bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of Natural‐Product‐Inspired ABCB1 Inhibitors Through Regioselective Tryptophan C3‐Benzylation
Authors: Mariya Vincent Dona , Mostafa Habib , Suneer Anza , Radha Krishnan Sabhashina , Ong Mingmin , Itahana Yoko , Itahana Koji , Viswanathan Rajesh 
Published: August 2024

AbstractThe emergence of drug resistance in cancer cells eventually causing relapse is a serious threat that demands new advances. Upregulation of the ATP‐dependent binding cassette (ABC) transporters, such as ABCB1, significantly contributes to the emergence of drug resistance in cancer. Despite more than 30 years of therapeutic discovery, and several generations of inhibitors against P‐gp, the search for effective agents that minimize toxicity to human cells, while maintaining efflux pump inhibition is still underway. Leads derived from natural product scaffolds are well‐known to be effective in various therapeutic approaches. Inspired by the biosynthetic pathway to Nocardioazine A, a marine alkaloid known to inhibit the P‐gp efflux pump in cancer cells, we devised a regioselective pathway to create structurally unique indole‐C3‐benzyl cyclo‐L‐Trp‐L‐Trp diketopiperazines (DKPs). Using bat cells as a model to derive effective ABCB1 inhibitors for targeting human P‐gp efflux pumps, we have recently identified exo‐C3‐N‐Dbn‐Trp2 (13) as a lead ABCB1 inhibitor. This C3‐benzylated lead inhibited ABCB1 better than Verapamil.[21] Additionally, C3‐N‐Dbn‐Trp2 restored chemotherapy sensitivity in drug‐resistant human cancer cells and had no adverse effect on cell proliferation in cell cultures. For a clearer structure‐activity relationship, we developed a broader screen to test C3‐functionalized pyrroloindolines as ABCB1 inhibitors and observed that C3‐benzylation is outperforming respective isoprenylated derivatives. Results arising from the molecular docking studies indicate that the interactions at the access tunnel between ABCB1 and the inhibitor result in a powerful predictor for the efficacy of the inhibitor. Based on fluorescence‐based assays, we conclude that the most efficacious inhibitor is the p‐cyano‐derived exo‐C3‐N‐Dbn‐Trp2 (33 a), closely followed by the p‐nitro substituted analogue. By combining assay results with molecular docking studies, we further correlate that the predictions based on the inhibitor interactions at the access tunnel provide clues about the design of improved ABCB1 inhibitors. As it has been well documented that ABCB1 itself is powerfully engaged in multi‐drug resistance, this work lays the foundation for the design of a new class of inhibitors based on the endogenous amino acid‐derived cyclo‐L‐Trp‐L‐Trp DKP scaffold.
Dirhodium(II)/XantPhos Catalyzed Synthesis of β‐(E)‐Vinylsilanes via Hydrosilylation and Isomerization from Alkynes
Authors: Yang Liqun , Yi Mingjun , Wu Xiaoyu , Lu Yan , Zhang Zhaoguo 
Published: August 2024

AbstractA concise hydrosilylation of alkynes for synthesizing β‐(E)‐vinylsilanes catalyzed by dirhodium(II)/XantPhos has been developed. In this reaction, β‐(E)‐vinylsilanes were generated from the isomerization of β‐(Z)‐vinylsilanes catalyzed by dirhodium(II) hydride species rather than the direct insertion of triple bond into M−H or M−Si bond (traditional Chalk‐Harrod mechanism or modified Chalk‐Harrod mechanism). The hydrosilylation displayed a broad substrate scope for alkynes and tertiary silanes, tolerating diverse functional groups including halides, nitriles, amines, esters, and heterocycles.
Columnar Organization of Nonalternant Fluorinated Dehydrobenzannulenes
Authors: Karki Sumitra , Jalife Said , Wang Xiqu , Lin Yun‐Hsien , Wu Judy I. , Miljanić Ognjen Š. 
Published: August 2024

AbstractTwo new partially fluorinated dehydrobenzannulenes have been prepared by inter‐ and intramolecular oxidative homocoupling of diyne precursors. These systems contain fluorinated and nonfluorinated arene rings in a desymmetrized non‐alternant arrangement. Both macrocycles are roughly planar and organize into extended columns in the solid state. The assembly of these columns is mediated by the combination of dispersion interactions, slipped [π⋅⋅⋅π] stacking interactions of the perfluorinated rings with each other, and their association with the nonfluorinated rings in the molecules of the neighboring macrocycles. These results suggest that partial fluorination of dehydrobenzannulenes can serve as a versatile motif for their assembly into columnar superstructures.
Cation Enrichment Promotes High‐rate CO Electroreduction to C2+ Liquid Products
Authors: Cui Chunyu , Xu Liang , Yu Peiping , Wang Nan , Ni Fenglou , Guo Wen , Yang Hao , Cheng Tao , Zhang Bo 
Published: August 2024

