bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microbes to Man: From Soils and the Depths to Drugs
Authors: Newman David J. 
Published: April 2021

AbstractThis article covers microbially sourced antibiotics and anticancer agents that have either been approved by regulatory agencies (US and EU), are awaiting approval or are generally in Phases I–Phase III (cancer) or Phase I–IV (antibiotics). Also included are discussions of compounds that have been “developed” by synthetic chemists using as their templates, materials originally from microbes. Included are discussions on developments with genetic analyses of as yet uncultured (perhaps unculturable in the case of some symbionts), including use of environmental DNA (eDNA) as routes to novel agents where the microbe is unknown, even “unknowable.” In addition, examples are given of how agents that are too toxic to act as pharmaceutical agents in their own right, have now become major components of novel treatments for cancer treatment by linking these “toxins” to monoclonal antibodies directed to particular epitopes on cancerous cells, thus delivering highly toxic and effective agents directly to the site(s) needed. Comments have also been made about the lack of new antimicrobials, in particular directed toward fungal infections and the ESKAPE pathogen series, where agents long out of use, are now acting as templates upon which to design novel potent compounds.
Structure Alerts
Authors: Norman Bryan 
Published: April 2021

Abstract
Structure alerts are classes of chemicals, functional groups, or substructures that, when present in drugs or drug candidates, have been linked to preclinical toxicity and/or adverse drug reactions (ADRs) in humans. The assignment of structure alerts, which includes a wide variety of structural types, has mostly emerged from retrospective analyses of drug or drug candidates that have demonstrated toxicity. Some compounds are inherently toxic, while others containing structure alerts manifest toxicity due to metabolism and formation of reactive metabolites. In many cases, the mechanisms associated with toxicity have been hypothesized to be the result of covalent binding of a drug or metabolite to endogenous nucleophiles in proteins and nucleic acids. Strategies to mitigate toxicity due to structure alerts have generally focused on avoidance and/or replacement of the structure alert. However, as many safe and successful drugs contain structure alerts, there is no industry‐wide alignment on which should always be avoided or replaced. It has been demonstrated that ADRs are more likely to occur in higher dose drugs (>100 mg) and more lipophilic drugs (LogP >3). The inclusion of structure alerts in drug candidates that have these liabilities may increase the risk of toxicity.
Structure‐Based Drug Design
Authors: Ferreira Leonardo L.G. , Andricopulo Adriano D. 
Published: April 2021

Abstract
Structure‐based drug design (SBDD) is the backbone of modern pharmaceutical research and development. Its origins date back to the 1950s and 1960s when the first X‐ray protein structures and pioneering studies correlating ligand–receptor binding and drug activity came out. With this foundation, seminal work on computer graphics enabled the first visualization and manipulation of virtual protein structures. These milestones opened the avenues for the growth of protein crystallography and molecular modeling, which thenceforth evolved side by side to culminate in modern SBDD. Today, SBDD can handle molecular targets previously regarded as intractable or undruggable, such as protein–protein interactions. Another advance coming from SBDD, fragment‐based drug discovery has excelled in optimizing weak ligands into drug‐like compounds. SBDD has provided groundbreaking drugs for many therapeutic areas, including highly complex conditions and diseases that were previously considered a death sentence. In fact, a substantial fraction of the drugs approved recently have been developed with the support of structural data. This article provides a perspective on the central aspects of this exciting field and explores the fundamentals of molecular modeling and its integration with X‐ray diffraction. The discussion of key concepts is followed by representative examples of the practice of SBDD.
Recent Advances in Catalyst Structure and Composition Engineering Strategies for Regulating CO2 Electrochemical Reduction
Authors: Zhu Shangqian , Delmo Ernest Pahuyo , Li Tiehuai , Qin Xueping , Tian Jian , Zhang Lili , Shao Minhua 
Published: April 2021

