bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alkaloids Isolated from Vepris glandulosa with Antidiabetic Properties: An In Vitro and In Silico Analysis
Authors: Ojuka Prince , Ochieng Charles O. , Ndarawit Wilberforce , Nyongesa Daniel W. , Mukavi Justus , Nyabuga Nyariki James , Apollo Seth , Santos Cleydson B. R. , Kimani Njogu M. 
Published: November 2024

AbstractDiabetes is a major global health issue and as current treatments fail, the search for new antidiabetic drugs is crucial. This investigation, focusing on identifying potential antidiabetic compounds from the endangered plant species Vepris glandulosa, led to the isolation of two known alkaloids, choisyine acetate (1) and choisyine (2). The study established the in vitro inhibitory activities and in silico molecular interaction of the two alkaloids with α‐amylase based on IC50 values, Linewaever‐Burk/Dixon plot kinetic analyses and Molecular docking, respectively. The α‐amylase inhibition assay revealed noncompetitive inhibition for both compounds with IC50 and Ki values of 4.74±0.17 and 4.75 mM for compound 1, and 11.29±0.44 and 12.37 mM for compound 2, respectively. In comparison, the standard drug acarbose displayed a competitive mode of inhibition, with IC50 and Ki values of 11.99±0.02 and 12.68 mM, respectively. The binding affinities with α‐amylase were −6.42 and −6.07 kcal/mol for compounds 1 and 2, respectively relative to acarbose −8.03 Kcal/mol. Moreover, these two compounds’ predicted physicochemical and ADMET properties justified their potential as lead compounds for drug discovery. These compounds demonstrated remarkable inhibition potential comparable to the standard drug, highlighting their potential as viable alternatives in managing diabetes.
Synthesis and Cytotoxic Activities of Novel Ether Conjugates of Dihydroartemisinin and Zerumbone: Evidenced by Integrating Network Pharmacology and In Vitro Assay
Authors: Hung Truong Ngoc , Hung Nguyen Phi , Nghi Do Huu , Ha Nguyen Xuan , Loc Vu Thanh , Hai Pham The , Trang Luu Hanh , Cuong Nguyen Manh , Luu Van Chinh 
Published: November 2024

AbstractO‐alkylation of the hydroxy compounds, including acetaminophen, starting compounds for the synthesis of the drug, and natural compounds with the bromides of dihydroartemisinin (DHA) and zerumbone, produced twenty novel ether conjugates 15a‐j and 16a‐j, respectively. Their structures were elucidated by 1D‐, 2D‐NMR, and HRMS data. Their in vitro cytotoxic activity was screened using three cancer cell lines: HepG2, HeLa, and PC‐12. The results showed that eight out of ten conjugates in series 15a‐j containing DHA skeleton exhibited activity against the tested cell lines, with IC50 values ranging from 4.26–47.37 μM. Notably, all conjugates in series 16a‐j containing zerumbone scaffolds inhibited the growth of HepG2, HeLa, and PC12 with IC50 in the range of 4.46–35.07 μM. Using network pharmacology and molecular docking to target anti‐liver cancer in the above 20 synthetic compounds, 271 intersection targets were discovered, including 5 targets with high degree values (EGFR, ESR1, AKT1, MDM2, and NFKB1). Artemisinin derivative 15i gave the highest binding energy for targets AKT1, EGFR, and NFKB1, while zerumbone‐murrayafoline A ether 16g in the remaining series also gave the highest energy for proteins EGFR, AKT1, and NFKB1.
Role of Surfactants on Electrocatalytic Activity of Co/Al Layered Double Hydroxides For Hydrogen and Oxygen Generation
Authors: Rosely C V Sijla , John Honey 
Published: November 2024

