bluuebunny/crossref_metadata_2025 huggingface dataset:
An epigenome‐wide study of a needs‐based family intervention for offspring of trauma‐exposed mothers in Kosovo
Authors: Ryan Joanne , Phyo Aung Zaw Zaw , Krasniqi Sebahate Pacolli , Carkaxhiu Selvi Izeti , Fransquet Peter , Kaas‐Petersen Sara Helene , Limani Dafina Arifaj , Xhemaili Vjosa Devaja , Salihu Mimoza , Prapashtica Qendresa , Zekaj Nebahate , Turjaka Vesa , Wang Shr‐Jie , Rushiti Feride , Hjort Line
Published: September 2024

Introduction

Maternal stress and trauma during pregnancy have been shown to influence cortisol levels and epigenetic patterns, including DNA methylation, in the offspring. This study aimed to determine whether a tailor‐made family intervention could help reduce cortisol levels in children born to traumatized mothers, and to determine whether it effected offspring DNA methylation. The secondary aim was to determine whether the family intervention influenced DNA methylation aging, a marker of biological aging.

Methods

A needs‐based family intervention was designed to help address relational difficulties and family functioning, and included a focus on family strengths and problem‐solving patterns. Women survivors of sexual violence during the Kosovar war in 1998–1999, and their families (children with or without partners) were randomly assigned to 10 sessions of a family therapy over a 3–5‐month period, or to a waitlist control group. Both mothers and children completed assessments prior to and after the intervention phase. Children's blood samples collected at these two time points were used to measure cortisol and epigenome‐wide DNA methylation patterns (Illumina EPIC array). Cortisol levels, and genome‐wide DNA methylation changes pre‐/postintervention were compared between children in the intervention and the waitlist groups. DNA methylation age and accelerated biological aging were calculated.

Results

Sixty‐two women–child dyads completed the study, 30 were assigned first to the intervention group, and 32 to the waitlist control group. In adjusted linear regression, the family intervention was associated with a significant decline in cortisol levels compared to the waitlist control (β = −124.72, 95% confidence interval [CI]: −197.4 to −52.1, p = .001). Children in the intervention group, compared to the waitlist control group, showed >1% differential methylation degree at 5819 CpG (5'—C—phosphate—G—3') sites across the genome (p < .01), with the largest methylation difference being 21%. However, none of these differences reached genome‐wide significant levels. There was no significant difference in DNA methylation aging between the two groups.

Conclusion

We find evidence that a tailored family‐based intervention reduced stress levels in the children (based on cortisol levels), and modified DNA methylation levels at a number of sites across the genome. This study provides some preliminary evidence to suggest the potential for tailored interventions to help break the intergenerational transmission of trauma, however, large studies powered to detect associations at genome‐wide significant levels are needed.
Macrophages overexpressing interleukin‐10 target and prevent atherosclerosis: Regression of plaque formation and reduction in necrotic core
Authors: Wang Mingyi , Zhou Shanshan , Hu Yingyun , Tong Wei , Zhou Hao , Ma Mingrui , Cai Xingxuan , Zhang Zhengbin , Zhang Luo , Chen Yundai
Published: September 2024

Atherosclerosis, a slowly progressing inflammatory disease, is characterized by the presence of monocyte‐derived macrophages. Interventions targeting the inflammatory characteristics of atherosclerosis hold promising potential. Although interleukin (IL)‐10 is widely acknowledged for its anti‐inflammatory effects, systemic administration of IL‐10 has limitations due to its short half‐life and significant systemic side effects. In this study, we aimed to investigate the effectiveness of an approach designed to overexpress IL‐10 in macrophages and subsequently introduce these genetically modified cells into ApoE−/− mice to promote atherosclerosis regression. We engineered RAW264.7 cells to overexpress IL‐10 (referred to as IL‐10M) using lentivirus vectors. The IL‐10M exhibited robust IL‐10 secretion, maintained phagocytic function, improved mitochondrial membrane potentials, reduced superoxide production and showed a tendency toward the M2 phenotype when exposed to inflammatory stimuli. IL‐10M can selectively target plaques in ApoE−/− mice and has the potential to reduce plaque area and necrotic core at both early and late stages of plaque progression. Moreover, there was a significant reduction in MMP9, a biomarker associated with plaque rupture, in IL‐10M‐treated plaques from both the early and late intervention groups. Additionally, the administration of IL‐10M showed no obvious side effects. This study serves as proof that cell therapy based on anti‐inflammatory macrophages might be a promising strategy for the intervention of atherosclerosis.
Phytochemical Characterization and Assessment of Antioxidant and Anti‐Alzheimer Effects of Algerian Seseli Tortuosum
Authors: Slimani Abdelkader , Akkal Wail , Acheraf Benmekhbi Ahmed , Mosbah Asma , Selim Cakmak Yavuz , Lefahal Mostefa , Bousetla Ahlem , Mokrani El Hassen , Bensouici Chawki , Laouer Hocine , Akkal Salah , Nieto Gema
Published: September 2024