AbstractElectrochemical reduction of CO into valuable multicarbon (C2+) liquids is crucial for reducing CO2 emissions and advancing clean energy, yet mastering efficiency and selectivity in this process remains a tough challenge. Herein, we employ a surface‐modification strategy using electrochemically active polymeric 1,4,5,8‐naphthalenete‐tracarboxylic dianhydride (PNTCDA)‐modified copper nanosheets (PM−Cu) to rearrange reactive species in the electric double layer, where the PNTCDA triggers a distinctive enolization that anchor potassium ions (K+) onto the cathode surface under reduction condition. Electrochemical analysis and computational simulations revealed that this approach fine‐tunes K+ distribution in the double layer, making the dehydration of hydrated K+ more efficient and reducing active water molecules at the interface, thus inhibiting the hydrogen evolution reaction while concurrently promoting CO reduction via enhanced C−C coupling. For the first time, the PM−Cu catalyst demonstrates ampere‐scale current densities with the exclusive selectivity of a C2+ liquid product yield exceeding 90 %. Thus, by tailoring the local microenvironment with electrochemically active organics, it is possible to modulate CO reduction, improve sustainable energy storage, and increase industrial carbon utilization.
Enhancing Oxygen Reduction Reaction of Single‐Atom Catalysts by Structure Tuning
Authors: Song Kexin , Jing Haifeng , Yang Binbin , Shao Jing , Tao Youkun , Zhang Wei 
Published: August 2024

AbstractDeciphering the fine structure has always been a crucial approach to unlocking the distinct advantages of high activity, selectivity, and stability in single‐atom catalysts (SACs). However, the complex system and unclear catalytic mechanism have obscured the significance of exploring the fine structure. Therefore, we endeavored to develop a three‐component strategy to enhance oxygen reduction reaction (ORR), delving deep into the profound implications of the fine structure, focusing on central atoms, coordinating atoms, and environmental atoms. Firstly, the mechanism by which the chemical state and element type of central atoms influence catalytic performance is discussed. Secondly, the significance of coordinating atoms in SACs is analyzed, considering both the number and type. Lastly, the impact of environmental atoms in SACs is reviewed, encompassing existence state and atomic structure. Thorough analysis and summarization of how the fine structure of SACs influences the ORR have the potential to offer valuable insights for the accurate design and construction of SACs.
A severe asthma phenotype of excessive airway Haemophilus influenzae relative abundance associated with sputum neutrophilia
Authors: Versi Ali , Azim Adnan , Ivan Fransiskus Xaverius , Abdel‐Aziz Mahmoud I , Bates Stewart , Riley John , Uddin Mohib , Zounemat Kermani Nazanin , Maitland‐Van Der Zee Anke‐H , Dahlen Sven‐Eric , Djukanovic Ratko , Chotirmall Sanjay H , Howarth Peter , Adcock Ian M , Chung Kian Fan ,   the U‐BIOPRED study group
Published: August 2024

AbstractBackgroundSevere asthma (SA) encompasses several clinical phenotypes with a heterogeneous airway microbiome. We determined the phenotypes associated with a low α‐diversity microbiome.MethodsMetagenomic sequencing was performed on sputum samples from SA participants. A threshold of 2 standard deviations below the mean of α‐diversity of mild‐moderate asthma and healthy control subjects was used to define those with an abnormal abundance threshold as relative dominant species (RDS).FindingsFifty‐one out of 97 SA samples were classified as RDSs with Haemophilus influenzae RDS being most common (n = 16), followed by Actinobacillus unclassified (n = 10), Veillonella unclassified (n = 9), Haemophilus aegyptius (n = 9), Streptococcus pseudopneumoniae (n = 7), Propionibacterium acnes (n = 5), Moraxella catarrhalis (n = 5) and Tropheryma whipplei (n = 5). Haemophilus influenzae RDS had the highest duration of disease, more exacerbations in previous year and greatest number on daily oral corticosteroids. Hierarchical clustering of RDSs revealed a C2 cluster (n = 9) of highest relative abundance of exclusively Haemophilus influenzae RDSs with longer duration of disease and higher sputum neutrophil counts associated with enrichment pathways of MAPK, NF‐κB, TNF, mTOR and necroptosis, compared to the only other cluster, C1, which consisted of 7 Haemophilus influenzae RDSs out of 42. Sputum transcriptomics of C2 cluster compared to C1 RDSs revealed higher expression of neutrophil extracellular trap pathway (NETosis), IL6‐transignalling signature and neutrophil activation.ConclusionWe describe a Haemophilus influenzae cluster of the highest relative abundance associated with neutrophilic inflammation and NETosis indicating a host response to the bacteria. This phenotype of severe asthma may respond to specific antibiotics.
Possible interactions between gut microbiome and division of labor in honey bees
Authors: Wang Kang , Zheng Ming , Cai Minqi , Zhang Yi , Fan Yuanchan , Lin Zheguang , Wang Zhi , Niu Qingsheng , Ji Ting 
Published: August 2024