AbstractElectrochemical CO2 reduction has been recognized as a promising solution in tackling energy‐ and environment‐related challenges of human society. In the past few years, the rapid development of advanced electrocatalysts has significantly improved the efficiency of this reaction and accelerated the practical applications of this technology. Herein, representative catalyst structures and composition engineering strategies in regulating the CO2 reduction selectivity and activity toward various products including carbon monoxide, formate, methane, methanol, ethylene, and ethanol are summarized. An overview of in situ/operando characterizations and advanced computational modeling in deepening the understanding of the reaction mechanisms and accelerating catalyst design are also provided. To conclude, future challenges and opportunities in this research field are discussed.
Engineering a Hydrogen‐Sulfide‐Based Nanomodulator to Normalize Hyperactive Photothermal Immunogenicity for Combination Cancer Therapy
Authors: Li Jie , Xie Lisi , Li Bei , Yin Chao , Wang Guohao , Sang Wei , Li Wenxi , Tian Hao , Zhang Zhan , Zhang Xuanjun , Fan Quli , Dai Yunlu 
Published: April 2021

AbstractPhotothermal therapy (PTT), one of the most‐potent cancer therapeutic strategies known, is highlighted with excessive inflammatory response, while ablating cancer with immunogenic death. This hyperactive immune response may override PTT‐triggered immunogenicity, exacerbate skin empyrosis, and incur permanent tissue injury and high‐profile tumor regeneration. Therefore, an anticancer balance between pathological and protective immune response is urgently needed for an advanced photothermal therapeutic tactic. Herein, a gas‐modulated photothermal immunogenicity strategy is proposed by integrating an amphiphilic‐conjugated polymer with a polysulfide‐based hydrogen sulfide (H2S) donor (2,2′‐dipyridyl tetrasulfide@CP‐PEG) (where CP = conjugated polymer and PEG = poly(ethylene glycol)). The CP is endowed with NIR‐II fluorescence capacity and favorable photothermal effect, tracing the tumor for precise therapeutics. The polysulfide donor can release H2S triggered by intracellular glutathione, which elicits mitochondrial dysfunction and robust anti‐inflammation effect. Ultimately, this gas‐modulated PTT strategy inhibits tumor growth remarkably and limits the magnitude of PTT‐induced proinflammatory tumor necrosis factor‐alpha (TNF‐α), interleukin‐6 (IL‐6), and interleukin‐1beta (IL‐1β) cytokines. Moreover, the regulated inflammation accelerates PTT‐induced wound healing. A H2S‐modulated PTT with adaptive immune response is thus recommended as an advanced strategy to cancer therapeutics.
Surfactant and irrigation impacts on soil water content and leachate of soils and greenhouse substrates
Authors: Abagandura Gandura Omar , Park Dara , Bridges William C. 
Published: April 2021

AbstractWater retentionx is considered an important characteristic for determining the efficiency and effectiveness of soils and greenhouse substrates. Surfactants have the potential to improve water infiltration and distribution uniformity throughout the soil profile. In addition, efficient irrigation can improve the wettability of soils. The objective of this study was to determine how surfactants and irrigation influence soil water content (SWC), leachate volume, and pH in soils and greenhouse substrates. This study was conducted at Clemson University, SC, on two soils (sandy loam and sand) and two substrates (Fafard 3B‐SURF and 80% sand, 20% peat). Four surfactants (a) 10% oleic acid esters of block copolymers (OAC), (b) 30% alkoxylated polyols and 21% glucoethers (APG), (c) 50% nonionic polyols and 5% 1,2‐propanediol (NIPP), and (d) water control (CNT) with two irrigation regimes (ONCE and SPLIT) were applied to PVC columns. Based on the leachate results, applying irrigation volume as SPLIT in conjunction with using a surfactant reduced leachate up to 75%. The soils retained more water when OAC and NIPP surfactants were applied. When the soil was left to dry out, the SWC was 5 and 9% higher from SPLIT irrigation compared with ONCE irrigation in the sand–peat and the sand soils, respectively. Surfactants can increase SWC, and combining split irrigation with surfactants can play an important role in reducing leaching from soils and greenhouse substrates, resulting in water quality and quantity conservation, and an economic advantage to the grower.
Low‐Temperature Nickel‐Catalyzed C−N Cross‐Coupling via Kinetic Resolution Enabled by a Bulky and Flexible Chiral N‐Heterocyclic Carbene Ligand
Authors: Wang Zi‐Chao , Xie Pei‐Pei , Xu Youjun , Hong Xin , Shi Shi‐Liang 
Published: April 2021

