bluuebunny/crossref_metadata_2025 huggingface dataset:
Knockdown of the ZcVgR Gene Alters the Expression of Genes Related to Reproduction and Lifespan in Zeugodacus cucurbitae (Coquillett) Under Extreme Heat Conditions
Authors: Lian Yuyang , Zhang Mengjie , Yang Shuyan , Peng Sihua , Wang Aqiang , Jia Jingjing , Feng Xuejie , Wu Qianxing , Yang Xiaofeng , Zhou Shihao
Published: December 2024

Zeugodacus cucurbitae (Coquillett) is an important migratory vegetable pest. Previous research has demonstrated that short‐term high temperatures induce differential expression of the vitellogenin receptor (ZcVgR) gene, reducing the number of eggs laid and the lifespan of female Z. cucurbitae. In this paper, we used Tandem Mass Tags (TMT) quantitative proteomics and Illumina high‐throughput sequencing to determine the proteomic and transcriptomic information of female Z. cucurbitae after siRNA‐mediated silencing of the target gene (ZcVgR) to gain a comprehensive understanding of the molecular mechanism of this gene in the regulation of reproduction and lifespan. The findings demonstrated that following the target gene's silencing, the ZcVgR gene's transcriptional expression was significantly downregulated, and there was no significant difference in protein level. The transcriptome and proteome had a low correlation; when the ZcVgR gene was silenced, vitellogenin‐1 (ZcVg1), juvenile hormone epoxide hydrolase (JHEH), troponin C (TnC), heat shock protein 70 (HSP70), and other related genes were downregulated at the transcriptional level. By silencing the ZcVgR gene, transcriptionally level immune‐related pathways were activated and energy metabolism‐related pathways were inhibited; protein‐level glycometabolism and phagosome pathways were activated, while phototransduction‐fly and autophagy‐animal pathways were inhibited. The findings of this study might offer a theoretical foundation for integrated management of Z. cucurbitae in the summertime.
Genetic Architecture of Idiopathic Inflammatory Myopathies From Meta‐Analyses
Authors: Zhu Catherine , Han Younghun , Byun Jinyoung , Xiao Xiangjun , Rothwell Simon , Miller Frederick W. , Lundberg Ingrid E. , Gregersen Peter K. , Vencovsky Jiri , Shaw Vikram R. , McHugh Neil , Limaye Vidya , Selva‐O'Callaghan Albert , Hanna Michael G. , Machado Pedro M. , Pachman Lauren M. , Reed Ann M. , Rider Lisa G. , Molberg Øyvind , Benveniste Olivier , Radstake Timothy , Doria Andrea , De Bleecker Jan L. , De Paepe Boel , Maurer Britta , Ollier William E. , Padyukov Leonid , Wedderburn Lucy R. , Chinoy Hector , Lamb Janine A. , Amos Christopher I. ,   for the Myositis Genetics Consortium
Published: December 2024

Objective

Idiopathic inflammatory myopathies (IIMs, myositis) are rare systemic autoimmune disorders that lead to muscle inflammation, weakness, and extramuscular manifestations, with a strong genetic component influencing disease development and progression. Previous genome‐wide association studies identified loci associated with IIMs. In this study, we imputed data from two prior genome‐wide myositis studies and analyzed the largest myositis data set to date to identify novel risk loci and susceptibility genes associated with IIMs and its clinical subtypes.

Methods

We performed association analyses on 14,903 individuals (3,206 patients and 11,697 controls) with genotypes and imputed data from the Trans‐Omics for Precision Medicine reference panel. Fine‐mapping and expression quantitative trait locus colocalization analyses in myositis‐relevant tissues indicated potential causal variants. Functional annotation and network analyses using the random walk with restart (RWR) algorithm explored underlying genetic networks and drug repurposing opportunities.

Results

Our analyses identified novel risk loci and susceptibility genes, such as FCRLA, NFKB1, IRF4, DCAKD, and ATXN2 in overall IIMs; NEMP2 in polymyositis; ACBC11 in dermatomyositis; and PSD3 in myositis with anti–histidyl–transfer RNA synthetase autoantibodies (anti–Jo‐1). We also characterized effects of HLA region variants and the role of C4. Colocalization analyses suggested putative causal variants in DCAKD in skin and muscle, HCP5 in lung, and IRF4 in Epstein‐Barr virus (EBV)‐transformed lymphocytes, lung, and whole blood. RWR further prioritized additional candidate genes, including APP, CD74, CIITA, NR1H4, and TXNIP, for future investigation.

Conclusion

Our study uncovers novel genetic regions contributing to IIMs, advancing our understanding of myositis pathogenesis and offering new insights for future research.
Ultrashort Peptide Hydrogels Biomaterials with Potent Antibacterial Activity
Authors: Pramanik Bapan , Mukherjee Payel , Ahmed Sahnawaz
Published: December 2024

For the past few decades, ultrashort peptide hydrogels have been at the forefront of biomaterials due to their unique properties like biocompatibility, tunable mechanical properties, and potent antibacterial activity. These ultrashort peptides self‐assemble into a hydrogel matrix with nanofibrous networks. In this minireview, we have explored the design and self‐assembly of these ultrashort peptide hydrogels by focusing on their antibacterial properties. Cationic and hydrophobic residues are incorporated to engineer the peptides, facilitating interaction with bacterial membranes and leading to membrane disruption and cell death. The hydrogels exhibit broad‐spectrum antibacterial activity against both Gram‐positive and Gram‐negative bacteria. Overall, this minireview highlights the potential of ultrashort peptide hydrogels as versatile and practical antibacterial biomaterials, providing a novel approach to combating bacterial infections and addressing the growing challenge of antibiotic resistance.
Accretion Onto Weakly Magnetized Neutron Stars: Polarization Theory and Its Application to X‐Ray Burster GX 13+1
Authors: Bobrikova Anna , Forsblom Sofia V.
Published: December 2024

