bluuebunny/crossref_metadata_2025 huggingface dataset:
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

A 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

Sulfonylated 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

Photo‐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

BIII 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

We 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

The 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

A 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

Efficient 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

Great 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

We 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.
New gold(III) chlorophenyl terpyridine complex: Biomolecular interactions and anticancer activity against human oral squamous cell carcinoma
Authors: Radisavljević Snežana , Kesić Ana , Ćoćić Dušan , Marković Vladimir , Milovanović Jelena , Petrović Biljana , Simović Ana Rilak
Published: October 2022

In this work we synthesized new monofunctional gold(III) complex [Au(Cl‐Ph‐tpy)Cl]Cl2 (Cl‐Ph‐tpy = 4′‐[4‐chlorophenyl]‐2,2′:6′, 2″‐terpyridine). This complex was characterized by UV–Vis, NMR, IR, and ESI‐MS spectrometry. The kinetic study of the substitution reactions of the Au‐Cl‐Ph‐tpy complex with biomolecules showed that the rate constants depend on the nature of the entering nucleophile. Based on the calculated values of entropy (∆H≠ > 0) and enthalpy (∆S≠ < 0) the proposed substitution mechanism is associative. Additionally, the relative stability and thermodynamic properties of Au‐Cl‐Ph‐tpy complex were compared with the analogue Au‐tpy complex by the B3LYP/def2‐svp method. DNA/BSA binding studies showed that Au‐Cl‐Ph‐tpy complex interacts with CT DNA through the intercalation and moderately quenches the fluorescence of tryptophan residues in serum albumin (BSA). Molecular docking confirmed results obtained by spectroscopic experiments and suggested site I (subdomain IIA) for binding of Au complex to BSA. We demonstrated that the Au chlorophenyl terpyridine complex possessed significant in vitro cytotoxic activity against human oral squamous carcinoma cells (CAL‐27), induced apoptosis, inhibited proliferation of CAL‐27 cells, and induced cell cycle disturbance. Treatment of CAL‐27 cells with the Au complex enhanced expression of cyclin‐dependent kinase inhibitors p21 and p27, resulting in cell cycle arrest in the G1 phase, reduced the percentage of CAL‐27 cells in S phase and decreased expression of Ki‐67. Additionally, Au complex reduced expression of phosphorylated STAT3 and downstream regulated molecules associated with cancer stemness, NANOG, and Sox2 protein.
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

Rational 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

Isoprenoids 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

α‐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

Microheterogeneity 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

The 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.
Explore or exploit? A model‐based screening strategy for PETase secretion by Corynebacterium glutamicum
Authors: Helleckes Laura M. , Müller Carolin , Griesbach Tim , Waffenschmidt Vera , Moch Matthias , Osthege Michael , Wiechert Wolfgang , Oldiges Marco
Published: October 2022

Extracellular production of target proteins simplifies downstream processing due to obsolete cell disruption. However, optimal combinations of a heterologous protein, suitable signal peptide, and secretion host can currently not be predicted, resulting in large strain libraries that need to be tested. On the experimental side, this challenge can be tackled by miniaturization, parallelization, and automation, which provide high‐throughput screening data. These data need to be condensed into a candidate ranking for decision‐making to focus bioprocess development on the most promising candidates. We screened for Bacillus subtilis signal peptides mediating Sec secretion of two polyethylene terephthalate degrading enzymes (PETases), leaf‐branch compost cutinase (LCC) and polyester hydrolase mutants, by Corynebacterium glutamicum. We developed a fully automated screening process and constructed an accompanying Bayesian statistical modeling framework, which we applied in screenings for highest activity in 4‐nitrophenyl palmitate degradation. In contrast to classical evaluation methods, batch effects and biological errors are taken into account and their uncertainty is quantified. Within only two rounds of screening, the most suitable signal peptide was identified for each PETase. Results from LCC secretion in microliter‐scale cultivation were shown to be scalable to laboratory‐scale bioreactors. This work demonstrates an experiment‐modeling loop that can accelerate early‐stage screening in a way that experimental capacities are focused to the most promising strain candidates. Combined with high‐throughput cloning, this paves the way for using large strain libraries of several hundreds of strains in a Design–Build–Test–Learn approach.
Mapping of Methyl Epitopes of a Peptide‐Drug with Its Receptor by 2D STDD‐Methyl TROSY NMR Spectroscopy
Authors: Dey Anomitra , Mitra Debarghya , Rachineni Kavitha , Khatri Lakshya Raj , Paithankar Harshad , Vajpai Navratna , Kumar Ashutosh
Published: October 2022

