bluuebunny/crossref_metadata_2025_split huggingface dataset:
Different coding characteristics between flight and freezing in dorsal periaqueductal gray of mice during exposure to innate threats
Authors: Liu Denghui , Li Shouhao , Ren Liqing , Liu Xinyu , Li Xiaoyuan , Wang Zhenlong 
Published: October 2022

AbstractBackgroundFlight and freezing are two vital defensive behaviors that mice display to avoid natural enemies. When they are exposed to innate threats, visual cues are processed and transmitted by the visual system into the emotional nuclei and finally transmitted to the periaqueductal gray (PAG) to induce defensive behaviors. However, how the dorsal PAG (dPAG) encodes the two defensive behaviors is unclear.MethodsMulti‐array electrodes were implanted in the dPAG nuclei of C57BL/6 mice. Two kinds of visual stimuli (looming and sweeping) were used to induce defensive behaviors in mice. Neural signals under different defense behaviors were recorded, and the encoding characteristics of the two behaviors were extracted and analyzed from spike firing and frequency oscillations. Finally, synchronization of neural activity during the defense process was analyzed.ResultsThe neural activity between flight and freezing behaviors showed different firing patterns, and the differences in the inter‐spike interval distribution were mainly reflected in the 2–10 ms period. The frequency band activities under both defensive behaviors were concentrated in the theta band; the active frequency of flight was ~8 to 10 Hz, whereas that of freezing behavior was ~6 to 8 Hz. The network connection density under both defense behaviors was significantly higher than the period before and after defensive behavior occurred, indicating that there was a high synchronization of neural activity during the defense process.ConclusionsThe dPAG nuclei of mice have different coding features between flight and freezing behaviors; during strong looming stimulation, fast neuro‐instinctive decision making is required while encountering weak sweeping stimulation, and computable planning late behavior is predicted in the early stage. The frequency band activities under both defensive behaviors were concentrated in the theta band. There was a high synchronization of neural activity during the defense process, which may be a key factor triggering different defensive behaviors.
A Sensitive and Reversible Labeling Strategy Enables Global Mapping of the Core‐Fucosylated Glycoproteome on Cell Surfaces
Authors: Tian Yinping , Wang Yuqiu , Yin Hongbo , Luo Yawen , Wei Fangyu , Zhou Hu , Wen Liuqing 
Published: October 2022

AbstractCore fucosylation, the attachment of α1,6‐fucose to the innermost N‐acetylglucosamine (GlcNAc) residue of N‐glycans, has a strong relationship with tumor growth, invasion, metastasis, prognosis, and immune evasion by regulating many membrane proteins. However, details about the functional mechanism are still largely unknown due to the lack of an effective analytical method to identify cell‐surface core‐fucosylated glycoproteins, and especially glycosylation sites. Here, we developed a sensitive and reversible labeling strategy for probing core fucosylation, by which core‐fucosylated glycoproteins that located on cell‐surface were selectively tagged by a biotinylated probe with high sensitivity. The labeled probe can be further broken enzymatically after the capture by affinity resin. The on‐bead traceless cleavage allowed the global mapping of core‐fucosylated glycoproteins and glycosylation sites by mass spectrometry (MS). The profile of core‐fucosylated glycoproteome provides an in‐depth understanding of the biological functions of core fucosylation.
Transition‐Metal‐Catalyzed Denitrogenative Annulation to Access High‐ValuedN‐Heterocycles
Authors: Das Sandip Kumar , Roy Satyajit , Chattopadhyay Buddhadeb 
Published: October 2022

AbstractOver the past few years, the development of efficient methods to construct high‐valuedN‐heterocyclic molecules have received massive attention owing to their extensive application in the areas of medicinal chemistry, drug discovery, natural product synthesis and so on. To access those high‐valued N‐heterocycles, many methods have been developed. In this context, transition‐metal‐catalyzed denitrogenative annulation of 1,2,3‐triazoles and 1,2,3,4‐tetrazoles has appeared as a powerful synthetic tool because it offers a step‐ and atom‐economical route for the preparation of the nitrogen‐rich molecules. Compared with the denitrogenative annulation of various 1,2,3‐triazole frameworks, annulation of 1,2,3,4‐tetrazole remains more challenging due to the inertness of the tetrazole moiety. This Review summarizes the significant achievements made in the field of denitrogenative annulation of various 1,2,3‐triazoles and 1,2,3,4‐tetrazoles including some pioneering examples in this area of research. We anticipate that this denitrogenative annulation reaction will find broad applications in the pharmaceutical industry, drug discovery and other fields of medicinal chemistry.
Total Synthesis of Spiro[cyclohexane‐2‐indoline] Alkaloids: A Regio‐ and Diastereoselective Spirocyclization Approach
Authors: Chen Lu , Xie Kejing , Zhang Jingyang , Zu Liansuo 
Published: October 2022

