bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancing Microdomain Consistency in Polymer Electrolytes towards Sustainable Lithium Batteries
Authors: Feng Yang , Fan Yanpeng , Zhao Lingfei , Yu Jiangtao , Liao Yaqi , Zhang Tongrui , Zhang Ruochen , Zhu Haitao , Sun Xingwei , Hu Zhe , Zhang Kai , Chen Jun
Published: December 2024

Polymer electrolytes incorporated with fillers possess immense potential for constructing the fast and selective Li+ conduction. However, the inhomogeneous distribution of the fillers usually deteriorates the microdomain consistency of the electrolytes, resulting in uneven Li+ flux, and unstable electrode‐electrolyte interfaces. Herein, we formulate a solution‐process chemistry to in situ construct gel polymer electrolytes (GPEs) with well‐dispersed metal–organic frameworks (MOFs), leading to a uniform microdomain structure. Through the integration of X‐ray computed tomography analyses and theoretical simulations, our research identifies that the improvement of microdomain consistency in GPEs is beneficial for enhancing its mechanical strength, homogenizing ionic/electronic field distribution and upgrading the interface stability with the elctrodes. Moreover, consistently spread MOFs bind effectively with Lewis‐base anions of Li salts, enhancing Li+ kinetics. Owing to these advantages, the developed GPEs achieve a high conductivity of 1.51 mS cm−1 and a Li+ transference number of 0.66, resulting in exceptional cyclability of lithium metal electrodes (over 1800 hours). Additionally, the solid‐state NCM811//Li pouch batteries exhibit an impressive capacity retention of 94.2 % over 200 cycles with an N/P ratio of 1.69. This study emphasizes the significant impact of microdomain structural chemistry on the advancement of solid‐state batteries.
Unlocking Mesoscopic Disorder in Graphitic Carbon with Spectroelectrochemistry
Authors: Papadopoulos Ry , Masters Benjamin , Kundu Arpan , Maldonado Nicholas , Filatov Alexander S. , Liu Yuzi , Kim Taemin , Galli Giulia , Wuttig Anna
Published: December 2024

Intrinsic structural and oxidic defects activate graphitic carbon electrodes towards electrochemical reactions underpinning energy conversion and storage technologies. Yet, these defects can also disrupt the long‐range and periodic arrangement of carbon atoms, thus, the characterization of graphitic carbon electrodes necessitates in‐situ atomistic differentiation of graphitic regions from mesoscopic bulk disorder. Here, we leverage the combined techniques of in‐situ attenuated total reflectance infrared spectroscopy and first‐principles calculations to reveal that graphitic carbon electrodes exhibit electric‐field dependent infrared activity that is sensitive to the bulk mesoscopic intrinsic disorder. With this platform, we identify graphitic regions from amorphous domains by discovering that they demonstrate opposing electric‐field‐dependent infrared activity under electrochemical conditions. Our work provides a roadmap for identifying mesoscopic disorder in bulk carbon materials under potential bias.
Inverting Methanol Dehydrogenation Selectivity by Crowding Atomic Ni Species over α‐MoC Catalysts
Authors: Ge Yuzhen , Gao Zirui , Xu Yao , Xu Ming , Qin Xuetao , Peng Mi , Wang Shuai , Gao Rui , Zhou Wu , Ma Ding
Published: December 2024

Metal carbides with earth‐abundant elements are widely regarded as promising alternatives to noble metal catalysts. Although comparable catalytic performances have been observed for metal carbides in several types of reactions, precise control of reaction pathways on them remains a formidable challenge, partially due to strong adsorption of reactants or intermediates. In this study, we show that bimolecular dehydrogenation of methanol to methyl formate and H2 is kinetically favored on bare α‐MoC catalysts, while monomolecular dehydrogenation to CO and H2 becomes the dominant pathway when α‐MoC is decorated with crowding atomic Ni species. Under optimal conditions, excellent selectivities of the target products (>90 %) were achieved in both cases, with unprecedented production rates of methyl formate and H2 for the former and latter mechanisms, respectively. Kinetic, spectroscopic, and computational assessments were integrated to clarify the mechanism driving this remarkable selectivity inversion. Isolated Ni sites bound to α‐MoC exhibit superior dehydrogenation activity, which promotes complete cleavage of C−H bonds in methanol‐derived intermediates rather than the C−O coupling between them. Our study offers an effective approach to modulating the selectivity of carbide‐based catalysts in alcohol dehydrogenation towards different target products.
Towards Rational Design of Confined Catalysis in Carbon Nanotube by Machine Learning and Grand Canonical Monte Carlo Simulations
Authors: Yang Chenyu , Fu Xiaoyan , Luan Dong , Xiao Jianping
Published: December 2024

The microenvironment is recognized to be as crucial as active sites in heterogeneous catalysis. It was found that the catalytic activity of a set of chemical reactions can be significantly influenced by the confined space of carbon nanotubes (CNTs), with some reactions showing superior activity, while others experience a negative impact. The rational design of confined catalysis must rely on the accurate insights of confined microenvironment. However, the structural complexity of confined catalysts and the interaction with microenvironment hinders the deciphering of chemical origins behind experiments. In this work, Grand‐canonical Monte Carlo (GCMC) simulations are conducted for confined catalysis in CNTs at various reaction atmospheres, accelerated by machine learning potentials. The statistical outcomes of GCMC simulations corroborate a general feature that the electronic interaction (binding energy) inside CNTs is weaker than outside cases. By using Random Forest (RF) model, we ascertain that the shortening of the bond lengths of catalysts within the confined space is the dominant factor, resulting in the weakened binding energy and the downshift of the d‐band center. Using the bond length variation as a simplified descriptor, our microkinetic models successfully reproduced the seemingly contradictive experiments, namely, the observed enhancement and suppression for the same reaction.
Reinforcing Coverage of Self‐assembled Monomolecular Layers for Inverted Perovskite Solar Cells with Efficiency of 25.70 %
Authors: Zhang Xiwen , Wang Yang , Zhang Kun , Tao Mingquan , Guo Haodan , Guo Lutong , Song Zhaofei , Wen Jinxu , Yang Yongrui , Hou Yuqing , Song Yanlin
Published: December 2024

