bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enabling the Operation of Highly Compatible LiI‐3‐Hydroxypropionitrile Small‐Molecule Solid‐State Electrolytes in Lithium Metal Batteries via Stepped‐Amorphization Strategy
Authors: Song Tao , Wang Da , Wang Hongxia , Yu Jia , Shi Siqi 
Published: May 2023

AbstractIntegrating the advantages of both inorganic ceramic and organic polymer solid‐state electrolytes, small‐molecule solid‐state electrolytes represented by LiI‐3‐hydroxypropionitrile (LiI‐HPN) inorganic–organic hybrid systems possess good interfacial compatibility and high modulus. However, their lack of intrinsic Li+ conduction ability hinders potential application in lithium metal batteries until now, despite containing LiI phase composition. Herein, inspired by evolution tendency of ionic conduction behaviors together with first‐principles molecular dynamics simulations, we propose a stepped‐amorphization strategy to break the Li+ conduction bottleneck of LiI‐HPN. It involves three progressive steps of composition (LiI‐content increasing), time (long‐time standing), and temperature (high‐temperature melting) regulations, to essentially construct a small‐molecule‐based composite solid‐state electrolyte with intensified amorphous degree, which realizes efficient conversion from an I− to Li+ conductor and improved conductivity. As a proof, the stepped‐optimized LiI‐HPN is successfully operated in lithium metal batteries cooperated with Li4Ti5O12 cathode to deliver considerable compatibility and stability over 250 cycles. This work not only clarifies the ionic conduction mechanisms of LiI‐HPN inorganic–organic hybrid systems, but also provides a reasonable strategy to broaden the application scenarios of highly compatible small‐molecule solid‐state electrolytes.
Dissection of the Catalytic Mechanisms of Transmembrane Terpene Cyclases Involved in Fungal Meroterpenoid Biosynthesis
Authors: Tang Jia , Matsuda Yudai 
Published: May 2023

AbstractPyr4‐family terpene cyclases are noncanonical transmembrane terpene cyclases involved in the biosynthesis of microbial meroterpenoids and catalyze diverse cyclization reactions. Despite the ubiquity of Pyr4‐family terpene cyclases in microorganisms, their three‐dimensional structures have never been experimentally determined. Herein, we focused on AdrI, the Pyr4‐family enzyme for the andrastin A pathway, and its homologues, and performed a series of mutational experiments using their AlphaFold2‐generated structures. Intriguingly, we found that AdrI and InsA7, which both accept the same substrate, use different amino acid residues for the initiation of the cyclization cascade. Furthermore, we obtained several AdrI variants with altered product selectivity, one of which dominantly yielded a new meroterpenoid species. Collectively, our study provides important insights into the catalytic functions of Pyr4‐family terpene cyclases and will facilitate the engineering of these enzymes.
A Chemical Proteomic Strategy Reveals Inhibitors of Lipoate Salvage in Bacteria and Parasites
Authors: Dienemann Jan‐Niklas , Chen Shu‐Yu , Hitzenberger Manuel , Sievert Montana L. , Hacker Stephan M. , Prigge Sean T. , Zacharias Martin , Groll Michael , Sieber Stephan A. 
Published: May 2023

AbstractThe development of novel anti‐infectives requires unprecedented strategies targeting pathways which are solely present in pathogens but absent in humans. Following this principle, we developed inhibitors of lipoic acid (LA) salvage, a crucial pathway for the survival of LA auxotrophic bacteria and parasites but non‐essential in human cells. An LA‐based probe was selectively transferred onto substrate proteins via lipoate protein ligase (LPL) in intact cells, and their binding sites were determined by mass spectrometry. Probe labeling served as a proxy of LPL activity, enabling in situ screenings for cell‐permeable LPL inhibitors. Profiling a focused compound library revealed two substrate analogs (LAMe and C3) as inhibitors, which were further validated by binding studies and co‐crystallography. Importantly, LAMe exhibited low toxicity in human cells and achieved killing of Plasmodium falciparum in erythrocytes with an EC50 value of 15 μM, making it the most effective LPL inhibitor reported to date.
Synthesis and SARs study of novel spiro‐oxindoles as potent antiproliferative agents with CDK‐2 inhibitory activities
Authors: Al‐Jassas Refaah Mousa , Islam Mohammad Shahidul , Al‐Majid Abdullah Mohammed , Nafie Mohamed S. , Haukka Matti , Rahman A.F.M. Motiur , Alayyaf Abdul Majeed Abdullah , Barakat Assem 
Published: May 2023

