bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dipeptidyl Peptidase 4 Inhibitors
Authors: Weber Ann E. , Thornberry Nancy A. 
Published: April 2021

AbstractType 2 diabetes (T2DM) is a growing worldwide epidemic. While a number of oral agents have been available to treat T2DM, they suffer from safety and tolerability issues and lack durability. In the 1990s, glucagon‐like peptide 1 (GLP‐1) emerged as a new approach to glucose lowering. Endogenous GLP‐1 is rapidly inactivated through the action of dipeptidyl peptidase 4 (DPP‐4), a serine dipeptidyl aminopeptidase that cleaves its N‐terminal two amino acids. Blocking DPP‐4 with a small molecule inhibitor was shown to increase circulating levels of GLP‐1 in rodent models and humans, leading to improved glucose control. Early DPP‐4 inhibitors were dipeptide mimetics, some of which bound to the DPP‐4 active site serine in a covalent manner. Screening and structure‐based drug design led to the identification of many other structural classes. In 2006, sitagliptin became the first DPP‐4 inhibitor approved by the FDA. Inhibitors now available include two for once‐weekly administration. Over 10 years of clinical experience has shown DPP‐4 inhibition to be safe and effective with a low risk of hypoglycemia, no weight gain, and no increased cardiovascular risk. Used as monotherapy or in combination with other glucose‐lowering medications, DPP‐4 inhibitors have become an important class of oral agents to treat T2DM.
Anti‐DNA Virus Agents
Authors: Herdewijn Piet , Gu Weijie , De Clercq Erik 
Published: April 2021

Abstract
Although most of the drugs that are used to treat deoxyribonucleic acid (DNA) virus infections have been on the market for more than 10 years, anti‐DNA virus drug discovery remains an active field of research. There are still DNA viruses that are important human pathogens for which no therapy is available (i.e. adenovirus), for which the available drugs show considerable toxicity (i.e. cytomegalovirus), or for which the current drug therapy is insufficient to eradicate the virus (i.e. hepatitis B virus). In this article, we have provided an overview of the anti‐DNA virus drugs that are presently on the market together with a description of the new compounds, all active against DNA viruses, covering the literature of the past 10 years. We have focused on the structure of newly discovered compounds, and the mechanism of action and clinical data, when available.
Although the major efforts are still in the nucleotide antimetabolite field, the anti‐DNA virus field of research and development has shifted recently in the direction of the study of more common heterocyclic structures as protein inhibitors.
Enzymes as Drug Targets
Authors: Meek Thomas D. 
Published: April 2021

Abstract
Many drugs commonly used today to treat infectious diseases, cancers, inflammatory, cardiovascular, and metabolic diseases, are enzyme inhibitors or inactivators. Examples exist for all six classes of enzymes, but inhibitors of hydrolases, transferases, and oxidoreductases predominate. Typically, enzyme inhibitors or inactivators that progress to become drugs exert high potency toward their targets at concentrations of 100 nanomolar or less, and attending these potencies is high selectivity for their targets. Drugs that block the activity of enzymes do so by either covalent reaction with nucleophilic enzymatic residues, or by noncovalent binding. Covalent inactivation by affinity agents and mechanism‐based inactivators is generally irreversible, leading to time‐dependent loss of enzyme activity that is normally un‐recoverable. Drugs that are noncovalent enzyme inhibitors, including bi‐substrate analogs, and analogs of enzyme reaction intermediates and transition states, like their covalent counterparts, often display time‐dependent inhibition despite the absence of covalent reaction. This pseudoirreversible inhibition is manifest at nanomolar concentrations of inhibitor, and is due to the isomerization of an initial enzyme–inhibitor complex to a tighter binary complex which reverses very slowly, if at all. Natural‐product enzyme inhibitors have provided the blueprints for many drugs, including the statins, epoxomicin, and inhibitors of HIV protease. We describe herein the aforementioned types of enzyme inhibitors and inactivators that, through the application of medicinal chemistry have rendered new therapies, including case histories of many of the more important drugs that block the action of enzymes.
FDA‐Approved Medicines
Authors: Kinch Michael S. 
Published: April 2021