Self‐assembled monolayers (SAM) as hole transport layers have been widely used in high‐efficiency inverted perovskite solar cells (PSCs) exceeded 26 %. However, the poor coverage and non‐uniform distribution on the substrate of SAM further restrict the improvement of device performance. Herein, we utilize the mixed SAM strategy via the MeO‐2PACz along with perfluorotripropylamine (FC‐3283) to improve the SAM coverage, aiming to accelerate the carrier transport, promote the perovskite growth, regulate the surface energy levels and suppress the nonradiative recombination. The champion device with the mixed‐SAM achieves an efficiency of 25.70 % (certified efficiency of 25.6 %) with long‐term stability (maintained the initial efficiency of 90 % after 1000 h and 180 h under ISOS‐L‐1 and ISOS‐L‐2).
Preparation of Polyvinyl Alcohol/Carboxymethyl Cellulose Composite Loaded With Chromatin for the Efficient Adsorption of Dibenz[a,h]Anthracene From Aqueous Solutions
Authors: Hu Baopeng , Li Junsheng , Huang Guoxia , Ma Ji , Yan Liujuan
Published: December 2024

In this study, to solve the problems of water solubility and difficulty in separation of chromatin after treatment with dibenz[a,h]anthracene (DBA) contaminants, we successfully prepared a chromatin‐based composite for the efficient adsorption of DBA from pollutants. The fluorescence microscopy images and SEM images showed that the composite had dense and porous morphology characteristics, which not only effectively improved the aggregation of chromatin but also showed good adsorption impact. FTIR, TGA, and XRD analyses revealed that chromatin was evenly distributed throughout the composite and formed effective physical crosslinks. Its DBA adsorption efficiency could exceed 93.6%, and its DBA adsorption amount was 0.015 mg·g−1. The results of the adsorption isotherm and adsorption kinetics demonstrated that the adsorption of DBA by the composite followed the pseudo‐second‐order kinetic model (0.9913 ≤ R2 ≤ 0.9970) and Langmuir isotherm model (0.9930 ≤ R2 ≤ 0.9982). The results of adsorption thermodynamics indicated that the adsorption process was spontaneous (ΔG < 0). This work provided a new idea and reference for removing DBA from pollutants.
Characterization of Machine Learning‐Based Surrogate Models of Neural Activation Under Electrical Stimulation
Authors: Toni Laura , Pierantoni Luca , Verardo Claudio , Romeni Simone , Micera Silvestro
Published: December 2024

Electrical stimulation of peripheral nerves via implanted electrodes has been shown to be a promising approach to restore sensation, movement, and autonomic functions across a wide range of illnesses and injuries. While in principle computational models of neuromodulation can allow the exploration of large parameter spaces and the automatic optimization of stimulation devices and strategies, their high time complexity hinders their use on a large scale. We recently proposed the use of machine learning‐based surrogate models to estimate the activation of nerve fibers under electrical stimulation, producing a considerable speed‐up with respect to biophysically accurate models of fiber excitation while retaining good predictivity. Here, we characterize the performance of four frequently employed machine learning algorithms and provide an illustrative example of their ability to generalize to unseen stimulation protocols, stimulating sites, and nerve sections. We then discuss how the ability to generalize to such scenarios is relevant to different optimization protocols, paving the way for the automatic optimization of neuromodulation applications.
Highly Reliable Organisations and Sustainability Risk Management: Safety Cultures in the Nigerian Oil and Gas Supply Chain Sector
Authors: Egila Ashem Emmanuel , Kamal Muhammad Mustafa , Kumar Mangla Sachin , Rich Nick , Tjahjono Benny
Published: December 2024

This study investigates the environmental consequences of pursuing profits in the oil and gas industry, focusing on Nigeria. It examines the role of top management commitment, safety culture and stakeholder risk prioritisation in the industry. By surveying 441 stakeholders, this study highlights the importance of extensive stakeholder engagement and a systemic supply chain approach in building resilience and shaping sustainable practices. The findings reveal that stakeholder risk perception influences sustainability risk management; however, variations in risk prioritisation between internal and external stakeholders remain a challenge. The study advocates for a paradigm shift and emphasises the crucial role of high‐reliability management in guiding organisations towards effective risk mitigation strategies for the industry's immediate health, communities, environment and future.
Exploring Materiality and Stakeholder Engagement in European Water Utilities' Sustainability Strategies, Organizational Practices, and Reporting
Authors: Giacomini Davide , Rocca Laura , Tonoli Davide
Published: December 2024

