bluuebunny/crossref_metadata_2025 huggingface dataset:
Liposomal Antibiotic Booster Potentiates Carbapenems for Combating NDMs‐Producing Escherichiacoli
Authors: Wu Sixuan , Wei Yongbin , Wang Yang , Zhang Zhenzhong , Liu Dejun , Qin Shangshang , Shi Jinjin , Shen Jianzhong
Published: November 2023

Infections caused by Enterobacterales producing New Delhi Metallo‐β‐lactamases (NDMs), Zn(II)‐dependent enzymes hydrolyzing carbapenems, are difficult to treat. Depriving Zn(II) to inactivate NDMs is an effective solution to reverse carbapenems resistance in NDMs‐producing bacteria. However, specific Zn(II) deprivation and better bacterial outer membrane penetrability in vivo are challenges. Herein, authors present a pathogen‐primed liposomal antibiotic booster (M‐MFL@MB), facilitating drugs transportation into bacteria and removing Zn(II) from NDMs. M‐MFL@MB introduces bismuth nanoclusters (BiNCs) as a storage tank of Bi(III) for achieving ROS‐initiated Zn(II) removal. Inspired by bacteria‐specific maltodextrin transport pathway, meropenem‐loaded BiNCs are camouflaged by maltodextrin‐cloaked membrane fusion liposome to cross the bacterial envelope barrier via selectively targeting bacteria and directly outer membrane fusion. This fusion disturbs bacterial membrane homeostasis, then triggers intracellular ROS amplification, which activates Bi(III)‐mediated Zn(II) replacement and meropenem release, realizing more precise and efficient NDMs producer treatment. Benefiting from specific bacteria‐targeting, adequate drugs intracellular accumulation and self‐activation Zn(II) replacement, M‐MFL@MB rescues all mice infected by NDM producer without systemic side effects. Additionally, M‐MFL@MB decreases the bacterial outer membrane vesicles secretion, slowing down NDMs producer's transmission by over 35 times. Taken together, liposomal antibiotic booster as an efficient and safe tool provides new strategy for tackling NDMs producer‐induced infections.
Quinolinoacridine as High Efficiency Building Unit in Single‐Layer Phosphorescent Organic Light‐Emitting Diodes
Authors: Brouillac Clément , Lucas Fabien , Ari Denis , Tondelier Denis , Meot Jonathan , Malvaux Marc , Jadaud Cyril , Lebreton Christophe , Rault‐Berthelot Joëlle , Quinton Cassandre , Jacques Emmanuel , Poriel Cyril
Published: November 2023

The performances of simplified single‐layer phosphorescent organic light‐emitting diodes (SL‐PhOLEDs) have significantly increased and they now appear to be a promising alternative to multi‐layer PhOLEDs. The blue and white emissions, far more challenging than all the other colours, are still particularly desired. Herein, a high efficiency host material for blue emitting SL‐PhOLED using the blue emitter FIr6 is reported, which is particularly interesting as it displays an emission at shorter wavelengths than the well‐known FIrpic emitter, almost exclusively reported in the SL‐PhOLEDs literature. The host material investigated herein is constructed on the electron‐rich quinolinoacridine and displays when incorporated in FIr6‐based SL‐PhOLEDs, an external quantum efficiency (EQE)⟩10% and a low Von of 3.1 V. This is the first work passing an EQE of 10% with FIr6 as an emitter. This host also reaches a very high EQE of 19% when used with the green emitter Ir(ppy)2acac, this performance being among the highest recorded for green SL‐PhOLEDs. Finally, as white SL‐PhOLEDs involve blue emitting SL‐PhOLEDs, this host is also used with a combination of blue and yellow emitters. An extremely high EQE of 24% is reached with CIE coordinates of (0.40;0.48). These findings show the real potential of the quinolinoacridine fragment to reach high performance multi‐colour SL‐PhOLEDs.
Furan‐modified thiadiazolo quinoxaline as an electron acceptor for constructing second near‐infrared aggregation‐induced emission fluorophores for beyond 1300 nm fluorescence/photoacoustic imaging and photothermal therapy
Authors: Liang Mengke , Liu Luyu , Sun Ying , Li Jia , Zhang Ling'e , Jiang Xiqun , Wu Wei
Published: November 2023

Creation of new fluorophores is important for understanding the structure–property relationship, by which the required optical properties are likely to be attained. Herein, through theory calculation, it is found that furan‐modified thiadiazolo quinoxaline acting as an electron acceptor can endow donor–acceptor–donor (D–A–D) type second near‐infrared (NIR‐II) fluorophores with longer emission wavelength than the other thiadiazolo quinoxaline‐based acceptors containing pyridine, pyrrole, thiophene, and phenyl groups, respectively. On the basis of this theoretical prediction, a D–A–D type NIR‐II fluorophore with 6,7‐di(furan‐2‐yl)‐[1,2,5]thiadiazolo[3,4‐g] quinoxaline (DFTQ) as the acceptor and dithieno[3,2‐b:2′,3′‐d]pyrrole (DTP) as the donor is designed and synthesized, and the aggregation‐induced emission (AIE) function is further achieved by introducing the AIE units of tetraphenylethylene (TPE) and triphenylamine (TPA), respectively, totally forming three NIR‐II fluorophores DFTQ–DTP, DFTQ–DTPE, and DFTQ–DTPA. For biological applications, the fluorophores are encapsulated by amphiphilic DSPE–PEG2000 to generate water‐dispersible nanoparticles (NPs). Almost the whole emission of each of the NPs falls into the NIR‐II spectral range, with part emission beyond 1300 nm. By using DFTQ–DTPA NPs as the contrast and photothermal therapy (PTT) agent, high‐resolution in vivo fluorescence imaging is achieved in the greater than 1300 nm window, and their good performance in photoacoustic imaging and high tumor PTT efficacy in tumor‐bearing mice are also demonstrated. Taken together, this work mainly provides a strong electron acceptor for constructing long‐emitting fluorophores, and by using the electron acceptor, a AIE fluorophore with desirable quantum yield (QY) and photothermal conversion efficienciy (PCE) is synthesized and demonstrated to be promising in fluorescence/photoacoustic imaging and PTT.
Photo‐Driven Quasi‐Topological Transformation Exposing Highly Active Nitrogen Cation Sites for Enhanced Photocatalytic H2O2 Production
Authors: Hao Feini , Yang Chao , Lv Ximeng , Chen Fangshuai , Wang Shengyao , Zheng Gengfeng , Han Qing
Published: November 2023