HPLC analysis, phytochemical screening, thin layer chromatography, polyphenols and flavonoid contents were conducted to determine the bioactive contents of the Algerian Seseli tortuosum plant. Antioxidant activity was tested using DPPH and ABTS scavenging assays, reducing power, phenanthroline and silver nanoparticle (SNP) assays. The anti–Alzheimer's activity of extracts was also performed in vitro and in silico. Phytochemical analysis highlighted the richness ofthe extracts in terms of coumarins, terpenoids and quercetin. The quantitative determination of total polyphenols and flavonoids showed that the highest amounts occurredinthe dichloromethane (DCME) and methanolic (MeOH) extracts. The antioxidant activities indicated a moderate potential. Compared with galantamine, DCME had a significantly greater anti–Alzheimer effect on BChE(CI50=9.14±1.74 μg/ml and 34.75±1.99 μg/ml respectively). An in silicostudy of anti–Alzheimer activity revealed a significant effect of quercetin(−30,13 KJ/mol). Conclusion: This study demonstrated the richness of the phytochemical components of seseli tortuosum,which are responsible for several biological properties, mainly their anti‐Alzheimer potential.
Allosteric Inhibition of the β2‐Adrenergic Receptor: Design and Synthesis of Cmpd‐15 Analogs
Authors: Ye Kexin , Li Qing , Luo Zhijie , Lu Qianchen , Rui Xue , Li Yan , Jin Jie , Jing Chenchen , Hong Meiling , Qian Mingcheng , Zhao Shuai , Hou Yanan , Chen Xin
Published: September 2024

We designed and synthesized 27 new amide and dipeptide derivatives containing a substituted phenylalanine as negative allosteric modulators (NAMs) for the beta‐2 adrenergic receptor (β2AR). These analogs aimed to improve the activity of our lead compound, Cmpd‐15, by introducing variations in three key regions: the meta‐bromobenzyl methylbenzamide (S1), para‐formamidophenylalanine (S2), and 1‐cyclohexyl‐1‐phenylacetyl (S3) groups. The synthesis involved the Pd‐catalyzed β‐C(sp3)‐H arylation of N‐acetylglycine with 1‐iodo‐4‐substituent‐benzenes as the key step. GloSensor cAMP accumulation assay revealed that six analogs (A1, C5, C6, C13, C15 and C17) surpass Cmpd‐15 in β2AR allosteric function. This highlights the crucial role of the S1 region (meta‐bromobenzyl methylbenzamide) in β2AR allostery while suggesting potential replaceability of the S2 region (para‐formamidophenylalanine). These findings serve as a valuable springboard for further optimizing Cmpd‐15, potentially leading to smaller, more active, and more stable β2AR‐targeting NAMs.
Diagnostic challenge of an untypical cutaneous drug reaction from modafinil
Authors: Harvima Rauno J. , Heiskanen‐Kosma Tarja , Arvonen Miika , Harvima Ilkka T.
Published: September 2024

Key Clinical Message

Modafinil used for narcolepsy caused an atypical adverse reaction, as itchy acneiform lesions, subcutaneous nodules and superficial skin wounds after 2 years of use. After extensive examinations for 5 years, modafinil was discontinued, and the healing process began in 3 weeks with completion in 1.5 years.
Multiple, giant lymphangectatic pilomatricomas: A rare clinical entity
Authors: Mohaghegh Fatemeh , Shoushtarizadeh Mohammad , Tabatabaei Elham Tavousi , Derakhshan Maryam , Ghadirian Ali
Published: September 2024

Key Clinical Message

This case highlights the rare and atypical presentation of giant, multiple pilomatricomas (PMs) with a pseudo‐bullous appearance and lymphangiomatous pathology. It underscores the importance of considering PM in the differential diagnosis of atypical lesions, especially those mimicking cystic or hemorrhagic malignant conditions, to prevent misdiagnosis and ensure appropriate management.
Possible thoracic metastasis from squamous cell carcinoma of the external auditory canal: A case report
Authors: Takehara Hiroshi , Kodama Ken , Momozane Toru , Takeda Masashi , Shigetsu Kaichi , Kishima Hiroki
Published: September 2024

Key Clinical Message

An 80‐year‐old never‐smoking woman, who underwent radiotherapy in combination with simultaneous intra‐arterial chemotherapy for external auditory canal squamous cell carcinoma (SCC) 10 years ago, was referred to our department due to a painful huge chest wall tumor. We conducted surgical resection combined with the right upper lobe and chest wall including the 3rd to 5th ribs and affected serratus anterior muscle. Histologically, atypical keratotic cells with the same morphology as external auditory canal SCC proliferated without the figure of carcinoma in situ or squamous dysplasia of the bronchial epithelium of the lung parenchyma adjacent to the tumor. Take Home Message: If long‐term imaging follow‐up had been performed, it would have been easier to detect it early and differentiate it from metastasis or primary lung cancer.
Fluidized Bed Chemical Vapor Deposition of Copper on Micronic Alumina Powders
Authors: Jellal Ilyass , Vergnes Hugues , Caussat Brigitte
Published: September 2024

Uniformly coating micronic particles with metals is of main interest for a broad range of applications. This study demonstrates the feasibility of depositing pure copper on the surface of micronic alumina particles by the fluidized bed chemical vapor deposition process from the cheap and nontoxic copper acetylacetonate precursor. Thanks to the development of a preconditioning protocol, a complete fluidization of the particles organized as porous agglomerates was reached. The coating of the individual particles was favored by using conditions involving low deposition rates. The influence of key operating parameters on the process behavior and on the characteristics of the deposit was studied. The deposited copper was of cubic crystal structure without carbon nor oxide contamination.
Melanin and Light
Authors: Menichetti Arianna , Mordini Dario , Montalti Marco
Published: September 2024