Materiality is a key principle enabling organizations to determine what information to disclose, serving as both a filtering mechanism and a strategic tool shaped by institutional dynamics. Institutional logics, which inform and legitimize organizational practices, significantly influence accountability and reporting processes, including the application of materiality. Effective water management is essential for sustainable development, making the water industry a key sector for exploring materiality and stakeholder engagement within sustainability strategies. This study explores the integration of the materiality principle, stakeholder engagement, and related organizational practices into the sustainability strategies and reporting of the European water industry between 2020 and 2022. Through content analysis of sustainability reports from 26 European water utilities, the study identifies three primary stakeholder engagement approaches: one‐way communication, dialogic interaction, and multi‐directional dialog. The prevailing trend is a dialogic approach that has evolved over time, though concerns about its relevance and effectiveness remain. Additionally, the study examines disclosed material topics, noting a dominant focus on environmental concerns and health and safety, with economic and governance issues receiving comparatively less attention. It emphasizes the need to improve the materiality process by integrating insights from accounting research into organizational practices and underscores the importance of effective stakeholder engagement for fostering trust and collaboration, particularly in vital sectors like water management. The findings offer valuable perspectives for policymakers, emphasizing the need to design robust mechanisms that promote stakeholder engagement. While progress in this area in recent years is evident, as demonstrated by this research, it must quickly evolve into a fundamental component of effective water management to avoid the risk of becoming merely an organizational façade.
A Clinical Prediction Model for Pathologic Upgrade to Invasive Carcinoma Following Conization of Cervical High‐Grade Squamous Intraepithelial Lesions
Authors: Liu Qiao , Yang Jing , Cheng Hui , Shu Chuqiang , Tang Yi , Zhao Jing
Published: December 2024

Objective

To explore the risk factors associated with the pathological progression to invasive carcinoma following the conization of cervical high‐grade squamous intraepithelial lesions (HSIL) and to construct a risk prediction model to guide preoperative risk assessment and optimize the selection of surgical approaches.

Methods

A retrospective analysis was conducted on the clinical data of 3337 patients who underwent cervical conization for HSIL at Hunan Provincial Maternal and Child Health Care Hospital from December 2016 to March 2022. The patients were categorized into the pathological progression group (398 cases) and the nonprogression group (2939 cases) based on postconization pathology results. Statistical significance factors were selected by least absolute shrinkage and selection operator regression and then multivariate logistic regression was utilized to build predictive models, which were presented as a nomogram and evaluated for discriminability, calibration, and decision curves. The Bootstrap method was utilized for internal validation. A total of 277 patients were enrolled from April 2022 to October 2022 for external validation.

Results

The percentage of pathologic upgrades to invasive carcinoma following cervical conization was 11.9%. The predictive model included age, contact bleeding symptoms, HPV16/18 infection, HSIL cytology, cervical biopsy pathology diagnosis level, suspicious stromal infiltration in the biopsy pathology diagnosis, and endocervical curettage HSIL. The model demonstrated good overall discrimination in predicting the risk of HSIL progression to early invasive cancer, and internal validation confirmed its reliability (C‐index = 0.787). Area under the curve analysis indicated good model discriminability across external datasets. The decision curve analysis also suggested that this model is clinically useful.

Conclusion

We developed and validated a nomogram incorporating multiple clinically relevant variables to better identify cases of HSIL progressing to early cervical cancer, providing a basis for individualized treatment and surgical approach selection.
Efficacy and Safety of Chemotherapy or EGFR‐TKIs as First‐Line Therapy in NSCLC Patients Harboring Non‐Ex 20 Ins Uncommon EGFR Mutations: A Retrospective Study in China
Authors: Liao Chen , Bai Li , He Tingting , Liang Qingle , Hu Defeng , Lei Shipeng , He Yong , Wang Yubo
Published: December 2024

Background

Uncommon EGFR mutations are a kind of heterogeneous group of mutations with various responses to EGFR‐TKIs and are often excluded from most prospective clinical trials. In this real‐world retrospective study, we retrospectively compared the efficacy and safety of chemotherapy or various generations of EGFR‐TKIs as first‐line therapy in NSCLC Chinese patients harboring non‐ex 20 ins uncommon EGFR mutations.

Methods

We enrolled 139 NSCLC patients with non‐ex 20 ins uncommon EGFR mutations in this study retrospectively. Patients' clinical characteristics and the efficacy and safety of different first‐line therapies were analyzed and compared.

Results

Our data reviewed that for first‐line therapy, NSCLC patients harboring non‐ex 20 ins uncommon EGFR mutations benefited more from EGFR‐TKIs compared with chemotherapy. Afatinib performed with great efficacy for the majority of non‐ex 20 ins uncommon EGFR mutations (N = 43, ORR = 41.86%, mPFS = 13.5 months, mOS = 20.8 months), especially in L861Q mutation (mPFS = 18.4 months). Osimertinib also demonstrated efficacy in patients harboring non‐ex 20 ins uncommon EGFR mutations (N = 36, ORR = 27.78%, mPFS = 10.0 months, mOS = 21.0 months), especially in those without L861Q and G719X mutations (mPFS = 12.1 months). When treated with afatinib, patients harboring non‐ex 20 ins uncommon EGFR mutations should pay attention to the management of safety, especially for gastrointestinal‐related AE and rash, while osimertinib was safer.

Conclusion

Taking into account both efficacy and safety, afatinib and osimertinib are better choices than chemotherapy and first‐generation EGFR‐TKIs for NSCLC patients with non‐ex 20 ins uncommon EGFR mutations. L861Q showed a trend toward a better response to afatinib, while in those without L861Q and G719X mutations, osimertinib might be a better choice. Safety also should be a concern when choosing EGFR‐TKI for treatment, patients should pay attention to the management of safety when using afatinib while osimertinib is safer.
Phase I Trial of Upamostat Combined With Gemcitabine in Locally Unresectable or Metastatic Pancreatic Cancer: Safety and Preliminary Efficacy Assessment
Authors: Lai Xiuping , Cheng Di , Xu Huixin , Wang Jingshu , Lv Xiaozhi , Yao Herui , Li Liuning , Wu Junyan , Ye Suiwen , Li Zhihua
Published: December 2024

Aim

This study aimed to determine the maximum tolerated dose (MTD) of the urokinase plasminogen activator (uPA) inhibitor upamostat (LH011) in combination with gemcitabine for locally advanced unresectable or metastatic pancreatic cancer.