AbstractAlthough medicines have been needed for the entire span of human existence, the age of pharmaceuticals is a relatively recent era. The benefits accompanying the introduction of new medicines meant to combat age‐old maladies have dramatically altered public health and society. Herein, we review the history of drug discovery, demonstrating a constant evolution in both the approaches utilized and the outcomes of technological and scientific advances. These innovations have come with a cost as reflected in the ever‐increasing amounts of resources to develop a medicine. Indeed, we see the industry, as currently configured, is faced with unprecedented challenges that could soon threaten its very existence.
Therapeutic Strategies for the Treatment of Sickle Cell Disease
Authors: Safo Martin K. , Aljahdali Anfal , Burnett James , Abraham Donald J. , Abdulmalik Osheiza 
Published: April 2021

Abstract

There are many important new advances in the development of clinically viable therapeutic options to mitigate the pathophysiology of sickle cell disease (SCD). Some of the most promising new clinical candidates reported herein directly address the primary cause of the disease by allosterically modifying sickle hemoglobin (HbS). In particular, one family of small molecules stabilizes the high oxygen (O
2
)‐affinity R‐state of the protein, which, unlike the low O
2
‐affinity T‐state, does not present the polymerization promoting βVal6 residue. Several compounds employing this mechanism are currently at various stages of preclinical and clinical investigations. Another series of compounds that engage in a covalent bond with the surface‐located residue βCys93 of HbS, and thus destabilize the T‐state to increase Hb affinity for oxygen, is currently under preclinical development. Furthermore, promising new compounds that, similar to hydroxyurea also induce fetal Hb production, are at various stages of clinical development. Finally, compounds that target the secondary pathophysiology of SCD, including those that counter the dehydration of sickle erythrocyte; endothelial adhesion and vasculature damage; nitroxide donors providing vasodilatory and anti‐inflammatory effects; and a myriad of anti‐inflammatory and anticoagulation candidate molecules, are also being investigated in early‐ and/or late‐stage clinical trials.
Bacterial Efflux Pumps and Their Inhibitors
Authors: Zgurskaya Helen I. , Rybenkov Valentin V. , Walker John K. , Parks Jerry M. 
Published: April 2021

AbstractBacterial multidrug efflux transporters have distinct molecular features and mechanisms that enable their impressive substrate polyspecificity. These transporters are involved in all physiological processes where nonspecific but active transport across membranes is critical for survival and proliferation. Importantly, efflux pumps contribute to bacterial virulence and pathogenesis, as well as the spread of antibiotic resistance in clinics. Transporters belonging to several protein superfamilies have been selected for polyspecificity by evolution and augmented with accessory proteins that extend and couple transport reactions across the inner and outer membranes of the bacterium. As a result, bacteria are equipped with diverse efflux machines that protect cells from a broad variety of toxic compounds including antibiotics and other small molecule therapeutics. The inhibition of such polyspecific biomolecular machines is a challenging task, which still awaits an efficient solution. Here, we review the molecular mechanisms of efflux pumps from Gram‐negative bacteria and recent advances and challenges associated with the discovery of effective inhibitors of these pumps.
Computational Chemistry Tools
Authors: Metcalf Rainer , Daniel Kenyon , Brooks Wesley , Guida Wayne 
Published: April 2021

AbstractThis article expounds on some of the current computational tools and programs available and the best practices associated with their use. A high‐level introduction, intended for both novices and the semi‐experienced, focusing on the more common programs used in scientific literature is the scope of this article. Both classical and quantum techniques are described. Classical methodologies include molecular dynamics, Monte Carlo, energy minimization methods, molecular docking, low‐mode, and homology modeling. Quantum chemistry techniques are also discussed, encompassing Hartree–Fock, Post‐Hartree–Fock theories, and Density Functional Theory along with associated basis sets. A summary is provided to give a general overview of common modeling software and their functionality.
Genetic Code and Its Variations
Authors: Suzuki Tsutomu , Nagao Asuteka 
Published: April 2021

Abstract

The standard genetic code is a common language used by almost all organisms to translate nucleotide sequences from DNA and RNA into the amino acid sequences of proteins. However, the standard code is not used in all cases, and some organisms and organelles use variant codes.

The genetic code is a basic grammar for translating genetic information into amino acid sequence of protein. Most organisms use the same genetic code, so‐called standard genetic code, assuming that all domains of life evolved from a single organism.

Transfer RNA (tRNA)is an adaptor molecule that links the genetic code with its corresponding amino acid via codon‐anticodon interaction.

A wide variety of chemical modifications in the tRNA anticodons play an important role in accurate protein synthesis by restriction, expansion and alteration of codon recognition.

Natural instances of genetic code variation in several organisms and organelles violated a concept that the genetic code is frozen, but proposed it has continued to evolve.