Herein, the exposure of highly‐active nitrogen cation sites has been accomplished by photo‐driven quasi‐topological transformation of a 1,10‐phenanthroline‐5,6‐dione‐based covalent organic framework (COF), which contributes to hydrogen peroxide (H2O2) synthesis during the 2‐electron O2 photoreduction. The exposed nitrogen cation sites with photo‐enhanced Lewis acidity not only act as the electron‐transfer motor to adjust the inherent charge distribution, powering continuous and stable charge separation, and broadening visible‐light adsorption, but also providing a large number of active sites for O2 adsorption. The optimal catalyst shows a high H2O2 production rate of 11965 μmol g−1 h−1 under visible light irradiation and a remarkable apparent quantum yield of 12.9 % at 400 nm, better than most of the previously reported COF photocatalysts. This work provides new insights for designing photo‐switchable nitrogen cation sites as catalytic centers toward efficient solar to chemical energy conversion.
Iron‐Catalyzed Stereoconvergent 1,4‐Hydrosilylation of Conjugated Dienes
Authors: Sun Wei , Hu Meng‐Yang , Lu Zhan‐Sheng , Huang Ming‐Yao , Zhang Xin‐Yu , Zhu Shou‐Fei
Published: November 2023

Stereoconvergent transformation of E/Z mixtures of olefins to products with a single steric configuration is of great practical importance but hard to achieve. Herein, we report an iron‐catalyzed stereoconvergent 1,4‐hydrosilylation reactions of E/Z mixtures of readily available conjugated dienes for the synthesis of Z‐allylsilanes with high regioselectivity and exclusive stereoselectivity. Mechanistic studies suggest that the reactions most likely proceed through a two‐electron redox mechanism. The stereoselectivity of the reactions is ultimately determined by the crowded reaction cavity of the α‐diimine ligand‐modified iron catalyst, which forces the conjugated diene to coordinate with the iron center in a cis conformation, which in turn results in generation of an anti‐π‐allyl iron intermediate. The mechanism of this stereoconvergent transformation differs from previously reported mechanisms of other related reactions involving radicals or metal‐hydride species.
Water‐Induced Micro‐Hydrophobic Effect Regulates Benzene Methylation in Zeolite
Authors: Wang Chao , Chu Yueying , Xiong Danfeng , Wang Haifeng , Hu Min , Wang Qiang , Xu Jun , Deng Feng
Published: November 2023

Water is a ubiquitous component in heterogeneous catalysis over zeolites and can significantly influence the catalyst performance. However, the detailed mechanism insights into zeolite‐catalyzed reactions under microscale aqueous environment remain elusive. Here, using multiple dimensional solid‐state NMR experiments coupled with ultrahigh magic angle spinning technique and theoretical simulations, we establish a fundamental understanding of the role of water in benzene methylation over ZSM‐5 zeolite under water vapor conditions. We show that water competes with benzene for the active sites of zeolite and facilitates the bimolecular reaction mechanism. The growth of water clusters induces a micro‐hydrophobic effect in zeolite pores, which reorients benzene molecules and drives their interactions with surface methoxy species (SMS) on zeolite. We identify the formation and evolution of active SMS‐Benzene complexes in a microscale aqueous environment and demonstrate that their accumulation in zeolite pores boosts benzene conversion and methylation.
Natural flavonoids as promising 6‐phosphogluconate dehydrogenase inhibitor candidates: In silico and in vitro assessments
Authors: Adem Şevki , Yırtıcı Ümit , Aydın Mesut , Rawat Ravi , Eyüpoğlu Volkan
Published: November 2023

The primary strategy in the fight against cancer is to screen compounds that may be effective on different types of cancer. Compounds from plants seem to be a good source. The present study investigated the inhibitory effects of some flavonoids on the 6‐phosphogluconate dehydrogenase (6‐PGD) enzyme. We determined that quercetin, myricetin, fisetin, morin, apigenin, and baicalein exhibited powerful inhibition effects with IC50 values between 4.08 and 21.26 µM, while luteolin, kaempferol, apiin, galangin, and baicalin showed moderate effects with IC50 values between 54.15 and 138.91 µM. Quercetin competitively inhibited the binding of NADP and 6‐phosphogluconate to the 6‐PGD enzyme with Ki values of 0.527 ± 0.251 and 0.374 ± 0.138 µM, respectively. We calculated Ki values using the Cheng–Prusoff equation as between 0.44 and 14.88 µM. The possible interaction details of polyphenols with the active site of 6‐PGD were analyzed with docking software. In silico and in vitro studies indicated that the –OH groups on the A and C ring of flavonoids bind to the enzyme's active site via hydrogen bonding, while the –OH groups on the C ring contributed significantly to the increase in the inhibitory potentials of the molecules. Molecular dynamic simulations tested the stability of the 6‐PGD‐quercetin complex during 100 ns. These phytochemicals were suitable for drug use when optimized with absorption, distribution, metabolism, excretion, and toxicity (ADMET) criteria. The effects of the studied compounds on cancer cell lines of potential targets were demonstrated by network analysis. In conclusion, this study suggests that flavonoids found to be potent inhibitors could serve as leading candidates to treat many cancers via 6‐PGD inhibition.
Pancreatic index: A prognostic factor of upfront surgery for body or tail pancreatic ductal adenocarcinoma with vascular involvement—A retrospective study
Authors: Qian Lihan , Li Jingfeng , Sun Yanjun , Chai Weimin , Deng Xiaxing , Wang Weishen , Shen Baiyong
Published: November 2023

Background

The pancreatic index (PI) is a useful preoperative imaging predictor for pancreatic ductal adenocarcinoma (PDAC). In this retrospective study, we determined the predictive effect of PI to distinguish patients of pancreatic body/tail cancer (PBTC) with vascular involvement who can benefit from upfront surgery.