Method

Seventeen patients were enrolled and received escalating doses of oral LH011 (100, 200, 400, or 600 mg) daily alongside 1000 mg/m2 of gemcitabine. Safety profiles, tumor response (including response rate and progression‐free survival), pharmacokinetics, and changes in CA199 and D‐dimer levels were assessed.

Results

During the study period (Day0–Day49), no patients achieved partial response. Stable disease (SD) was observed in 12 patients (70.6%), while four patients (23.5%) experienced progressive disease (PD). One patient withdrew due to a serious adverse event (SAE) on D47. Pharmacokinetic analysis revealed a dose‐related increase in LH011 and its metabolite WX‐UK1 exposure from 100 to 400 mg but not in the 600 mg group. Hematological toxicity, mainly attributable to gemcitabine, was the predominant grade 3 or 4 adverse event, with additional occurrences of loss of appetite, rash, and interstitial lung disease. Sinus bradycardia possibly linked to LH011 rather than gemcitabine was noted. The MTD was not reached.

Conclusion

Combining LH011 at doses ranging from 100 to 600 mg with gemcitabine every 21 days demonstrated manageable safety and tolerability. However, tumor response did not significantly differ among the dose groups, suggesting the need for further investigation.

Trial Registration

NCT05329597
Hit Selection of Dipeptidyl Peptidase‐4 Inhibitors Bearing Thieno[2,3‐d]Pyrimidine Scaffold
Authors: Pavlović Katarina Tomović , Ilić Budimir S. , Dimov Stefan , Yancheva Denitsa , Mavrova Anelia Ts , Šmelcerović Andrija
Published: December 2024

The thieno[2,3‐d]pyrimidine fragment is in the structure of many drug‐like candidate derivatives with a wide range of biological activities. However, very few dipeptidyl peptidase‐4 (DPP‐4) inhibitors with this building block are currently known. Here, the selection of a novel DPP‐4 inhibitor based on the thienopyrimidine scaffold is reported. In the performed study, ethyl 4‐amino‐5‐methyl‐2‐(3‐(trifluoromethyl)phenyl)thieno[2,3‐d]pyrimidine‐6‐carboxylate (compound 22) demonstrated DPP‐4 inhibitory potential about twice higher than that of the reference inhibitor diprotin A. The manner of inhibition is noncompetitive, a rare type among DPP‐4 inhibitors. The molecular docking highlighted the importance of Ser349, Asn377, Glu378, Phe396, and Asp588 in forming the inhibitor/DPP‐4 complex. Compound 22 might be useful as a source of ideas contributing to the design and further changes and optimizations of thieno[2,3‐d]pyrimidine‐based DPP‐4 inhibitors.
Phytochemical Profiling and Biological Activities of Nigella sativa Vinegar Extract: An Insight Into Hypoglycemic Potential Using In Vivo and In Silico Studies
Authors: Akhtar Muhammad Tahir , Qadir Rahman , Altaf Uzma , Almas Tahira , Batool Sajida , Ikram Muhammad Salman , Meor Hussin Anis Shobirin , Perveen Kahkashan , Alshaikh Najla A. , Saadia Mubshara
Published: December 2024

The current study was conducted to characterize the vinegar extract of Nigella sativa and evaluate its biological activities using in vitro and in vivo studies. The N. sativa extract (NSE) was prepared by macerating seeds in a mixture of water and synthetic vinegar (1:10). The antioxidant potential of NSE was assessed, revealing high total phenolic contents (431.66 mg/100 g), total flavonoid contents (73.45 mg/100 g), total antioxidant capacity (118.55 mg/100 g), and strong radical scavenging potential (89.67%). The anticancer activity of NSE showed insignificant cytotoxic effects on HepG2 liver cell lines (96.61 ± 3.00). An in vivo animal trial was performed, and NSE significantly (p < 0.05) lowered the blood glucose (−47.71%), total cholesterol (−37.86%), total glycerides (39.42%), low‐density lipoproteins (−29.36%), and very low‐density lipoproteins (−30.60%), while increasing the high‐density lipoproteins (26.92%) in alloxan‐induced diabetic rats. GC–MS analysis of NSE revealed a diverse range of bioactive compounds, including alkaloids, phenolics, and flavonoids. In silico studies using molecular docking simulations showed that pyrrolo[1,2‐a] pyrazine‐1,4‐dione, hexahydro‐3‐(2‐methylpropyl) demonstrated a strong inhibitory action (6.6 kcal/mol) against alpha‐amylase enzyme. These findings suggest that NSE is a promising natural remedy for managing diabetes and related metabolic disorders, and its potential as a nutraceutical ingredient in functional food applications is significant.
Inhibition of Clinical Multidrug‐Resistant Pseudomonas aeruginosa Biofilms by Cinnamaldehyde and Eugenol From Essential Oils: In Vitro and In Silico Analysis
Authors: Benaissa Asma , Bouali Wafaa , Ngenge Tamfu Alfred , Ammara Bousselham , Kucukaydin Selcuk , Latti Nawel , Khadir Abdelmounaim , Bendahou Mourad , Anouar El Hassane , Ceylan Ozgur
Published: December 2024