The current trend in the biopharmaceutical market has boosted the development and production of biological drugs with high efficacy and fidelity for receptor binding. While high‐resolution structural insights into binding epitopes of the receptor are indispensable for better therapeutic design, it is tedious and costly. In this work, we develop a protocol by integrating two well‐known NMR‐based solution‐state methods. Saturation transfer double‐difference with methyl‐TROSY (STDD‐Methyl TROSY NMR) was used to probe methyl binding epitopes of the ligand in a label‐free environment. This study was carried out with Human insulin as a model peptide drug, with the insulin growth factor receptor (IGFR), which is an off‐target receptor for insulin. Methyl epitopes identified from STDD‐Methyl TROSY NMR spectroscopy were validated through the HADDOCK platform to generate a drug‐receptor model. Since this method can be applied at natural abundance, it has the potential to screen a large set of peptide‐drug interactions for optimum receptor binding. Thus, we propose STDD‐Methyl TROSY NMR spectroscopy as a technique for rapid screening of biologics for the development of optimized biopharmaceutics.
Reconstitution of bran components with refined flour: Impact on protein solubility and their associations with whole wheat bread‐baking quality
Authors: Simsek Senay , Khalid Khairunizah Hazila , Ohm Jae‐Bom
Published: October 2022

Background and Objectives

Bran components cause poor dough and end‐product quality for whole wheat flour. However, there are few reports on the impacts of bran components on protein functionality in whole wheat bread‐baking. Therefore, a reconstitution research was performed to evaluate bran components' effects on proteins in whole‐wheat bread‐baking.

Findings

The bran components showed significant (p < .05) and complex impacts on the solubility of proteins in bread crumbs. Specifically, the fiber had synergetic interactions with extractable phenolics and hydrolyzable phenolics (HP) to increase the sonication extractability of insoluble polymeric proteins in bread crumb. The HP also had a synergistic interaction to increase low molecular weight monomeric proteins and peptides in bread crumb.

Conclusions

The fiber and HP were major components in increasing solubility of proteins in the crumb, which was indicative of interactive and deteriorative impacts of the bran components on protein functionality in association with degradation of dough stability and bread‐making quality in whole‐wheat baking.

Significance and Novelty

This research discovered novel information on the impact of bran components on the solubility of proteins in bread crumb. The information will be a valuable reference to enhance the knowledge of the function of bran components in whole wheat bread‐baking.
Primary synovial sarcoma of the prostate: A case report and literature review
Authors: Emadi Torghabe Ali , Ebrahimi Ramin , Pishevar Feizabad Zohreh
Published: October 2022

Synovial sarcoma arising from the prostate is extremely rare. Synovial sarcoma of the prostate is usually identified at a late stage and makes the treatment challenging. Here, we report a case of 30‐year‐old man with advanced metastatic synovial sarcoma of prostate gland at diagnosis and his poor prognosis.
Aluminium‐Catalyzed Selective Hydroboration of Esters and Epoxides to Alcohols: C−O Bond Activation
Authors: Sarkar Nabin , Kumar Sahoo Rajata , Nembenna Sharanappa
Published: October 2022

