bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design and synthesis of novel tetrabromophthalimide derivatives as potential tubulin inhibitors endowed with apoptotic induction for cancer treatment
Authors: Abdel‐Motaal Marwa , Aldakhili Dalal A. , Abo Elmaaty Ayman , Sharaky Marwa , Mourad Mai A. E. , Alzahrani Abdullah Y. A. , Mohamed Nadia A. , Al‐Karmalawy Ahmed A. 
Published: May 2024

AbstractAlthough various approaches exist for treating cancer, chemotherapy continues to hold a prominent role in the management of this disease. Besides, microtubules serve as a vital component of the cellular skeleton, playing a pivotal role in the process of cell division making it an attractive target for cancer treatment. Hence, the scope of this work was adapted to design and synthesize new anti‐tubulin tetrabromophthalimide hybrids (3‐17) with colchicine binding site (CBS) inhibitory potential. The conducted in vitro studies showed that compound 16 displayed the lowest IC50 values (11.46 µM) at the FaDu cancer cell lines, whereas compound 17 exhibited the lowest IC50 value (13.62 µM) at the PC3 cancer cell line. However, compound 7b exhibited the lowest IC50 value (11.45 µM) at the MDA‐MB‐468 cancer cell line. Moreover, compound 17 was observed to be the superior antitumor candidate against all three tested cancer cell lines (MDA‐MB‐468, PC3, and FaDu) with IC50 values of 17.22, 13.15, and 13.62 µM, respectively. In addition, compound 17 showed a well‐established upregulation of apoptotic markers (Caspases 3, 7, 8, and 9, Bax, and P53). Moreover, compound 17 induced downregulation of the antiapoptotic markers (MMP2, MMP9, and BCL‐2). Furthermore, the colchicine binding site inhibition assay showed that compounds 15a and 17 exhibited particularly significant inhibitory potentials, with IC50 values of 23.07 and 4.25 µM, respectively, compared to colchicine, which had an IC50 value of 3.89 µM. Additionally, cell cycle analysis was conducted, showing that compound 17 could prompt cell cycle arrest at both the G0‐G1 and G2‐M phases. On the other hand, a molecular docking approach was applied to investigate the binding interactions of the examined candidates compared to colchicine towards CBS of the β‐tubulin subunit. Thus, the synthesized tetrabromophthalimide hybrids can be regarded as outstanding anticancer candidates with significant apoptotic activity.
Applying causal reasoning to investigate multicausality in microbial systems
Authors: Potter Teal S. , Zalewski Zachary , Miao Max , Allsup Cassandra , Thompson Kathleen M. , Hayden Daniel , George Isabelle , Lankau Richard A. , Lankau Emily W. 
Published: May 2024

AbstractMicrobial communities contribute to many essential ecological functions, from carbon cycling in soil to healthy functioning of the human body. Yet, determining how the make‐up of microbial communities is causally linked to a particular function remains a huge challenge. Despite improved tools for characterizing microbiomes at increasingly finer phylogenetic and functional scales, researchers are still unable to perform direct experimental hypothesis testing as is performed in plant and animal ecology. However, microbial ecology is not the only scientific field tasked with drawing firm causal inferences from correlational data. Here we introduce microbial ecologists to a framework used by epidemiologists: the Bradford Hill Causal Criteria. Hill posited that as a field accrues different types of evidence to support a hypothesis, it increases confidence in claiming that the hypothesized relationship is causal. A set of nine criteria help distinguish different types of evidence. Our goal was to illustrate how these causal criteria can be used in microbial ecology to retrospectively evaluate a body of research to determine the strength of a causal claim and judge the value of future research directions. We illustrate how this framework can help researchers organize their understanding of a body of literature to reveal knowledge gaps and analytical approaches that have been underutilized. We then discuss the types of causality and illustrate how investigating multicausal systems requires an updated application of older frameworks that assume one causal agent is at play for each functional outcome. We also examine analytical approaches that are appropriate for distinguishing the types of causality.
Shifts in host–parasitoid networks across community garden management and urban landscape gradients
Authors: Lucatero Azucena , Smith Noah R. , Bichier Peter , Liere Heidi , Philpott Stacy M. 
Published: May 2024