Melanin is responsible, in Nature, for photoprotection, for this reason it is expected to be poorly photoreactive. However, the photo‐reactivity of melanin and related materials is well documented. Here we discuss some relevant recent examples to demonstrate that, indeed, the actual mechanism of interaction of melanin with light is complex and still not completely understood. Photochemical and photothermal processes are involved, giving a contribution that strongly depends on light wavelength and intensity. Moreover, some interesting experiments demonstrated that photochemical reactivity of melanin related compounds is likely to be indirect, in the sense that the effect of light is to increase the number of radical species rather than creating photoreactive excited state. These suggestions open‐up new perspectives in the interpretation of the role of melanin in photoprotection and in the design of new melanin based photoactive materials for energy conversion, environmental remediation, and nanomedicine. Further complication is given by the role of atmospheric oxygen and humidity in the photoinduced processes. Beside this complexity of behavior makes it difficult a systematic understanding of the interaction of melanin with light, it surely strongly contributes to make the properties of melanin and related materials unique.
Tuning The Intracellular Distribution of [3+2+1] Iridium(III) Complexes In Bacterial And Mammalian Cells By iClick Reaction With Biomolecular Carriers Functionalized With Alkynone Groups
Authors: Müller Victoria V. L. , Moreth Dominik , Kowalski Konrad , Kowalczyk Aleksandra , Gapińska Magdalena , Kutta Roger Jan , Nuernberger Patrick , Schatzschneider Ulrich
Published: September 2024

Three iridium(III) triazolato complexes of the general formula [Ir(triazolatoR,R’)(ppy)(terpy)]PF6 with ppy=2‐phenylpyridine and terpy=2,2’:6’,2’’‐terpyridine were efficiently prepared by iClick reaction of [Ir(N3)(ppy)(terpy)]PF6, with alkynes and alkynones, which allowed facile introduction of biological carriers such as biotin and cholic acid. In contrast to the precursor azido complex, which decomposed upon photoexcitation on a very short time scale, the triazolato complexes were stable in solution for up to 48 h. They emit in the spectral region around 540 nm with a quantum yield of 15–35 % in aerated acetonitrile solution and exhibit low cytotoxicity with IC50 values >50 μM for most complexes in L929 and HeLa cells, demonstrating their high suitability as luminescent probes. Cell uptake studies with confocal luminescence microscopy in prokaryotic Gram‐positive S. aureus and Gram‐negative E. coli bacteria as well as eukaryotic mammalian L929 and HeLa cells showed significant uptake in particular of the cholic acid conjugates iridium(III) moiety and distinct intracellular distribution modulated by the nature of the peripheral functional groups that can easily be modified by the iClick reaction.
6th Symposium on Advanced Biological Inorganic Chemistry (SABIC), 2024
Authors: Datta Ankona , Dey Somdatta Ghosh
Published: September 2024

The history of the Symposium on Advanced Biological Inorganic Chemistry (SABIC) is discussed in the editorial. The most recent one (SABIC 2024) took place during January 7‐11, 2024 in Kolkata, India. It was jointly organized by IACS Kolkata and TIFR Mumbai. In collaboration with the organizers of SABIC 2024, six Wiley journals (Chemistry‐A European Journal, Chemistry‐An Asian Journal, European Journal of Inorganic Chemistry, Small, ChemBioChem and ChemMedChem) have decided to publish a collection of articles celebrating the recent developments of bioinorganic chemistry research presented at the conference.
Global dynamic features and information of adjacent hidden layer enhancement based on autoencoder for industrial process soft sensor application
Authors: Guo Xiaoping , Pan Sulei , Li Yuan
Published: September 2024

There is a lack of consideration of temporal and spatial correlation in the process variables and adjacent hidden layers correlation in the soft sensor model of stacked autoencoders. To address the issue, a novel global dynamic adjacent layer information enhancement auto encoder (GD‐ALIEAE) method is proposed to improve the poor prediction performance. The gated recurrent unit (GRU) and uniform manifold approximation and projection (UMAP) are applied to the GD‐ALIEAE model for obtaining global dynamic features of the temporal and spatial information of process variables by parallel computation. An adjacent layer information correlation algorithm is proposed to avoid the loss of hidden layers information during the stacking process. The algorithm enhances the features of the low layer through nonlinear mapping, combining the low layer and its adjacent layer as input. The input then is fed to the multi‐head attention mechanism to obtain features that contain adjacent layer correlation. Finally, a prediction model is established through a fully connected layer. Through simulation experiments on two industrial cases of sulphur recovery unit and thermal power plant, and compared with models of stacked autoencoder (SAE), stacked isomorphic autoencoder (SIAE), and target‐related stacked autoencoder (TSAE), the effectiveness of the proposed method was verified.
Computational modelling and optimization of physicochemical absorption of CO2 in rotating packed bed
Authors: Zahir Abdul , Kumar Perumal , Saptoro Agus , Shah Milinkumar , Tiong Angnes Ngieng Tze , Kurnia Jundika Candra , Hameed Samreen
Published: September 2024