AbstractLayered double hydroxides (LDHs) have recently attracted much attention in the scientific community as a prominent catalyst for oxygen evolution reaction (OER) because they are economical, extremely stable, and highly active. Literature on LDH alone and their hybrids for catalyzing water oxidation are readily available, but LDH catalyzing hydrogen evolution reaction (HER) is meager. Here, we synthesized Co/Al‐based LDH systems that efficiently perform as bifunctional electrocatalysts for both HER and OER. Exfoliation of this layered material via anion intercalation into a few layers further enhanced its activity. In this work, we reported the synthesis of Co/Al LDHs via coprecipitation followed by hydrothermal method and different surfactant‐functionalized LDHs (with anionic surfactant: SDS, cationic surfactant: CTAB, and nonionic surfactant: PEG 4000). SDS‐modified LDH (s LDH) showed notable stability and competent results in hydrogen evolution in addition to oxygen evolution. The exfoliation of s LDH caused enhancement in the high specific surface area about 6.8 times compared to pristine LDH, as evident from BET data. The onset potential for HER as obtained from the polarization curve for s LDH is −0.41 V versus RHE, with Tafel slope of 67.4 mV/dec. Similarly, OER onset potential and corresponding Tafel slope are 1.53 V versus RHE at 10 mA/cm2 and 90.2 mV/dec, respectively.
Trimethyl Lock Based Tools for Drug Delivery and Cell Imaging – Synthesis and Properties
Authors: Skwarecki Andrzej S. , Stefaniak‐Skorupa Joanna , Nowak Michał G. 
Published: November 2024

AbstractTrimethyl lock (TML) systems have become increasingly important in medicinal and bioorganic chemistry, particularly for their roles in the targeted delivery of therapeutic agents and as integral components in fluorogenic probes for cellular imaging. The simplicity and efficiency of their synthesis have established TML systems as versatile platforms for the controlled release of active molecules under particular physiological conditions. This review consolidates recent advancements in the application of TML systems, with a focus on their use in drug delivery, cellular imaging, and other areas where precise molecular release is crucial. Additionally, we discuss the synthetic strategies employed to construct TML‐based conjugates, underscoring their potential to enhance the specificity and efficacy of bioactive compounds in various biomedical applications.
Insights into C−H Activation Reactivity of Fe (IV)O Porphyrinoid Complexes: A Computational Investigation
Authors: Kaur Lovleen , Mandal Debasish 
Published: November 2024

AbstractThis work presents a detailed comparative analysis of C−H activations catalyzed by three different Fe(IV)O porphyrinoid complexes. The study considers the usual heme porphyrin (complex I) as the base compound, porphyrazine (complex II), which is obtained by replacing carbon with nitrogen at the meso position, and phthalocyanine (complex III), which is obtained through the peripheral benzoannulation of porphyrazine. The main focus here is to explore the impact of bridging groups and peripheral functionalization in heme systems on reactivity. Chloride is used as the axial ligand for all complexes and dihydroanthracene (DHA) is used as the substrate. Factors such as distortion energy and different electron acceptor orbitals significantly affect the overall reactivity. The effect of substitution on quantum mechanical tunneling, using H/D kinetic isotope effect studies, is also included. The results reveal a fascinating reactivity order: meso nitrogen substitution enhances reactivity, while additional benzo‐annulation hinders reactivity, leading to the order complex II >complex I >complex III. In comparison to the usual model compound I, which is Fe(IV)O‐porphyrin π cation radical with an −SH axial ligand, complex II was found to be more reactive. The electron affinity of the Fe(IV)O complexes and the dissociation energy of the forming Fe(IV)O−H bond aligns with observed reactivity trend. These findings support the use of accessible iron frameworks derived from porphyrin in C−H activation processes.
Ferrofluid Droplet Chains in Thermotropic Nematic Liquid Crystals
Authors: Chandrasekar Varun , Lu Jian Ren , Dierking Ingo 
Published: November 2024

AbstractDispersing ferrofluids in liquid crystals (LCs) produces unique systems which possess magnetic functionality and novel phenomena such as droplet chaining. This work reports the formation of ferrofluid droplet chains facilitated by the topological defects within the LC director field, induced by the dispersed ferrofluid. The translational and rotational motion of these chains could be controlled via application of external magnetic fields. The process of the droplet chain formation in LCs can be stabilized by the addition of surfactants. The magnetic colloidal particles in the ferrofluid located at the interface between the ferrofluid and the LC are arranged so that a boundary layer was formed. The velocities and boundary layer thickness values of ferrofluid droplet chains in nematic 5CB (4‐Cyano‐4′‐pentylbiphenyl) were investigated for varying average droplet sizes and number of droplets in a chain. The creation and behaviour of ferrofluid droplet chains in 5CB with the addition of the surfactant polysorbate 60 (Tween‐60) and without, was comparatively investigated. The integration of liquid crystals and ferrofluids along with the incorporation of functional materials facilitates the innovative development of advanced materials for future applications.
Still dare to be different? Peers' CSR engagement and analysts' response to focal firms' CSR strategies
Authors: Zou Hailiang , Qi Guoyou , Ma Hanyang 
Published: November 2024