AbstractBiological pest control relies on interactions between herbivores and their natural enemies. Maintaining this ecosystem service requires considering herbivore and natural enemy interactions and their response to anthropogenic change at multiple scales. In this study, we used ecological networks to quantify the network structure of interactions between herbivorous insects and their parasitoids. We examined how herbivore host abundance, parasitism rates, and shifts in network structure relate to changes in local habitat management and landscape context. We sampled herbivores and parasitoids in Brassica oleracea plants at 22 urban gardens in the Central Coast of California. At each site, we measured local management characteristics (e.g., vegetation, ground cover, canopy cover) and quantified surrounding landscape composition (e.g., urban, natural, open, and agricultural cover). For the eight sites with large enough networks, we calculated three network structure metrics (interaction richness, vulnerability, and functional complementarity). We then used generalized linear and mixed models to examine relationships between herbivore host abundance, parasitism rates, garden management and landscape characteristics, and network metrics. We found that both local management and landscape composition influenced parasitism, while only local factors affected host abundance and network structure. Higher network interaction richness was marginally associated with enhanced parasitism rates for two host species and lower parasitism rates for one host species. Our results suggest that local garden management decisions may shift the structure of host–parasitoid networks, which may subsequently affect host parasitism rates, but outcomes for biological pest control will likely vary across host species.
Structure Directing Effects of the Tetraphenylphosphonium Cation upon the Formation of Lanthanoid Anilate Coordination Polymers
Authors: Hua Carol 
Published: May 2024

AbstractFour lanthanoid anilate coordination polymers (CPs) were synthesised using fluoranilate and chloranilate ligands with La(III), Eu(III) and Dy(III), and PPh4+ as the countercation. The presence of the PPh4+ countercation had a structure directing effect on the CP topology, with a 3D diamondoid (dia) network obtained with La(III) whilst 2D square grid (sql) networks were obtained with Eu(III) and Dy(III). This work represents the first use of fluoranilate in lanthanoid anilate CPs. The additional hydrogen bonding sites afforded by the fluorine substituent influences the packing of the crystal structure whilst the variation in lanthanoid ion size helps determine the topology of the CP.
Development and application of an integrated methodology for post‐disaster field investigation of debris floods
Authors: Po Yang , Xiekang Wang , Dongya Sun , Zexing Xu , Weizhen Lu 
Published: May 2024

AbstractDebris floods commonly occur in steep channels with an abundant sediment supply, and they can cause significant damage, primarily due to their higher sediment concentrations and negative impacts upon bank erosion, deep scouring and aggradation. These key hazards pose challenges for traditional assessment methods, making quantification difficult. This became obvious during a recent catastrophic debris flood that occurred on July 12, 2022, in the Heishuigou catchment (102 km2), northern Sichuan Province, China. In this case study, we developed an integrated methodology for assessing this debris flood event by incorporating field surveys, hydrological and hydraulic modelling and sediment transport calculations. Detailed information such as topographic maps, photographs, deposits, grain size distributions and inundation depths was collected to analyse the material sources, validate the parameters and conduct model calculations. The peak debris flood discharge and the supra‐critical bed shear stress ratios, estimated from hydrological and dynamic models, were incorporated to analyse the debris flood's typology and characterize its destructive mechanisms. The regional frequency–volume relationship established through bedload transport calculations was calibrated using the volume of the deposits determined via field investigation. These methods not only contribute to a comprehensive understanding of debris floods but also provide valuable support for future risk assessments and mitigation designs.
Exploring free amino acid profiles in CCHF patients: Implications for disease progression
Authors: Büyüktuna Seyit Ali , Yerlitaş Serra İlayda , Zararsız Gözde Ertük , Doğan Kübra , Kablan Demet , Bağcı Gökhan , Özer Selda , Baysal Cihad , Çakır Yasemin , Cephe Ahu , Koçhan Necla , Zararsız Gökmen , Doğan Halef Okan 
Published: May 2024