In this work, the molecular aluminium dihydride complex bearing anN, N’‐chelated conjugated bis‐guanidinate (CBG) ligand is used as a catalyst for reducing a wide range of aryl and alkyl esters with good tolerance of alkene (C=C), alkyne (C≡C), halides (Cl, Br, I and F), nitrile (C≡N), and nitro (NO2) functionalities. Further, we investigated the catalytic application of aluminium dihydride in the C−O bond cleavage of alkyl and aryl epoxides into corresponding branched Markovnikov ring‐opening products. In addition, the chemoselective intermolecular reduction of esters over other reducible functional groups, such as amides and alkenes, has been established. Intermediates are isolated and characterized by NMR and HRMS studies, which confirm the probable catalytic cycles for the hydroboration of esters and epoxides.
Recent Developments of Atomically Dispersed Metal Electrocatalysts for Oxygen Reduction Reaction†
Authors: Pang Ruoyu , Xia Hongyin , Li Jing , Guo Shaojun , Wang Erkang
Published: October 2022

Comprehensive Summary

Oxygen reduction reaction (ORR) is the pivotal portion in many electrochemical energy conversion and storage technologies. However, the complex mechanisms and sluggish kinetics of ORR have also become one of the key issues hindering the development and application of these technologies. Recently, single‐atom catalysts (SACs) with well‐defined atomic active centers and theoretical 100% atomic utilization have attracted broad interests in the area of electrocatalytic ORR. The electrocatalytic ORR performance of SACs is fundamentally determined by the intrinsic activity of the single‐atom active site and increasing the number of active sites involved in the ORR can further enhance the ORR activity of SACs. In this review, advances in atomically dispersed metal electrocatalysts for ORR in the last three years are summarized. Three main regulation strategies for achieving SACs with excellent intrinsic activity in the context of the ORR mechanism are involved including modulation of coordination environments, the construction of intrinsic defects, and the introduction of dual active sites. Moreover, discussions on improving the loading and utilization of active sites are given. Finally, the current challenges and opportunities for the development of SACs for ORR are presented.
Visible Light‐Promoted Ring‐Opening Alkenylation of Cyclic Hemiacetals through β‐Scission of Alkoxy Radicals
Authors: Shi Jiang‐Ling , Wang Zixuan , He Zeyu , Dou Bowen , Wang Jianbo
Published: October 2022

Comprehensive Summary

The chemistry of alkoxy radicals was extensively explored during the period of 1960s to 1990s, but it has remained dormant for the past few decades. Recently, alkoxy radicals attract the attentions again, because new methods for generating alkoxy radical species have emerged. These newly developed methods are mainly based on the photolysis by visible light under mild conditions, thus allowing for new transformations of the carbon‐centered radical species that are generated from the β‐scission or hydrogen abstraction of the alkoxy radicals. Herein, we demonstrate that the alkoxy radicals derived from cyclic hemiacetals can be generated through visible‐light‐induced electron transfer with sodium iodide and triphenylphosphine as the catalyst. The alkoxy radicals subsequently undergo β‐scission to generate carbon‐centered radicals, which are trapped by cinnamic acids, aryl alkenes, vinylboronic acid and silyl enol ether to deliver the corresponding C—C bond forming products. This catalytic method for ring‐opening alkenylation reaction of cyclic hemiacetal derivatives under visible‐light irradiation conditions demonstrates the compatibility of the visible light‐promoted alkoxy radical generation method with various carbon radical trapping processes. This work opens up new possibilities for the application of alkoxy radicals in organic synthesis.
Guest Binding with Sulfated Cyclodextrins: Does the Size of Cavity Matter?
Authors: Singh Gaurav , Pandey Shrishti P. , Singh Prabhat K.
Published: October 2022