AbstractA direct spirocyclization approach for the chemical synthesis of spiro[cyclohexane‐2‐indoline] alkaloids is reported. The absolute stereochemistry was introduced by a desymmetrizing Dieckmann condensation, and the relative stereochemistry was controlled by the manipulation of the kinetic and thermodynamic pathways of the spirocyclization. By contrast to the biogenetic proposal involving the diester‐type alkaloid as the precursor, we demonstrate that chemically a common lactone‐type intermediate could bridge the chemical synthesis of this class of natural products.
Rapid and Scalable Halosulfonylation of Strain‐Release Reagents**
Authors: Pickford Helena D. , Ripenko Vasyl , McNamee Ryan E. , Holovchuk Serhii , Thompson Amber L. , Smith Russell C. , Mykhailiuk Pavel K. , Anderson Edward A. 
Published: October 2022

AbstractSulfonylated aromatics are commonplace motifs in drugs and agrochemicals. However, methods for the direct synthesis of sulfonylated non‐classical arene bioisosteres, which could improve the physicochemical properties of drug and agrochemical candidates, are limited. Here we report a solution to this challenge: a one‐pot halosulfonylation of [1.1.1]propellane, [3.1.1]propellane and bicyclo[1.1.0]butanes that proceeds under practical, scalable and mild conditions. The sulfonyl halides used in this chemistry feature aryl, heteroaryl and alkyl substituents, and are conveniently generated in situ from readily available sulfinate salts and halogen atom sources. This methodology enables the synthesis of an array of pharmaceutically and agrochemically relevant halogen/sulfonyl‐substituted bioisosteres and cyclobutanes, on up to multidecagram scale.
Assembling Phenothiazine into a Porous Coordination Cage to Improve Its Photocatalytic Efficiency for Organic Transformations
Authors: Lin Hengyu , Xiao Zhifeng , Le Khoa N. , Yan Tian‐hao , Cai Peiyu , Yang Yihao , Day Gregory S. , Drake Hannah F. , Xie Haomiao , Bose Riya , Ryan Conor A. , Hendon Christopher H. , Zhou Hong‐Cai 
Published: October 2022

AbstractPhoto‐catalysis by small‐molecules is often limited by catalyst degradation and low electron‐transfer efficiency. Herein we report a stable N‐phenyl‐phenothiazine (PTH)‐derived porous coordination cage (PCC) as a highly efficient photocatalyst. By the incorporation of the photocatalytic PTH moiety into a PCC, aggregation‐induced quenching (AIQ) was shown to be reduced. An improvement in catalyst stability was discovered, ascribed to the synergistic effects of the PTH moieties. The catalyst, operating through a photolytic single‐electron transfer, was utilized for photo‐catalyzed dehalogenation and borylation. Evaluation of the catalytic mechanism in the borylation reaction showed that the improved performance results from the more efficient formation of the electron donor‐acceptor (EDA) complex with the cage. This discovery provides a potential strategy to improve the photophysical properties and stabilities of small‐molecule organic photocatalysts via supramolecular chemistry.
Synthesis of Subporphyrin Free Bases
Authors: Liu Le , Kim Jinseok , Xu Ling , Rao Yutao , Zhou Mingbo , Yin Bangshao , Oh Juwon , Kim Dongho , Osuka Atsuhiro , Song Jianxin 
Published: October 2022

AbstractBIII subporphyrins are the legitimate ring‐contracted porphyrins consisting of three pyrroles and three meso‐carbons and their chemistry has been extensively developed since the first synthesis in 2006. However, subporphyrin free bases have never been synthesized, despite tremendous attempts to remove the BIII ion. Here we report that Suzuki–Miyaura coupling between α,α′‐diborylated tripyrrane 1 and tetrabromide 5 gave subporphyrin free bases 6, 6 A, and free base dimer 7 in 6 %, 4 %, and 2 % yields as the first examples. Subporphyrin free bases exhibit curved bowl‐like structures and distinct 14π‐aromaticity. Steady‐state and time‐resolved spectroscopy revealed that the excited‐state behaviors of the subporphyrin free bases are comparable with those of the corresponding BIII subporphyrins. Rotational relaxation processes in the excited states have been revealed, which enhance the electronic interactions with the meso‐aryl substituents and between the two subporphyrins.
Photo‐Induced Homologation of Carbonyl Compounds for Iterative Syntheses
Authors: Wang Hua , Wang Shun , George Vincent , Llorente Galder , König Burkhard 
Published: October 2022