AbstractThis study investigates how security analysts' response to focal firms' corporate social responsibility (CSR) strategies varies with the level of CSR engagement among peer firms, about which contradictory arguments can be drawn from the perspectives of legitimacy and competitive dynamics. Legitimacy theory underscores the importance of conformity to peers' behaviors, while the competitive dynamics perspective suggests that firms should differentiate from their peers. The optimal distinctiveness theory suggests an orchestration between CSR conformity and CSR differentiation, combining the arguments of legitimacy and competitive dynamics. Based upon a sample of Chinese listed companies from 2009 to 2018, this study uses a second‐hand panel dataset and employs three‐way interactions and the generalized method of moments (GMM) system. The empirical results show that as CSR engagement among peer firms increases, heavier legitimacy pressure is imposed on focal firms, and their CSR scope conformity attracts more analyst coverage, and this effect is more prominent for firms in institutionally developed regions. On the other hand, the competitive advantage gained from CSR emphasis differentiation is weakened by rivals' engagement in CSR, and the influence of CSR emphasis differentiation on analyst recommendation is weakened by peers' CSR engagement, and in highly competitive industries, this effect of peers' CSR engagement is stronger. We propose that peers' CSR engagement has different impacts on the importance of CSR conformity and differentiation. Finally, both the theoretical and practical implications are discussed.
The macrophage migration inhibitory factor/CD74 axis in traumatic spinal cord injury: lessons learned from animal and human studies
Authors: Rubio Serina , Somers Veerle , Fraussen Judith 
Published: November 2024

AbstractTraumatic spinal cord injury (SCI) is a severe condition leading to long‐term impairment of motor, sensory, and autonomic functions. Following the initial injury, a series of additional events is initiated further damaging the spinal cord. During this secondary injury phase, both an inflammatory and immune modulatory response are triggered that have damaging and anti‐inflammatory properties, respectively. The proinflammatory cytokine macrophage migration inhibitory factor (MIF) and its receptor CD74 have been extensively studied in traumatic SCI. MIF expression is increased in spinal cord tissue after experimental SCI, mainly in astrocytes and microglia, as well as in the plasma of SCI patients. Functionally, MIF and CD74 were shown to regulate astrocyte viability, proliferation and cholesterol metabolism, microglia migration, and neuronal viability. Moreover, inhibition of the MIF/CD74 axis improved the functional recovery of SCI animals. We provide a detailed overview of studies analyzing the role of MIF and CD74 in traumatic SCI. We describe results from animal studies, using rat and mouse models for SCI, and human studies. Furthermore, we propose a new path for investigation, focused on B cells, that might lead to a better understanding of how MIF and CD74 contribute to the secondary injury cascade following traumatic SCI.
Exploitation of Mining Resources in El Argar Culture: Bronze Age Metallurgy in the Hinterland of the Western Betic Cordillera (Southeastern Iberian Peninsula)
Authors: Murillo‐Barroso M. , Aranda Jiménez G. , Lozano Rodríguez J. A. , Lackinger A. , Stos‐Gale Z. , Rodríguez J. , Álvarez‐Valero A. M. , Gil Ibarguchi J. I. , Montero‐Ruiz I. 
Published: November 2024

ABSTRACTThis research addresses the territorial organisation of metallurgical production during the El Argar Bronze Age (2200–1550 cal bc) in the inner areas of El Argar territory through lead‐isotope and trace element analyses of geological copper ores, archaeometallurgical remains and copper‐based artefacts. Results from 31 mineral and 35 archaeological samples suggest that the exploitation of copper resources in the studied region was significant and had a similar impact than other mining districts of El Argar territory. This, therefore, leads the hierarchical and centralised production model to be questioned. It also appears that the copper ore deposits in the coastal regions that were intensively exploited during the Copper Age were used less intensively in the El Argar period. At that time, copper was mostly procured from ore deposits in the inland areas of El Argar territory: that is, ore deposits within the Alpine orogeny hinterland (inland areas of the Betic Cordillera, from Granada to Baza). Other artefacts were sourced from outside the Alpine geological domain, but still on the fringe of El Argar territory (the foothills of the Sierra Morena‐Linares mining district) or even from ore deposits definitely outside El Argar territory itself (the Los Pedroches Variscan region and elsewhere).
Nationwide cohort study on the risk of high‐grade cervical dysplasia and carcinoma after conservative treatment or hysterectomy for adenocarcinoma in situ
Authors: Schaafsma Mirte , Schuurman Teska N. , Kootstra Pien , Issa Deli , Hermans Ivo , Bleeker Maaike C. G. , Zusterzeel Petra L. M. , Bekkers Ruud L. M. , Siebers Albert G. , Mom Constantijne H. , van Trommel Nienke E. 
Published: November 2024