Sulfated cyclodextrins have recently emerged as potential candidates for producing host–induced guest aggregation with properties better than p‐sulfonatocalixarenes that have previously shown numerous applications involving the phenomena of host‐induced guest aggregation. In the class of sulfated cyclodextrins (SCD), sulfated β‐cyclodextrin (β‐SCD) remains the most extensively investigated host molecule. Although it is assumed that the host‐induced guest aggregation is predominantly an outcome of interaction of the guest molecule with the charges on the exterior of SCD cavity, it has not been deciphered whether the variation in the cavity size will make a difference in the efficiency of host‐induced guest‐aggregation process. In this investigation, we present a systematic study of host–induced guest aggregation of a cationic molecular rotor dye, Thioflavin T (ThT) with three different sulfated cyclodextrin molecules, α‐SCD, β‐SCD and γ‐SCD, which differ in their cavity size, using steady‐state emission, ground‐state absorption and time‐resolved emission measurements. The obtained photophysical properties of ThT, upon interaction with different SCD molecules, indicate that the binding strength of ThT with different SCD molecules correlate with the cavity size of the host molecule, giving rise to the strongest complexation of ThT with the largest host molecule (γ‐SCD). The binding affinity of ThT towards different host molecules has been supported by molecular docking calculations. The results obtained are further supported with the temperature and ionic strength dependent studies performed on the host‐guest complex. Our results indicate that for host–induced guest aggregation, involving oppositely charged molecules, the size of the cavity also plays a crucial role beside the charge density on the exterior of host cavity.
Research on the correlation between the size of condyle and occlusion plane in skeletal Class II malocclusions
Authors: Hu Hainan , Lin Wanrong , Wu Jun , Xu Haisong
Published: October 2022

Objectives

This study was designed to investigate the relationship between the morphological structure of condyle and occlusal plane in skeletal Class II malocclusions by imaging measurement.

Materials and Methods

This study included 65 skeletal Class II adult patients (18–35 years old) who met the criteria, and all were taken with cone beam computed tomography (CBCT) images (skeletal Class II high angle 38 cases, average angle 18 cases, and low angle nine cases). The statistical methods of mean standard deviation, Pearson correlation, and analysis of variance were used to study the correlation between the size of the condyle and occlusal plane in skeletal Class II malocclusion.

Results

The FMA and SN‐OP between the groups in skeletal Class II malocclusion are considered statistically significant, p < .05 high angle group > average angle group > low angle group, whereas there are significant correlations between FMA, FH‐OP, SN‐OP, and the medial–lateral diameter (MLD) of the condyle, p < .05, showing a negative correlation. The anteroposterior diameter of the condyle has no significant correlation with these angles, and the high‐angle group size is smaller than the other groups.

Conclusion

In patients with skeletal Class II high angle malocclusion, the MLD and anteroposterior diameters of condyle were smaller than those of average angle and low angle groups, and negatively correlated with the FMA and SN‐OP. That is the steeper occlusal plane, the smaller MLD of the condyle. It suggests whether orthodontists can promote the stability of the morphological structure of the condyle by changing the inclination of the occlusal plane during the orthodontic process.
Clinical application of cell‐based therapies opportunities and challenges
Authors: Gao Jie , Wu Duojiao
Published: October 2022

Immune checkpoint inhibitors or anti‐cancer immunotherapy using cellular transfer have emerged as new therapies in this field. These therapies work to overcome or alleviate tumour‐induced immunosuppression, resulting in immune‐mediated tumour clearance. Cellular therapies have the largest number of active agents and clinical trials. More targets have been explored, more trials have been opened and more patients have been recruited for trials as a result of recent advancements. In this article, we describe the latest developments and major obstacles in cell therapy for cancer treatment, starting with tumour‐infiltrating T cells.
Radical Amido‐ and Azido‐Fluorination of α‐Fluorostyrene Derivatives: An Innovative Approach Towards β‐Aryl‐β,β‐difluoroamino Motifs
Authors: Ngo Ndimba Alphonsine , Vincent Émilie , Brioche Julien
Published: October 2022

An innovative one‐step synthesis towards β‐aryl‐β,β‐difluorocarbamates and β‐aryl‐β,β‐difluoroazides is presented. The described approach relies on the use of α‐fluorostyrene substrates in a radical addition/fluorination reaction with N‐centered radicals in the presence of Selectfluor®. The best results were obtained for the azidofluorination reaction. The resultant β‐aryl‐β,β‐difluoroazides were further transformed into Nitrogen‐based heterocycles (e. g. pyrrole, triazole, and tetrazole) and in more elaborated azide derivatives.
A study of factors influencing self‐stigma in people with epilepsy: A nationwide online questionnaire survey in Japan
Authors: Kuramochi Izumi , Iwayama Takayuki , Oga Koko , Shiganami Takafumi , Umemura Tomoki , Kobayashi Sayaka , Yasuda Takaaki , Yoshimasu Haruo
Published: October 2022