AbstractThe transition‐metal‐catalyzed C−N cross‐coupling has revolutionized the construction of amines. Despite the innovations of multiple generations of ligands to modulate the reactivity of the metal center, ligands for the low‐temperature enantioselective amination of aryl halides remain a coveted target of catalyst engineering. Designs that promote one elementary reaction often create bottlenecks at other steps. We here report an unprecedented low‐temperature (as low as −50 °C), enantioselective Ni‐catalyzed C−N cross‐coupling of aryl chlorides with sterically hindered secondary amines via a kinetic resolution process (s factor up to >300). A bulky yet flexible chiral N‐heterocyclic carbene (NHC) ligand is leveraged to drive both oxidative addition and reductive elimination with low barriers and control the enantioselectivity. Computational studies indicate that the rotations of multiple σ‐bonds on the C2‐symmetric chiral ligand adapt to the changing needs of catalytic processes. We expect this design would be widely applicable to diverse transition states to achieve other challenging metal‐catalyzed asymmetric cross‐coupling reactions.
Socrates on the Farm: Agricultural Improvement and Rural Knowledge in Eighteenth‐Century Germany and Switzerland
Authors: Phillips Denise 
Published: April 2021

AbstractIn many eighteenth‐century agricultural texts, peasants were depicted as an impediment to agrarian improvement, superstitious and resistant to novelty. That was the stereotype one often encountered, in any case, in more programmatic writing about agriculture from this period. A closer look at the era's technical literature tells a more complicated story, however. Much as traveling European naturalists relied on local intermediaries in far corners of the globe, elite agricultural improvers back home relied on local rural knowledge as they drafted a new technical literature on farming. This article looks at Jacob Guyer (also known as Kleinjogg), a Swiss farmer who became an enlightened celebrity after the Zurich doctor Hans Caspar Hirzel published a biography of him in 1761. Hirzel called Kleinjogg a “philosophical farmer”; the article explores the implications of this title, and examines the various ways that elite eighteenth‐century authors used contact with rural people and direct experience of farming as a source of authority.
Ultra‐sensitive detection of ATP in serum and lysates based on nitrogen‐doped carbon dots
Authors: Qin Yaning , Yan Zhaoyue , Liu Rui , Qu Chaojie , Mao Haichen , Qu Lingbo , Yang Ran 
Published: April 2021

AbstractIn this work, novel types of nitrogen‐doped carbon dots (N‐CDs) were prepared from citric acid and glycine (GLY) as precursors through a simple pyrolysis method. The GLY‐CDs showed strong fluorescence with a fluorescence quantum yield as high as 33.34% and good water solubility. The fluorescence of GLY‐CDs could be selectively quenched by iron(III) ion (Fe3+) resulting in the non‐fluorescent complex. Due to the high affinity of Fe3+ to adenosine‐5′‐triphosphate (ATP), the fluorescence of the GLY‐CDs in GLY‐CDs‐Fe3+ could be recovered by ATP. Thereby, quantitatively fluorescent turn‐on detection of ATP could be achieved. The fluorescence recovery ratio was linearly proportional to the concentration of ATP with a detection limit as low as 15.0 nM, indicating the CDs have high sensitivity. The GLY‐CDs were successfully employed in the detection of ATP in serum and cell lysates.
Surface Roughness Effects of Pd‐loaded Magnetic Microspheres on Reduction Kinetics of Nitroaromatics
Authors: An Seonghwi , Manivannan Shanmugam , Viji Mayavan , Shim Min Suk , Hwang Byeong Hee , Kim Kyuwon 
Published: April 2021