AbstractRecent studies have provided new insights into the role of the microbiome in shaping host behavior. However, the relationship between the temporal division of labor among honey bees (Apis mellifera) and their gut microbial community has not been widely studied. Therefore, we aimed to evaluate the link between the gut microbiome and division of labor in honey bees by examining the microbial absolute abundance and relative composition of 7‐day‐old nurse bees and 28‐day‐old forager bees from a natural hive, as well as those of worker bees of the same 14‐day‐old age showing different behaviors in a manipulated hive. We found that forager bees had fewer core bacteria, particularly gram‐positive fermentative genera such as Lactobacillus and Bifidobacterium, with Bifidobacterium asteroides being the most sensitive to host behavioral tasks. Our results showed that forager bees have lower gut community stability compared to nurse bees, suggesting that their gut community is more susceptible to invasion by non‐core members. Furthermore, a pollen limitation experiment using caged honey bees indicated that dietary changes during behavioral shifts may be a driving factor in honey bee microbial diversity. This study contributes to a greater understanding of the interaction between the gut microbiome and behavioral tasks and provides a foundation for future assays.
A Practical Zinc Metal Anode Coating Strategy Utilizing Bulk h‐BN and Improved Hydrogen Redox Kinetics
Authors: Kim Dong Il , Jeong Hee Bin , Lim Jungmoon , Jeong Hyeong Seop , Kim Min Kyeong , Pak Sangyeon , Lee Sanghyo , An Geon‐Hyoung , Chee Sang‐Soo , Hong Jin Pyo , Cha SeungNam , Hong John 
Published: August 2024

Achieving high‐performance aqueous zinc‐ion batteries requires addressing the challenges associated with the stability of zinc metal anodes, particularly the formation of inhomogeneous zinc dendrites during cycling and unstable surface electrochemistry. This study introduces a practical method for scattering untreated bulk hexagonal boron nitride (h‐BN) particles onto the zinc anode surface. During cycling, stabilized zinc fills the interstices of scattered h‐BN, resulting in a more favorable (002) orientation. Consequently, zinc dendrite formation is effectively suppressed, leading to improved electrochemical stability. The zinc with scattered h‐BN in a symmetric cell configuration maintains stability 10 times longer than the bare zinc symmetric cell, lasting 500 hours. Furthermore, in a full cell configuration with α‐MnO2 cathode, increased H+ ion activity can effectively alter the major redox kinetics of cycling due to the presence of scattered h‐BN on the zinc anode. This shift in H+ ion activity lowers the overall redox potential, resulting in a discharge capacity retention of 96.1% for 300 cycles at a charge/discharge rate of 0.5 A g−1. This study highlights the crucial role of surface modification, and the innovative use of bulk h‐BN provides a practical and effective solution for improving the performance and stability.
The complement system: A key player in the host response to infections
Authors: Jayaraman Archana , Walachowski Sarah , Bosmann Markus 
Published: August 2024