AbstractInternationally, little consensus exists about the best treatment for cervical adenocarcinoma in situ (AIS). This study aimed to determine the incidence of recurrent high‐grade cervical dysplasia and development of local cervical cancer after treatment for AIS. This nationwide, retrospective cohort study included patients with AIS, who were treated by a large loop excision of the transformation zone (LLETZ), cold‐knife conization (CKC), or hysterectomy between January 1, 1990 and December 31, 2021 in the Netherlands. Pathology reports were retrieved from the Dutch Nationwide Pathology Databank (Palga). Primary outcomes were the cumulative incidences of high‐grade cervical dysplasia (cervical intraepithelial neoplasia grade 2 or 3, and AIS) and local cervical cancer up to 20 years after primary treatment. In total, 4243 patients with AIS were included. The primary treatment was a LLETZ, CKC, or hysterectomy in 1593, 2118, and 532 patients, respectively. The incidence of recurrent high‐grade cervical dysplasia after LLETZ (10.5%; 95%CI: 8.6–12.3) was higher than after CKC (5.5%; 95%CI: 4.4–6.6, p <.0001). When a radical excision, that is, surgical margins free of dysplasia at end of treatment, was achieved, the incidence of recurrent high‐grade dysplasia and local cervical cancer did not differ between LLETZ (5.6% [95%CI: 3.3–7.9] and 1.9% [95%CI: 0–4.4]) and CKC (4.7% [95%CI: 3.5–5.8], p = .631 and 1.5% [95%CI: 0.7–2.3], p = .918). After hysterectomy, none of the patients developed cervical dysplasia or local cervical cancer. Conservative treatment for AIS can be considered a safe and final treatment modality when a radical excision is achieved.
Excited state relaxation mechanisms of paracetamol and acetanilide
Authors: Valverde Danillo , Beal Roiney , Gonçalves Paulo Fernando Bruno , Borin Antonio Carlos 
Published: November 2024

AbstractThe photochemical pathways of acetanilide and paracetamol were investigated using the XMS‐CASPT2 quantum chemical method and the cc‐pVDZ (correlation consistent polarized valence double‐) basis set. In both compounds, the bright state is the second excited state, designated as a La) state. Through a detailed exploration of the potential energy profile and the conical intersection structure between the La) and ground states, we gained a better understanding of how cleavage might occur in both molecules upon photoexcitation. Other potential relaxation mechanisms, including crossings with the dark and La) states, are also discussed in detail.
The Role of Pain Medications in Modulating Peripheral Nerve Injury Recovery
Authors: Allgood JuliAnne E. , Whitney Logan , Goodwin Jeffrey , Chong Brian S. H. , Brooks Amanda , Pullan Jessica 
Published: November 2024

AbstractPeripheral nerve injuries (PNIs) are common, costly, and cause significant pain. Effective management of PNIs involves tailoring medications to the injury type as well as understanding the pharmacokinetics/pharmacodynamics to support nerve regeneration and reduce pain. Opioids act on opioid receptors to significantly reduce pain for many patients, but there are significant addiction risks and side effects. In addition, opioids may exacerbate pain sensitivity and affect nerve regeneration. Non‐steroidal anti‐inflammatory drugs or acetaminophen act on cyclooxygenase enzymes and are commonly used for nerve pain, with 34.7% of people using them for neuropathic pain. While effective for mild pain, they are often combined with opioids, gamma‐aminobutyric acid (GABA) analogs, lidocaine, or corticosteroids for more severe pain. Corticosteroids, mimicking adrenal hormones like cortisol, treat PNI‐related inflammation and pain. Their pharmacokinetics are complex, often requiring local injections in order to minimize systemic risks while effectively treating PNIs. Lidocaine, a common local anesthetic, blocks ion channels in the central nervous system (CNS) and peripheral nerves, providing strong analgesic and anti‐inflammatory effects. If used improperly, lidocaine can cause neuronal toxicity instead of anesthetic effect. GABA acts as an inhibitory neurotransmitter in the CNS and its drug analogs like pregabalin and gabapentin can alleviate neuropathic pain by binding to voltage‐gated Ca2+ channels, inhibiting neurotransmitter release. These pain medications are commonly prescribed for PNIs despite a limited guidance on their effects on nerve regeneration. This review will discuss these drug's mechanisms of action, pharmacokinetics/pharmacodynamics, and their clinical application to highlight their effect on the PNI recovery.
Role of Orphan ParA Proteins in Replication and Cell Division in Rhodococcus erythropolis PR4
Authors: Parwin Shabnam , Srivastava Preeti 
Published: November 2024