AbstractA series of 16 novel spirooxindole analogs 8a–p were designed and constructed via cost‐effective single‐step multicomponent [3+2] cycloaddition reaction of azomethine ylide (AY) generated in situ from substituted isatin (6a–d) with suitable amino acids (7a–c) and ethylene‐engrafted pyrazole derivatives (5a,b). The potency of all compounds was assayed against a human breast cancer cell line (MCF‐7) and a human liver cell line (HepG2). Spiro compound 8c was the most active member among the synthesized candidates, with exceptional cytotoxicity against the MCF‐7 and HepG2 cell lines, with IC50 values of 0.189 ± 0.01 and 1.04 ± 0.21 µM, respectively. The candidate 8c exhibited more potent activity (10.10‐ and 2.27‐fold) than the standard drug roscovitine (IC50 = 1.91 ± 0.17 µM (MCF‐7) and 2.36 ± 0.21 µM (HepG2)). Compound 8c was investigated for epidermal growth factor receptor (EGFR) inhibition; it exhibited promising IC50 values of 96.6 nM compared with 67.3 nM for erlotinib. The IC50 value of 8c (34.98 nM) exhibited cyclin‐dependent kinase 2 (CDK‐2) inhibition, being more active than roscovitine the (IC50 = 140 nM) in targeting the CDK‐2 kinase enzyme. Additionally, for apoptosis induction of compound 8c in MCF‐7, it upregulated the expression levels of proapoptotic genes for P53, Bax, caspases‐3, 8, and 9 at up to 6.18, 4.8, 9.8, 4.6, 11.3 fold‐change, respectively, and downregualted the level of the antiapoptotic gene for Bcl‐2 by 0.14‐fold. Finally, a molecular docking study of the most active compound 8c highlighted a good binding affinity with Lys89 as the key amino acid for CDK‐2 inhibition.
24‐hour movement guidelines and weight status among preschool‐aged children in Bangladesh: A community‐level cross‐sectional study
Authors: Hossain Mohammad Sorowar , Raheem Enayetur , Okely Anthony D 
Published: May 2023

AbstractBackgroundIncreasing levels of urbanization and digitization in Bangladesh may be adversely associated with children's weight status and related movement behaviors. This study examined the prevalence of obesity, physical activity (PA), sedentary behavior, and sleep among young children from a district town in northern Bangladesh and identified factors associated with unhealthy weight status.MethodsPopulation‐based cross‐sectional study involving all kindergarten schools in Jamalpur District town. Schools and children aged 4–7 years were randomly selected and had their weight and height measured. Mothers completed a questionnaire on their child's PA, recreational screen time, and sleep and sociodemographic factors. Children's weight status was based on World Health Organization (WHO) categories. Meeting the PA recommendation was based on the WHO guidelines for children and adolescents, and meeting the sedentary behavior and sleep recommendations was based on the Canadian/Australian 24‐hour movement guidelines for children and young people.ResultsA total of 585 children and their parents were included in the study. Overall, 15% of children were overweight or obese. Three‐quarters of children met the sleep guideline, and 50% met the PA guideline. Less than one third of children (31%) met the recreational screen time guideline, whereas 15% met all three guidelines. However, when adjusted for all predictors in the model, maternal education, family income, and child's age were significantly associated with overweight/obesity. Children with higher maternal education level were 2.3 times (AOR = 2.33, 95% CI: 1.19–4.78) more likely to be overweight/obese. Children in families with a higher monthly income had 1.9 times (AOR = 1.95, 95% CI: 1.14, 3.35) higher risk of being overweight/obese.ConclusionsPrioritizing maternal education (mother‐centric interventions) can help address the high levels of childhood obesity in Bangladesh.
Advances in experimental animal models of hepatocellular carcinoma
Authors: Li Jing , Wang Xin , Ren Mudan , He Shuixiang , Zhao Yan 
Published: May 2023

AbstractHepatocellular carcinoma (HCC) is a common malignant tumor with insidious early symptoms, easy metastasis, postoperative recurrence, poor drug efficacy, and a high drug resistance rate when surgery is missed, leading to a low 5‐year survival rate. Research on the pathogenesis and drugs is particularly important for clinical treatment. Animal models are crucial for basic research, which is conducive to studying pathogenesis and drug screening more conveniently and effectively. An appropriate animal model can better reflect disease occurrence and development, and the process of anti‐tumor immune response in the human body. This review summarizes the classification, characteristics, and advances in experimental animal models of HCC to provide a reference for researchers on model selection.
Molecular risk factors for locoregional recurrence in resected non‐small cell lung cancer
Authors: Guo Wei , Zhang Tao , Li Runze , Chen Xiaoxi , Pang Jiaohui , Bao Hua , Wu Xue , Shao Yang , Qiu Bin , Gao Shugeng , He Jie 
Published: May 2023