Method

All patients who received distal pancreatectomy for PDAC from 2016 to 2020 at the Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine were considered for the study. A total of 429 patients with PBTC were assessed in relation to the value of PI. Fifty‐five patients were eventually included and divided into low PI group and 29 patients in the normal PI group.

Results

The median overall survival (mOS) was significantly shorter in the low PI group (13.1 vs. 30.0 months, p = 0.002) in this study, and PI ≥ 0.78 (OR = 0.552, 95% CI: 0.301–0.904, p = 0.020) was an independent influencing factor confirmed by multivariate analysis. Subgroup analysis showed that PI was an independent prognostic factor for LA‐PBTC (OR = 0.272, 95% CI: 0.077–0.969, p = 0.045). As for BR PBTC, PI (OR = 0.519, 95% CI: 0.285–0.947, p = 0.033) combined with carbohydrate antigen 125 (CA125) (OR = 2.806, 95% CI: 1.206–6.526, p = 0.017) and chemotherapy (OR = 0.327, 95% CI: 0.140–0.763, p = 0.010) were independent factors.

Conclusion

This study suggests that the PI can be used as a predictive factor to optimize the surgical indication for PBTC with vascular involvement. Preoperative patients with normal PI and CA125 can achieve a long‐term prognosis comparable to that of resectable PBTC patients.
Antibacterial Activity of Quinoline‐Based Derivatives against Methicillin‐Resistant Staphylococcus aureus and Pseudomonas aeruginosa: Design, Synthesis, DFT and Molecular Dynamic Simulations
Authors: Sabt Ahmed , Abdelraof Mohamed , Hamissa Mohamed Farouk , Noamaan Mahmoud A.
Published: November 2023

Bacterial virulence becomes a significant challenge for clinical treatments, particularly those characterized as Multi‐Drug‐Resistant (MDR) strains. Therefore, the preparation of new compounds with active moieties could be a successful approach for eradication of MDR strains. For this purpose, newly synthesized quinoline compounds were prepared and tested for their antimicrobial activity against Methicillin‐Resistant Staphylococcus Aureus (MRSA) and Pseudomonas Aeruginosa (PA). Among the synthesized derivatives, compounds 1‐(quinolin‐2‐ylamino)pyrrolidine‐2,5‐dione (8) and 2‐(2‐((5‐methylfuran‐2‐yl)methylene)hydrazinyl)quinoline (12) were shown to possess the highest antimicrobial activity with the minimum inhibitory concentration with the values of 5±2.2 and10±1.5 μg/mL towards Pseudomonas aeruginosa without any activity towards MRSA. Interestingly, compounds 2‐(2‐((1H‐indol‐3‐yl)methylene)hydrazinyl)quinoline (13) and 2‐(4‐bromophenyl)‐3‐(quinolin‐2‐ylamino)thiazolidin‐4‐one (16c) showed significant inhibition activity against Staphylococcus aureus MRSA and Pseudomonas aeruginosa. Compound 13 (with indole moiety) particularly displayed excellent bactericidal activity with low MIC values 20±3.3 and 10±1.5 μg/mL against Staphylococcus aureus MRSA and Pseudomonas aeruginosa, respectively. Effects molecular modelling was used to determine the mode of action for the antimicrobial effect. The stability of complexes formed by docking and target‐ligand pairing was evaluated using molecular dynamics simulations. The compounds were also tested for binding affinity to the target protein using MM‐PBSA. Density‐functional theory (DFT) calculations were also used to investigate the electrochemical properties of various compounds.
Mesenchymal stem cell‐derived extracellular vesicles for metabolic syndrome therapy: Assessing efficacy with nuclear magnetic resonance spectroscopy
Authors: Ling Magdalene Tan Mei , Govindaraju Kayatri , Lokanathan Yogeswaran , Abidin Asmaa' Zainal , Ibrahim Baharudin
Published: November 2023

Metabolic syndrome (MetS) represents a cluster of metabolic abnormalities. The prevalence of MetS has surged, transforming it into a pressing public health concern that could potentially affect around 20%–25% of the global population. As MetS continues its ascent, diverse interventions, pharmacological, nonpharmacological and combined have been deployed. Yet, a comprehensive remedy that fully eradicates MetS symptoms remains elusive, compounded by the risks of polypharmacy's emergence. Acknowledging the imperative to grasp MetS's intricate pathologies, deeper insights for future research and therapy optimisation become paramount. Conventional treatments often target specific syndrome elements. However, a novel approach emerges in mesenchymal stem cell‐derived extracellular vesicles (MSC‐EVs) therapy, promising a holistic shift. MSC‐EVs, tiny membranous vesicles secreted by mesenchymal stem cells, have garnered immense attention for their multifaceted bioactivity and regenerative potential. Their ability to modulate inflammation, enhance tissue repair and regulate metabolic pathways has prompted researchers to explore their therapeutic application in MetS. This review primarily aims to provide an overview of how MSC‐EVs therapy can improve metabolic parameters in subjects with MetS disease and also introduce the usefulness of NMR spectroscopy in assessing the efficacy of MSC‐EVs therapy for treating MetS.
Fluorimetric Cell Analysis with 9‐Aryl‐Substituted Berberine Derivatives as DNA‐Targeting Fluorescent Probes
Authors: Groß Philipp , Hoffmann Renée S. , Müller Mareike , Schönherr Holger , Ihmels Heiko
Published: November 2023