Pseudomonas aeruginosa causes nosocomial infections and chronic diseases. Cinnamomum cassia and Syzygium aromaticum are used natural antimicrobials. Essential oil (EO) from C. cassia (CCEO) and S. aromaticum (CEO) was characterized using GC‐MS analysis. Eugenol (82.31%), eugenol acetate (10.57%), and β‐caryophyllene (3.41%) were major constituents in CEO while cinnamaldehyde (88.18%), cinnamyl acetate (2.85%) and 2‐methoxy cinnamaldehyde (1.77%) were main components in CCEO. The EOs and major constituents exhibited good antimicrobial activity against clinical strains of P. aeruginosa. Cinnamaldehyde exhibited the best antimicrobial effect with minimal inhibitory concentration (MIC) as low as 0.031% ± 0.07% (v/v) and inhibition zones reaching 30 ± 0.5 mm diameter. Test samples showed antibiofilm activities against two culture types and seven clinical strains of P. aeruginosa at concentrations of 2MIC to MIC/4. CCEO and its major constituent cinnamaldehyde were more active, compared to CEO and its major constituent eugenol. Scanning electron microscopy images showed untreated colonies with well‐developed biofilms while there was significant reduction of biofilms with distorted architecture and cell shrinkage upon treatment with test samples. In silico studies indicated great interactions between the major compounds, eugenol and cinnamaldehyde, with the receptor proteins of P. aeruginosa revealed by negative binding energies. Eugenol and cinnamaldehyde exhibited appreciable druglikeness.
Application of Cas9‐Based Gene Editing to Engineering of Nonribosomal Peptide Synthetases
Authors: Hashimoto Takuya , Suenaga Hikaru , Shin‐ya Kazuo
Published: December 2024

Engineering of nonribosomal peptide synthetases (NRPSs) could transform the production of bioactive natural product derivatives. A number of recent reports have described the engineering of NRPSs without marked reductions in yield. Comparative analysis of evolutionarily related NRPSs can provide insights regarding permissive fusion sites for engineering where recombination may occur during evolutionary processes. Studies involving engineering of NRPSs using these recombination sites showed that they have great potential. Moreover, we highlight recent advances in engineering of NRPSs using CRISPR‐associated protein 9 (Cas9)‐based gene editing technology. The use of Cas9 facilitates the editing of even larger biosynthetic gene clusters (BGCs) close to or over 100 kb in size by precisely targeting and digesting DNA sequences at specific sites. This technology combined with growing understanding of potential fusion sites from large‐scale informatics analyses will accelerate the scalable exploration of engineered NRPS assembly lines to obtain bioactive natural product derivatives in high yields.
Molecular Insights into the Heme‐Binding Potential of Plant NCR247‐Derived Peptides
Authors: Vaidya Sonali M. , Rathod Dhruv C. , Ramoji Anuradha , Neugebauer Ute , Imhof Diana
Published: December 2024

Heme is involved in many critical processes in pathogenic bacteria as iron acquisition by these microorganisms is achieved by either direct uptake of heme or use of heme‐binding proteins called hemophores. Exploring the underlying mechanisms on a molecular level can open new avenues in understanding the host‐pathogen interactions. Any imbalance of the heme concentration has a direct impact on the bacterial growth and survival. Thus, heme‐regulated proteins that are involved in heme homeostasis poise to be promising targets for research. Similarly, naturally occurring compounds, including cysteine‐rich peptides from either plant secondary metabolites or venom toxins from vertebrates and invertebrates, have been studied for their therapeutic potential. NCR247 is such a cysteine‐rich peptide, known to be crucial for nitrogenase activity in M. truncatula and its symbiotic relation with S. meliloti. NCR247‐derived peptides were suggested to serve as high‐affinity heme‐binding molecules with remarkable heme‐capturing properties. A comprehensive biochemical and computational analysis of NCR247‐derived peptides, however, redefines their heme‐binding capacity and consequently their potential therapeutic role.
Advances in Drug Delivery Systems for Atopic Dermatitis Treatment
Authors: Yang Jingyi , Jin Ling , Li Yuhao , Deng Dan , Miao Yuqing
Published: December 2024

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by pruritus and impaired skin barrier function. Advances in drug delivery systems have transformed AD treatment by enhancing drug stability, bioavailability, and targeted delivery. Drug delivery systems such as liposomes, hydrogels, and microneedles enable deeper skin penetration, prolonged drug retention, and controlled release, reducing side effects and treatment frequency. Liposomes improve drug absorption and stability, while hydrogels offer high water content and responsive drug release. Microneedles facilitate painless, localized drug delivery, enhancing patient compliance. These systems address the limitations of traditional therapies like topical corticosteroids and systemic immunosuppressants, which are associated with adverse effects and poor patient adherence. Recent innovations include Janus kinase (JAK) inhibitors and biologics targeting immune pathways, demonstrating significant efficacy in reducing inflammation and symptoms. Drug delivery systems offer a safer, more efficient alternative for delivering these advanced therapies. By improving therapeutic outcomes and patient experience, drug delivery systems represent a crucial advancement in AD management.
Intramolecular Inhibition by Imidazole in Acid‐Catalyzed Hydrolysis of Protected Carbohydrates
Authors: Szaniszló Szebasztián , Csizmadia Imre G. , Jákli Imre , Farkas Viktor , Láng András , Sulyok‐Eiler Máté , Harmat Veronika , Pintér István , Perczel András
Published: December 2024