Recoding is an alternative usage of genetic code in some special biological contexts. including programmed ribosome frameshifting, stop‐codon read‐through, insertion of nonstandard amino acids and translational bypassing.
3D Porous Honeycomb‐Like CoN‐Ni3N/N‐C Nanosheets Integrated Electrode for High‐Energy‐Density Flexible Supercapacitor
Authors: Li Kunzhen , Zhao Bangchuan , Zhang Hui , Lv Hongyan , Bai Jin , Ma Hongyang , Wang Peiyao , Li Wanyun , Si Jianguo , Zhu Xuebin , Sun Yuping 
Published: April 2021

AbstractTransition metal nitrides (TMNs) are considered as potential electrode materials for high‐performance energy storage devices. However, the structural instability during the electrochemical reaction process severely hinders their wide application. A general strategy to overcome this obstacle is to fabricate nanocomposite TMNs on the conducting substrate. Herein, the honeycomb‐like CoN‐Ni3N/N‐C nanosheets are in situ grown on a flexible carbon cloth (CC) via a mild solvothermal method with post‐nitrogenizing treatment. As an integrated electrode for the supercapacitor, the optimized CoN‐Ni3N/N‐C/CC achieves remarkable electrochemical performance due to the enhanced intrinsic conductivity and increased concentration of the active sites. In particular, the flexible quasi‐solid‐state asymmetric supercapacitor assembled with CoN‐Ni3N/N‐C/CC cathode and VN/CC anode delivers an excellent energy density of 106 μWh cm−2, maximum power density of 40 mW cm−2, along with an outstanding cycle stability. This study provides a neoteric perspective on construction of high‐performance flexible energy storage devices with novel metallic nitrides.
Amorphous Domains in Black Titanium Dioxide
Authors: Kang Jianxin , Zhang Yan , Chai Ziwei , Qiu Xiaoyi , Cao Xingzhong , Zhang Peng , Teobaldi Gilberto , Liu Li‐Min , Guo Lin 
Published: April 2021

AbstractAlthough oxygen vacancies (Ovs) play a critical role for many applications of metal oxides, a controllable synthetic strategy for anisotropic Ovs remains a great challenge. Here, a novel strategy is proposed to achieve the regional dual structure with anisotropic Ovs at both the surface and in the interior of TiO2 by constructing amorphous domains. The as‐prepared black TiO2 with amorphous domains exhibits superior activity in degrading rhodamine B (RhB) solutions, which can instantly decompose RhB with just a shake. First‐principle simulations reveal that subsurface Ovs in TiO2 are energetically favored, resulting in the formation of amorphous domains in the interior region via diffusion of surface‐formed Ovs into the subsurface. The stable Ov‐induced amorphous domains in TiO2 with enhanced catalytic performances provide a scalable strategy to practical Ov engineering in functional metal oxides.
MIL‐101‐Derived Mesoporous Carbon Supporting Highly Exposed Fe Single‐Atom Sites as Efficient Oxygen Reduction Reaction Catalysts
Authors: Xie Xiaoying , Peng Lishan , Yang Hongzhou , Waterhouse Geoffrey I. N. , Shang Lu , Zhang Tierui 
Published: April 2021

AbstractFe single‐atom catalysts (Fe SACs) with atomic FeNx active sites are very promising alternatives to platinum‐based catalysts for the oxygen reduction reaction (ORR). The pyrolysis of metal–organic frameworks (MOFs) is a common approach for preparing Fe SACs, though most MOF‐derived catalysts reported to date are microporous and thus suffer from poor mass transfer and a high proportion of catalytically inaccessible FeNx active sites. Herein, NH2‐MIL‐101(Al), a MOF possessing a mesoporous cage architecture, is used as the precursor to prepare a series of N‐doped carbon supports (denoted herein as NC‐MIL101‐T) with a well‐defined mesoporous structure at different pyrolysis temperatures. The NC‐MIL101‐T supports are then impregnated with a Fe(II)‐phenanthroline complex, and heated again to yield Fe SAC‐MIL101‐T catalysts rich in accessible FeNx single atom sites. The best performing Fe SAC‐MIL101‐1000 catalyst offers outstanding ORR activity in alkaline media, evidenced by an ORR half‐wave potential of 0.94 V (vs RHE) in 0.1 m KOH, as well as excellent performance in both aqueous primary zinc–air batteries (a near maximum theoretical energy density of 984.2 Wh kgZn−1) and solid‐state zinc–air batteries (a peak power density of 50.6 mW cm−2 and a specific capacity of 724.0 mAh kgZn−1).
Heterophase Interface Dominated Deformation and Mechanical Properties in Al‐Cu‐Li Alloys
Authors: Wang Shuo , Zhang Chi , Li Xin , Wang Junsheng 
Published: April 2021