DNA‐sensitive fluorescent light‐up probes based on berberine are presented. This biogenic fluorophore was chosen as central unit to use its potential biocompatibility and its DNA‐binding properties. To provide predictable fluorescence quenching in aqueous solution and a fluorescence light‐up effect upon DNA binding, aryl substituents were attached at the 9‐position by Suzuki‐Miyaura coupling reactions. The 9‐arylberberine derivatives have a very low fluorescence quantum yield (Φfl=<0.02), which is caused by the radiationless deactivation of the excited state by torsional relaxation about the biaryl axis. In addition, these berberine derivatives intercalate into DNA with high affinity (Kb=2.0−22×104 M−1). Except for the nitrophenyl‐ and hydroxyphenyl‐substituted derivatives, all tested compounds exhibited a pronounced fluorescence light‐up effect upon association with DNA, because the deactivation of the excited‐state by torsional relaxation is suppressed in the DNA binding site. Most notably, it was shown exemplarily with the 9‐(4‐methoxyphenyl)‐ and the 9‐(6‐methoxynaphthyl)‐substituted derivatives that these properties are suited for fluorimetric cell analysis. In particular, these probes generated distinct staining patterns in eukaryotic cells (NIH 3T3 mouse fibroblasts), which enabled the identification of nuclear substructures, most likely heterochromatin or nucleoli, respectively.
Necrotizing fasciitis in neonates: A case report and review of literature
Authors: Oboodi Roya , Barzegar Hamide , Behzadi Roozbeh
Published: November 2023

Key Clinical Message

Early recognition and treatment of necrotizing fasciitis reduce mortality rate which is 24.1% among neonates. Antibiotics and debridement are common treatments. Hyperbaric oxygen and negative pressure wound healing show potential but need further investigation.
Fibrodysplasia ossificans progressiva
Authors: Smit Chané , Uys André
Published: November 2023

Key Clinical Message

Fibrodysplasia ossificans progressiva is a progressively debilitating condition associated with significant morbidity caused by heterotopic ossification. Recognition of the early signs of hallux valgus and painful soft tissue nodules can assist in the early diagnosis of this condition. Periodic radiographic examination is mandatory to monitor the disease progression.

Fibrodysplasia ossificans progressiva is a rare condition with an estimated prevalence of one in two million individuals. The condition is characterized by widespread heterotrophic ossification of skeletal muscles and ligaments. We report the case of an 8‐year‐old female patient and show the radiological progression of the condition.
Two‐Dimensional β‐Ketoenamine‐Linked Covalent Organic Frameworks for Visible Light Photocatalysis
Authors: Zhang Fulin , Xiong Kanghui , Lang Xianjun
Published: November 2023

To date, two‐dimensional (2D) β‐ketoenamine‐linked covalent organic frameworks (COFs) have exhibited tremendous potential in visible light photocatalysis due to their broad absorption and favorable stability provided by the linkage. Here, with 1,3,5‐triformylphloroglucinol as the stationary building block, various COFs can be constructed to address different challenges. To inspire state‐of‐the‐art advancements toward photocatalysis, in this Concept article, the rational design of 2D β‐ketoenamine‐linked COFs is summarized. First, the dimension of engineering the linker is considered to improve the activity of the COFs. The photocatalysis could be extended by inserting a functional group to the other building block. Second, the other dimension of integrating cocatalysts like transition metals or 2,2,6,6‐tetramethylpiperidine‐N‐oxyl with β‐ketoenamine‐linked COFs could further expand the potential in photocatalytic reactions. These prior accomplishments establish that the rational design of 2D β‐ketoenamine‐linked COFs is instrumental in improving the photocatalytic activity, laying the foundation for future explorations.
Electrochemical Approximation to Bronze Age Chronology via Multiple Scan Voltammetry
Authors: Doménech‐Carbó Antonio , Mödlinger Marianne , Osete‐Cortina Laura , Doménech‐Carbó María Teresa
Published: November 2023

Insert A multiple‐scan voltammetry strategy is described and applied to a set of 107 Bronze Age and later copper/bronze objects, mainly from sites in Central Europe. This methodology allows the study of the compositional and textural properties (compactness, crystallinity, degree of hydration) of the patina to be studied from the accumulated peak current values for the characteristic signals corresponding to the reduction of cuprite and tenorite to metallic copper. A new model for the relationship between peak current and the depth reached in successive scans is presented and used to discriminate samples of different provenance and manufacturing technique, as well as their ascription to different Bronze Age periods
Towards the Enhanced Lithium‐Ion Batteries by Designing (N, Co, Zr, P) Tetra‐Doped Porous Carbon Anode
Authors: Jin Huibin , Zhang Zehao , Feng Guolin , Li Haibo
Published: November 2023