AbstractThis study investigated the intricate interplay between Crimean‐Congo hemorrhagic fever virus (CCHFV) infection and alterations in amino acid metabolism. Our primary aim is to elucidate the impact of Crimean‐Congo hemorrhagic fever (CCHF) on specific amino acid concentrations and identify potential metabolic markers associated with viral infection. One hundred ninety individuals participated in this study, comprising 115 CCHF patients, 30 CCHF negative patients, and 45 healthy controls. Liquid chromatography‐tandem mass spectrometry techniques were employed to quantify amino acid concentrations. The amino acid metabolic profiles in CCHF patients exhibit substantial distinctions from those in the control group. Patients highlight distinct metabolic reprogramming, notably characterized by arginine, histidine, taurine, glutamic acid, and glutamine metabolism shifts. These changes have been associated with the underlying molecular mechanisms of the disease. Exploring novel therapeutic and diagnostic strategies addressing specific amino acids may offer potential means to mitigate the severity of the disease.
Rhodotorula mucilaginosa A8, a potential helper strain in a vitamin C microbial fermentation process
Authors: Zhang Qian , Liao Lin , Lyu Shuxia 
Published: May 2024

AbstractIn the vitamin C microbial fermentation system, oxidative stress limits the growth and 2‐keto‐l‐gulonic acid (2‐KLG, the precursor of vitamin C) production of Ketogulonicigenium vulgare. Most Bacillus strains, as helper strains, have been reported to release key biomolecules to reduce oxidative stress and promote the growth and 2‐KLG production of K. vulgare. To understand the specific mechanism by which the helper strain and K. vulgare interact to reduce oxidative stress, a novel helper strain, Rhodotorula mucilaginosa A8, was used to construct a consortium in the co‐culture fermentation system. Based on the activities of the antioxidant enzymes and quantitative polymerase chain reaction (qPCR) analysis, R. mucilaginosa A8 could reduce oxidative stress and increase 2‐KLG production in K. vulgare by upregulating antioxidant enzyme activities and related gene‐expression levels. In addition, the carotenoids of R. mucilaginosa promoted 2‐KLG production in K. vulgare. Coculture of R. mucilaginosa with K. vulgare increased the yield of carotenoids. This study suggested that helper strains with the ability to reduce oxidative stress in K. vulgare would likely act as potential helper strains for facilitating 2‐KLG biosynthesis. This work could provide a theoretical basis for the search for potential helper strains for vitamin C microbial fermentation and for the construction of synthetic microbial communities to produce valuable products.
Trends in temperature and precipitation at high and low elevations in the main mountain ranges of the Iberian Peninsula (1894–2020): The Sierra Nevada and the Pyrenees
Authors: Sigro Javier , Cisneros Mercè , Perez‐Luque Antonio J. , Perez‐Martinez Carmen , Vegas‐Vilarrubia Teresa 
Published: May 2024

AbstractThis study describes temperature and precipitation trends in the two National Parks located in the two highest mountain ranges on the Iberian Peninsula: the Sierra Nevada (Sierra Nevada National Park, SN) and the Pyrenees (Aigüestortes i Sant Maurici National Park, ASM). Special focus is placed on analysing disparities between the lowlands and the highlands, as well as the agreement between observational data and grid data (IBERIA01 and E‐OBS). For this purpose, a quality‐controlled and homogeneity‐adjusted database of the daily maximum temperature, minimum temperature and precipitation (SMADS database) has been generated. Regional trends in mean temperature indicate that warming in ASM (0.17°C·decade−1) was greater than in the Sierra Nevada (SN) (0.13°C·decade−1) in the longest joint period, 1930–2020. For annual precipitation, the trends over the past nine decades were negative, although not significantly. Only the summer in SN showed a significant negative trend, which has intensified in recent decades to −13.4%·decade−1 for 1975–2020. A parallel evolution was observed in the annual mean temperature of the highlands (>1500 m) and lowlands (<1500 m) of ASM, with a common trend of 0.17°C·decade−1, while in SN negative elevation‐dependent warming was detected. Differences between lowlands and highlands were also noted in precipitation trends in both mountain ranges: a positive trend in precipitation was found in the lowlands while in the highlands practically null trends (ASM) or decreasing precipitation trends (SN) were detected. The comparison of the Spanish Mountain Adjusted Daily Series (SMADS) results with the IBERIA01 and E‐OBS grid series yielded differences no greater than ±0.2°C·decade−1. No notable differences were detected between the regional trends calculated with observational series or with grid series. These results worsened when the differences in the trends detected in the individual observed temperature series were compared against the corresponding grid series.
Potential historically intertropical stable areas during the Late Quaternary of South America
Authors: Dantas Mário André Trindade , Pansani Thais Rabito , Asevedo Lidiane , Araújo Thaísa , França Lucas de Melo , de Aragão Wilcilene Santos , da Silva Santos Franciely , Cravo Elisa , Waldherr Felipe Rodrigues , Ximenes Celso Lira 
Published: May 2024