AbstractInfections are one of the most significant healthcare and economic burdens across the world as underscored by the recent coronavirus pandemic. Moreover, with the increasing incidence of antimicrobial resistance, there is an urgent need to better understand host–pathogen interactions to design effective treatment strategies. The complement system is a key arsenal of the host defense response to pathogens and bridges both innate and adaptive immunity. However, in the contest between pathogens and host defense mechanisms, the host is not always victorious. Pathogens have evolved several approaches, including co‐opting the host complement regulators to evade complement‐mediated killing. Furthermore, deficiencies in the complement proteins, both genetic and therapeutic, can lead to an inefficient complement‐mediated pathogen eradication, rendering the host more susceptible to certain infections. On the other hand, overwhelming infection can provoke fulminant complement activation with uncontrolled inflammation and potentially fatal tissue and organ damage. This review presents an overview of critical aspects of the complement‐pathogen interactions during infection and discusses perspectives on designing therapies to mitigate complement dysfunction and limit tissue injury.
Denitrative Functionalization of Nitroarenes: Recent Progress and Future Perspectives
Authors: Li Haiyan , Lei Zhiguo , Yang Xun , Xiao Yuxuan , Yin Ying , Du Jiahui , Duan Wengui , Yu Lin 
Published: August 2024

AbstractNitroarenes are fundamental feedstocks in the chemical industry. Their relatively inert C−NO2 bond allows for late‐stage modifications of molecules and exhibits complete orthogonality to the reactivity of C‐halogen bond in cross‐coupling reactions. The denitrative functionalization of nitroarenes holds significant appeal due to it avoids the use of aryl halides, thereby simplifying reaction steps and improving atom and step economy. Recent progress in direct denitrative functionalization of nitroarenes includes palladium‐catalyzed denitrative coupling, copper‐catalyzed denitrative coupling, as well as metal‐free one‐pot C−NO2 functionalization. In this review, we provide a concise overview of these advancements, detailing the reaction features and mechanisms. This summary aims to highlight the versatility and efficiency of denitrative functionalization methodologies, offering insights into their potential applications and inspiring further research in this promising area of organic synthesis.
ART26.12, a novel fatty acid‐binding protein 5 inhibitor, shows efficacy in multiple preclinical neuropathy models
Authors: Warren W. G. , Osborn M. , David‐Pereira A. , Tsantoulas C. , Xue Wenwen , Yates A. , OSullivan S. E. 
Published: August 2024

AbstractBackgroundPainful neuropathy is a pathological condition caused by numerous factors including diabetes, chemotherapy or cancer. ART26.12 is a novel fatty acid‐binding protein 5 inhibitor, which our group showed could prevent and treat persistent pain in a preclinical model of oxaliplatin‐induced peripheral neuropathy.MethodsIn the current study, the efficacy of orally dosed ART26.12 was tested in multiple neuropathy models of different aetiology. Paw withdrawal threshold to von Frey monofilaments and latency to escape a cold plate were used as measurements of mechanical and cold sensitivity.ResultsART26.12 (25 and 50 mg/kg BID), dosed prior to the induction of paclitaxel‐induced peripheral neuropathy (PIPN), reversed mechanical allodynia induced by paclitaxel in both male and female rats, and ART26.12 (50 mg/kg BID) prevented the induction of PIPN in female rats. ART26.12 (50 mg/kg BID) also had a protective effect on body weight in the PIPN model. ART26.12 (25 and 100 mg/kg BID) reversed mechanical allodynia when treating established streptozotocin‐induced diabetic neuropathy in male rats. In a model of breast cancer‐induced bone pain in female rats, ART26.12 (100 mg/kg BID) reversed mechanical allodynia within 1 h of dosing. In the same model, ART26.12 (25 mg/kg BID) reversed mechanical allodynia from day 4 of treatment.ConclusionOverall, these preclinical data suggest that ART26.12 is a safe and efficacious therapeutic drug for continued development towards the prevention and treatment of peripheral neuropathy.Significance StatementThis work now shows that ART26.12, a novel and selective inhibitor of FABP5, can prevent and treat multiple preclinical models of peripheral neuropathy. Given its excellent safety profile, further work is warranted to develop ART26.12 as a potential therapeutic tool for pain management.
Microbial Squalene: A Sustainable Alternative for the Cosmetics and Pharmaceutical Industry – A Review
Authors: Shalu Saseendran , Karthikanath Panam Kunnel Raveendranathan , Vaidyanathan Vinoth Kumar , Blank Lars M. , Germer Andrea , Balakumaran Palanisamy Athiyaman 
Published: August 2024

ABSTRACTSqualene is a natural triterpenoid and a biosynthetic precursor of steroids and hopanoids in microorganisms, plants, humans, and other animals. Squalene has exceptional properties, such as its antioxidant activity, a high penetrability of the skin, and the ability to trigger the immune system, promoting its application in the cosmetic, sustenance, and pharmaceutical industries. Because sharks are the primary source of squalene, there is a need to identify low‐cost, environment friendly, and sustainable alternatives for producing squalene commercially. This shift has prompted scientists to apply biotechnological advances to research microorganisms for synthesizing squalene. This review summarizes recent metabolic and bioprocess engineering strategies in various microorganisms for the biotechnological production of this valuable molecule.
A hierarchical constrained density regression model for predicting cluster‐level dose‐response
Authors: Pennell Michael L. , Wheeler Matthew W. , Auerbach Scott S. 
Published: August 2024