Objective

Epilepsy carries a significant stigma. While there is some evidence that self‐stigma accompanies a lack of knowledge about epilepsy, there are no studies in Japan. This study aimed to determine factors contributing to self‐stigma in Japan.

Methods

We conducted an online questionnaire survey. Three hundred and ten patients completed the questionnaire (mean age of 47.8 ± 11.9) in contrast to the total registered users on the questionnaire site as 28 315 from Jul 29 to Aug 2, 2021. We asked about demographic variables, satisfaction with treatment, limitations in life, support status, seizure frequency, the Epilepsy Self‐Stigma Scale (ESSS), the Rosenberg Self‐Esteem Scale (RSES), and the Epilepsy Knowledge Scale (EKS). We conducted the statistical analysis on self‐stigma, self‐esteem, knowledge of epilepsy, and seizure frequency associations by Spearman's rank correlation.

Results

The mean value of the EKS was 40.19 ± 18.75, the ESSS was 17.69 ± 6.25, and the RSES was 26.02 ± 6.13. We identified a significant moderate negative correlation between self‐esteem and self‐stigma (P < .001, ρ = −.423), a significant weak positive correlation between self‐esteem and knowledge (P = .005, ρ = .177), and a significant weak negative correlation between seizure frequency and self‐stigma (P < .001, ρ = −.162). Of the 186 respondents who were working or studying, 91 (49%) participants had experienced any discrimination due to epilepsy. The use of psychosocial support, that is, participating in epilepsy self‐help groups and educational programs, was 5.8%.

Significance

There was no correlation between the strength of self‐stigma and the knowledge, while there was a positive correlation between self‐esteem and knowledge (P = .005, ρ = .177). There was a negative and weak correlation between seizure frequency and self‐stigma (p < .001, ρ = −.162). These results suggest that sufficient knowledge may improve the self‐esteem and thus reduce the self‐stigma. In addition, short‐term treatment for seizure control is insufficient to reduce self‐stigma. The dissemination for people to enable sufficient epilepsy knowledge and positive perceptions of epilepsy by increasing self‐efficacy throughout a lifetime may reduce self‐stigma.
Semiparametric estimation of expected shortfall and its application in finance
Authors: Fang Yan , Li Jian , Liu Yinglin , Zhao Yunfan
Published: October 2022

Measuring risk effectively is crucial for managing risk in financial markets. The expected shortfall has become an increasingly popular metric for risk in recent years. How to estimate it is important in statistics and financial econometrics. Based on the single index quantile regression, we introduce a new semiparametric approach, namely, weighted single index quantile regression. We assess the performance of the proposed expected shortfall estimator with backtesting. Our simulation results indicate that the estimator has a good finite sample performance and often outperforms existing methods. By applying the new method to both a market index and individual stocks, we show that it not only exhibits the best performance but also reveals an insight about the effect of the COVID pandemic, that is, the pandemic increases the market risk.
Dietary acid load is associated with primary osteoporosis in postmenopausal women aged 50–65 years: A cross‐sectional study
Authors: Farshbaf‐Khalili Azizeh , Ostadrahimi Alireza , Heris Javad Ahmadian , Sarrafi Somayyeh , Mohammadisima Neda
Published: October 2022