AbstractAs a common phenomenon in multiphase systems, interfacial deformation has a significant impact on the mechanical properties of materials. By utilizing the brittle cleavage and plastic slip modes, the deformation mechanism is tracked and mechanical properties of precipitate/matrix and precipitate/precipitate heterophase interfaces are induced in third‐generation Al‐Li alloys, including δ'(Al3Li)/α‐Al, θ'(Al2Cu)/α‐Al, and δ'(Al3Li)/θ'(Al2Cu) (depending on the ultrafine δ'/θ'/δ' composite precipitate). Based on bond energy and ideal stress calculations under tensile and shear deformations, it is noted that the universal interface separating the two phases is not the weakest link in these systems. In δ'/θ'/δ', specifically, the defined coherent interface I closing to the δ' may become a weak cracking point under tensile loading. Whereas, the semi‐coherent interface II on the edge of the δ'/θ'/δ' tends to undergo interplanar slip along the [001] direction at relatively low shear stress. By releasing a partial dislocation under shear deformation, the local stable stacking fault can occur in this semi‐coherent interface. And the interface‐mediated plasticity within the ultrafine δ'/θ'/δ' composite precipitate could be expected to solve the origin of the strength‐ductility conflict in modern Al‐Li alloys. Besides, the electronic structures and atomic bonding are performed to reveal the mechanism behind the improved interface strength.
Spread of X‐chromosome inactivation into autosomal regions in patients with unbalanced X‐autosome translocations and its phenotypic effects
Authors: Favilla Bianca Pereira , Meloni Vera Ayres , Perez Ana Beatriz , Moretti‐Ferreira Danilo , de Souza Deise Helena , Bellucco Fernanda Teixeira , Melaragno Maria Isabel 
Published: April 2021

AbstractPatients with unbalanced X‐autosome translocations are rare and usually present a skewed X‐chromosome inactivation (XCI) pattern, with the derivative chromosome being preferentially inactivated, and with a possible spread of XCI into the autosomal regions attached to it, which can inactivate autosomal genes and affect the patients' phenotype. We describe three patients carrying different unbalanced X‐autosome translocations, confirmed by G‐banding karyotype and array techniques. We analyzed their XCI pattern and inactivation spread into autosomal regions, through HUMARA, ZDHHC15 gene assay and the novel 5‐ethynyl‐2′‐deoxyuridine (EdU) incorporation assay, and identified an extremely skewed XCI pattern toward the derivative chromosomes for all the patients, and a variable pattern of late‐replication on the autosomal regions of the derivative chromosomes. All patients showed phenotypical overlap with patients presenting deletions of the autosomal late‐replicating regions, suggesting that the inactivation of autosomal segments may be responsible for their phenotype. Our data highlight the importance of the XCI spread into autosomal regions for establishing the clinical picture in patients carrying unbalanced X‐autosome translocations, and the incorporation of EdU as a novel and precise tool to evaluate the inactivation status in such patients.
Hybrid Electrolyte Engineering Enables Safe and Wide‐Temperature Redox Flow Batteries
Authors: Zhang Leyuan , Yu Guihua 
Published: April 2021

AbstractElectrolyte is an important component in redox flow batteries (RFBs) that determines the current capability, potential window, and safety, but both aqueous and nonaqueous electrolytes have their intrinsic limits. Here, we develop the proof‐of‐concept hybrid electrolyte chemistry to enable the design of safe and wide‐temperature RFBs. In addition to the non‐flammable characteristics, the hybrid electrolyte also inherits the high electrochemical stability and wide operational temperature range. It can show a potential window of 2.5 V and maintain high ion conductivities at low temperatures. It also enables LiI to achieve high Coulombic efficiencies of >99.9 %, showing long cycling stability over 800 cycles. Moreover, it enables the successful operation of Zn/LiI RFBs at −20 °C for 150 cycles with nearly no capacity loss. This study highlights the great potential of hybrid electrolyte chemistry for the approach of safe and high‐performance large‐scale energy storage systems in wide temperature ranges.
Direct Observation of Metal Oxide Nanoparticles Being Transformed into Metal Single Atoms with Oxygen‐Coordinated Structure and High‐Loadings
Authors: Liu Jian , Cao Changyan , Liu Xiaozhi , Zheng Lirong , Yu Xiaohu , Zhang Qinghua , Gu Lin , Qi Ruilian , Song Weiguo 
Published: April 2021