The current study developed a novel computational fluid dynamics (CFD) model that accounted for both physical and chemical absorption in the multiphase flow and captured the relative dominance of chemical absorption over physical by employing a tunable model parameter ‘enhancement factor’. The CFD model was validated against experimental data in a rotating packed bed, and then the validated model was used to investigate the effect of operational parameters such as rotational speed, monoethanolamine (MEA) concentration, inlet velocity, and MEA‐packing contact angle on the physiochemical absorption. The significance of each operational parameter was then evaluated by the ANOVA analysis, which inferred that the enhancement factor is sensitive to rotational speed, MEA concentration, inlet velocity, and contact angle. The p‐value of MEA concentration and inlet velocity was less than 0.05, which implies that these two variables are the most significant variables for the chemical absorption of CO2. The response surface methodology (RSM) and the artificial neural network (ANN) were also employed to develop the predictive model for the enhancement factor. Among the employed techniques, ANN resulted in R2 closer to 0.99 and could better predict the enhancement factor. The modelling approach and findings of the current study are useful in optimizing the operation of rotating packed‐bed reactor (RPB) for CO2 absorption on the industrial scale.
Medicinal Chemistry in Bosnia and Herzegovina ‐ Past, Present and Perspectives**
Authors: Kondža Martin
Published: September 2024

Although Bosnia and Herzegovina has had a rich history in medicines and traditional medicines, it historically had poor activity regarding the field of medicinal chemistry in the country. However, this has changed recently as Bosnia and Herzegovina has shown immense potential in this field. A significant milestone occurred in 2019, with the establishment of the Organization Pharmaceutical Research Institute. This non‐governmental organization aims to improve medicinal chemistry in Bosnia and Herzegovina. Through research, partnerships, and educational initiatives, the organization has made substantial strides in promoting pharmaceutical research, education, and innovation. Moreover, the country‘s membership in the European Federation for Medicinal Chemistry and Chemical Biology (EFMC) has further facilitated collaboration with European experts, access to cutting‐edge knowledge and technologies, and harmonization with European standards. Looking to the future, this organization endeavors to improve healthcare, encourage innovation in medicinal chemistry, and promote the development of new therapies. With the efforts to establish an Association of Chemists in Bosnia and Herzegovina, the nation‘s scientific community is poised to flourish, contributing to the advancement of medicinal chemistry and healthcare in the region.
Probing the Electric Field Response of a Water Molecule Confined in Small Carbon Nanocages: A Density Functional Theory Investigation
Authors: Rai Smita , Rai Dhurba
Published: September 2024

We consider a water molecule under tight confinement in the small‐sized fullerenes (C
, C
, C
) within the density functional theory (DFT) calculations with suitable exchange‐correlation functionals. Such nanoscopic molecular cages provide an ideal setup to study their characteristic properties not present in the condensed phase. The water molecule entirely loses its feature of typical water when it is confined in small fullerenes of size equal to C
or smaller, in which the asymmetric O−H stretching vibration occurs at a lower wavenumber than the symmetric stretching. We study the response of the confined water molecule to the applied electric fields in terms of change in geometrical parameters, NMR spin‐spin coupling constants, dipole moment, HOMO‐LUMO (HL) gap, and vibrational frequency shift. The electric field shielding property of small‐sized fullerene cages is explored and found to be strongly correlated with the HL gap. Since the electric field modulates the gap to decrease generally, shielding efficiency varies with field strength, thereby making large fields better shielded than small fields for the small penetration factor at large fields. The results that hold significance for technological applications are discussed.
Coadsorption of ZnTPP and 2HMCTPP on Rutile TiO2(110)
Authors: Muth Maximilian , Wolfram Alexander , Steinrück Hans‐Peter , Lytken Ole
Published: September 2024

Pure zinc tetraphenylporphyrin (ZnTPP) adsorbs on rutile TiO2(110) as flat‐lying molecules, mostly interacting with the surface through weak van‐der‐Waals interactions. Pure monocarboxyphenyl triphenylporphyrin (2HMCTPP) forms a covalent bond to the rutile TiO2(110) surface through the carboxylic acid group, yielding densely‐packed layers of upright‐standing molecules. If given the chance, 2HMCTPP could therefore be expected to displace the weaker‐bonding ZnTPP molecules. However, if 2HMCTPP is deposited on top of a ZnTPP layer, a coadsorption structure instead forms, with the carboxylic‐acid groups of the 2HCMTPP molecules bonding to titanium atoms of the surface exposed by gaps between the molecules in the flat‐lying ZnTPP adsorption structure.
An Innovative Approach to Optimize First‐In‐Human Minimal Anticipated Biological Effect Level Based Starting Dose in Oncology Trials for Bispecific T‐Cell Engagers: Experience from A Solid Tumor Bispecific T‐Cell Engager
Authors: Zhou Di , Kischel Roman , Stienen Sabine , Townsley Danielle , Sternjak Alexander , Lutteropp Michael , Bailis Julie , Friedrich Matthias , Rattel Benno , Mehta Khamir , Upreti Vijay V.
Published: September 2024