The present study reveals an unexpected anomaly observed in the acid‐catalyzed hydrolysis of the 5,6‐O‐isopropylidene group in 3‐O‐protected D‐gluco‐ and D‐allofuranose derivatives. Although the removal of the 5,6‐O‐isopropylidene protecting group is typically rapid and quantitative under acidic conditions, an unexpected inhibition of this reaction is observed for the two C3‐epimers, 3‐O‐imidazole sulfonyl moiety. X‐ray data show a two‐faced imidazole ring orientation in the crystal, while solution state NOE data reveal a critical interaction type between the isopropylidene and the imidazole rings. Advanced conformational searches coupled with ab initio molecular modeling illuminate and explain the NMR and kinetic data and lay the groundwork for the most plausible mechanism of this unprecedented inhibition. These results provide valuable insights into the cross‐coupling of carbohydrate O‐protecting groups and shed light on how specific ring orientations and steric effects can trigger the inhibition of an otherwise easily feasible reaction, such as an acid‐catalyzed hydrolysis.
Anodic Activation of Prussian Blue Analog Leads to Highly Active Cobalt‐Doped Nickel (Oxy)Hydroxide for Organic Oxidation Reactions
Authors: Ansari Toufik , Bagchi Debabrata , Ghosh Suptish , Niklas Hausmann Jan , Indra Arindam , Menezes Prashanth W.
Published: December 2024

Water‐assisted electrocatalytic oxidation of alcohols into valuable chemicals is a promising strategy to circumvent the sluggish kinetics of water oxidation, while also reducing cell voltage and improving energy efficiency. Recently, transition metal (TM)‐based catalysts have been investigated for anodic alcohol oxidation, but success has been limited due to competition from the oxygen evolution reaction (OER) within the working regime. In this study, NiCo‐based Prussian blue analog (PBA) was electrochemically activated at the anodic potential to produce a Co−Ni(O)OH active catalyst with a nanosheet‐like architecture. This catalyst was further employed for the selective oxidation of benzyl alcohol (PhCH2OH) to benzoic acid (PhCOOH), achieving a 97 % Faradaic efficiency (FE). The electrochemical activity of Co−Ni(O)OH was also compared with hydrothermally prepared CoNi‐LDH, demonstrating that the PBA‐derived Co−Ni(O)OH was more effective.
Transition Metal Based Spin‐Tuned Charge Transfer in Single‐Molecule Junctions
Authors: Cui Xingyuan , Shang Yiting , Li Jingtai , Xing Yalin , Fang Jiuhong , Qu Fayu , Liu Xunshan , Liu Wei , Wang Lin
Published: December 2024

Investigating the correlation between metal coordination and molecular conductivity in single‐molecule systems is essential for advancing our knowledge of molecular electronics, particularly in the realm of spintronics. In the present study, we developed two complex wires utilizing the bipyridine ligand and two transition metal ions, Co2+ and Zn2+, aiming to study the impact of different spin characters on single‐molecule charge transport properties. Single‐molecule conductance was investigated using scanning tunnelling microscope breaking junctions (STM‐BJ) technique and the underlying mechanism was analysed by density functional theory (DFT) calculations. We demonstrated that the conductance predominantly increases after inserting Zn2+, indicating a conducting channel has been constructed. In contrast, the conductance of the analogue coordinated with Co2+ does not change significantly, this can be explained by distinct disparities between spin‐up and spin‐down channels, in which destructive quantum interference in spin‐down state counteracts the enhancement of molecular conductance. Our study establishes the groundwork for a systematic approach to the design, fabrication, and implementation of single‐complex conductance explorations.
Design, Synthesis and Biological Evaluation of Ethyl 5‐(1‐benzyl‐1H‐indol‐5‐yl) Isoxazole‐3‐Carboxylates as Antimycobacterial Agents
Authors: Bandela Rani , Sahoo Santosh Kumar , Mukhopadhyay Atri , Imran Mohmmad , Singampalli Anuradha , Maddipatla Sarvan , Bellapukonda Sri Mounika , Panchal Devdhar , Nanduri Srinivas , Dasgupta Arunava , Chopra Sidharth , Yaddanapudi Venkata Madhavi
Published: December 2024

The continued prevalence of drug‐resistant Mycobacterium tuberculosis (Mtb) strains, particularly against first‐line antitubercular (anti‐TB) drugs, presents an impending public health threat that necessitates the exploration and development of New Chemical Entities (NCEs). In search of new anti‐TB leads, a library of ethyl 5‐(1‐benzyl‐1H‐indol‐5‐yl) isoxazole‐3‐carboxylates were generated through a strategy of scaffold hopping from the proven isoxazole‐3‐carboxylate‐based anti‐TB pharmacophore. We evaluated their antibacterial potential against a panel of pathogenic bacteria and Mtb H37Rv strains. The majority of the compounds exhibited notable in vitro efficacy against the H37Rv strains (MIC 0.25 to 16 μg/mL) and were not cytotoxic with a Selectivity Index (SI) >10. Compound 5e (3,4‐dichlorobenzyl substituent) was found to be optimally active in the lot (MIC 0.25 μg/mL) and SI >200. It also displayed equipotent activity against drug‐resistant Mtb (DR‐Mtb) strains. In addition, it demonstrated concentration‐dependent bactericidal activity in a time‐kill kinetic assay similar to first‐line anti‐TB drugs besides exhibiting synergistic activity with Streptomycin. Moreover, it complies with the drug‐likeness characteristic, making it a promising candidate for further exploration as a probable anti‐TB lead.
An Echo Pressure Model Based on Mutil‐Gaussian Beam Theory for Measuring the Liquid Level in Special Field
Authors: Zhang Bin , Wei Yuejuan , Zang Shuqui , Li Qing , Qiang Yan
Published: December 2024