Observations show that the x‐ray emission of the accreting weakly magnetized neutron stars (WMNSs) is polarized. In this article, we summarize the analytical models for the polarized emission of various components of the WMNSs. We introduce a missing theoretical model, where we assume the emission comes from the spreading layer, the extension of the boundary layer between the accretion disk and the neutron star. We show how these models and the results of the simulations provide new insights into the x‐ray polarization from weakly magnetized neutron stars observed with the imaging x‐ray polarimetry explorer (IXPE). We specifically focus on the most peculiar case of the X‐ray burster GX 13+1.
Toward improved understanding and treatment of self‐injurious behaviors in autistic individuals with profound intellectual disability
Authors: Ferguson Emily F. , Russell Kaylin M. , Licona Sarely J. , Cai Ru Ying , Frazier Thomas W. , Vivanti Giacomo , Gengoux Grace W. , Hardan Antonio Y. , Uljarević Mirko
Published: December 2024

Self‐injurious behaviors (SIB) commonly occur in autism spectrum disorder (ASD) and span diverse topographies of self‐inflicted behaviors ranging from head banging to hitting oneself against hard objects. Despite the high rates of SIB in autistic individuals, relatively little research has focused on psychological factors associated with the development and maintenance of SIB in individuals with autism and moderate‐profound intellectual disability (ID). This commentary synthesizes existing literature on SIB and highlights the need for more research focused on psychological correlates and mechanisms in autistic individuals with moderate‐profound ID. We highlight the key role of difficulties in emotion regulation (ER) and co‐occurring internalizing symptoms in the manifestation of self‐harm behaviors in clinical samples and autism. Furthermore, this commentary proposes a framework for understanding the interplay between poor ER and internalizing symptoms in the development and maintenance of SIB in autistic individuals with moderate‐profound ID. Specifically, we explore the emergence of SIB in the context of precipitating cues that trigger strong emotions, ER processes and strategy deployment, and co‐occurring internalizing symptoms. Future directions and implications for longitudinal research, measurement development, and clinical treatments are discussed.
Perspective on Death: A Gateway to a New Biology
Authors: Noble Peter A. , Pozhitkov Alexander
Published: December 2024

Organismal death has long been considered the irreversible ending of an organism's integrated functioning as a whole. However, the persistence of functionality in organs, tissues, and cells postmortem, as seen in organ donation, raises questions about the mechanisms underlying this resilience. Recent research reveals that various factors, such as environmental conditions, metabolic activity, and inherent survival mechanisms, influence postmortem cellular functionality and transformation. These findings challenge our understanding of life and death, highlighting the potential for certain cells to grow and form new multicellular entities. This opens new avenues in biology and medicine, expanding our comprehension of life's complexity.
MnCo2O4 Nanostructure Anchored on Functionalized Carbon Black for the Enhanced Bifunctional Electrocatalytic Performance of OER and HER
Authors: Chandrasekaran Sharmila , Vignesh Shanmugam , Al‐Sadoon Mohammad Khalid , Mythili Raja , Alagumalai Krishnapandi , Arumugam Elangovan
Published: December 2024

The electrocatalytic oxygen and hydrogen evolution reactions (OER and HER) are key processes used in energy storage and conversion. We have developed a highly efficient MnCo2O4 nanostructure anchored with functionalized carbon black (MnCo2O4/f‐CB), which has been characterized by XRD, FT‐IR, Raman spectra, FE‐SEM, and HR‐TEM analyses as robust bifunctional electrocatalysts for both HER and OER. At a characteristic 10 mA cm−2 current density, the MnCo2O4/f‐CB composite ECs exhibit low overpotentials of 330 mV for OER and 360 mV for HER, respectively. Furthermore, the MnCo2O4/f‐CB composite ECs exhibit superior current density, the shortest Tafel slope, and admirable durable stability in OER and HER together. Due to the supported f‐CB, the MnCo2O4 composite catalyst has more active sites, effective charge transfer, and longer durability. A high‐efficiency dual electrocatalyst can be developed from these highly efficient and dual ECs, which are comparable to standard noble metal–based catalysts. The synergetic coupling effects of high‐activity f‐CB and MnCo2O4 composites with appropriate morphologies are critical factors for the enhanced catalytic performances of the MnCo2O4/f‐CB composite.
Tailoring Gelatin Films: Functionality, Stability, and Beyond Biodegradability
Authors: Bhardwaj Nikita , Ashraf Mohd. Tashfeen , Maitra Jaya
Published: December 2024