Heteroatom‐doped porous carbons have stable structures, high electron/ion transport efficiencies, and rich electroactive sites, which are of great significance to energy storage devices. The potential synergistic effects arising from the multi‐element doping benefit to improve the electrochemical behavior of porous carbon. In this paper, a facile doping strategy has been proposed to prepare the (N, Co, Zr, P) tetra‐doped porous carbon spheres (PCS) for enhanced lithium‐ion batteries (LIBs). The metal‐organophosphine framework (MOPF) as precursor is synthesized by utilizing riboflavin sodium phosphate as organic ligand coordinating with cobalt and zirconium ions. Through carbonizing MOPF, the (N, Co, Zr, P) tetra‐doped PCS can be obtained. As the anode for LIBs, the (N, Co, Zr, P) tetra‐doped PCS exhibits highly reversible capacity of 761 mAh g−1 at 0.1 A g−1 after 100 cycles, excellent rate performance of 126 mAh g−1 even at a high current density of 2 A g−1. The results feature that the unique 3D structure and superior local electron transport properties of (N, Co, Zr, P) tetra‐doped PCS promote the Li+ diffusion and adsorption, which improve the electrochemical properties. Moreover, the mechanism analysis realizes that the Li+ storage of (N, Co, Zr, P) tetra‐doped PCS is determined by the capacitive behavior at high scan rate, highlighting the significance of the heteroatom doping. Therefore, the (N, Co, Zr, P) tetra‐doped PCS should be considered as prominent candidate for high‐performance LIBs anodes.
Perspectives on the impact of crystallization in bioactive glasses and glass‐ceramics
Authors: Montazerian Maziar , Shearer Adam , Mauro John C.
Published: November 2023

Both unwanted and induced crystallization can impact bioactivity, physical and mechanical properties of bioactive glasses (BGs). Uncontrolled crystallization has negative consequences, rendering BGs unreliable. However, by manipulating the type, size, shape, and quantity of crystals in BGs, plenty of opportunities arise for controlling, for example, mechanical properties and degradability, leading to unique applications and improved performance. Understanding crystallization is a key step in developing bioactive glasses and glass‐ceramics (BGCs), and both fundamental and experimental research can aid in the design of BGCs for processing and biological function. In this perspective, we discuss the sources of crystallization and how controlled crystallization facilitates the functionalization of bioactive scaffolds, hybrids, coatings, composites, cements, and fibers.
Non‐Innocent π Linkers Affect Cooperativity in Hydrogen‐Bonded Macrocycles
Authors: Almacellas David , van der Lubbe Stephanie C. C. , Grosch Alice A. , Tsagri Iris , Vermeeren Pascal , Poater Jordi , Fonseca Guerra Célia
Published: November 2023

Rigid, linear π‐conjugated acetylene linkers connecting a hydrogen‐bond acceptor to a hydrogen‐bond donor are established building blocks for self‐assembled hydrogen‐bonded macrocycles. Kohn‐Sham molecular orbital and Voronoi deformation density analyses reveal that the acetylene linker plays an unprecedented, non‐innocent role in the cooperativity of these hydrogen‐bonded macrocycles. The acetylene linker can abstract electron density from the hydrogen‐bond acceptor and donor, due to the linkers’ low‐lying π‐LUMO. As a result, the hydrogen‐bond acceptor becomes less negatively charged, which both hampers the cooperativity, as well as the hydrogen bond strength, in the hydrogen‐bonded macrocycles. This effect becomes more pronounced when the size of the acetylene linker increases. The findings presented in this work can act as design principles for the development of novel supramolecular macrocycles based on hydrogen bonds.
Symmetrical and Mixed Tris(acyl)phosphines: Synthesis, Oxidation and Photochemistry
Authors: Wiesner Tanja , Neshchadin Dmytro , Glotz Gabriel , Gfader Zeno , Schrader Erik , Christen Samuel , Fischer Roland C. , Kelterer Anne‐Marie , Gescheidt Georg , Grützmacher Hansjörg , Haas Michael
Published: November 2023

Invited for the cover of this issue are the groups of M. Haas, G. Gescheidt and H. Grützmacher from the Graz University of Technology and the ETH Zürich. The image depicts a phosphorus mine, where the workers are acid chlorides using their shovels and red phosphorus to provide the chemicals necessary to produce novel reagents. Read the full text of the article at 10.1002/chem.202302535.
Predictive value of valvular calcification for the recurrence of persistent atrial fibrillation after radiofrequency catheter ablation
Authors: Liu Tong , Li Meng‐Meng , Long De‐Yong , Yang Jie , Zhao Xin , Li Chang‐Yi , Wang Wei , Jiang Chen‐Xi , Tang Ri‐Bo
Published: November 2023

Background

Valvular calcification (VC) is an independent risk factor for cardiovascular diseases. The relationship between VC and atrial fibrillation is not clear.

Hypothesis

We treated the aortic valve, mitral valve, and tricuspid valve as a whole and considered the possible association between VC and recurrence of persistent atrial fibrillation (PsAF) after radiofrequency catheter ablation (RFCA).

Methods

This study involved 2687 PsAF patients who underwent RFCA. Data were collected to explore the relationship between VC and outcome. VC was defined by echocardiography in aortic valve, mitral valve, or tricuspid valve. After 1 year follow‐up, subgroup analysis, mixed model regression analysis, and score system analysis were performed. The external validation of 133 patients demonstrated the accuracy of this clinical prediction model.

Results

Overall, 2687 inpatients were assigned to the recurrence group (n = 682) or the no recurrence group (n = 2005) with or without VC. Compared to patients with no recurrence, the incidence of VC was higher in recurrence patients. Recurrence was present in 18.5%, 34.9%, 39.3%, and 52.0% of the four groups, which met VC numbers of 0, 1, 2, and 3, respectively. After adjustment for potential confounding factors, VC was an independent risk factor for AF recurrence in several models. For multivariable logistic regression, a scoring system was established based on the regression coefficient. The receiver operating characteristic area of the scoring system was 0.787 in the external validation cohort.