AbstractBackgroundLocoregional recurrence is of high risk and is associated with a poor prognosis in terms of OS for non‐small cell lung cancer (NSCLC). Local control is essential for radical cure of NSCLC. Previous studies have investigated the clinicopathological risk factors for locoregional recurrence, but the genomic biomarkers associated with locoregional recurrence have been inadequately studied.MethodsA total of 118 patients who underwent tumor resection with mutation‐detected tumor specimens were included. Tumor samples at surgery and pretreatment/postoperative blood samples were collected for mutational profiling.ResultsAmong 48 patients with disease recurrence, 46% developed locoregional recurrence (LR) and 75% developed distant metastasis (DM). The 3‐year actuarial risk of LR and DM was 25% and 43%, respectively. The first sites of failure were locoregional only (29%), locoregional and distant (10%), and distant only (61%). Patients with LR showed significantly higher ctDNA level than those with only DM at the time of initial recurrence. On multivariate analysis of baseline risk factors, the presence of allele frequency heterogeneity and baseline ctDNA shedding were found to be independently associated with a higher risk of LR. Patients with disruptive TP53 mutations had significantly lower LR‐free survival as compared to patients with wild‐type TP53 or nondisruptive mutations. EGFR mutations showed a favorable prognostic value for LR and is not induced by EGFR tyrosine kinase inhibitor therapy. Both disruptive TP53 mutation and EGFR mutation remained the significant prognostic factor after adjustment for histological type, pathologic nodal stage and adjuvant therapy.ConclusionsNearly half of disease recurrences after surgery for NSCC involved locoregional sites. We identified genomic biomarkers from baseline tumor and ctDNA samples which showed promising prognostic value for LR only. This can help identify patients who had a higher risk of locoregional recurrence regardless of the risk of distant metastasis.
Metabolomic Profile by GC/MS and Antioxidant, Antidiabetic and Anti‐Inflammatory Activities of Green Solvent Extracts of Heterospathe elata Leaves
Authors: Dubey Supriya , Shukla Abha , Kumar Shukla Rishi 
Published: May 2023

AbstractPlants are the prime source of phytoconstituents that can act as potent agents for the prevention and treatment of various diseases. Heterospathe elata is a plant belonging to the Arecaceae family having numerous medicinal properties. The present study was undertaken to prepare crude extracts of Heterospathe elata leaves with solvents of different polarity dimethyl carbonate (DMC), isopropyl alcohol (IPA), hydro alcohol (HYA) and water (WTR) by using successive Soxhlet extraction method. Further, the antioxidant, antidiabetic, and anti‐inflammatory activities were assessed by the spectrophotometric method and possible bioactive phytoconstituents from the hydro alcohol extract of Heterospathe elata leaves using GC/MS. In our study, it was found that the GC/MS analysis revealed the presence of nineteen bioactive phytoconstituents. The highest antioxidant activity was found in the water extract. In antidiabetic and anti‐inflammatory activity highest potential was shown by hydro alcohol extract and the lowest was in the dimethyl carbonate extract. These findings support the Heterospathe elata leaves showed the high biological potential attributed to a high amount of bioactive phytoconstituents and could be utilized as value‐added functional food and medicine.
Hydroxy Acid Activation in Fungal Non‐Ribosomal Peptide Synthesis Assessed by Site‐Directed Mutagenesis
Authors: Hoffmann Sylvester , Damm Maik , Roth Leonard , Süssmuth Roderich D. 
Published: May 2023

AbstractThe fungal cyclodepsipeptides (CDPs) enniatin, beauvericin, bassianolide, and PF1022 consist of alternating N‐methylated l‐amino and d‐hydroxy acids. They are synthesized by non‐ribosomal peptide synthetases (NRPS). The amino acid and hydroxy acid substrates are activated by adenylation (A) domains. Although various A domains have been characterized thus giving insights into the mechanism of substrate conversion, little is known about the utilization of hydroxy acids in NRPSs. Therefore, we used homology modelling and molecular docking of the A1 domain of enniatin synthetase (EnSyn) to gain insights into the mechanism of hydroxy acid activation. We introduced point mutations into the active site and used a photometric assay to study the substrate activation. The results suggest that the hydroxy acid is selected by interaction with backbone carbonyls rather than by a specific side chain. These insights enhance the understanding of non‐amino acid substrate activation and could contribute to the engineering of depsipeptide synthetases.
Chemoenzymatic Catalysis: Cooperativity Enables Opportunity
Authors: Hessefort Logan Z. , Harstad Lauren J. , Merker Kayla R. , Ramos Lauren P. T. , Biegasiewicz Kyle F. 
Published: May 2023