Metal nanoparticles decoration on magnetically active semiconductor materials is a common strategy to improve the colloidal stability, catalyst harvesting, and reuse. In this study, a surfactant‐free solvothermal method followed by a heat treatment to prepare highly surface roughened α‐Fe2O3 (Hematite)/Pd microspheres (MSPs) is reported. Amine‐functionalized silicate sol‐gel matrix is used as a stabilizing agent for the solvothermal synthesis of Prussian blue (PB) MSPs using HCl at 80 °C for 20 h. It is observed that modulating HCl concentration in a medium led to a high degree of improvement in surface roughness. Employing heat treatment at 350 °C for 6 h, PB MSPs are transformed into α‐Fe2O3, Hematite phase. Fabricated Hematite/Pd MSPs have shown high catalytic reduction activity over p‐nitrophenol. Reduction kinetics of nitroaromatics is monitored using UV‐vis absorption spectroscopy and product formation is confirmed by 1H and 13C NMR analyses.
Carbo‐mer of Barrelene: A Rigid 3D‐Carbon‐Expanded Molecular Barrel
Authors: Zhu Chongwei , Poater Albert , Duhayon Carine , Kauffmann Brice , Saquet Alix , Rives Arnaud , Maraval Valérie , Chauvin Remi 
Published: April 2021

AbstractAfter extensive studies of 1D and 2D skeletal carbo‐mers based on C8 π‐conjugating dialkynylbutatriene units (DABs: ∼C≡C−(R)C=C=C=C(R)−C≡C∼) bridging sp or sp2 centers in carbo‐butene, carbo‐xylylene or carbo‐benzene derivatives, 3D versions are envisaged through carbo‐barrelenes and partially reduced derivatives thereof where two or three DAB blades span a bridge between sp3 carbinol vertices or ether thereof. For R=Ph, stable representatives were synthesized through a pivotal [6]pericyclynedione, and extensively characterized by spectroscopic, electrochemical and crystallographic methods. Density functional theory calculations allow detailed analysis of structural and electronic features of the 7 Å high C26 barrel‐shaped molecules, and show that they can behave as cages for ionic species. Beyond aesthetical concerns, the results could open prospects of applications in host‐guest supramolecular chemistry and single molecule charge transport.
Morphology Engineering of Fullerene[C70] Microcrystals: From Perfect Cubes, Defective Hoppers to Novel Cruciform‐Pillars
Authors: Xu Ting , Chen Ning , He Zhimin , Yu Pengwei , Shen Wangqiang , Akasaka Takeshi , Lu Xing 
Published: April 2021

AbstractControlled crystallization of fullerene molecules into ordered molecular assemblies is important for their applications. However, the morphology engineering of fullerene[C70] assemblies is challenging, and complicated architectures have rarely been reported due to the low molecular symmetry of C70molecules, which makes their crystallization difficult to control and the low production yield as well. Herein, with the assistance of solvent intercalation, a general reprecipitation approach is reported to prepare morphologically controllable C70microcrystals with mesitylene as a good solvent andn‐propanol as a poor solvent in one solvent system without replacing specific solvents. A series of C70microcrystals with high uniformity from perfect cubes and defective hoppers to novel cruciform‐pillars are obtained by intentionally tuning C70concentration and the volume ratio of mesitylene ton‐propanol. Among them, novel cruciform‐pillar‐shaped microcrystals are obtained for the first time by further decreasing the amount of mesitylene in the solvent‐intercalated microcrystals. Notably, the C70concentration is a key parameter for the selective growth of C70hopper, rather than the volume ratio of mesitylene ton‐propanol. Interestingly, the hopper‐shaped microcrystals exhibit excellent photoluminescence properties relative to those of cubes and cruciform‐pillars owing to the enhanced light absorption, proving their potential applications in optoelectronic devices. This study offers new insights into the morphology‐controlled synthesis of other micro/nanostructured organic microcrystals and the fine tuning of photoluminescence properties of organic crystals.
Thermally Activated Delayed Fluorescence and Phosphorescence Quenching in Iminophosphonamide Copper and Zinc Complexes
Authors: Goswami Bhupendra , Feuerstein Thomas J. , Yadav Ravi , Lebedkin Sergei , Boden Pit J. , Steiger Sophie T. , Niedner‐Schatteburg Gereon , Gerhards Markus , Kappes Manfred M. , Roesky Peter W. 
Published: April 2021