Conclusions

VC was an independent risk factor for AF recurrence in PsAF after RFCA. The scoring system may be a useful clinical tool to assess AF recurrence.
Revolutionizing cancer drug development: Harnessing the potential of basket trials
Authors: Subbiah Vivek , Burris Howard A. , Kurzrock Razelle
Published: November 2023

The landscape of cancer therapy has been transformed by advances in clinical next‐generation sequencing, genomically targeted therapies, and immunotherapies. Well designed clinical trials and efficient clinical trial conduct are crucial for advancing our understanding of cancer, improving patient outcomes, and identifying personalized treatments. Basket trials have emerged as one of the efficient modern clinical trial designs that evaluate the efficacy of these therapies across multiple cancer types based on specific molecular alterations or biomarkers, irrespective of histology or anatomic location. This review delves into the evolution of basket trials in cancer drug development, highlighting their potential prospects and current obstacles. The design of basket trials involves screening patients for specific molecular alterations or biomarkers and enrolling them in the trial to receive the targeted therapy under investigation. Statistical considerations play a crucial role in the design, analysis, and interpretation of basket trials. Several notable examples of basket trials that have led to US Food and Drug Administration approval for uncommon molecular alterations (e.g., NTRK fusions, BRAF mutations, RET and FGFR1 alterations) are discussed, including LOXO‐TRK (ClinicalTrials.gov identifier NCT02122913)/SCOUT (ClinicalTrials.gov identifier NCT02637687)/NAVIGATE (ClinicalTrials.gov identifier NCT02576431)/STARTRK (ClinicalTrials.gov identifiers NT02097810, NT02568267), VE‐BASKET (ClinicalTrials.gov identifier NCT01524978), ROAR Basket (ClinicalTrials.gov identifier NCT02034110), LIBRETTO‐001 (ClinicalTrials.gov identifier NCT03157128), ARROW (ClinicalTrials.gov identifier NCT03037385), FIGHT‐203 (ClinicalTrials.gov identifier NCT03011372), and the National Cancer Institute‐Molecular Analysis for Therapy Choice trial (ClinicalTrials.gov identifier NCT02465060). Basket trials have the potential to revolutionize cancer treatment by identifying effective therapies for patients based on specific molecular alterations or biomarkers rather than traditional histology‐based approaches.

Plain Language Summary

To gain more knowledge about cancer, improve patient outcomes, and discover personalized treatments, it is crucial to conduct clinical trials efficiently.

One effective type of clinical trial is called a basket trial.

In basket trials, new treatments are tested on various types of cancer, regardless of their location in the body; instead, researchers focus on specific abnormalities in the cancer cells.

Basket trials offer hope that we can find personalized treatments that are more effective for each individual battling cancer.
The impact of air pollution on neurocognitive development: Adverse effects and health disparities
Authors: Pham Kim‐Chi T. , Chiew Kimberly S.
Published: November 2023

Air pollution is recognized as a major public health concern. The number of deaths related to ambient air pollution has increased in recent years and is projected to continue rising. Additionally, both short‐ and long‐term air pollution exposure has been linked with deleterious effects on neurocognitive function and development. While air pollution poses as a threat to everyone, people of color and individuals of lower socioeconomic status are often exposed to elevated levels of air pollution as a function of systemic racism and classism. Further, given additional disparities in access to healthcare and other compounding stressors, adverse effects of air pollution on neurocognitive health are exacerbated among individuals who hold marginalized identities—making effects both less likely to be detected and treated. This review examines evidence of the effects of air pollution on neurocognitive development across the lifespan and incorporates an environmental justice perspective to highlight disparities in air pollution exposure across race and socioeconomic status. Last, upon the reviewed evidence, limitations of past research and recommendations for policy are discussed.
Development and application of novel high‐efficiency composite ultrafine cement grouts for roadway in fractured surrounding rocks
Authors: Tian Maolin , Chen Shaojie , Han Lijun , Xiao Hongtian
Published: November 2023

The fractured surrounding rocks of roadways pose major challenges to safe mining. Grouting has often been used to reinforce the surrounding rocks to mitigate the safety risks associated with fractured rocks. The aim of this study is to develop highly efficient composite ultrafine cement (CUC) grouts to reinforce the roadway in fractured surrounding rocks. The materials used are ultrafine cement (UC), ultrafine fly ash (UF), ultrafine slag (US), and additives (superplasticizer [SUP], aluminate ultrafine expansion agent [AUA], gypsum, and retarder). The fluidity, bleeding, shrinkage, setting time, chemical composition, microstructure, degree of hydration, and mechanical property of grouting materials were evaluated in this study. Also, a suitable and effective CUC grout mixture was used to reinforce the roadway in the fractured surrounding rock. The results have shown that the addition of UF and US reduces the plastic viscosity of CUC, and the best fluidity can be obtained by adding 40% UF and 10% US. Since UC and UF particles are small, the pozzolanic effect of UF promotes the hydration reaction, which is conductive to the stability of CUC grouts. In addition, fine particles of UC, UF, and US can effectively fill the pores, while the volumetric expansion of AUA and gypsum decreases the pores and thus affects the microstructure of the solidified grout. The compressive test results have shown that the addition of specific amounts of UF and US can ameliorate the mechanical properties of CUC grouts. Finally, the CUC22‐8 grout was used to reinforce the No. 20322 belt roadway. The results of numerical simulation and field monitoring have indicated that grouting can efficaciously reinforce the surrounding rock of the roadway. In this research, high‐performance CUC grouts were developed for surrounding rock reinforcement of underground engineering by utilizing UC and some additives.
A global‐scale study on decision making in renewable energy policy: Internal and external factors driving the adoption of Feed‐in Tariffs and Renewable Portfolio Standards
Authors: Döme Viktória
Published: November 2023

