxorubicin prodrug activation and instantaneous fluorescence imaging in living cells. By combining a tHCA probe and a pretargeted bioorthogonal approach, real‐time, non‐invasive tumour visualization with a high target‐to‐background ratio was achieved in a xenograft mice tumour model. The combined advantages of enhanced stability, kinetics and biocompatibility, and the superior pharmacokinetics of tetrazine‐functionalised SWCNTs could allow application of targeted bioorthogonal decaging approaches with minimal off‐site activation of fluorophore/drug.
ECNU‐36: A Quasi‐Pure Polymorph CH Beta Silicate Composed of Hierarchical Nanosheet Crystals for Effective VOCs Adsorption
Authors: Jiao Meichen , Huang Ju , Xu Hao , Jiang Jingang , Guan Yejun , Ma Yanhang , Wu Peng 
Published: June 2020

AbstractA quasi‐pure CH polymorph of microporous zeolite beta, named ECNU‐36, was obtained as a highly crystalline silicate using 1,5‐bis(tetramethylimidazolium) hydroxide as organic structure‐directing agent (OSDA) in fluoride media. An appropriate concentration of free fluoride in the synthetic mother liquor was crucial to purify the CH‐phase. The framework structure of ECNU‐36 consists of polymorph CH (>95 %) and polymorph B, elucidated by a combination of PXRD data, DIFFaX simulation, EDT, and HRTEM techniques. For the first time, the framework structure of beta CH polymorph was directly confirmed and solved using electron diffraction data. The pure‐silica ECNU‐36 showed an unusual crystal morphology, composed of stacked nanosheets, with typical 17 nm thickness and exposed {100} facets, which exhibited attractive adsorption performance for hydrocarbons and aromatics.
Template‐Directed Copying of RNA by Non‐enzymatic Ligation
Authors: Zhou Lijun , O'Flaherty Derek K. , Szostak Jack W. 
Published: June 2020

AbstractThe non‐enzymatic replication of the primordial genetic material is thought to have enabled the evolution of early forms of RNA‐based life. However, the replication of oligonucleotides long enough to encode catalytic functions is problematic due to the low efficiency of template copying with mononucleotides. We show that template‐directed ligation can assemble long RNAs from shorter oligonucleotides, which would be easier to replicate. The rate of ligation can be greatly enhanced by employing a 3′‐amino group at the 3′‐end of each oligonucleotide, in combination with an N‐alkyl imidazole organocatalyst. These modifications enable the copying of RNA templates by the multistep ligation of tetranucleotide building blocks, as well as the assembly of long oligonucleotides using short splint oligonucleotides. We also demonstrate the formation of long oligonucleotides inside model prebiotic vesicles, which suggests a potential route to the assembly of artificial cells capable of evolution.
Biocatalysis: Enzymatic Synthesis for Industrial Applications
Authors: Wu Shuke , Snajdrova Radka , Moore Jeffrey C. , Baldenius Kai , Bornscheuer Uwe T. 
Published: June 2020

AbstractBiocatalysis has found numerous applications in various fields as an alternative to chemical catalysis. The use of enzymes in organic synthesis, especially to make chiral compounds for pharmaceuticals as well for the flavors and fragrance industry, are the most prominent examples. In addition, biocatalysts are used on a large scale to make specialty and even bulk chemicals. This review intends to give illustrative examples in this field with a special focus on scalable chemical production using enzymes. It also discusses the opportunities and limitations of enzymatic syntheses using distinct examples and provides an outlook on emerging enzyme classes.
Intermarriage of Halide Perovskites and Metal‐Organic Framework Crystals
Authors: Hou Jingwei , Wang Zhiliang , Chen Peng , Chen Vicki , Cheetham Anthony K. , Wang Lianzhou 
Published: June 2020