This study investigates the enhancement of biodegradable gelatin films through the incorporation of glycerol as a plasticizer, and citric acid and zinc oxide as cross‐linkers. The results showed notable improvements in various properties, including solubility, swelling behavior, thickness, pH, biodegradability, and both mechanical and thermal characteristics. The films demonstrated complete water solubility and UV–visible light absorbance in the 280–480 nm range. Soil burial tests indicated gradual weight loss over 15 days, leading to complete degradation. Structural and thermal analyses via FTIR and TGA confirmed the films' integrity and stability. Additionally, the study highlighted the effectiveness of these modified films in adsorbing copper (II) ions from acidic solutions, showcasing their potential for environmental applications like heavy metal remediation. These findings emphasize the potential of tailored additive combinations to produce biodegradable films with enhanced properties and functionality.
An Additive‐Fabricated Biphasic Scaffold for Procedurally Promoting Bone Regeneration via Antioxidant and Osteogenesis
Authors: Han Chunyu , Wu Zhenxu , Gao Yuqi , Yang Shuang , Wang Yu , Guo Min , Li Yueyue , Yin Wanzhong , Liu Ling , Song Wenzhi , Zhang Peibiao , Wang Liqiang
Published: December 2024

The repair process of bone tissue includes the early inflammatory response period and the late tissue repair period. It has been widely approved to be beneficial to the repair of bone injury by procedurally inhibiting the inflammatory response in the early stage and promoting bone regeneration in the late stage. In this study, the nano‐hydroxyapatite/Poly(glycolide‐co‐caprolactone) (n‐HA/PGCL) scaffold loaded with icariin was fabricated by fused deposition modeling technique, and the quercetin‐loaded GelMA was further filled into the scaffold pores via light‐curing methods to form a biphasic scaffold loaded with dual molecules (PHI + GQ scaffold). The releases of icariin and quercetin were sequential due to different degradation rates of GelMA and PGCL. In vitro, the scaffold not only scavenged reactive oxygen species production, but also promoted osteogenic differentiation of the MC‐3T3‐E1 cells. Furthermore, in vivo bone reconstruction of PHI + GQ scaffold was better than other groups by assessment of micro‐CT data. In addition, the immunofluorescence staining of Arg‐1 and iNOS indicated that PHI + GQ scaffold created an immune microenvironment conducive to bone repair due to the release of quercetin in the early stage, and HE and Masson staining suggested that PHI + GQ scaffold induced more new bone formation. These results demonstrated that the biphasic scaffold loaded with icariin and quercetin had both antioxidants in the early stage and osteogenesis properties in the late stage, obtaining satisfactory bone repair outcomes. Thus, the biphasic scaffold loaded with icariin and quercetin for sequential release could provide a promising solution for the restoration of bone defects and represent a potential strategy for bone regeneration.
Identification of Barriers and Driving Forces for Circular Economy (CE) Implementation in Water and Wastewater Companies
Authors: Smol Marzena , Szołdrowska Dominika , Duda Joanna
Published: December 2024

Water and wastewater management sector is one of the basic areas of implementing a circular economy (CE). Enterprises operating in this sector are mainly wastewater treatment plants (WWTPs) managed by municipalities or private companies. They encounter various barriers and facilitators to implement CE, in the area of technology development and management. However, a limited number of works in the available literature focus on nontechnological aspects of implementing CE in WWTPs. Therefore, this paper presents a comprehensive analysis of challenges (including driving forces and barriers) for WWTPs in the process of implementing CE policy goals. The PESTEL strategic analysis method was used, taking into account the identification of political, economic, social, technological, environmental, and legal factors. It was confirmed that there are more incentives than barriers to actively implementing CE model in analyzed enterprises. The most important driving forces include: (i) favorable European CE policy, as recommendations and law regulations in the area of water, raw materials, and energy recovery; (ii) society's pressure on resource protection; (iii) possible revenues from the sale of recovered water, energy or CE‐fertilizers; (iv) financial support for CE solutions. Among defined barriers that could slow down the circular transformation, the most important are: (i) lack of clearly stated regulations regarding water, energy, and raw materials recovery, as well as transparency and regulatory risk; (ii) limited own financial resources of WWTPs operators; (iii) high cost of investments and maintaining recovery/recycling technologies. Those results may be of key importance to practitioners in strategic decision making for the improved application of circularity in the operating process. Because the implementation of CE solutions should have an integrated approach throughout the enterprise, it is recommended to develop circular business models for these companies, that would take into account both the core business (water and wastewater management) as well as possibilities of further CE implementation, such as recovery of water, energy, and raw materials. In the coming years, such solutions could be financially supported by the national and European sources, which may have a positive impact on the acceleration to the CE model.
Bawei Chenxiang Powder Protects Cardiomyocytes From Myocardial Ischemia/Reperfusion Injury via the PI3K–AKT Pathway
Authors: Gong Baihui , Zhang Xingfang , Yue Dongfang , Ma Chunxiu , Kou Yiying , Li Yongfang
Published: December 2024