This study aimed to investigate the association between dietary acid load (DAL) and primary osteoporosis. This was a cross‐sectional study. Among 850 randomly selected postmenopausal women aged 50–65 years, 232 women consisted of 124 women with normal bone mineral density (BMD) and 108 with primary osteoporosis were selected after examining the eligibility criteria. Demographic characteristics, anthropometric indices, and physical activity were collected through questionnaires. Osteoporosis was diagnosed using the dual‐energy X‐ray absorptiometry method. DAL was assessed by a valid and reliable semiquantitative food frequency questionnaire during the last year. Independentt‐test, Mann–Whitney, Chi‐square, and adjusted binary logistic regression were used for data analysis through SPSS/24. There were significant differences between the two groups in terms of age, body mass index (BMI), number of deliveries, and years after menopause (p < .05). The mean (standard deviation (SD)) potential renal acid load (PRAL) and net endogenous acid production (NEAP) were higher in postmenopausal women with osteoporosis than those with normal BMD (PRAL: −13.1 ± 11.1 mEq/day vs. −10.8 ± 12.7 mEq/day; NEAP: 29.5 ± 8.5 mEq/day vs. 31.2 ± 9.2 mEq/day). The mean consumption of potassium, magnesium, and calcium in the osteoporosis group was significantly lower than in the other group (p < .05). There were significant associations between osteoporosis with PRAL (odds ratio (OR) = 1.030; 95% confidence interval (CI): 1.001 to 1.060,p = .027) and NEAP scores (OR = 1.041; 95% CI: 1.003 to 1.081,p = .037). The odds of osteoporosis increased by 3% following one unit increase in PRAL score. Similarly, it increased by 4% with increasing NEAP score up to one unit. Therefore, dietary patterns that produce high DAL can have a detrimental effect on bone health.
Einfluss der Dichte auf den Suffosionsverlauf in binären granularen Packungen
Authors: Welsch Johannes , Herle Ivo
Published: October 2022

Suffosion ist ein hydromechanischer Prozess, welcher die Umlagerung und den Transport der feinen Partikel eines Bodens infolge einer Wasserströmung beschreibt. Um die Auswirkungen des Materialverlustes infolge Suffosion auf das Materialverhalten zu verstehen, wurden der Einfluss der Ausgangsdichte des Bodens auf die Masse des Materialverlusts, die volumetrische Verformung und die Änderung der Wasserdurchlässigkeit untersucht. Hierfür wurde die Struktur (Kontakt‐ und Kontaktkraftverteilung) eines suffosionsanfälligen Bodens qualitativ mithilfe von DEM‐Simulationen dargestellt und ausgewertet. Anhand von Laborversuchen unter isotroper Belastung und konstanter Durchströmung wurden die Auswirkungen verschiedener Dichten experimentell untersucht. Mit steigender Materialdichte zeigten sich eine Abnahme des Materialverlustes, eine Abnahme der Verformungen und eine Abnahme der Wasserdurchlässigkeit infolge der Suffosion. Um die Änderung des mechanischen Verhaltens beschreiben zu können, wurden drainierte Triaxialversuche an nichtdurchströmten und durchströmten Proben durchgeführt. Hierbei zeigte sich, dass die drainierte Scherfestigkeit hauptsächlich von der Porenzahl des Grobmaterials vor der Scherung abhängt, unabhängig davon, ob diese künstlich oder infolge Durchströmung entstand.
Building reflective capacity and improving well‐being of early childhood professionals through an embedded cross‐system model of infant early childhood mental health consultation
Authors: Spielberger Julie , Burkhardt Tiffany , Herriott Anna L. , Winje Carolyn J.
Published: October 2022