AbstractThis Review examines how the intermarriage of perovskite and metal‐organic framework crystals brings new paradigms for material design and functionality. The strategic combination of halide perovskites and metal–organic frameworks (MOFs) has generated a new family of porous composite materials that will enable new applications, including optoelectronic, catalysis, sensing, and data encryption. This Review surveys the current progress of this exciting new area. Fundamental aspects, including perovskite nucleation and growth, heterojunction electron–hole transfer, electronic structure, and luminescence within confined spaces, are highlighted, with suggestions of approaches by which guest confinement within MOFs can be synthetically designed. We further address the underlying principles and discuss the new insights and tools for the manipulation of these composite materials for the development of synthetic microporous semiconducting composites, as well as new strategies for host–guest interfacial engineering.
Sox genes in Agasicles hygrophila (Coleoptera: Chrysomelidae) are involved in ovarian development and oogenesis
Authors: Dong Wan‐Ying , Wang Yao , Zhou Zhong‐Shi , Guo Jian‐Ying 
Published: June 2020

AbstractThe alligator weed flea beetle, Agasicles hygrophila is a monophagous natural enemy of the invasive alligator weed Alternanthera philoxeroides. Oogenesis plays a vital role in the process of individual development and population continuation of oviparous insects. Sox is an ancient and ubiquitous metazoan gene family that plays a key regulatory role in various physiological processes, including oogenesis, which is closely related to fecundity. In this study, two Sox genes AhDichaete and AhSox3 were cloned and characterized, and then the expression profiles of AhDichaete and AhSox3 were qualified by a quantitative reverse transcription‐polymerase chain reaction. The result showed that these two Sox genes were expressed significantly higher in ovary, especially in the adult developmental stage. Furthermore, the functions of AhDichaete and AhSox3 in A. hygrophila females were studied using RNA interference (RNAi). Fewer offsprings were produced when AhDichaete and AhSox3 RNAi females mated with wild‐type males. Moreover, dsAhSox3 injection reduced the hatching rate of eggs but injection with dsAhDichaete did not. Further study of the reproductive system of AhDichaete and AhSox3 RNAi females showed that yolk protein deposition reduction in the ovarioles, then the expression of vitellogenin gene AhVg2 in ovaries was decreased. These results indicate that AhDichaete and AhSox3 play an important regulatory role in the process of ovarian development and oogenesis by affecting yolk synthesis in the ovary of A. hygrophila.
New applications of squalene synthase inhibitors: Membrane cholesterol as a therapeutic target
Authors: Kourounakis Angeliki P. , Bavavea Eugenia 
Published: June 2020

AbstractSqualene synthase (SQS) inhibitors, mostly known as antihyperlipidemic agents for controlling blood cholesterol levels, have been increasingly used to study alterations of the cholesterol content in cell membranes. As such, SQS inhibitors have been demonstrated to control cellular activities related to cancer cell proliferation and migration, neuron degeneration, and parasite growth. While the mechanisms behind the effects of cellular cholesterol are still being revealed in detail, the evidence for SQS as a therapeutic target for several seemingly unrelated diseases is increasing. SQS inhibitors may be the next promising candidates targeting the three remaining primary therapeutic areas, beyond cardiovascular disease, which still need to be addressed; their application as anticancer, antimicrobial, and antineurodegenerative agents appears promising for new drug discovery projects underway.
Development of a prediction model with serum tumor markers to assess tumor metastasis in lung cancer
Authors: Wang Jiasi , Chu Yanpeng , Li Jie , Zeng Fanwei , Wu Min , Wang Tingjie , Sun Liangli , Chen Qianlai , Wang Pingxi , Zhang Xiuqin , Zeng Fanxin 
Published: June 2020