AbstractThe synthesis of copper and zinc complexes of four variably substituted iminophosphonamide ligands is presented. While the copper complexes form ligand‐bridged dimers, the zinc compounds are monomeric. Due to different steric demand of the ligand the arrangement of the ligands within the dimeric complexes varies. Similar to the structurally related iminophosphonamide complexes of alkali metals and calcium, the steady‐state and time‐resolved photoluminescence (PL) of four of the seven compounds studied here as solids in a temperature range of 5–295 K can be described within the scheme of thermally activated delayed fluorescence (TADF). Accordingly, they exhibit bright blue‐green phosphorescence at low temperatures (<100 K), which turns into delayed fluorescence by increasing the temperature. However, unusually, the fluorescence is practically absent in two copper complexes which otherwise still conform to the TADF scheme. In these cases, the excited singlet states decay essentially non‐radiatively and their thermal population from the corresponding low‐lying triplet states efficiently quenches PL (phosphorescence). Three other copper and zinc complexes only exhibit prompt fluorescence, evidencing a wide variation of photophysical properties in this class of compounds. The excited states of the copper complex with especially pronounced phosphorescence quenching were also investigated by low‐temperature time‐resolved infrared spectroscopy and quantum chemical calculations.
Self‐Assembled Porphyrinoids: One‐Component Nanostructured Photomedicines
Authors: Paramio Irene , Torres Tomás , de la Torre Gema 
Published: April 2021

AbstractPhotodynamic therapy (PDT) is becoming a promising way to treat various kinds of cancers, with few side effects. Porphyrinoids are the most relevant photosensitizers (PS) in PDT, because they present high extinction coefficients, biocompatibility, and excellent photochemical behavior. To maximize therapeutic effects, polymer‐PS conjugates, and PS‐loaded nanoparticles have been developed, with insights in improving tumor delivery. However, some drawbacks such as non‐biodegradability, multistep fabrication, and low reagent loadings limit their clinical application. A novel strategy, noted by some authors as the “one‐for‐all” approach, is emerging to circumvent the use of additional delivery agents. This approach relies on the self‐assembly of amphiphilic PS to fabricate nanostructures with improved transport properties. In this review we focus on different rational designs of porphyrinoid PS to achieve some of the following attributes in nanoassembly: i) selective uptake, through the incorporation of recognizable biological vectors; ii) responsiveness to stimuli; iii) combination of imaging and therapeutic functions; and iv) multimodal therapy, including photothermal or chemotherapy abilities.
Financial toxicity, mental health, and gynecologic cancer treatment: The effect of the COVID‐19 pandemic among low‐income women in New York City
Authors: Chen Yiting Stefanie , Zhou Zhen Ni , Glynn Shannon M. , Frey Melissa K. , Balogun Onyinye D. , Kanis Margaux , Holcomb Kevin , Gorelick Constantine , Thomas Charlene , Christos Paul J. , Chapman‐Davis Eloise 
Published: April 2021

BACKGROUNDNew York City (NYC) emerged as an epicenter of the COVID‐19 pandemic, and marginalized populations were affected at disproportionate rates. The authors sought to determine the impact of COVID‐19 on cancer treatment, anxiety, and financial distress among low‐income patients with gynecologic cancer during the peak of the NYC pandemic.METHODSMedicaid‐insured women who were receiving gynecologic oncology care at 2 affiliated centers were contacted by telephone interviews between March 15 and April 15, 2020. Demographics and clinical characteristics were obtained through self‐report and retrospective chart review. Financial toxicity, anxiety, and cancer worry were assessed using modified, validated surveys.RESULTSIn total, 100 patients completed the telephone interview. The median age was 60 years (range, 19‐86 years), and 71% had an annual income <$40,000. A change in employment status and early stage cancer (stage I and II) were associated with an increase in financial distress (P < .001 and P = .008, respectively). Early stage cancer and telehealth participation were significantly associated with increased worry about future finances (P = .017 and P = .04, respectively). Lower annual income (<$40,000) was associated with increased cancer worry and anxiety compared with higher annual income (>$40,000; P = .036 and P = .017, respectively). When controlling for telehealth participation, income, primary language, and residence in a high COVID‐19 prevalence area, a delay in medical care resulted in a 4‐fold increased rate of anxiety (P = .023, 95% CI, 1.278‐14.50). Race was not significantly associated with increased financial distress, cancer worry, or anxiety.CONCLUSIONSLow socioeconomic status was the most common risk factor for increased financial distress, cancer worry, and anxiety. Interventions aimed at improving access to timely oncology care should be implemented during this ongoing pandemic.