Infant and Early Childhood Mental Health Consultation (IECMHC) aims to improve early childhood professionals’ abilities to promote children's mental health through relationship building and collaboration. Using a longitudinal, matched‐comparison group design, a 3‐year pilot study of a cross‐system, embedded model of IECMHC assessed teachers and home visitors in intervention and comparison programs in reflective capacity, burnout, and perceptions of children's behavior. A sample of 136 staff (n = 72 intervention group; n = 64 comparison group; 21% Black; 51% White; 28% Latina/Hispanic) participated in surveys over a 21‐month implementation period. A subsample of staff (n = 26) participated in interviews that included a narrative measure of reflective capacity; and a smaller subsample of teachers only (n = 21) completed assessments of children. Staff in the intervention group significantly increased reflective capacity after 21 months. For the staff interview subsample, receiving the intervention predicted lower levels of burnout at 12–15 months post‐baseline. Among teachers completing child assessments, those with higher reflective capacity rated children's behaviors more positively than teachers with lower reflective capacity. We conclude that this IECMHC model successfully improved reflective capacity in staff. Future research should investigate reflective capacity as a potential mechanism of change for IECMHC.
Designing strategy formulation in the midst of uncertainty in digital citizen engagement: A critical reflection of the application of Design Science Research augmented by Soft Systems Methodology to the design of strategy formulation
Authors: Osah Umeoniso Joshua , Pade‐Khene Caroline
Published: October 2022

This manuscript details a critical reflection on how Design Science Research (DSR) was applied to the guided development and implementation of a strategy formulation process for a civic tech project called MobiSAM, which was executed in a marginalized local government context. It also demonstrates how the application of DSR is augmented by Soft Systems Methodology (SSM), to ensure that the unstructured properties typically present in multi‐stakeholder deliberation (required in civic tech project strategizing) are accounted for in the strategy formulation exercise. To underpin this critical reflection on the emergence and application of the civic tech project strategy framework (the artifact), pragmatist interpretivism is employed. This qualitative paradigm underpinning the critical reflection supports better understanding of strategy related challenges primarily through participant observation and interviews with actors in the civic tech context. The findings reveal that for an unstructured problem like civic tech project strategizing, SSM is particularly instrumental to the application of four DSR guidelines, namely—problem relevance, design evaluation, research contribution and communication of DSR.
Overexpression of miR‐383‐3p protects cardiomyocytes against hypoxia/reoxygenation injury via regulating PTEN/PI3K/AKT signal pathway
Authors: Zeng Huan , Li Ying , Liu Xinzong , Li Xinxin , Zhou Tian , Cao Shanshan , Wang Mingjuan , Ju Mingfei
Published: October 2022

MicroRNAs are widely reported as biomarkers and therapeutic targets in cardiovascular diseases. This study is aimed to expound on the regulatory responsibility of miR‐383‐3p in H/R‐induced injury of H9c2 cells. In this study, H9c2 cells were administrated with H/R. MiR‐383‐3p expression was measured using qRT‐PCR. ELISA was used to determine lactate dehydrogenase (LDH), superoxide dismutase (SOD), and malondialdehyde (MDA) levels. Reactive oxygen species (ROS) were detected with 2,7‐Dichlorodihydrofluorescein diacetate probe. 3‐(4,5)‐dimethylthiahiazo (‐z‐y1)‐3,5‐di‐ phenytetrazoliumromide, flow cytometry, and TUNEL experiments were conducted to measure cell viability and apoptosis. Cleaved caspase‐3, caspase‐3, Bax, Bcl‐2, PTEN, PI3K, p‐PI3K, Akt, p‐AKT expression levels were examined by Western blot. Cleaved caspase‐3 expression was also measured by immunofluorescence staining. Dual‐luciferase reporter gene assay was applied to validate the binding sites in miR‐383‐3p and the 3′UTR of PTEN. We reported that, miR‐383‐3p expression in H9c2 cells treated with H/R was remarkably decreased. MiR‐383‐3p overexpression ameliorated oxidative stress and apoptosis and promoted cell viability in H9c2 cells treated with H/R, while miR‐383‐3p inhibitor showed the reverse effects. PTEN was identified as a target gene of miR‐383‐3p. Additionally, enhancement of PTEN expression abolished the influences of miR‐383‐3p on H9c2 cells. MiR‐383‐3p mimics could significantly decrease PTEN expression in H9c2 cells while increasing p‐PI3K expression and p‐AKT expression, while the miR‐383‐3p inhibitors showed the opposed effects. In conclusion, miR‐383‐3p protected H9c2 cells from H/R‐induced injury via regulating PTEN/PI3K/AKT signal pathway.