In aviation, petroleum and chemical industries and other special areas of production, since the liquid in containers mostly are flammable, explosive, volatile, and corrosive mixtures, the accurate measurement of the liquid level is essential to the real‐time control and production process. In this study, an approximation algorithm based on echo pressure model for measuring the liquid level in special field is proposed in this paper. According to the model, a complete lateral incident ultrasonic measurement system is constructed for the inductive liquid level detection technology in special applications, an algorithm model of the echo pressure is established, which provides the determination of the liquid level relying on the characteristic curve of the echo pressure. The model in this study converts complex interaction problems of sound fields into the echo pressure calculation, which quickly determines performance parameters of sound fields, and a virtual reflection method is used to calculate the sound pressure of the receiving transducer in different states, which reduces computational complexity, finally, through the simulation and experiment, the algorithm is validated. The results are consistent with expectations, and the algorithm can be further applied in practice.
Design of Neko—A Scalable High‐Fidelity Simulation Framework With Extensive Accelerator Support
Authors: Jansson Niclas , Karp Martin , Wahlgren Jacob , Markidis Stefano , Schlatter Philipp
Published: December 2024

Recent trends and advancements in including more diverse and heterogeneous hardware in High‐Performance Computing (HPC) are challenging scientific software developers in their pursuit of efficient numerical methods with sustained performance across a diverse set of platforms. As a result, researchers are today forced to re‐factor their codes to leverage these powerful new heterogeneous systems. We present our design considerations of Neko—a portable framework for high‐fidelity spectral element flow simulations. Unlike prior works, Neko adopts a modern object‐oriented Fortran 2008 approach, allowing multi‐tier abstractions of the solver stack and facilitating various hardware backends ranging from general‐purpose processors, accelerators down to exotic vector processors and Field‐Programmable Gate Arrays (FPGAs). Focusing on the performance and portability of Neko, we describe the framework's device abstraction layer managing device memory, data transfer and kernel launches from Fortran, allowing for a solver written in a hardware‐neutral yet performant way. Accelerator‐specific optimizations are also discussed, with auto‐tuning of key kernels and various communication strategies using device‐aware MPI. Finally, we present performance measurements on a wide range of computing platforms, including the EuroHPC pre‐exascale system LUMI, where Neko achieves excellent parallel efficiency for a large direct numerical simulation (DNS) of turbulent fluid flow using up to 80% of the entire LUMI supercomputer.
What drives the cost of strategic planning?
Authors: Freebairn‐Smith Laura
Published: December 2024

You think you need a strategic plan. How much will it cost to write one?
Applications of Single‐Cell Sequencing in Airway Inflammatory Diseases: Progress and Perspectives
Authors: Liu Huifang , Yin Jiali , Yang Yujuan , Xu Xinjun , Yu Jingyi , Luo Xianghuang , Zhang Yu , Song Xicheng
Published: December 2024

Airway inflammatory diseases include allergic rhinitis (AR), chronic rhinosinusitis (CRS), bronchial asthma (BA), chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Single‐cell sequencing (SCS), as a powerful tool for revealing cellular and molecular landscapes at single‐cell resolution, which has revealed many of the intrinsic biological features and dynamics of airway inflammation, viral infections and other pathologies, as well as constructing immune landscapes of health and disease states. We reviewed the literature focusing on the past several years have focused on using SCS technology increased our understanding of the airway immune cell landscape of airway diseases, including CRS, AR, BA, COPD, IPF, as well as the landscape of airway immune cells in healthy and pathological conditions. We also have elucidated the role of a subset of T cells, myeloid cell, basophils and mast cells in airway diseases revealed by SCS. Meanwhile we also highlighted the use of SCS to explore the potential mechanisms of immune cell interactions.
Nutritional Advantages of Walnut (Juglans regia L.) for Cardiovascular Diseases: A Comprehensive Review
Authors: Rashki Mostafa , Ghasemzadeh Rahbardar Mahboobeh , Boskabady Mohammad Hossein
Published: December 2024

Cardiovascular diseases (CVDs) remain one of the leading causes of morbidity and mortality worldwide. In recent years, the potential role of dietary interventions in preventing and managing CVDs has gained significant attention. Among these dietary components, walnuts (Juglans regia L.) have emerged as a promising candidate due to their unique nutrient profile and potential cardiovascular benefits. This review aims to provide a comprehensive analysis of the existing literature on the role of walnuts in cardiovascular health. Using databases from Scopus, Google Scholar, and PubMed, the most relevant in vitro, in vivo, and clinical trial research has been collected from the time of inception until 2024. Several studies have shown that walnut consumption has a positive effect on a variety of cardiovascular risk factors. Walnut bioactive ingredients, including omega‐3 fatty acids, antioxidants, fiber, and polyphenols, have been demonstrated to improve lipid profiles, blood pressure, endothelial function, inflammation, oxidative stress, and thrombosis. These processes all contribute to the possible cardioprotective properties of walnuts. Epidemiological and clinical research indicates that daily walnut consumption can reduce the risk of CVDs like coronary heart disease and stroke. Walnuts may aid in managing CVDs through mechanisms such as enhancing lipid profiles, reducing inflammation, and improving overall cardiovascular function. This review highlights the potential role of walnuts as a dietary strategy for the prevention and management of CVDs. Further understanding of the mechanisms and long‐term effects of walnut consumption is crucial for optimizing their therapeutic potential and integrating them into clinical practice. Future research should focus on elucidating specific dose–response relationships and exploring the synergistic effects of walnuts in combination with other dietary and lifestyle interventions.
Extremophilic Microorganisms as a Source of Emerging Enzymes for the Food Industry: A Review
Authors: Ashaolu Tolulope Joshua , Malik Tanu , Soni Rakhi , Prieto Miguel A. , Jafari Seid Mahdi
Published: December 2024