Ischemia–reperfusion damage to cardiomyocytes is one of the main directions of cardiovascular disease research, and Bawei Chenxiang powder (BWCX) is a traditional ethnomedicinal compound preparation mainly used in the treatment of cardiovascular diseases. On the basis of serum pharmacology, the present study aimed to explore the potential mechanism of BWCX against myocardial ischemia–reperfusion damage to cardiomyocytes. We prepared BWCX‐serum containing. Using serum pharmacology and bioinformatics approaches, we explored its protective effects on H9C2 cells in a hypoxia/reoxygenation (H/R) model. Additionally, we investigated the underlying mechanisms. BWCX‐containing serum can increase the survival rate of H9C2 cells and reduce oxidative stress levels in an H/R model. Specifically, it decreases the release of malondialdehyde (MDA), lactate dehydrogenase (LDH), creatine kinase (CK), and reactive oxygen species (ROS), while increasing the levels of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH‐PX), and Complex I. Additionally, it downregulates the expression of NADH dehydrogenase (ubiquinone) 1 alpha sub‐Complex 10 (NDUFA‐10), thioredoxin (Trx), heme oxygenase 1 (HO‐1), and kelch‐like ECH‐associated protein 1 (Keap1), and it upregulates the expression of nuclear factor erythroid 2–related factor 2 (Nrf2). These effects are potentially mediated through the PI3K–AKT pathway. In the present study, we found that BWCX powder exhibited significant ameliorative and reparative effects on H/R‐induced cardiomyocyte injury by alleviating the level of oxidative stress during H/R and acting on the PI3K–AKT pathway.
Evaluating the Antimalarial Potential of d‐α‐Tocopherol Polyethylene Glycol 1000 Succinate and α‐Tocopherol, In Vivo Studies in Plasmodium berghei‐Infected Mice and Molecular Docking Insights
Authors: dos Santos Guimarães Mariana , Varela Everton Luiz Pompeu , Quadros Gomes Antônio Rafael , de Carvalho Eliete Pereira , Ferreira Oberdan Oliveira , Horchani Mabrouk , Edziri Hayet , Andrade Eloisa Helena de Aguiar , de Oliveira Mozaniel Santana , Percário Sandro
Published: December 2024

Oxidative stress is a pivotal factor in the pathogenesis of malaria, contributing to the development of conditions such as anemia, respiratory complications, and cerebral malaria. To counteract oxidative damage, we evaluated the effects of vitamin E (α‐TOH) and d‐α‐tocopherol polyethylene glycol 1000 succinate (TPGS) supplementation on parasitemia progression, mortality rate, and blood‐brain barrier (BBB) permeability in Plasmodium berghei ANKA‐infected mice. The mice were divided into four groups: a control group (untreated and uninfected), an infected group (Pb), a TPGS + Pb group, and an α‐TOH + Pb group. The results demonstrated that TPGS was more effective than α‐TOH, exhibiting a lower parasitemia (9.59%) and mortality (40%) by Day 12 and superior BBB protection in advanced infection stages. These findings suggest that TPGS may represent a promising therapeutic strategy for the management of malaria. Molecular docking analysis indicated that TPGS exhibited the highest binding affinity with plasmepsin 2 (−7.3 kcal/mol), whereas vitamin E demonstrated the strongest binding with plasmepsin 1 (−7.2 kcal/mol).
Detecting the Undetectable: Advances in Methods for Identifying Small Tau Aggregates in Neurodegenerative Diseases
Authors: Böken Dorothea , Wu Yunzhao , Zhang Ziwei , Klenerman David
Published: December 2024

Tau, a microtubule‐associated protein, plays a critical role in maintaining neuronal structure and function. However, in neurodegenerative diseases such as Alzheimer's disease and other tauopathies, tau misfolds and aggregates into oligomers and fibrils, leading to neuronal damage. Tau oligomers are increasingly recognised as the most neurotoxic species, inducing synaptic dysfunction and contributing to disease progression. Detecting these early‐stage aggregates is challenging due to their low concentration and high heterogeneity in biological samples. Traditional methods such as immunostaining and enzyme‐linked immunosorbent assay (ELISA) lack the sensitivity and specificity to reliably detect small tau aggregates. Advanced single‐molecule approaches, including single‐molecule fluorescence resonance energy transfer (smFRET) and single‐molecule pull‐down (SiMPull), offer improved sensitivity for studying tau aggregation at the molecular level. These emerging tools provide critical insights into tau pathology, enabling earlier detection and characterisation of disease‐relevant aggregates, thereby offering potential for the development of targeted therapies and diagnostic approaches for tauopathies.
Vanadium Complexes for Mitochondria‐Targeted Photodynamic Therapy
Authors: Raza Md Kausar , Kumar Arun
Published: December 2024

Metal‐based drugs have the potential to significantly improve therapeutic efficacy by exhibiting key properties such as appropriate charge, thermodynamic stability, hydrolytic stability, oral bioavailability, and dual functional capability. These properties are critical for effective intracellular uptake, as drugs or prodrugs must cross cellular membranes to target specific organelles like mitochondria, essential for maximizing therapeutic impact. Bio‐essential metal ions such as copper, zinc, and iron are transported through specialized active channels, whereas others depend on passive diffusion to enter cells. Vanadium has gained significant attention in research because of its remarkable coordination flexibility, lipid‐lowering characteristics, and potential anticancer effects. The coordination flexibility of vanadium has led to its investigation in pharmaceuticals, given its demonstrated insulin‐mimetic effects, lipid‐lowering properties, and promising antitumor activities. Photodynamic therapy (PDT) offers a targeted cancer treatment approach through light‐activated compounds that selectively generate reactive oxygen species (ROS) to induce cell death. Among metal‐based photosensitizers, vanadium complexes are emerging as effective agents due to their unique redox properties and known biological activity. This minireview explores mitochondria‐targeting vanadium complexes within PDT. Mitochondria serve as an ideal ROS generation site, triggering apoptosis while minimizing damage to healthy cells. We examine key strategies in designing vanadium complexes that enhance mitochondrial localization, photodynamic efficiency, and cytotoxic effects on cancer cells. This review highlights the challenges like photostability and selective targeting, and future directions for advancing vanadium‐based photosensitizers as next‐generation PDT cancer therapies.
Proton Occupancies in Histidine Side Chains of Carbonic Anhydrase II by Neutron Crystallography and NMR – Differences, Similarities and Opportunities
Authors: Zoë Fisher Suzanne , Raum Heiner N. , Weininger Ulrich
Published: December 2024