Bispecific T‐cell engagers (Bi‐TCEs) have revolutionized the treatment and management of both hematological and solid tumor indications with opportunities to become best‐in‐class therapeutics for cancer. However, defining the dose and dosing regimen for the first‐in‐human (FIH) studies of Bi‐TCEs can be challenging, as a high starting dose can expose subjects to serious toxicity while a low starting dose based on traditional minimal anticipated biological effect level (MABEL) approach could lead to lengthy dose escalations that exposes seriously ill patients to sub‐therapeutic dosing. Leveraging our in‐depth and broad clinical development experience across three generations of Bi‐TCEs across both liquid and solid tumor indications, we developed an innovative modified MABEL approach for starting dose selection that integrates knowledge based on the target biology, indication, toxicology, in vitro, in vivo pharmacological evaluations, and translational pharmacokinetic/pharmacodynamic (PK/PD) modeling, together with anticipated safety profile. Compared to the traditional MABEL approach in which high effector to target (E:T) cell ratios are typically used, our innovative approach utilized an optimized E:T cell ratio that better reflects the tumor microenvironment. This modified MABEL approach was successfully applied to FIH dose selection for a half‐life extended (HLE) Bi‐TCE for gastric cancer. This modified MABEL approach enabled a 10‐fold higher starting dose that was deemed safe and well tolerated and saved at least two dose‐escalation cohorts before reaching the projected efficacious dose. This approach was successfully accepted by global regulatory agencies and can be applied for Bi‐TCEs across both hematological and solid tumor indications for accelerating the clinical development for Bi‐TCEs.
Dielectric‐Controlled Ultrafast Twisted Intramolecular Charge‐Transfer VS trans to cis Isomerization Pathways in a Push‐Pull Stilbene: Global Analysis Perspectives
Authors: Dhamija Shaina , K. De Arijit
Published: September 2024

We explore excited‐state dynamics of 4,4’‐dimethylaminonitrostilbene (DNS), a push‐pull stilbene, undergoing twisted intramolecular charge transfer and/or trans to cis isomerization, which is dependent on solvent polarity. We show how global analysis of femtosecond pump/broadband‐probe data aids in elucidating the involvement of interconverting conformers and/or isomers, and the timescales associated with such interconversion, often unexplored in single‐wavelength kinetic analysis.
Synergizing lean management and circular economy: Pathways to sustainable manufacturing
Authors: Sasso Ricardo Aparecido , Filho Moacir Godinho , Ganga Gilberto Miller Devós
Published: September 2024

Our research focuses on integrating circular economy (CE) and Lean Management (LM) within the manufacturing sector, a proactive response to the escalating pressures of globalization, environmental sustainability, and market competition. Through a comprehensive systematic literature review, the research uncovers how CE principles can fortify and enrich LM practices, the role of LM in facilitating a transition towards CE, their combined impact on manufacturing performance, and the crucial environmental factors influencing this integration. The findings underscore that CE principles significantly strengthen LM practices by advocating waste minimization and resource optimization, thereby contributing to operational efficiency and sustainability. Conversely, LM aids the transition to a CE by optimizing resource use and minimizing waste, aligning with sustainability goals. LM supports recycling and remanufacturing by employing Just‐in‐Time and value stream mapping methodologies, augmented by Industry 4.0 technologies for seamless CE integration. Despite challenges like integration barriers and the need for organizational change, the synergy between CE and LM offers substantial benefits for environmental performance, operational efficiency, and competitive advantage. Our paper enriches academic knowledge and provides practical applications in sustainable manufacturing practices, offering a roadmap for organizations striving for sustainable operational excellence. Moreover, it also paves the way for future studies to further explore the synergistic potential of CE and LM through empirical studies, quantitative analyses, and the exploration of Industry 4.0 technologies.
Extending the boundaries of financial reporting in the extractive industries: Insights from bibliometric analysis
Authors: Centorrino Giovanna , Naciti Valeria , Rupo Daniela
Published: September 2024

Financial reporting in extractive industries (EIs) is a crucial function that warrants further attention in the literature. Previous studies have identified several issues related to financial reporting quality, its impact on stock prices, and the relationship between financial reporting and corporate governance. However, significant gaps remain in understanding the impact of the extractive industry's unique characteristics and the role of regulators in enhancing financial reporting practices. This study aims to illuminate the research trajectory affecting extractive firms by describing the state‐of‐the‐art regarding related accounting standards through a mapping of currently accessible studies. To achieve this, we applied a bibliometric analysis methodology. Bibliometric techniques provide a quantitative approach for objectively assessing literature, offering a comprehensive overview of influential authors, journals, themes, and countries within a specific research field. This approach also facilitates the identification of research trends and the prediction of future developments. The study highlights the growing demand for sustainability reports as the primary formalized means for companies to disclose their sustainable development efforts. Research on sustainability reporting in the mining sector underscores the importance of integrated sustainability reporting, with a focus on understanding the evolution and advancement of reporting methodologies across all dimensions of corporate social responsibility.
ANKRD1 aggravates renal ischaemia‒reperfusion injury via promoting TRIM25‐mediated ubiquitination of ACSL3
Authors: Han Shangting , Guo Jiayu , Kong Chenyang , Li Jun , Lin Fangyou , Zhu Jiefu , Wang Tianyu , Chen Qi , Liu Yiting , Hu Haochong , Qiu Tao , Cheng Fan , Zhou Jiangqiao
Published: September 2024

Background

Renal ischaemia‒reperfusion injury (IRI) is the primary cause of acute kidney injury (AKI). To date, effective therapies for delaying renal IRI and postponing patient survival remain absent. Ankyrin repeat domain 1 (ANKRD1) has been implicated in some pathophysiologic processes, but its role in renal IRI has not been explored.

Methods

The mouse model of IRI‐AKI and in vitro model were utilised to investigate the role of ANKRD1. Immunoprecipitation‐mass spectrometry was performed to identify potential ANKRD1‐interacting proteins. Protein‒protein interactions and protein ubiquitination were examined using immunoprecipitation and proximity ligation assay and immunoblotting, respectively. Cell viability, damage and lipid peroxidation were evaluated using biochemical and cellular techniques.