AbstractBackgroundThis study aimed to explore the possibility of serum tumor markers (TMs) combinations in assessing tumor metastasis in patients with lung cancer.MethodsWe performed a retrospective analysis of 541 patients diagnosed with lung cancer between January 2016 and December 2017 at the Pneumology Department of Dazhou Central Hospital. Serum carcinoembryonic antigen (CEA), carbohydrate antigen (CA)125, CA153, CA199, CA724, cytokeratin 19 fragment (CYFRA), and neuron‐specific enolase (NSE) levels were quantified in each patient at the time of lung cancer diagnosis. Metastasis was confirmed by computed tomography, and/or positron emission tomography, and/or surgery or other necessary methods. Receiver operating characteristic (ROC) curves and calibration curves were used to evaluate the performance of the model.ResultsOf the 541 patients eligible for final analysis, 253 were detected with metastasis and 288 were detected without metastasis. Compared with those in nonmetastatic patients, the serum CEA, CA125, CA199, CA153, CYFRA, and NSE levels were notably higher in metastatic patients (P < .05). The ROC curve demonstrated that the CEA‐CA125‐CA199‐CA153‐CYFRA‐NSE‐CA724 combination based on the cut‐off value had an optimal area under the curve and specificity in assessing tumor metastasis. The decision tree model is a convenient and valuable tool for guiding the appropriate application of our model to assess metastasis in lung cancer patients.ConclusionsOur study suggested that the nomogram of the regression model is valuable for assessing tumor metastasis in newly diagnosed lung cancer patients before traditional standard methods are used. These findings could aid in the evaluation of metastasis in the clinic.
Recent survival trends in diffuse large B‐cell lymphoma––Have we made any progress beyond rituximab?
Authors: Epperla Narendranath , Vaughn John L. , Othus Megan , Hallack Abrahao , Costa Luciano J. 
Published: June 2020

AbstractBackgroundPopulation‐based studies previously showed an improvement in overall survival (OS) for patients with diffuse large B‐cell lymphoma (DLBCL) who received chemoimmunotherapy with rituximab. However, there is limited data (especially at the population level) that show a similar trend in OS improvement, in the most recent time period. We hypothesized that survival for DLBCL patients diagnosed in the United States has continued to improve in recent years and intended to measure outcome improvements.MethodsUsing the SEER‐18 registries, we compared the incidence and relative survival rates (RSRs) of DLBCL patients between 2002‐2007 and 2008‐2013 (availability of novel agents, broader use of autologous hematopoietic cell transplantation and improvement in supportive care). Multivariable Cox regression models were used to assess associations between the year of diagnosis and OS while controlling for age, gender, stage, and ethnicity.ResultsThere were a total of 53 439 patients with DLBCL who were diagnosed between 2002 and 2013. Of these, 25 810 were diagnosed during time period‐1 and 27 629 diagnosed during time period‐2. There was a slight decline in incidence of DLBCL (time period‐1 vs time period‐2), 7.75 (95% CI = 7.66‐7.84) vs 7.43 (95% CI = 7.34‐7.52) cases per 100 000 persons, respectively (P < .0001). Overall, there was a modest improvement in DLBCL RSRs, with 5‐year RSR improving from 61% (time period‐1) to 64% (time period‐2) and the improvement was noted across all subsets of patients. On multivariable analysis, patients diagnosed in time period‐2 had lower mortality relative to time period‐1 (HR = 0.87, 95% CI = 0.85‐0.89).ConclusionsOur study shows an improvement in the outcomes of DLBCL patients beyond the introduction of rituximab, although the magnitude of improvement is small. It will be interesting to see the impact of chimeric antigen receptor‐T cell therapy translating to population‐level survival in the next 5 years.
Detecting Cysteine in Bioimaging with a Near‐Infrared Probe Based on a Novel Fluorescence Quenching Mechanism
Authors: Tao Yuanfang , Ji Xin , Zhang Jian , Jin Yue , Wang Nannan , Si Yubing , Zhao Weili 
Published: June 2020

AbstractNear‐infrared (NIR) fluorescent probes are very significant for detecting cysteine in biological systems. Herein, we report a highly selective and sensitive NIR turn‐on fluorescent probe (BDP‐NIR) based on BODIPY with large Stokes shift (105 nm) for detecting Cys. We clarified the sensing mechanism based on the different thiol‐induced SNAr substitution/rearrangement reaction of the probe with cysteine and homocysteine/glutathione, which leads to the corresponding amino‐ and thiol‐BODIPY dyes with distinct photophysical properties. Moreover, a novel mechanism of fluorescence quenching was demonstrated by density functional theory calculation. The reason for the fluorescence quenching of the probe might be intersystem crossing (from singlet to triplet excited state). Moreover, BDP‐NIR had a high linear dynamic range of 0–500 μM, which was promising for detecting cysteine quantificationally. Significantly, BDP‐NIR was capable of sensing endogenous cysteine in living cells and in vivo.
Endocrine markers of puberty timing and antisocial behaviour in girls and boys
Authors: Michielsen Philip Jules Simon , Roza Sabine Judith , van Marle Hjalmar Johan Carel 
Published: June 2020