Histidine is a key amino‐acid residues in proteins that can exist in three different protonation states: two different neutral tautomeric forms and a protonated, positively charged one. It can act as both donor and acceptor of hydrogen bonds, coordinate metal ions, and engage in acid/base catalysis. Human Carbonic Anhydrase II (HCA II) is a pivotal enzyme catalyzing the reversible hydration of carbon dioxide. It contains 12 histidine residues: six are surface exposed, two buried, three are active site zinc ion ligands, and one is a proton shuttle. Comparing results from NMR spectroscopy with previously determined neutron protein crystal structures enabled a side‐by‐side investigation of the proton occupancies and preferred tautomeric states of the histidine residues in HCA II. Buried and zinc coordinating histidines remain in one neutral tautomeric state across the entire pH range studied, as validated by both methods. In contrast, solvent‐exposed histidines display high variability in proton occupancies. While the data were overall remarkably consistent between methods, some discrepancies were observed, shedding light on the limitations of each technique. Therefore, combining these methods with full awareness of the advantages and drawbacks of each, provides insights into the dynamic protonation landscape of HCA II histidines, crucial for elucidating enzyme catalytic mechanisms.
Impact of Mild Hypothermia As Adjunctive Therapy in Patients With ST‐Elevation Myocardial Infarction: A Meta‐Analysis and Trial Sequential Analysis of Randomized Controlled Trials
Authors: Laborante Renzo , Paglianiti Donato Antonio , Galli Mattia , Patti Giuseppe , D'Amario Domenico
Published: December 2024

Background

The prevention of reperfusion injury remains an unmet need in ST‐elevation myocardial infarction (STEMI) patients. Several randomized controlled trials (RCTs) evaluated mild hypothermia as adjunctive therapy during STEMI, with conflicting results.

Aims

To summarize the evidence about the efficacy and safety of mild hypothermia in patients with STEMI, as well as its conclusiveness through a trial sequential analysis (TSA).

Methods

PubMed and Scopus electronic databases were screened for eligible studies until August 12, 2024. Efficacy endpoints were all‐cause death, infarct size (IS), left ventricular ejection fraction (LVEF), the occurrence of microvascular obstruction (MVO), thrombolysis in myocardial infarction (TIMI) flow grade 3, and the resolution of ST‐segment elevation (i.e., > 50−70% from baseline) after the procedure. Safety endpoints included: the incidence of atrial fibrillation (AF), infections, any bleeding, major bleeding, acute and subacute stent thrombosis (STh), cardiogenic shock/pulmonary oedema, and ventricular fibrillation/tachycardia. “Door‐to‐balloon time” was indicated as the procedural endpoint. Two pre‐specified subgroup analyses were planned according to the mean ischemic time and the site of hypothermia induction (intra‐coronary vs. extra‐coronary). A TSA was run to explore whether the effect estimate of each efficacy outcome could be influenced by further studies.

Results

Ten RCTs were included. Hypothermia did not provide a benefit for any of the specified efficacy endpoints. Furthermore, it enhanced the risk of infection, the risk of STh in patients with a mean ischemic time of less than 4 h, and the risk of AF in patients undergoing extra‐coronary hypothermia. Finally, it was also associated with an increased “door‐to‐balloon time”, and a trend toward an increased risk of any bleeding. No significant difference was found for the other endpoints. TSA showed conclusive evidence of an absence of benefit of hypothermia on IS, MVO, LVEF, and TIMI three flow.

Conclusions

Mild hypothermia is not beneficial and causes relevant delays in clinical management of STEMI patients, raising safety issues mainly related to the occurrence of STh, AF, and infections.
Graphene Acid: A Potent Carbocatalyst for the Friedel–Crafts Arylation of Aldehydes with Indoles
Authors: Galathri Eirini M. , Hrubý Vítězslav , Mountanea Olga G. , Mantzourani Christiana , Chronopoulos Demetrios D. , Otyepka Michal , Kokotos Christoforos G.
Published: December 2024

Carbocatalysis represents a highly attractive and effective field within the realm of metal‐free nanocatalysis, significantly advancing sustainability in synthetic chemistry. Graphene acid (GA) emerges as a well‐defined graphene derivative, characterized by a high density of homogeneously distributed carboxylic groups over graphene lattice. This unique and uniform structure positions GA as an elegant alternative to other 2D carbocatalysts, namely graphene oxide. GA was successfully employed as the catalyst in a Friedel–Crafts‐type reaction between indoles and aldehydes, facilitating the synthesis of bis(indolyl)methanes, organic compounds exhibiting interesting biological properties and significant pharmaceutical potential. The metal‐free nature of GA, combined with the performance of the reaction “on water” under mild conditions, highlight the green credentials of the developed protocol. Comprehensive substrate screening, including a plethora of aliphatic or aromatic aldehydes and various 1‐ or 2‐substituted indoles, resulted in moderate to high yields of variously functionalized bis(indolyl)methanes. Mechanistic and recovering studies showed that GA acts catalytically as a Brønsted acid, maintaining its catalytic activity at a high rate for six subsequent cycles.
Fisetin as a Blueprint for Senotherapeutic Agents — Elucidating Geroprotective and Senolytic Properties with Molecular Modeling
Authors: Spiegel Maciej
Published: December 2024