AbstractThe application of enzymes in synthetic organic chemistry has emerged as a powerful means to generate molecular complexity in a highly selective, efficient, and sustainable manner. While enzymes have increasingly been incorporated into synthetic sequences for numerous academic and industrial applications on their own and in sequential processes, their utility in cooperative catalysis with small molecule catalytic platforms has recently drawn increased attention across the field of organic synthesis. In this review, we present a selection of notable accomplishments in cooperative chemoenzymatic catalysis and provide a perspective on its future directions.
Conserved Active Site Architecture Between Bacterial Cellulose and Chitin Synthases
Authors: Shamshoum Melina , Natalio Filipe 
Published: May 2023

AbstractGlycosyltransferases (GTs) are a large and diverse group of enzymes responsible for catalyzing the formation of a glycosidic bond between a donor molecule, usually a monosaccharide, and a wide range of acceptor molecules, thus, playing critical roles in various essential biological processes. Chitin and cellulose synthases are two inverting processive integral membrane GTs, belonging to the type‐2 family involved in the biosynthesis of chitin and cellulose, respectively. Herein, we report that bacterial cellulose and chitin synthases share an E‐D‐D‐ED‐QRW‐TK active site common motif that is spatially co‐localized. This motif is conserved among distant bacterial evolutionary species despite their low amino acid sequence and structural similarities between them. This theoretical framework offers a new perspective to the current view that bacterial cellulose and chitin synthases are substrate specific and that chitin and cellulose are organism specific. It lays the ground for future in vivo and in silico experimental assessment of cellulose synthase catalytic promiscuity against uridine diphosphate N‐acetylglucosamine and chitin synthase against uridine diphosphate glucose, respectively.
Design of multifunctional polymeric binders in silicon anodes for lithium‐ion batteries
Authors: Ramdhiny Masytha Nuzula , Jeon Ju‐Won 
Published: May 2023

AbstractSilicon (Si) is a promising anode material for lithium‐ion batteries (LIBs) owing to its tremendously high theoretical storage capacity (4200 mAh g−1), which has the potential to elevate the energy of LIBs. However, Si anodes exhibit severe volume change during lithiation/delithiation processes, resulting in anode pulverization and delamination with detrimental growth of solid electrolyte interface layers. As a result, the cycling stability of Si anodes is insufficient for commercialization in LIBs. Polymeric binders can play critical roles in Si anodes by affecting their cycling stability, although they occupy a small portion of the electrodes. This review introduces crucial factors influencing polymeric binders' properties and the electrochemical performance of Si anodes. In particular, we emphasize the structure–property relationships of binders in the context of molecular design strategy, functional groups, types of interactions, and functionalities of binders. Furthermore, binders with additional functionalities, such as electrical conductivity and self‐healability, are extensively discussed, with an emphasis on the binder design principle.
Capture and Stabilization of the Hydroxyl Radical in a Uranyl Peroxide Cluster**
Authors: Lottes Brett , Carter Korey P. 
Published: May 2023

AbstractHere we describe the synthesis and characterization of a new uranyl peroxide cluster (UPC), U60Ox30*, which captures and stabilizes oxygen‐based free radicals for more than one week. These radical species were first detected with a nitroblue tetrazolium colorimetric assay and U60Ox30* was characterized by single crystal X‐ray diffraction as well as infrared (IR), Raman, UV‐Vis‐NIR, and electron paramagnetic resonance (EPR) spectroscopies. Identification of the free radicals present in U60Ox30* was done via room temperature solid and solution state X‐band EPR studies using spin trapping methods. The spin trapping agent 5,5‐dimethyl‐1‐pyrroline N‐oxide (DMPO) was definitive for identifying the free radicals in U60Ox30*, which are hydroxyl radicals (⋅OH) that are stable for up to ten days that also persist upon addition of the metalloenzymes catalase and superoxide dismutase. Addition of the spin trapping agent α‐(4‐pyridyl N‐oxide)‐N‐tert‐butylnitrone (POBN) further confirmed the radicals were oxygen based, and deuteration experiments showed that the origin of the free radicals was from the decomposition of H2O2 in water. These results demonstrate that highly oxidizing species such as the ⋅OH radical can be stabilized in UPCs, which alters our understanding of the role of free radicals present in spent nuclear fuel.
Hexalacunary [α‐H2P2W12O48]12− Wells‐Dawson Anion: X‐ray Crystal Structural Evidence and Oligomerization to WO(OH2)4+‐Bridged Dimer and Trimers
Authors: Sugiarto  , Sadakane Masahiro 
Published: May 2023