AbstractWe describe a photo‐induced reaction for the in situ generation of highly reactive alkyl diazo species from carbonyl precursors via photo‐excitation of N‐tosylhydrazone anions. The diazo intermediates undergo efficient C−H insertion of aldehydes, leading to the productive synthesis of aldehydes and ketones. The method is applicable to the iterative synthesis of densely functionalized carbonyl compounds through sequential trapping of the diazo species with various aldehydes. The reaction proceeds without the need of any catalyst by light irradiation and features high functional group tolerance. More than 70 examples, some performed on a gram‐scale, demonstrate the broad applicability of this reaction sequence in synthesis.
General Access to N−CF3 Secondary Amines and Their Transformation to N−CF3 Sulfonamides
Authors: Wang Leibing , Wang Jieping , Ye Sitao , Jiang Beihan , Guo Zihao , Mumtaz Yasir , Yi Wenbin 
Published: October 2022

AbstractThe synthesis of N−CF3 compounds through fluorination or trifluoromethylation of N‐containing compounds has been extensively investigated. However, general access to N−CF3 compounds simply from N−CF3 secondary amines is hampered by the challenging preparation and instability of these amines, as well as a much lower reactivity due to the strong electron‐withdrawing nature and steric bulk of the trifluoromethyl moiety. Herein, we report a general and highly efficient synthesis of N−CF3 secondary amines with excellent isolated yields via the addition of the in situ generated difluoromethyl imine (R−N=CF2) intermediates with hydrogen fluoride, which is mildly produced by triethylsilane and silver fluoride. N−CF3 sulfonamides, highly desirable but scarce at present, are easily accessible from these valuable building blocks through an unprecedented route. This study will bring new vitality to the synthesis of N−CF3 compounds.
Rhodium‐Catalyzed Divergent Arylation of Alkenylsulfonium Salts with Arylboroxines
Authors: Ye Yun , Zhu Jie , Xie Haijiao , Huang Yinhua 
Published: October 2022

AbstractA ligand‐controlled rhodium‐catalyzed regiodivergent arylation of alkenylthianthrenium salts with arylboroxines which allows the synthesis of terminal and internal alkene products in a switchable manner is reported. The use of a diene ligand guides the reaction toward cine‐arylation affording terminal alkenes, while the use of a phosphine ligand switches the reaction to ipso‐arylation exclusively giving internal alkenes. Deuterium labelling studies and DFT computations were carried out to investigate the mechanism.
Efficient Removal of Perfluorinated Chemicals from Contaminated Water Sources Using Magnetic Fluorinated Polymer Sorbents
Authors: Tan Xiao , Dewapriya Pradeep , Prasad Pritesh , Chang Yixin , Huang Xumin , Wang Yiqing , Gong Xiaokai , Hopkins Timothy E. , Fu Changkui , Thomas Kevin V. , Peng Hui , Whittaker Andrew K. , Zhang Cheng 
Published: October 2022

AbstractEfficient removal of per‐ and polyfluoroalkyl substances (PFAS) from contaminated waters is urgently needed to safeguard public and environmental health. In this work, novel magnetic fluorinated polymer sorbents were designed to allow efficient capture of PFAS and fast magnetic recovery of the sorbed material. The new sorbent has superior PFAS removal efficiency compared with the commercially available activated carbon and ion‐exchange resins. The removal of the ammonium salt of hexafluoropropylene oxide dimer acid (GenX) reaches >99 % within 30 s, and the estimated sorption capacity was 219 mg g−1 based on the Langmuir model. Robust and efficient regeneration of the magnetic polymer sorbent was confirmed by the repeated sorption and desorption of GenX over four cycles. The sorption of multiple PFAS in two real contaminated water matrices at an environmentally relevant concentration (1 ppb) shows >95 % removal for the majority of PFAS tested in this study.
Acceleration of Cathode Interfacial Kinetics by Liquid Organosulfides in Lithium Metal Batteries
Authors: Lv Xucheng , Yang Qilong , Zhang Xie , Song Jiahan , Guo Wei , Wang Qi 
Published: October 2022