Targeting senescent cells and the factors that accelerate this pathological state has recently emerged as a novel field in medicinal chemistry. As attention shifts to synthetic substances, studies on natural agents are often overlooked. In this paper, we present a detailed computational modeling study that encompasses quantum mechanics and molecular dynamics to elucidate the senotherapeutic activity of fisetin. The mitochondrial environment, serving as a proxy for senescence, received special attention. Throughout the study, fisetin’s outstanding geroprotective properties—exhibiting significant potential against •OOH, O2•–, and •OH radicals, surpassing those of Trolox or ascorbate—were identified. Furthermore, fisetin demonstrated a high capacity to restore oxidatively damaged biomolecules to their pristine forms, thereby renewing the functionality of proteins and amino acids. The senolytic properties were examined in terms of Bcl–2 and Bcl–xL inhibition. The results indicated that fisetin not only binds effectively to these proteins but also, with appropriate modifications, may exhibit specific selectivity toward either target. This study highlights fisetin’s remarkable activity in these areas and provides a molecular description of the underlying processes, paving the way for future research.
Structural Characteristics of a Partially Planarized Triarylmethyl Cation with Unsymmetrical Push–Pull Structure
Authors: Ito Masato , Endoh Naoki , Kyoya Moe , Shimajiri Takuya , Kubo Yuji
Published: December 2024

We report the physical properties of a new class of triarylmethyl‐based carbocations containing both an electron‐donating diphenyl ether moiety and an electron‐accepting carbonyl group with a helical plane framework. Their unique packing patterns were clarified by X‐ray crystallographic analysis, which depend on the counter anions to influence their photophysical properties in the solid states. Notably, the interactions between π‐cation species and planar anion species lead to a unique panchromatic property, accompanying a near‐infrared absorption with a λonset value of 1030 nm, which can be assigned to intermolecular charge transfer transition. We found that the π‐cation species with planar anion formed cation dimers, being stacked in opposite directions. The two cation molecules are flanked by two anions on both the top and bottom side. Pair interaction energy decomposition analysis (PIEDA) calculations imply that the origins of the unique packing patterns of the π‐cations originate from the electrostatic forces of four neighbouring π‐anion species.
Defluorinative Diazolation‐Cyclization Relay for Synthesis of Furan‐Bridged Triheterocycles and Colorimetric Sensor Application
Authors: Feng Man‐Hang , Chen Da‐Qing , Gao Shu‐Ji , Ge Danhua , Chen Xiaojun , Ma Mengtao , Shen Zhi‐Liang , Chu Xue‐Qiang
Published: December 2024

Polyaromatics, as the assembly of diverse cyclic π‐systems, exhibit unique physicochemical properties when compared to their individual constituents. In this study, we developed a strategic connection of two azacycles via a furan bridge through a defluorinative diazolation‐cyclization reaction of trifluoromethyl enones and N‐heterocycles. A range of modular 2,4‐furan‐bridged triheterocycles (FBTHs), featuring a C3‐trifluoromethyl group, was synthesized with broad substrate scope and good regioselectivity under transition metal‐free conditions. This three‐component protocol was achieved through successive C(sp3)‐F bond functionalization of one trifluoromethyl group, which is recognized for its stability and durability. Moreover, the synthetically useful functionalities such as bromide and formyl group could be easily installed on the resulting products, and the imidazole‐containing FBTH could serve as a valuable ligand in the preparation of an advanced colorimetric sensor, thereby underscoring their potential applications.
Health‐Risk Assessment of Groundwater Arsenic Levels in Bhagalpur, India, and Development of a Cost‐Effective Paper‐Based Arsenic Testing‐Kit
Authors: Maity Sourav , Dokania Puja , Goenka Manav , Patil Pritam Bajirao , Sarkar Angana
Published: December 2024

Arsenic is considered one of the most hazardous trace metals in groundwater researched to date because of the hazardous impacts like cancer, skin irritation, and other skin‐related diseases. The present study involved collecting 60 water samples from Bhagalpur district, Bihar, India, to estimate the arsenic concentration. The human health risk assessment of the samples concerning children and adults was also performed, and the maximum concentration of arsenic was found to be relatively high in some sample sites. Prolonged exposure to arsenic could be fatal to the local population. The current study also focuses on developing a low‐cost paper‐based arsenic detection kit. The paper‐based test kit was tested for parameters like color development for different forms and concentrations of arsenic, storage conditions for the test strips, the effect of different interfering agents on color development, and optimization of the AgNO3 solution. The cost analysis was carried out, and it was found that the kit would cost 0.046 USD per sample, which is 70–100 times lower than the cost of current methods.
Investigating the C2 Modulation of the Imidazo[1,2‐a]pyrazine‐Based Hit Compound CTN1122: Synthesis, in vitro Antileishmanial Activity, Cytotoxicity and Casein Kinase 1 Inhibition
Authors: Tisseur Lhana , Cojean Sandrine , Gassama Khadidiatou , Logé Cédric , Pagniez Fabrice , Cavé Christian , Bernadat Guillaume , Loiseau Philippe M. , Bach Stéphane , Thiéfaine Jérôme , Picot Carine , Tomasoni Christophe , Leclercq Olivier , Baratte Blandine , Robert Thomas , Le Pape Patrice , Rachidi Najma , Bazin Marc‐Antoine , Marchand Pascal
Published: December 2024