Results

First, we unveiled that ANKRD1 were significantly elevated in renal IRI models. Global knockdown of ANKRD1 in all cell types of mouse kidney by recombinant adeno‐associated virus (rAAV9)‐mitigated ischaemia/reperfusion‐induced renal damage and failure. Silencing ANKRD1 enhanced cell viability and alleviated cell damage in human renal proximal tubule cells exposed to hypoxia reoxygenation or hydrogen peroxide, while ANKRD1 overexpression had the opposite effect. Second, we discovered that ANKRD1's detrimental function during renal IRI involves promoting lipid peroxidation and ferroptosis by directly binding to and decreasing levels of acyl‐coenzyme A synthetase long‐chain family member 3 (ACSL3), a key protein in lipid metabolism. Furthermore, attenuating ACSL3 in vivo through pharmaceutical approach and in vitro via RNA interference mitigated the anti‐ferroptotic effect of ANKRD1 knockdown. Finally, we showed ANKRD1 facilitated post‐translational degradation of ACSL3 by modulating E3 ligase tripartite motif containing 25 (TRIM25) to catalyse K63‐linked ubiquitination of ACSL3, thereby amplifying lipid peroxidation and ferroptosis, exacerbating renal injury.

Conclusions

Our study revealed a previously unknown function of ANKRD1 in renal IRI. By driving ACSL3 ubiquitination and degradation, ANKRD1 aggravates ferroptosis and ultimately exacerbates IRI‐AKI, underlining ANKRD1's potential as a therapeutic target for kidney IRI.

Key Points/Highlights

Ankyrin repeat domain 1 (ANKRD1) is rapidly activated in renal ischaemia‒reperfusion injury (IRI) models in vivo and in vitro.

ANKRD1 knockdown mitigates kidney damage and preserves renal function.

Ferroptosis contributes to the deteriorating function of ANKRD1 in renal IRI.

ANKRD1 promotes acyl‐coenzyme A synthetase long‐chain family member 3 (ACSL3) degradation via the ubiquitin‒proteasome pathway.

The E3 ligase tripartite motif containing 25 (TRIM25) is responsible for ANKRD1‐mediated ubiquitination of ACSL3.
When Oxybutynin Becomes a Decoy for Oxycodone: A Case Report of Diversion Through Substitution
Authors: Verdiner Ricardo E. , Voils Alissa , Seim Lynsey , Koball Krystal , Verdiner Maxwell , Mardian Aram , Milam Adam J.
Published: September 2024

This case report describes the novel use of oxybutynin and acetaminophen as a substitution for oxycodone for the express purpose of diverting oxycodone in a hospital‐based post‐anesthesia care unit (PACU). The report outlines how the physical properties and pharmacologic effects of non‐controlled medications in the PACU, like oxybutynin, can be visually mistaken and even mimic the side effects of controlled substances like oxycodone. Substituting oxybutynin for controlled substances can circumvent diversion surveillance software. The authors describe how the diversion was identified and the process improvements that should be implemented for proactive identification moving forward.
Beta diversity subcomponents of plant species turnover and nestedness reveal drivers of community assembly in a regenerating subtropical forest
Authors: Guclu Coskun , Luk Chung‐Lim , Ashton Louise Amy , Abbas Sawaid , Boyle Michael J. W.
Published: September 2024

Secondary forests represent a significant proportion of global forest cover, with over 70% of forests in East Asia classified as regenerating. While succession has been studied extensively in temperate systems, trajectories of subtropical succession remain poorly characterized in highly disturbed, urban‐adjacent forests. Investigating the additive beta diversity components of turnover and nestedness may reveal community assembly mechanisms driving secondary succession. The present study investigates plant community assembly along a successional gradient from 7 to 70 years following the onset of succession in secondary subtropical forests in Hong Kong, China. Plant survey data for 28 plots were analysed, generating additive Simpsons turnover and nestedness beta diversity metrics. Dissimilarity matrices were generated and modelled as a function of environmental matrices including forest plant community age (years following onset of secondary succession), inter‐community distance (metres), and soil moisture saturation (%) across three elevational bands using generalized dissimilarity models. Nonmetric multidimensional scaling of plant communities was conducted with Bray–Curtis dissimilarity matrices. Inter‐community distance and successional age differentially influenced plant species turnover between lowland and Montane forest types. Models of nestedness found that plot age and soil moisture saturation were significant drivers of nestedness patterns in plant communities across elevational classes. Turnover represented a higher proportion of Sorensen beta diversity than nestedness, while ANOSIM found significant differentiation between plant communities at different successional stages. Turnover patterns suggest a deterministic model of community assembly, with strong patterns of species replacement between communities at fine spatial scales and successional stages, as well as clear compositional shifts between lowland and montane forest types. NMDS analysis and functional compositional assessments suggested a transition from early successional communities with a high proportion of shrub species, to later successional communities with a higher proportion of tree species, with an increase in species turnover with greater age dissimilarity.
Frailty in heart failure according to the presence or absence of wild‐type transthyretin cardiac amyloidosis
Authors: Broussier Amaury , Paugam Marie , Liu Nina , Oghina Silvia , Kharoubi Mounira , Lafont Charlotte , Zaroui Amira , Galat Arnault , Hittinger Luc , Teiger Emmanuel , David Jean Philippe , Bastuji‐Garin Sylvie , Damy Thibaud
Published: September 2024

Aims

Wild‐type transthyretin cardiac amyloidosis (ATTRwt CA) is a common, underdiagnosed cause of heart failure (HF) in the elderly. Concurrent extracardiac amyloid infiltration might be responsible for a specific frailty phenotype. This study aims to compare the prevalence and characteristics of frailty parameters in HF patients, with or without ATTRwt CA.