AbstractBackgroundEarly puberty is associated with higher than average risk of antisocial behaviour, both in girls and boys. Most studies of such association, however, have focused on psychosocial mediating and moderating factors. Few refer to coterminous hormonal measures.AimThe aim of this review is to consider the role of hormonal markers as potential mediating or moderating factors between puberty timing and antisocial behaviour.MethodA systematic literature search was conducted searching Medline, Embase, Web of Science, Scopus, Psycinfo, Cochrane and Google Scholar.ResultsJust eight studies were found to fit criteria, all cross‐sectional. Measurements were too heterogeneous to allow meta‐analysis. The most consistent associations found were between adrenal hormones—both androgens and cortisol—which were associated with early adrenarche and antisocial behaviours in girls and later adrenarche and antisocial behaviour in boys.ConclusionsThe findings from our review suggest that longitudinal studies to test bidirectional hormone–behaviour associations with early or late puberty would be worthwhile. In view of the interactive processes between hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes, integrated consideration of the hormonal end products is recommended.
Graphitic‐shell encapsulated FeNi alloy/nitride nanocrystals on biomass‐derived N‐doped carbon as an efficient electrocatalyst for rechargeable Zn‐air battery
Authors: Wu Mingjie , Zhang Gaixia , Hu Yongfeng , Wang Jian , Sun Tianxiao , Regier Tom , Qiao Jinli , Sun Shuhui 
Published: June 2020

AbstractOxygen reduction/evolution reactions (ORR/OERs) catalysts play a key role in the metal‐air battery and water‐splitting process. Herein, we developed a facile template‐free method to fabricate a new type of non–noble metal‐based hybrid catalyst which consists of binary FeNi alloy/nitride nanocrystals with graphitic‐shell and biomass‐derived N‐doped carbon (NC) (FexNiyN@C/NC). This novel nanostructure exhibits superior performance for ORR/OER, which can be attributed to the strong interactions between the graphitic‐shell encapsulated FeNi alloy/nitride nanocrystals and the N‐doped porous carbon substrate. The X‐ray absorption spectroscopy technique was employed to reveal the underlying mechanisms for the excellent performance. The assembled Zn‐air battery device exhibits outstanding charging/discharging performance and cycling stability, indicating the great potential of this type of novel catalysts.
Transition Metal Promoted Cascade Heterocycle Synthesis through C−H Functionalization
Authors: Baccalini Alessio , Faita Giuseppe , Zanoni Giuseppe , Maiti Debabrata 
Published: June 2020

AbstractSequential, domino and tandem reactions could be defined as a sequence of synthetic transformations that occur one after the other, in the same reaction flask. This Review highlights recent advances at the overlap of two worlds: transition‐metal mediated C−H activation as a trigger of cascade reaction, for the heterocycles synthesis. To shed some light on this intricate “middle‐earth”, focus was put on the reaction mechanism rather than the type of metal or the chronological order of the reaction. The aim is to separate, and then highlight, the true domino reactions initiated by C−H activation, compared to other examples of C−H functionalization for heterocycle syntheses.
Phosphorus‐Containing Dibenzonaphthanthrenes: Electronic Fine Tuning of Polycyclic Aromatic Hydrocarbons through Organophosphorus Chemistry
Authors: Ascherl Johannes D. R. , Neiß Christian , Vogel Alexander , Graf Jürgen , Rominger Frank , Oeser Thomas , Hampel Frank , Görling Andreas , Kivala Milan 
Published: June 2020