Our research group previously discovered CTN1122, an imidazo[1,2‐a]pyrazine compound with promising antileishmanial activity against intramacrophage amastigotes of Leishmania major and L. donovani strains. CTN1122 effectively targets Leishmania casein kinase 1 (L–CK1.2) and exhibits a favorable safety profile. To further explore its chemical space, we developed a convergent strategy to modify the C2 position of the imidazo[1,2‐a]pyrazine core using Suzuki‐Miyaura coupling of the corresponding triflate intermediate. Among 15 newly synthesized analogs, seven derivatives featuring variously substituted phenyl rings at C2 demonstrated L–CK1.2 inhibition within micromolar to submicromolar ranges and antileishmanial activity in vitro with low cytotoxicity in macrophages. Compounds 7 d and 7 l were particularly potent, with IC50 values of 1.25 μM and 0.92 μM against L. major, and 1.44 μM and 2.34 μM against L. donovani, respectively. They showed IC50 L–CK1.2=0.30 μM and 0.57 μM with enhanced selectivity indices (SI=3.8 and 1.6) over the human CK1ϵ ortholog. Additionally, four C2 analogs and two C5 isomers exhibited notable antiparasitic effects without strongly inhibiting L–CK1.2, indicating a possible alternative mechanism of action. Compound 7 k displayed the highest general activity, with IC50 values of 0.31 μM on L. major and 0.27 μM on L. donovani, coupled with favorable selectivity indexes.
Clinical Actionability of the NUDT15 *4 (p.R139H) Allele and Its Association With Hispanic Ethnicity
Authors: Maillard Maud , Nguyen Jenny Q. , Yang Wenjian , Hoshitsuki Keito , Relling Mary V. , Caudle Kelly E. , Crews Kristine R. , Jeha Sima , Inaba Hiroto , Pui Ching‐Hon , Bhatia Smita , Karol Seth E. , Antillon‐Klussmann Federico G. , Haidar Cyrine E. , Bhojwani Deepa , Yang Jun J.
Published: December 2024

Nudix hydrolase 15 (NUDT15) deficiency is strongly associated with thiopurine‐induced myelosuppression. Currently, testing for NUDT15 deficiency is based on the genotyping of the most frequent and clinically characterized no‐function variants, that is, *2, *3 and *9. The Hispanic/Latino‐predominant variant NUDT15 *4 (p.R139H) is classified as “uncertain function” by the Clinical Pharmacogenetics Implementation Consortium, because of insufficient data to ascertain its clinical actionability. In this study, we evaluated the association of NUDT15 *4 with mercaptopurine (6‐MP) tolerance in a retrospective cohort of 1,399 patients with acute lymphoblastic leukemia (ALL) of diverse ancestries. All patients were wildtype for thiopurine methyltransferase gene. Patients were treated with 6‐MP in the context of ALL frontline clinical trials. The tolerated dose of 6‐MP was used to assess drug toxicity during the maintenance phase of ALL therapy. Patients with NUDT15 *1/*4 (n = 16, all of whom self‐identified as Hispanic/Latino) tolerated a significantly lower dose of 6‐MP than did those with NUDT15 *1/*1: median [interquartile range] of 39.0 [21.2–52.8] mg/m2, vs. 62.2 [47.9–71.6] mg/m2, P value < 0.001. No patient homozygous for *4 was detected. In a separate retrospective validation study, six patients were identified as having NUDT15 *1/*4 by routine clinical pharmacogenetics testing and tolerated a 6‐MP median dose of 38.7 mg/m2 (IQR, 33.7–54.0), confirming the need for dose reduction attributed to the NUDT15 *4 variant. These results point to the need to include NUDT15 *4 in pharmacogenetics‐guided thiopurine dosing algorithms.
Association Between Self‐Reported Oral Health and Dental Fear Among Illicit Drug Users in Northern Finland
Authors: Vainionpää Raija , Tiisanoja Antti , Kokkola Outi , Riipinen Pirkko , Anttonen Vuokko
Published: December 2024

Objectives

About 10% of adults in northern Finland have severe dental fear, but there is a lack of detailed knowledge about dental fear among illicit drug users. The aim of the study was to evaluate the prevalence of dental fear and its association with self‐reported oral health and health behavior as well as background factors of the customers of substance abuse services living in the region of Oulu, Northern Ostrobothnia, Finland.

Materials and Methods

One hundred seventeen volunteers, either active or former illicit drug users, were interviewed face‐to‐face about their background factors, health and health behaviors, and use of illicit drugs. The Modified Dental Anxiety Scale (MDAS) was used to assess a situation‐specific level of dental anxiety. For analyses, Pearson's χ2 test, Fisher's exact test, ANOVA, and logistic regression analysis were performed.

Results

Three out of four participants had at least moderate dental fear (MDAS ≥ 10) and 24% had severe dental fear (MDAS ≥ 19), with the average MDAS being 14.0 (SD 5.7). Participants in drug rehabilitation reported significantly more dental fear than the rest of the participants. Severe dental fear was associated (adjusted) with previous painful experiences OR 10.8 (2.3–52.0) and poor behavior by dental personnel OR 4.1 (1.2–13.9).