Methods

In a comparative cross‐sectional study, we prospectively included consecutive HF patients with or without ATTRwt CA (the HF + ATTRwt+ and HF + ATTRwt− groups, respectively) between April 2018 and April 2021. Logistic regression models were used to compare the groups with regard to frailty as assessed using multidimensional geriatric tools.

Results

We included 123 patients (68 HF + ATTRwt+ and 55 HF + ATTRwt−). The mean age was 80.9 (standard deviation 6.3) years, 87% were male, 34% had left ventricular systolic dysfunction and 34% were New York Heart Association (NYHA) III. Relative to the HF + ATTRwt− group, patients in the HF + ATTRwt+ group were more likely to have shrinking [odds ratios = 2.9 (95% confidence interval, 1.1 to 1.7), P = 0.03], balance disorders [1.8 (1.1 to 2.8), P = 0.02], memory complaints [2.5, (1.0 to 5.9), P = 0.05] and overactive bladder [1.5 (1.1 to 2.2), P = 0.03], independently of age, sex, NYHA class and diabetes status. The proportion of very frail patients was higher (albeit not significantly) in the HF + ATTRwt+ group than in the HF + ATTRwt− group [2.4 (0.9 to 6.9), P = 0.10].

Conclusions

ATTRwt CA is associated with a specific frailty phenotype. Patients with ATTRwt CA should be screened for frailty and managed collaboratively by cardiologists and geriatricians, with a view to improving quality of life.
Relationship between waist‐to‐height ratio and heart failure outcome: A single‐centre prospective cohort study
Authors: Wang Ping , Zhao Yang , Wang Danni , Wang Boxiang , Liu Hange , Fu Guotao , Tao Ling , Tian Gang
Published: September 2024

Aims

This study sought to evaluate the correlation between waist‐to‐height ratio (WHtR) and heart failure (HF) outcomes across different ejection fraction (EF) categories.

Methods and results

A prospective cohort study was conducted at a comprehensive tertiary hospital in China. The participants were categorized by WHtR and EF quartiles. Outpatient or telephone follow‐up occurred every 6 months after the diagnosis of heart failure. The primary endpoint was all‐cause mortality at 48 months. Cox proportional hazard regression analyses were employed to evaluate the association between WHtR and all‐cause mortality. Among 859 enrolled participants, 545 (63.4%) were male, and the mean age was 65.2 ± 11.1 years. After adjusting for age and sex, WHtR demonstrated a strong correlation with both BMI (correlation = 0.703, P = 0.000) and WHR (correlation = 0.609, P = 0.000). Individuals with a high WHtR (≥0.50) had a higher prevalence of hypertension (56.4% vs. 39.6%) and diabetes (26.5% vs. 13.7%), higher levels of TC (3.61 ± 1.55 vs. 3.36 ± 0.90 mmol/L), TG (1.40 ± 0.81 vs. 1.06 ± 0.59 mmol/L), and LDL‐C (2.03 ± 0.85 vs. 1.86 ± 0.76 mmol/L) compared with patients with low WHtR (<0.50). NT‐proBNP levels were inversely correlated with EF values in both low and high WHtR groups. A total of 149 (18.9%) patients died at the conclusion of the follow‐up period. The incidence of all‐cause and cardiovascular death was higher in the low WHtR group compared with the high WHtR group [HRs = 1.83 (1.30–2.58), 1.96 (1.34–2.88), respectively]. There was no significant difference in noncardiovascular mortality or rehospitalization rates between the two groups. Patients with HFrEF/low WHtR exhibited a markedly elevated risk of all‐cause mortality [HR = 2.31; (95% CI: 1.24–4.30)], heart failure mortality [HR = 3.52; (95% CI: 2.92–8.80)], and noncardiovascular mortality [HR = 4.59; (95% CI: 1.19–17.76)] compared with patients with HFrEF/high WHtR. WHtR has a negligible effect on the risk of all‐cause and cardiovascular mortality in heart failure patients with preserved EFs.

Conclusions

The obesity paradox, as delineated by WHtR, is observed in patients with HFrEF, yet absent in those with HFpEF.
Methanol‐Mediated One‐Pot Transformation of Benzonitriles to Five and Six‐Membered Heterocycles: Synthesis and Mechanistic Approach
Authors: Siakavaras Nikos , Kallitsakis Michael G. , Bakalbassis Evangelos G. , Sigalas Michael M. , Lykakis Ioannis N.
Published: September 2024

Herein we describe a facile methodology for the synthesis of heterocyclic molecules such as 2‐aryl‐substituted imidazolines, oxazolines and 1,4,5,6‐tetrahydropyrimidines, under one‐pot and metal‐free conditions. A series of electron‐poor substituted benzonitriles were used as starting materials with different available diamines and amino alcohols, producing the desired products in good to high yields within methanol and in the absence of catalyst or additives. This methodology can be easily scaled up to laboratory size of 3 mmol for both five‐ and six‐membered heterocycles. Detailed mechanistic and theoretical studies supported the dual role of methanolic media as solvent and as mediated agent. To shed light on the reaction mechanism, DFT mechanistic studies suggest a distinction in the first step, with the activation of the nitrile by methanol, and the formation of a benzimidamide and/or a benzimidate (observed by NMR) as intermediates. This facile synthetic procedure provides a green, metal‐free, and mild protocol for the synthesis of a series of imidazoline, oxazoline and tetrahydropyrimidine derivatives.
Visible‐Light‐Mediated Copper(I)‐Catalyzed Regiospecific Amino‐Hydroxylation and Amino‐Alkoxylation of Vinyl Arenes
Authors: Singh Baldau , Neeraj Brijbhushan Tiwari , Kumar Krishn , Pandey Piyush , Ganapathy Dhandapani
Published: September 2024