AbstractWith the advent of new alternative methods for rapid toxicity screening of chemicals comes the need for new statistical methodologies which appropriately synthesize the large amount of data collected. For example, transcriptomic assays can be used to assess the impact of a chemical on thousands of genes, but current approaches to analyzing the data treat each gene separately and do not allow sharing of information among genes within pathways. Furthermore, the methods employed are fully parametric and do not account for changes in distribution shape that may occur at high exposure levels. To address the limitations of these methods, we propose Constrained Logistic Density Regression (COLDER) to model expression data from different genes simultaneously. Under COLDER, the dose‐response function for each gene is assigned a prior via a discrete logistic stick‐breaking process (LSBP) whose weights depend on gene‐level characteristics (e.g., pathway membership) and atoms consist of different dose‐response functions subject to a shape constraint that ensures biological plausibility. The posterior distribution for the benchmark dose among genes within the same pathways can be estimated directly from the model, which is another advantage over current methods. The ability of COLDER to predict gene‐level dose‐response is evaluated in a simulation study and the method is illustrated with data from a National Toxicology Program study of Aflatoxin B1.
Study on the effective drainage range of long horizontal borehole for goaf gas drainage
Authors: Guo Mingjie , Guo Wenbing , Yuan Ruifu , Tan Yi , Bai Erhu 
Published: August 2024

AbstractLaying long horizontal borehole (LHB) in mining‐induced strata fractures for coal‐bed gas drainage in the goaf is a pivotal method for eliminating safety hazards, preventing atmospheric pollution, and realizing gas utilization. A crucial premise of this method is to determine the effective drainage range of the borehole, a key parameter directly affecting boreholes spacing and drainage efficiency. In this study, a model of gas seepage during LHB drainage within a circular equipotential boundary was presented, and the complex variable function theory and the mirror principle were adopted for deriving the complex potential function of gas flow under the condition of LHB drainage and the drainage volume function of a single center borehole. Besides, the main indicator to determinate the effective drainage range of LHB was given. Specifically, the indicator refers to the distance between the turning point (the point at which the change rate of the gas flow velocity is −0.002 around the borehole) and the center of the borehole. Subsequently, numerical simulation was conducted to obtain the effective drainage range of LHB within mining‐induced fractures of overlying strata, that is, 4 m < r < 7 m. Furthermore, discussion of the effective drainage range of LHB was carried out by analyzing gas flow velocity distributions and LHB drainage volumes. A case study demonstrates that a double‐borehole layout with a 10 m spacing can effectively control pressure‐relief gas in the goaf. Meanwhile, such a layout can achieve well‐balanced drainage efficiency of each borehole with a minimal difference of 0.31 m3 min−1, which is only about 7.9% of the average drainage volume of the two boreholes. The above results verify that the determined effective drainage range of LHB is reasonable. The research results can provide references for determining the drainage range of LHB in multi‐borehole layout of coal mines, and then determining the spacing of LHBs arrangement, thereby improving the efficiency of gas extraction.
The National Electrical Safety Code, powerline clearances, and wildfires
Authors: Babrauskas Vytenis 
Published: August 2024

AbstractThe provisions of the National Electrical Safety Code (NESC) have a long, but undocumented history. They are the primary means by which Public Utilities Commission agencies in various States in the United States enforce requirements for electrical clearances pertinent to high‐voltage powerlines. Examination of the NESC provisions for clearances between grounded guy wires and distribution phase conductors in the context of the Woolsey Fire indicates a comprehensive lack of realism in the Code provisions. While they may be entirely sufficient to prevent sparkover under normal operating conditions, they are wholly insufficient to cope with even modest adverse events. The profession should consider explicitly assessing factors beyond sparkover that affect the adequacy of clearance requirements. The provisions of the NESC (and California's parallel General Order No. 95) should be systematically reexamined in order to ensure that safety regulations can cope with adverse events that are serious, but not extreme. Since the vast majority of the electrical power network is aging and not new construction, a scheme should be developed to establish priorities for upgrading existing facilities at the highest risk of failure.