AbstractGreat efforts have been made to tackle the issues of the shuttle effect and kinetics hysteresis in lithium‐sulfur (Li−S) battery, but few on tuning the reaction path of sulfur cathode. Herein, we report a strategy to replace inorganic sulfur with liquid organosulfide and construct a novel liquid‐liquid interface between cathode and electrolyte, which effectively inhibits the shuttle effect and simplifies the solid‐liquid‐solid conversion reaction to only liquid‐solid process, thus greatly improving the reaction kinetics. The Li|PTS half‐cell exhibits excellent cycling stability at 0.5 C, with a capacity retention of 64.9 % after 750 cycles. The Li|PTS pouch cell with a high PTS loading of 3.1 g delivers a maximum capacity of 997 mAh and maintains 82.1 % of initial capacity after 50 cycles at the current of 100 mA. This work enriches the reaction mechanism of Li−S batteries and provides new insights for the development of interphase chemistry in the design of cathodes.
Catalytic Reversible (De)hydrogenation To Rotate a Chemically Fueled Molecular Switch
Authors: Olivieri Enzo , Shao Na , Rosas Roselyne , Naubron Jean‐Valère , Quintard Adrien 
Published: October 2022

AbstractWe report here the development of a rotating molecular switch based on metal‐catalyzed reversible (de)‐hydrogenation. Under an argon atmosphere, acceptorless dehydrogenation induces a switch from an alcohol to a ketone, while reversing to a hydrogen pressure switches back the system to the alcohol. Based on a tolane scaffold, such reversible (de)‐hydrogenation enables 180° rotation. The absence of waste accumulation in a switch relying on chemical stimuli is of great significance and could potentially be applied to the design of efficient complex molecular machines.
Recent developments in the creation of a single molecular sensing tool for ternary iron (III), chromium (III), aluminium (III) ionic species: A review
Authors: Saha Sudipta , Alam Rabiul 
Published: October 2022

AbstractRational design of a molecular sensing tool is an important topic in molecular recognition, signalling, and optoelectronics that has piqued the interest of chemists, biologists, and environmental scientists. Approximately 150 years have passed since the beginning of the fluorescent chemosensor sector. Due to the paramagnetic properties of Cr3+ and Al3+, it is tough to prepare a photoluminescence plug‐in detector. Most dye‐based Al3+ sensors must be utilized in organic or mixed solvents for robust hydration of Al3+ in water. The sophisticated molecular design of sensors, conversely, allows for the detection of these metal ions in aqueous medium. The design of chemosensors using various fluorophores and their mechanisms of action have been thoroughly discussed. A literature survey covering the design of chemosensors and their mechanisms of action have been thoroughly discussed covering the period 2010–2022 and that was carried out including innovative and exemplary activities from numerous groups throughout the world that have significantly contributed to this sector. The most important advantages of these probes are their aqueous solubility and quick response with outstanding selectivity and sensitivity for temporal distribution with high fidelity of metals in living cells.
Biosynthesis of geranate via isopentenol utilization pathway in Escherichia coli
Authors: Pan Qiuchi , Ma Xiaoqiang , Liang Hong , Liu Yurou , Zhou Ying , Stephanopoulos Gregory , Zhou Kang 
Published: October 2022

AbstractIsoprenoids are a large family of natural products with diverse structures, which allow them to play diverse and important roles in the physiology of plants and animals. They also have important commercial uses as pharmaceuticals, flavoring agents, fragrances, and nutritional supplements. Recently, metabolic engineering has been intensively investigated and emerged as the technology of choice for the production of isoprenoids through microbial fermentation. Isoprenoid biosynthesis typically originates in plants from acetyl‐coA in central carbon metabolism, however, a recent study reported an alternative pathway, the isopentenol utilization pathway (IUP), that can provide the building blocks of isoprenoid biosynthesis from affordable C5 substrates. In this study, we expressed the IUP in Escherichia coli to efficiently convert isopentenols into geranate, a valuable isoprenoid compound. We first established a geraniol‐producing strain in E. coli that uses the IUP. Then, we extended the geraniol synthesis pathway to produce geranate through two oxidation reactions catalyzed by two alcohol/aldehyde dehydrogenases from Castellaniella defragrans. The geranate titer was further increased by optimizing the expression of the two dehydrogenases and also parameters of the fermentation process. The best strain produced 764 mg/L geranate in 24 h from 2 g/L isopentenols (a mixture of isoprenol and prenol). We also investigated if the dehydrogenases could accept other isoprenoid alcohols as substrates.
Efficient biosynthesis of α‐aminoadipic acid via lysine catabolism in Escherichia coli
Authors: Zhang Yu , An Ning , Zhao Yan , Li Xueqi , Shen Xiaolin , Wang Jia , Sun Xinxiao , Yuan Qipeng 
Published: October 2022