ABSTRACTBacteria have a very well‐regulated mechanism for chromosome segregation and cell division. This process requires a large number of complex proteins to participate and mediate their functionality. Among these complex proteins, ParA and ParB play a vital role for the faithful segregation of chromosome. In Rhodococcus erythropolis PR4, besides the essential parAB operon, there are three orphan copies of parA genes. Here, we report that the orphan ParA2 and ParA3 have distinct roles in the cell cycle. The disruption of the orphan parA2 or parA3 gene resulted in elongated cells. Multiple septal rings and mislocalised septa were observed in ΔparA3 and ΔparA2 mutants, respectively. The subcellular localization of ParA2 revealed a distinct ring‐ and ribbon‐like structure. On the other hand, orphan ParA3 was localized slightly away from the poles. The orphan ParA proteins were found to interact with ParB, the strongest interaction was observed with ParA2. Further, asynchronous replication initiation was observed in ΔparA3 mutants suggesting its role in replication. This is the first report demonstrating the distinct roles of orphan parA genes from Rhodococcus.
Effects of Bacillus spp. inoculation on suggested shoot tolerance mechanisms in lowland rice (Oryza sativa L.) grown under iron toxicity
Authors: Weinand Tanja , Asch Julia , Asch Folkard 
Published: November 2024

AbstractBackgroundIn areas of lowland rice production, high iron concentrations in the soil often lead to yield reductions. Local adapted varieties possess different adaptation mechanisms, which, however, are not fully understood. Previous studies have shown that endophytic bacteria can influence plant tolerance to abiotic stresses, including iron toxicity.AimThis study aims at analyzing the effects of different Bacillus isolates on distinct shoot tolerance mechanism in different rice cultivars grown under iron toxicity.MethodsThree lowland rice cultivars, varying in their tolerance against iron toxicity (IR31785‐58‐1‐2‐3‐3, Sahel 108, Suakoko 8), were inoculated with three Bacillus strains (two of B. pumilus and one of B. megaterium). One week after Bacillus inoculation plants were subjected to high iron levels (1000 ppm) for 7 days. Leaf symptom scoring was used to assess tolerance levels. Activities of ascorbate peroxidase (APX), glutathione reductase (GR), catalase (CAT), superoxide dismutase (SOD), and guaiacol peroxidase (PRX) were measured by spectrophotometric assays. Transcription of genes related to iron toxicity (OsFER, OsFRO1, OsNRAMP6) was determined by RT‐qPCR. Bacterial production of NO was evaluated by measuring nitrite levels in the culture supernatants.ResultsIn general, iron toxicity affected the activities of APX, GR, CAT, and PRX but not SOD activity. Only PRX activity in response to iron differed between cultivars with a significantly stronger increase in IR31785‐58‐1‐2‐3‐3. Inoculation with B. pumilus Ni9MO12 led to higher activity of CAT in the leaf sheaths of all cultivars and an increase in GR activity in the sheaths that was significantly higher in Suakoko 8. In the young leaf blades of IR31785‐58‐1‐2‐3‐3, transcription of OsFRO1 and OsNRAMP6 was not significantly affected by Bacillus inoculation, whereas accumulation of OsFER mRNA was significantly higher in iron‐stressed, B. pumilus Ni9MO12 inoculated plants compared to non‐inoculated, non‐iron‐stressed plants. Nitrite concentration as an indicator for NO production was increased in B. pumilus Ni9MO12 culture supernatants.ConclusionOur results show that in the sensitive cultivar IR31785‐58‐1‐2‐3‐3 tolerance to iron toxicity increases when inoculated with B. pumilus Ni9MO12, coinciding with higher levels of ferritin transcription. NO production by the Bacillus isolate might confer the promotion of OsFER gene transcription in the inoculated plants.