To accelerate the clean energy transition, it is necessary to better understand the global policy dynamics and motivations behind clean energy policy adoptions and diffusion. This article examines the differential roles of internal and external diffusion factors on decisions to adopt renewable energy policies, that is, Feed‐In Tariffs (FIT) and Renewable Portfolio Standards (RPS), employing a unique blend of cluster analysis and event history analysis. Cluster analysis uncovers a dichotomy in adopting countries. First, early adopters emerge as high‐income, democratic countries, mostly energy importers with high CO2 emissions, with OECD and EU membership. Conversely, the second cluster consists of adopters from middle‐income, non‐OECD, and non‐EU nations with lower CO2 emissions. Strikingly, these clusters align with UNFCCC party classifications, underscoring the pivotal role of international agreements. Event history analysis suggests that especially environmental pressure, but also democratic governance and economic development are important when adopting renewable energy policies. Interestingly, environmental endowments seem to be less important. These findings lead to an important question: Are the requisite policy tools readily available to navigate diverse socio‐economic, political, and environmental landscapes, and are they deployed in a timely fashion? Beyond these findings, the study also shows that policy diffusion especially through normative emulation and social learning—operationalized as political globalization, OECD member and following regional neighbors—are important for policy adoption, suggesting the importance of such tools for promoting policies. Moreover, distinctive factors come into play when examining the adoption of FIT versus RPS policies, emphasizing the need for nuanced policy approaches.
Sacubitril/valsartan compared to ramipril in high‐risk post‐myocardial infarction patients stratified according to use of mineralocorticoid receptor antagonists: Insight from the PARADISE MI trial
Authors: Schou Morten , Claggett Brian , Miao Zi Michael , Fernandez Alberto , Filippatos Gerasimos , Granger Christopher , Jering Karola , Maggioni Aldo P. , McCausland Finnian , Villota Julio Nuñez , Rouleau Jean‐Lucien , Mody Freny Vaghaiwalla , van der Meer Peter , Vinereanu Dragos , McGrath Martina , Zhou Yinong , Mann Douglas L. , Solomon Scott D. , Steg Philippe Gabriel , Braunwald Eugene , McMurray John J.V. , Pfeffer Marc A. , Køber Lars
Published: November 2023

Aim

It is unknown whether safety and clinical endpoints by use of sacubitril/valsartan (an angiotensin receptor–neprilysin inhibitor [ARNI]) are affected by mineralocorticoid receptor antagonists (MRA) in high‐risk myocardial infarction (MI) patients. The aim of this study was to examine whether MRA modifies safety and clinical endpoints by use of sacubitril/valsartan in patients with a MI and left ventricular systolic dysfunction (LVSD) and/or pulmonary congestion.

Methods and results

Patients (n = 5661) included in the PARADISE MI trial (Prospective ARNI vs. ACE Inhibitor Trial to Determine Superiority in Reducing Heart Failure Events After MI) were stratified according to MRA. Primary outcomes in this substudy were worsening heart failure or cardiovascular death. Safety was defined as symptomatic hypotension, hyperkalaemia >5.5 mmol/L, or permanent drug discontinuation. A total of 2338 patients (41%) were treated with MRA. Safety of ARNI compared to ramipril was not altered significantly by ± MRA, and both groups had similar increase in symptomatic hypotension with ARNI. In patients taking MRA, the risk of hyperkalaemia or permanent drug discontinuation was not significantly altered by ARNI (p > 0.05 for all comparisons). The effect of ARNI compared with ramipril was similar in those who were and were not taking MRA (hazard ratio [HR]MRA 0.96, 95% confidence interval [CI] 0.77–1.19 and HRMRA– 0.87, 95% CI 0.71–1.05, for the primary endpoint; p = 0.51 for interaction [Clinical Endpoint Committee adjudicated]); similar findings were observed if investigator‐reported endpoints were evaluated (p = 0.61 for interaction).

Conclusions

Use of a MRA did not modify safety or clinical endpoints related to initiation of ARNI compared to ramipril in the post‐MI setting in patients with LVSD and/or congestion.
Tree removals as socioecological experiments in cities
Authors: Threlfall Caragh G , Ordóñez‐Barona Camilo , Livesley Stephen J , Baumann Jess , Callow David , Davern Melanie , English Alex , Fuller Richard A , Hertzog Kelly , Hochuli Dieter F , van der Ree Rodney , Kendal Dave
Published: November 2023

As keystone structures in urban ecosystems, trees are critical to addressing many of the current livability, health, and environmental challenges facing cities. Every day, trees are removed from urban landscapes as part of routine management. These tree removals are an opportunity for implementing manipulative experiments to directly measure the social and ecological functions of trees. Here we review the kinds of tree removals that commonly occur in cities, assess the relevant opportunities that arise for research–practice partnerships, and discuss the challenges posed when implementing experiments of this nature. We argue that experimental studies on the routine removal of urban trees will improve and expand the mechanistic understanding of how trees support biodiversity and human well‐being in cities beyond current knowledge, which is largely based on correlative studies. Finally, we highlight the opportunity for experiments to be co‐designed by scientists and urban land managers, and how “learning while doing” can generate tangible research impacts and improve urban forest decision making.
Anticonvulsant effect of equilibrative nucleoside transporters 1 inhibitor in a mouse model of Dravet syndrome
Authors: Ho Shih‐Yin , Chen I‐Chun , Tsai Che‐Wen , Chang Kai‐Chieh , Lin Chun‐Jung , Chern Yijuang , Liou Horng‐Huei
Published: November 2023