Abstractα‐Aminoadipic acid (AAA) is a nonproteinogenic amino acid with potential applications in pharmaceutical, chemical and animal feed industries. Currently, AAA is produced by chemical synthesis, which suffers from high cost and low production efficiency. In this study, we engineered Escherichia coli for high‐level AAA production by coupling lysine biosynthesis and degradation pathways. First, the lysine‐α‐ketoglutarate reductase and saccharopine dehydrogenase from Saccharomyces cerevisiae and α‐aminoadipate‐δ‐semialdehyde dehydrogenase from Rhodococcus erythropolis were selected by in vitro enzyme assays for pathway assembly. Subsequently, lysine supply was enhanced by blocking its degradation pathway, overexpressing key pathway enzymes and improving nicotinamide adenine dineucleotide phosphate (NADPH) regeneration. Finally, a glutamate transporter from Corynebacterium glutamicum was introduced to elevate AAA efflux. The final strain produced 2.94 and 5.64 g/L AAA in shake flasks and bioreactors, respectively. This work provides an efficient and sustainable way for AAA production.
Preferential precipitation of acidic variants from monoclonal antibody pools
Authors: Rumanek Tomasz , Kołodziej Michał , Piątkowski Wojciech , Antos Dorota 
Published: October 2022

AbstractMicroheterogeneity of monoclonal antibodies (mAbs) can impact their activity and stability. Formation of charge variants is considered as the most important source of the microheterogeneity. In particular, controlling the content of the acidic species is often of major importance for the production process and regulatory approval of therapeutic proteins. In this study, the preferential precipitation process was developed for reducing the content of acidic variants in mAb downstream pools. The process design was preceded by the determination of phase behavior of mAb variants in the presence of different precipitants. It was shown that the presence of polyethylene glycol (PEG) in protein solutions favored precipitation of acidic variants of mAbs. Precipitation yield was influenced by the variant composition in the mAb feed solutions, the concentration of the precipitant and the protein, and the ionic strength of the solutions. To improve yield, multistage precipitation was employed, where the precipitate was recycled to the precipitation process. The final product was a mixture of supernatants pooled together from the recycling steps. Such an approach can be potentially used either instead or in a combination with chromatography for adjusting the acidic variant content of mAbs, which can benefit in improvement in throughput and reduction in manufacturing costs.
A multiscale modeling method for therapeutic antibodies in ion exchange chromatography
Authors: Saleh David , Hess Rudger , Ahlers‐Hesse Michelle , Rischawy Federico , Wang Gang , Grosch Jan‐Hendrik , Schwab Thomas , Kluters Simon , Studts Joey , Hubbuch Jürgen 
Published: October 2022

AbstractThe development of biopharmaceutical downstream processes relies on exhaustive experimental studies. The root cause is the poorly understood relationship between the protein structure of monoclonal antibodies (mAbs) and their macroscopic process behavior. Especially the development of preparative chromatography processes is challenged by the increasing structural complexity of novel antibody formats and accelerated development timelines. This study introduces a multiscale in silico model consisting of homology modeling, quantitative structure–property relationships (QSPR), and mechanistic chromatography modeling leading from the amino acid sequence of a mAb to the digital representation of its cation exchange chromatography (CEX) process. The model leverages the mAbs' structural characteristics and experimental data of a diverse set of 21 therapeutic antibodies to predict elution profiles of two mAbs that were removed from the training data set. QSPR modeling identified mAb‐specific protein descriptors relevant for the prediction of the thermodynamic equilibrium and the stoichiometric coefficient of the adsorption reaction. The consideration of two discrete conformational states of IgG4 mAbs enabled prediction of split‐peak elution profiles. Starting from the sequence, the presented multiscale model allows in silico development of chromatography processes before protein material is available for experimental studies.