Aminohydroxylation of alkene is an important method for synthesizing 1,2‐amino alcohols, which are found in natural products, pharmaceutically active compounds, and several marketed drugs. Herein, we report the development of visible‐light mediated copper‐catalyzed aminohydroxylation and aminoalkoxylation of alkenes. In contrast to expensive iridium, ruthenium, or organic‐dyes‐based photocatalysts, this protocol takes advantage of economical copper phenanthroline complex as a photocatalyst for the generation of N‐centred radical from N‐amino pyridinium salt. Furthermore, this protocol features mild reaction conditions, a broad substrate scope, and regiospecific.
Engaging athletes as research participants. A document analysis of published sport science literature
Authors: Mitchell Lachlan , Ratcliff Josie , Burke Louise M. , Forsyth Adrienne
Published: September 2024

Sport science practitioners utilise findings from peer reviewed research to inform practice. Fewer studies are conducted with high performance athletes, however, than those involving recreationally active participants. Noting that research findings from recreational athletes may not be generalisable to the elite, there is a need to engage the latter cohort in research with better potential to influence health and performance. This study identified methods used to engage and recruit highly trained, elite and world class athletes as research participants. A document analysis was conducted using a purposive sample of peer‐reviewed sport science literature. All articles published in 2022 from 18 highly ranked sport science journals were screened for inclusion. Studies investigating athletes ranked as highly trained/national level or above were included. All details related to participant recruitment were extracted from included articles, with the content being coded and thematically analysed using an interpretivist approach. A total of 439 studies from the 2356 screened were included in the analysis. Five primary themes of recruitment strategies were identified, beneath an overarching strategy of purposeful, convenience sampling. Recruitment themes related to the use of a gatekeeper, the research environment providing convenient access to athletes, promoting the study electronically, utilising professional networks and recruiting at training or competition. Engaging athletes through a gatekeeper is a prominent strategy to involve elite athletes in research. It is suggested that researchers work collaboratively with team or organisation personnel to promote recruitment, creating co‐designed approaches that address issues most relevant to athletes and staff.
Charge variant analysis of monoclonal antibodies by CZE‐MS using a successive multiple ionic‐polymer layer coating based on diethylaminoethyl‐dextran
Authors: Höchsmann Alisa , Dhellemmes Laura , Leclercq Laurent , Cottet Hervé , Neusüß Christian
Published: September 2024

The characterization of the impurities of pharmaceutical monoclonal antibodies (mAbs) is crucial for their function and safety. Capillary zone electrophoresis (CZE) is one of the most efficient tools to separate charge variants of mAbs; however, peak characterization remains difficult, since the hereby used background electrolytes (BGEs) are not compatible with electrospray ionization‐mass spectrometry (ESI‐MS). Here, a method that allows the separation of intact mAb charge variants is presented using CZE‐ESI‐MS, combining a cationic capillary coating and an acidic BGE. Therefore, a successive multiple ionic‐polymer layer coating was developed based on diethylaminoethyl‐dextran–poly(sodium styrene sulfonate). This coating leads to a relatively low reversed electroosmotic flow (EOF) with an absolute mobility slightly higher than that of antibodies, enabling the separation of variants with slightly different mobilities. The potential of the coating is demonstrated using USP mAb003, where it was possible to separate C‐terminal lysine variants from the main form, as well as several acidic variants and monoglycosylated mAb forms. The presented CZE‐MS method can be applied to separate charge variants of a range of other antibodies such as infliximab, NISTmAB (Reference Material from the National Institute of Standards and Technology), adalimumab, and trastuzumab, demonstrating the general applicability for the separation of proteoforms of mAbs.
Electrophoresis of polyelectrolyte‐adsorbed soft particle with hydrophobic inner core
Authors: Mahata Asim , Pal Sanjib Kumar , Ohshima Hiroyuki , Gopmandal Partha P.
Published: September 2024

This article deals with the electrophoresis of hydrophobic colloids absorbed by a layer of polymers with an exponential distribution of the polymer segments. The functional groups present in the polymer layer further follow the exponential distribution. We made an extensive mathematical study of the electrophoresis of such core‐shell structured soft particles considering the combined impact of heterogeneity in polymer segment distribution, ion steric effect, and hydrodynamic slippage of the inner core. The mathematical model is based on the flat‐plate formalism and deduced numerical results for electrophoretic mobility are valid for weak to highly charged particles for which the particle size well exceeds the Debye‐layer thickness. In addition, we have derived closed form analytical results for electrophoretic mobility of the particle under several electrohydrodynamic limits. We have further illustrated the results for electrophoretic mobility considering a charged and hydrophobic inner core coated with an uncharged polymer layer or a polymer layer that entraps either positive or negatively charged functional groups. The impact of pertinent parameters on the overall electrophoretic motion is further illustrated.