AbstractWe report the first single‐crystal X‐ray structural evidence of the potassium salt of the hexalacunary [α‐H2P2W12O48]12− (abbreviated as {P2W12}) anion after its discovery by Contant and Ciabrini in 1977. In addition, we observed oligomerization of {P2W12} into a {WO(OH2)}4+‐bridged Pacman‐shaped [{WO(OH2)}(α‐HP2W12O48)2]22− ({P4W25}) dimer and a cyclic [{WO(OH2)}3(P2W12O48)3]30− ({P6W39}) trimer. The three phosphotungstate anions were synthesized through recrystallization of (NH4)12[α‐H2P2W12O48] from slightly alkaline (HOCH2)3CNH2/KCl, CH3NH3Cl/KCl, and CH3NH3Cl/NH4Cl solutions. The structure of {P2W12} is derived from [α‐P2W18O62]6− that has six tungsten atoms one from each polar group and four from the belt–removed, and the center of the lacunary site is capped by a potassium cation. Structures of {P4W25} and {P6W39} are constructed by connecting two and three {P2W12} units with {WO(OH2)}4+, respectively. The isolation of a pure {P6W39} phosphotungstate framework without coordination with transition metal cations is unprecedented. Powder X‐ray diffraction confirmed the bulk purity of these compounds, indicating that selective crystallization was achieved through the selection of countercations and pH.
The Bulk Breast Cancer Cell and Breast Cancer Stem Cell Activity of Binuclear Copper(II)‐Phenanthroline Complexes
Authors: Osei Priscilla B. , Northcote‐Smith Joshua , Fang Jiaxin , Singh Kuldip , Ortu Fabrizio , Suntharalingam Kogularamanan 
Published: May 2023

AbstractMononuclear copper(II)‐phenanthroline complexes have been widely investigated as anticancer agents whereas multinuclear copper(II)‐phenanthroline complexes are underexplored. Here the synthesis and characterisation of two new binuclear copper(II)‐phenanthroline complexes 1 and 2 is reported, comprising of 2,9‐dimethyl‐1,10‐phenanthroline or 2,9‐dimethyl‐4,7‐diphenyl‐1,10‐phenanthroline, terminal chloride ligands, and bridging chloride or hydroxide ligands. The binuclear copper(II) complex containing 2,9‐dimethyl‐1,10‐phenanthroline 1 displays nanomolar toxicity towards bulk breast cancer cells and breast cancer stem cells (CSCs) grown in monolayers, >50‐fold greater than cisplatin (an anticancer metallodrug) and salinomycin (a gold‐standard anti‐CSC agent). Spectacularly, 1 exhibits >100‐fold greater potency toward three‐dimensionally cultured mammospheres than cisplatin and salinomycin. Mechanistic studies show that 1 evokes breast CSC apoptosis by elevating intracellular reactive oxygen species levels and damaging genomic DNA (possibly by an oxidative mechanism). To the best of our knowledge, this is the first study to probe the anti‐breast CSC properties of binuclear copper(II)‐phenanthroline complexes.
Energy‐Dissipative Hydrogels: A Promising Material for Tissue Regeneration†
Authors: Li Mingrui , Lin Youshi , Zhang Yuxiao , Bian Liming , Zhang Kunyu 
Published: May 2023

Comprehensive SummaryHydrogels are promising candidates for mimicking native extracellular matrix (ECM) and are therefore widely adopted as scaffolds in tissue engineering. However, conventional hydrogels composed of static networks are prone to permanent structural damages and lack the ability to provide the time‐dependent mechanical cues, which are essential for cell development, ECM remodeling, and tissue regeneration. The recent substantial development in the structurally dynamic hydrogels with energy‐dissipative ability has demonstrated the unique capability of such viscoelastic hydrogels to withstand extreme biomechanical loads and regulate cellular behaviors not present in classical hydrogels. This review starts with the general design principles for energy‐dissipative hydrogels, followed by recent advancements in fabrication approaches for energy‐dissipative hydrogels. We then highlight some applications of energy‐dissipative hydrogels in tissue engineering, including bone and cartilage regeneration, vessel regeneration, nerve regeneration, and wound healing. Finally, we discuss about the key current challenges and future development of energy‐dissipative hydrogels for biomedical applications.