AbstractDirect conversion of bulk metal or nanoparticles into metal single atoms under thermal pyrolysis conditions is a highly efficient and promising strategy to fabricate single‐atom catalysts (SACs). Usually, nitrogen‐doped carbon is used as the anchoring substrate to capture the migrating metal ion species at high temperatures, and stable isolated SACs with nitrogen coordination are formed during the process. Herein, we report unexpected oxygen‐coordinated metal single‐atom catalysts (Fe‐, Co‐, Ni‐, Mn‐SACs) with high loadings (above 10 wt %) through direct transformation of metal oxide nanoparticles (Fe‐, Co‐, Ni‐, Mn‐NPs) in an inert atmosphere at 750 °C for 2 h. The atomic dispersion of metal single atoms and their coordinated structures were confirmed by aberration‐corrected scanning transmission electron microscopy and X‐ray absorption fine structures. In addition, the dynamic process of nanoparticles to atoms was directly observed by in situ transmission electron microscopy. The as‐prepared Fe SAC exhibited high activity and superior selectivity for catalytic oxidation of benzene to phenol with hydrogen peroxide.
Monitoring the curing processes of epoxy oligomers with partially substituted polyethoxymetallosiloxanes by IR spectroscopy and thermomechanical analysis
Authors: Parshina Maria S. , Tarasenkov Alexander N. , Aysin Rinat R. , Tebeneva Nadezhda A. , Buzin Michail I. , Afanasyev Egor S. , Serenko Olga A. , Muzafarov Aziz M. 
Published: April 2021

AbstractIn this work, the curing of «ED‐20» epoxy resin with partially siloxy‐substituted aluminum, iron, and zirconium siloxanes that we obtained previously was studied. The initial content of a metallosiloxane in the compositions was 5–50 wt% with respect to the resin. In all the cases, thermal curing was used to obtain a series of samples in the form of solid homogeneous materials. The fact of the epoxy ring opening in the resin was confirmed by IR spectroscopy. The catalytic properties of the metal atom in a metallosiloxane were found to affect the curing process. The samples demonstrate rather a high resistance to thermooxidative destruction, and in most cases, their glass transition temperatures are lower than those obtained upon standard curing of «ED‐20» resin with triethylenetetramine. Partially siloxy‐substituted metalloalkoxysiloxanes can be efficient agents for curing and formation of a hybrid material based on epoxy resins.
Hierarchical consensus problem in hybrid multiagent systems
Authors: Hou Jian , Tang Qingshi , Xiang Gang , Luo Shuyun 
Published: April 2021

AbstractThis paper considers a hierarchical consensus problem in hybrid multiagent systems. By partitioning the agents into several groups, each group contains a value concerning all the state information inside the group, which is called group information. For each single agent, its control input includes not only the inner‐group neighboring agent information but also the group information from its neighboring groups. Moreover, we discuss two kinds of hybrid systems composing of both continuous‐time and discrete‐time dynamic information and propose the corresponding control laws. Finally, simulations are provided to demonstrate the effectiveness of our theoretical results.
Cancer as a prospective sequela of long COVID‐19
Authors: Saini Geetanjali , Aneja Ritu 
Published: April 2021

AbstractAs the spread of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) continues to surge worldwide, our knowledge of coronavirus disease 2019 (COVID‐19) is rapidly expanding. Although most COVID‐19 patients recover within weeks of symptom onset, some experience lingering symptoms that last for months (“long COVID‐19”). Early reports of COVID‐19 sequelae, including cardiovascular, pulmonary, and neurological conditions, have raised concerns about the long‐term effects of COVID‐19, especially in hard‐hit communities. It is becoming increasingly evident that cancer patients are more susceptible to SARS‐CoV‐2 infection and are at a higher risk of severe COVID‐19 than the general population. Nevertheless, whether long COVID‐19 increases the risk of cancer in those with no prior malignancies, remains unclear. Given, the disproportionate impact of the disease on the African American community, yet another unanswered question is whether racial disparities are to be expected in COVID‐19 sequelae. Herein, we propose that long COVID‐19 may predispose recovered patients to cancer development and accelerate cancer progression. This hypothesis is based on growing evidence of the ability of SARS‐CoV‐2 to modulate oncogenic pathways, promote chronic low‐grade inflammation, and cause tissue damage. Comprehensive studies are urgently required to elucidate the effects of long COVID‐19 on cancer susceptibility.