Conclusions

Dental fear is common among illicit drug users, and it is, particularly, associated with previous painful experiences and poor behavior by dental personnel.
Exploring the role of environmental regulations in green marketing success
Authors: David Lemuel Kenneth , Wang Jianling , Cisse Idrissa I. , Angel Vanessa
Published: December 2024

In response to growing consumer demand for sustainability, this study examines the impact of green marketing on brand perception and consumer purchase intent across 80 countries from 2006 to 2023. Drawing on data from Bloomberg, Thomson Reuters Eikon, and Sustainalytics, this research employs structural equation modeling and hierarchical linear modeling to analyze the relationships between green marketing expenditure, brand perception, and consumer behavior. The findings reveal that increased investment in green marketing significantly enhances brand perception and purchase intent, with outcomes varying across different economic, cultural, and regulatory contexts. These results highlight the importance of tailoring green marketing strategies to specific regions, providing actionable insights for advertisers aiming to foster brand loyalty through sustainability. Implications suggest that both advertisers and policymakers can strengthen consumer trust and brand loyalty by aligning sustainable marketing efforts with local cultural and regulatory expectations.
Sulfur‐Bridged Iron and Molybdenum Catalysts for Electrocatalytic Ammonia Synthesis
Authors: Yuan Xiaojiao , Galán‐Mascarós J. R.
Published: December 2024

Carbon zero electrocatalytic nitrogen reduction reaction (NRR), converting N2 to NH3 under ambient temperature and pressure, offers a sustainable alternative to the energy‐intensive Haber‐Bosch process. Nevertheless, NRR still faces major challenges due to direct dissociation of the strong N≡N triple bond, poor selectivity, as well as other issues related to the inadequate adsorption, activation and protonation of N2. In nature's nitrogen fixation, microorganisms are able to convert N2 to ammonia at ambient temperature and pressure, and in aqueous environment, thanks to the nitrogenase enzymes. The core NRR performance is achieved with sulfur‐rich Fe transition metal clusters as active site cofactors to capture and reduce N2, with optimum performance found for Fe−Mo clusters. Because of this reason, artificial analogs in Fe−Mo coordination chemistry have been explored. However, the studies of sulfur coordinated Fe, Mo catalysts for electrocatalytic ammonia synthesis are scarce. In this review, the recent progress of Fe−Mo sulfur‐bridged catalysts (including sulfur‐coordinated single‐site catalysts in carbon frameworks and MoS2‐based catalysts) and their activities for the ammonia synthesis from nitrate reduction reaction (NO3–RR) and nitrogen reduction reaction (NRR) are summarized. Further existing challenges and future perspectives are also discussed.
Unique MIMO System Using Gaussian Signals and the Advantage of These Signals in Sensing CSI and Multipath Fading
Authors: Alyassri Salam , Ilyas Muhammad , Aljumaily Mustafa S. , Al‐jumaili Saif , Duru Adil Deniz
Published: December 2024

To improve communication network efficiency, researchers must look at all aspects of transmission and the mechanisms that regulate their evolution as a whole. These features include solutions for dealing with the channel's noise and interference. To decrease interference and increase spectrum efficiency, orthogonal frequency division multiple access (OFDMA) systems employ orthogonal signals. While transmitting and receiving signals, noise and numerous feeds can be done in diverse ways. It has become increasingly common to use 256 quadratic modulation (QAM), which is more vulnerable to noise and has a higher bit error rate (BER). BERs in OFDM systems were high when multiple feeds and noise were present, as demonstrated in this article. Starting with the transmission and reception of Gaussian subband signals, an improved system has been designed that includes numerous stages of development. Thus, the need for “orthogonally” of transmitted signals to increase spectrum efficiency has been eliminated, as has the effect of surrounding channels. We have created a header for every frame that has been transmitted. Several transmitters and numerous receivers send these frames in parallel so that the channel state information (CSI) attributes may be evaluated using parallel processing. Using the identical transmission conditions for both OFDM systems and the proposed system, the simulation results reveal a significant reduction in BER values. This results in BER values of fewer than 10−1 when there are two tabs and 10−1 when there are three tabs for multiple feeding in the OFDM system. This corresponds to BER values of 10−11 in a suggested system when there are three tabs. Some improvements have been made to the proposed design to make it distinctive and qualified to be regarded as a multiaccess system in today's contemporary communication infrastructures.
Fluorinated Sulfonamides: Synthesis, Characterization, In Silico, Molecular Docking, ADME, DFT Predictions, and Structure‐Activity Relationships, as Well as Assessments of Antimicrobial and Antioxidant Activities
Authors: Reheim Mohamed A. M. Abdel , Ghazal Basma , Abdelhamid Sayeda Abdelrazek , Elhagali Gameel A. M. , El‐Gaby Mohamed S. A.
Published: December 2024

The design and synthesis of unique two series of fluorinated sulfonamides 3a‐f and 5a‐g utilizing nucleophilic aromatic substitution reactions of tetrafluorophthalonitrile 1 with various sulfonamides 2 under a variety of different reactions conditions were the key goals of the current research. The chemical composition of the generated products has been investigated via mass spectroscopy, 1HNMR, 13CNMR, infrared, and elemental analyzes. Antimicrobial studies were conducted in vitro to evaluate the activity of all new synthesized compounds against resistant strains. The first series showed high potency in very low concentrations. All compounds were studied against DPPH Radical Scavenging Activity and the other series showed high activity even in low molar ratio. In silico molecular docking was used to investigate the potential binding pathways for different receptors: dihydroprotien synthase protein (ID Code: 1AJ0) as an antibacterial and EGFRWT co‐crystallized with erlotinib [PDB ID code 1m17]. Furthermore, synthesized compounds with good ADME predictions to the Lipinski rule of five demonstrated that the recently synthesized compounds had high drug‐likeness qualities when the physicochemical parameter for the most powerful novel candidates was determined. Moreover, the DFT/B3LYP method functionalized with a 6‐31G (d, p) basis set was employed to calculate quantum parameters, MEP analysis, HUMO, and LUMO.