There are limited therapeutic options for patients with Dravet syndrome (DS). The equilibrative nucleoside transporters 1 (ENT1) mediate both the influx and efflux of adenosine across the cell membrane exerted beneficial effects in the treatment of epilepsy. This study aimed to evaluate the anticonvulsant effect of the ENT1 inhibitor in an animal model of DS (Scn1aE1099X/+ mice). J7 (5 mg/kg) treatment was efficacious in elevating seizure threshold in Scn1aE1099X/+ mice after hyperthermia exposure. Moreover, the J7 treatment significantly reduced the frequency of spontaneous excitatory post‐synaptic currents (sEPSCs, ~35% reduction) without affecting the amplitude in dentate gyrus (DG) granule cells. Pretreatment with the adenosine A1 receptor (A1R) antagonist, DPCPX, abolished the J7 effects on sEPSCs. These observations suggest that the J7 shows an anticonvulsant effect in hyperthermia‐induced seizures in Scn1aE1099X/+ mice. This effect possibly acts on presynaptic A1R‐mediated signaling modulation in granule cells.
Healthy kids vids: Development and acceptability of narrative healthy lifestyle videos and text messages for parents of young children from socioeconomically disadvantaged populations
Authors: Hammersley Megan L. , Norman Jennifer , Smithers Lisa G. , Furber Susan , Plumb Melinda , Jones Rachel A.
Published: November 2023

Issue Addressed

Dietary intake and physical activity behaviours of many Australian children are not meeting recommendations, particularly for those living in socioeconomically disadvantaged circumstances. This study aimed to design and assess the feasibility and acceptability of a suite of narrative videos and text messages focused on healthy eating and physical activity behaviours appropriate for parents of young children from socioeconomically disadvantaged backgrounds.

Methods

Parents of 1–5‐year‐old children (n = 6) were recruited to develop a suite of 12 narrative videos on healthy eating and physical activity behaviours, underpinned by theory. Twelve complementary text messages were subsequently developed. A different group of parents (n = 16) recruited from socioeconomically disadvantaged areas reviewed the videos and text messages over 6 weeks and provided feedback via surveys and qualitative interviews (n = 13).

Results

There was a high level of engagement with and acceptability of the videos and text message content. Participants found the videos easy to access and they liked the narrative style. Screen time videos and text messages relating to screen time, play and physical activity, role modelling and fussy eating were most useful.

Conclusions

Narrative style healthy eating, physical activity and screen time videos and complementary text messages were highly acceptable to the sample of parents of 1–5‐year‐old children from socioeconomically disadvantaged areas recruited from the Illawarra Shoalhaven region of NSW, Australia.

So What?

Short narrative style videos and text messages are an easy to process and acceptable method of delivering healthy lifestyle promotion content to parents.
Identification of a novel cuproptosis‐related gene signature for multiple myeloma diagnosis
Authors: Zhu Yidong , Chang Shuaikang , Liu Jun , Wang Bo
Published: November 2023

Background

Multiple myeloma (MM) ranks second among the most prevalent hematological malignancies. Recent studies have unearthed the promise of cuproptosis as a novel therapeutic intervention for cancer. However, no research has unveiled the particular roles of cuproptosis‐related genes (CRGs) in the prediction of MM diagnosis.

Methods

Microarray data and clinical characteristics of MM patients were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed gene analysis, least absolute shrinkage and selection operator (LASSO) and support vector machine‐recursive feature elimination (SVM‐RFE) algorithms were applied to identify potential signature genes for MM diagnosis. Predictive performance was further assessed by receiver operating characteristic (ROC) curves, nomogram analysis, and external data sets. Functional enrichment analysis was performed to elucidate the involved mechanisms. Finally, the expression of the identified genes was validated by quantitative real‐time polymerase chain reaction (qRT‐PCR) in MM cell samples.

Results

The optimal gene signature was identified using LASSO and SVM‐RFE algorithms based on the differentially expressed CRGs: ATP7A, FDX1, PDHA1, PDHB, MTF1, CDKN2A, and DLST. Our gene signature‐based nomogram revealed a high degree of accuracy in predicting MM diagnosis. ROC curves showed the signature had dependable predictive ability across all data sets, with area under the curve values exceeding 0.80. Additionally, functional enrichment analysis suggested significant associations between the signature genes and immune‐related pathways. The expression of the genes was validated in MM cells, indicating the robustness of these findings.

Conclusion

We discovered and validated a novel CRG signature with strong predictive capability for diagnosing MM, potentially implicated in MM pathogenesis and progression through immune‐related pathways.
Crosslinking chitosan with glucose via the modified Maillard reaction promotes the osteoinduction of mouse MC3T3‐E1 pre‐osteoblasts
Authors: Huang Kuo‐Chin , Lee Ding‐Yu , Chuang Po‐Yao , Yang Tien‐Yu , Su Yu‐Ping , Chang Shun‐Fu
Published: November 2023

Bone defects are a common clinical issue, but therapeutic efficiency can be challenging in cases of more considerable traumas or elderly patients with degenerated physiological metabolism. To address this issue, a more suitable cell‐biomaterial construct promoting bone regeneration has been extensively investigated, with the chitosan scaffold being considered a potential candidate. In this study, chitosan was crosslinked with different doses of glucose (CTS‐10~50%Glc) using a modified Maillard reaction condition to develop a more appropriate cell‐biomaterial construct. Mouse MC3T3‐E1 pre‐osteoblasts were seeded onto the scaffolds to examine their osteoinductive capability. The results showed that CTS‐Glc scaffolds with higher glucose contents effectively improved the adhesion and survival of mouse MC3T3‐E1 pre‐osteoblasts and promoted their differentiation and mineralization. It was further demonstrated that the membrane integrin α5 subunit of pre‐osteoblasts is the primary adhesion molecule that communicates with CTS‐Glc scaffolds. After that, Akt signaling was activated, and then bone morphogenetic protein 4 was secreted to initiate the osteoinduction of pre‐osteoblasts. The prepared CTS‐Glc scaffold, with enhanced osteoinduction capability and detailed mechanism elucidations, offers a promising candidate material for advancing bone tissue engineering and clinical regenerative medicine. As a result, this study presents a potential tool for future clinical treatment of bone defects.