Modern‐day consumers are interested in highly nutritious and safe foods with corresponding organoleptic qualities. Such foods are increasingly subjected to various processing techniques which include the use of enzymes. These enzymes like amylases, lipases, proteases, xylanases, laccases, pullulanase, chitinases, pectinases, esterases, isomerases, and dehydrogenases could be derived from extremophilic organisms such as thermophiles, psychrophiles, acidophiles, alkaliphiles, and halophiles. As these organisms can grow under severe environmental conditions, they can produce functional enzymes (extremozymes) used in producing safe foods (such as gluten‐free, lactose‐free, lower acrylamide, or lower trans‐fat products). The extremozymes also enhance nutrient bioavailability and bioaccessibility (e.g., predigested nourishments like baby formulae), and improve nourishment functionalities such as surface, sensory, and bioactive properties. Therefore, exploring alternative sources of enzymes for better compatibility and long‐term adaptability in the processing stages is a promising approach for obtaining novel food products. This review will establish novel discovery methods of extremozymes from psychrophiles, thermophiles, acidophiles, alkaliphiles, and halophiles, the enzymes' types, mechanisms of action, and their food applications. It will also contribute to their commercial relevance and the furtherance of their discovery.
Change in transverse relaxation rates (R2) and change in cognition for older African Americans
Authors: Lamar Melissa , Arfanakis Konstantinos , Capuano Ana W. , Zhang Shengwei , Fleischman Debra A. , Han S. Duke , Poole Victoria N. , Leurgans Sue E. , Bennett David A. , Barnes Lisa L.
Published: December 2024

Despite transverse relaxation rate (R2) being one of the fundamental contrasts in MRI, most investigations of brain R2 and cognition have been cross‐sectional and conducted in predominantly non‐Latino White adults. We investigated the profile of R2 as related to cognition in 212 older African Americans (~75 years of age) with longitudinal 3T MRI scans and cognitive test data to determine how changes in R2 are associated with changes in cognition. For each participant, the slopes of global cognitive and five cognitive domain scores were each separately combined with voxel‐specific slopes of R2 in whole brain voxelwise analyses. Participants with less negative rates of R2 change within left basal ganglia and centrum semiovale, bilateral hippocampal complex and temporal gyri, parietooccipital white matter, as well as posterior cingulate displayed less negative slopes in global cognition. Similar associations were seen for regional R2 change and episodic memory (most robustly within bilateral hippocampi) as well as semantic memory (left greater than right hemisphere involvement). Results suggest a relatively wide distribution of regional associations between rates of changes in R2 and changes in global cognition for older African Americans; a profile that became more regionally specific when considering individual cognitive domains. Relative preservation of tissue integrity across grey and white matter, and in key regions associated with specific cognitive domains, is associated with slower cognitive decline for older African Americans. These results may lay the foundation for more directed work to support healthy brain aging in older African Americans.
Using Patient‐Reported Outcomes in Two Program Examples Measuring Health Status in Primary Care: An Observational Study
Authors: Soprovich Allison L. , Short Hilary , Ali Al‐Bakir , Brower Krista , Ohinmaa Arto , Johnson Jeffrey A.
Published: December 2024

Background and Aims

Patient‐reported outcome measures (PROMs) are increasingly used in primary care practices; however, the broad characteristics of this population pose unique challenges. Generic PROMs (e.g., EQ‐5D‐5L) measure general health status from the patient's perspective, contributing towards a comprehensive evaluation of health programming. This study describes the integration of the EQ‐5D‐5L within program evaluation in primary care in Alberta, Canada, using two program examples.

Methods

A retrospective, longitudinal, observational design was used. The Edmonton O‐day'min Primary Care Network (EOPCN) routinely collects the EQ‐5D‐5L in their exercise and active living and nutrition programs. Data collected between January 1, 2021 and March 31, 2022 was analyzed descriptively, by dimension, index, and visual analog scale (VAS) scores. Minimally important differences were used to interpret index (0.04) and VAS scores (7.0) and the Pareto Classification of Health Change was applied to the dimensions. Effect size of change in index and VAS scores and population comparisons were examined.

Results

In the exercise and active living program (n = 301), 72% were female with a mean age of 57 (±16) years, and 90.2% reported any problems (levels 2–5) in pain/discomfort. The mean index and VAS scores were 0.74 (±0.18) and 66.5 (±18.9), respectively. Among those with repeated measurement (n = 112), the greatest improvement was in usual activities (17%); the greatest deterioration was in pain/discomfort (25%). In the nutrition program (n = 573), 71% were female with a mean age of 50 (±17) years, and 75.9% reported any problems in pain/discomfort. The mean index and VAS scores were 0.77 (±0.19) and 70.1 (±15.6), respectively. Among those with repeated measurement (n = 212), the greatest improvement was in anxiety/depression (16%); the greatest deterioration was in pain/discomfort (26%). In both, health status was lower than the general Alberta population norms. No baseline characteristics were found to be statistically significant.

Conclusion

These results inform future programming, to help patient needs.