AbstractA concise synthetic route towards a new family of phosphorus‐containing polycyclic aromatic hydrocarbons starting from the versatile acridophosphine has been established. The structural and optoelectronic properties of these compounds were efficiently modulated through derivatization of the phosphorus center. X‐ray crystallographic analysis, UV/Vis spectroscopic, and electrochemical studies supported by DFT calculations identified the considerable potential of these scaffolds for the development of organophosphorus functional materials with tailored properties upon further functionalization.
Understanding the Effect of Hydroxypropyl‐β‐Cyclodextrin on Fenebrutinib Absorption in an Itraconazole–Fenebrutinib Drug–Drug Interaction Study
Authors: Durk Matthew R. , Jones Nicholas S. , Liu Jia , Nagapudi Karthik , Mao Chen , Plise Emile G. , Wong Susan , Chen Jacob Z. , Chen Yuan , Chinn Leslie W. , Chiang Po‐Chang 
Published: June 2020

Cyclodextrins are widely used pharmaceutical excipients, particularly for insoluble compounds dosed orally, such as the oral solution of itraconazole, which is frequently used in clinical drug–drug interaction studies to inhibit cytochrome P450 3A. Since cyclodextrins act by forming inclusion complexes with their coformulated drug, they could have an unintended consequence of affecting absorption if they form a strong complex with the potential victim drug in an itraconazole drug–drug interaction study. This observation was made in a drug–drug interaction study with the Bruton’s tyrosine kinase (BTK) inhibitor fenebrutinib and itraconazole, in which, relative to the control group, the expected increase in fenebrutinib maximum plasma concentration (Cmax) was not observed in the itraconazole group, and a delay in time to reach maximum plasma concentration (Tmax) was observed in the itraconazole group. The in vitro binding constant between fenebrutinib and hydroxypropyl‐β‐cyclodextrin was determined to be 2 × 105 M−1, and the apparent permeability of fenebrutinib across a Madin‐Darby canine kidney cell monolayer decreased in a cyclodextrin concentration‐dependent manner. This observation was confirmed in vivo, in a pentagastrin‐pretreated dog model, in which fenebrutinib was administered with or without cyclodextrin; a reduction in Cmax, a prolonged Tmax, and increased fenebrutinib recovery in feces replicated the previous observation in healthy volunteers and supported the hypothesis that complexation with cyclodextrin decreased rate and extent of fenebrutinib absorption. Physiologically‐based pharmacokinetic modeling was used to translate the in vitro effect of cyclodextrin on fenebrutinib apparent permeability to the in vivo effect on absorption, which was then confirmed using the in vivo dog pharmacokinetic data.
The variable association between expression and methylation of estrogen receptors and the survival of patients with different tumors
Authors: Hu Chao , Liu Yinhua , Jiang Shan , Chen Hongjin , Xu Haojun , Hu Junhong , Li Congzhu , Xia Hongping 
Published: June 2020

AbstractBackgroundEstrogen receptor (ER) is essential in reproductive development and is also the primary driver of breast cancers. Deregulation of ER may also be involved in tumorigenesis of other organs. To understand the role of ER in different tumor types, pan‐cancer analysis of estrogen receptor alpha (ESR1) and estrogen receptor beta (ESR2) in various tumors and association with patients' survival were conducted using The Cancer Genome Atlas (TCGA) data.ResultsGene methylation level was evaluated by the mean methylation level of CpG sites in the promoter region. The significant different DNA methylation between tumor and healthy tissues was shown in 10 tumor types for ESR1 and eight tumor types for ESR2. The methylation pattern was also varied across different TCGA tumors. The pan‐cancer analysis showed significantly different mRNA expression of ESR1 in nine tumor types and ESR2 in four tumor types. Survival analysis showed that the effects of ERs expression on survival are diverse in different tumors. The expression of ERs was associated with tumor molecular subtypes and various clinical characteristics. ER correlated genes were mainly enriched in cancer and immune‐related pathways.ConclusionsOur pan‐cancer analysis data indicated that ERs might be significantly associated with carcinogenesis and progression of some tumors, which may be potential therapeutic targets and prognosis biomarkers.