ABSTRACTSouth America is a pivotal paleontological setting for Late Quaternary megafaunal research. Nonetheless, its paleobiogeography and paleoecology, and the causes for the recent extinction of megafauna in the Late Pleistocene/Early Holocene are not yet fully understood. This study aimed to investigate the potential geographical distribution and historically intertropical stable areas (HISAs) of South American megafauna. We generated maps using Paleo‐Species Distribution Models for 12 megafaunal taxa (11 herbivores and one carnivore) during interglacial and glacial periods in the Late Quaternary: 120 and 21 ka. Our models, together with isotopic data, show that the HSIAs occurred mainly in low‐altitude plains (<1000 m) and were superimposed on seasonal dry forest biomes. We propose the occurrence of two HSIAs: the West Intertropical Region and the Brazilian Intertropical Region, the latter being redefined. We suggest that the Brazilian Intertropical Region is much smaller than previously proposed, but was still a key zoogeographical region for megafauna in South America during the Late Pleistocene.
Injectable Photothermal PDA/Chitosan/β‐Glycerophosphate Thermosensitive Hydrogels for Antibacterial and Wound Healing Promotion
Authors: Liu Dingkun , Chen Jinbing , Gao Linjuan , Chen Xing , Lin Liujun , Wei Xia , Liu Yuan , Cheng Hui 
Published: May 2024

AbstractControlling infections while reducing the use of antibiotics is what doctors as well as researchers are looking for. As innovative smart materials, photothermal materials can achieve localized heating under light excitation for broad‐spectrum bacterial inhibition. A polydopamine/chitosan/β‐glycerophosphate temperature‐sensitive hydrogel with excellent antibacterial ability is synthesized here. Initially, the hydrogel has good biocompatibility. In vitro experiments reveal its noncytotoxic property when cocultured with gingival fibroblasts and nonhemolytic capability. Concurrently, the in vivo biocompatibility is confirmed through liver and kidney blood markers and staining of key organs. Crucially, the hydrogel has excellent photothermal conversion performance, which can realize the photothermal conversion of hydrogel up to 3 mm thickness. When excited by near‐infrared light, localized heating is attainable, resulting in clear inhibition impacts on both Staphylococcus aureus and Escherichia coli, with the inhibition rates of 91.22% and 96.69%, respectively. During studies on mice's infected wounds, it is observed that the hydrogel can decrease S. aureus’ presence in the affected area when exposed to near‐infrared light, and also lessen initial inflammation and apoptosis, hastening tissue healing. These findings provide valuable insights into the design of antibiotic‐free novel biomaterials with good potential for clinical applications.
Development of potentiostatically deposited cerium conversion coating for Mg alloys
Authors: Jena Geetisubhra , Chellappandian Ramachandran , Neelakantan Lakshman , Adlakha Ilaksh 
Published: May 2024

AbstractIn this work, cerium conversion coating (CeCC) was deposited on AZ91D Mg alloy using potentiostatic polarization method combined with phosphate pore‐sealing treatment. Initially, the optimum deposition parameters to obtain a crack‐free surface were found. The characterization of coating revealed the presence of a nodular morphology of cerium oxide deposits. Next, the electrochemical behavior of the coated surface was assessed using potentiodynamic polarization and electrochemical impedance spectroscopy in 3.5 wt% NaCl solution. Based on electrochemical characterization, the coating exhibited a fivefold increase in the charge transfer resistance and a corresponding 76% reduction in corrosion rate, when compared to the bare surface. Furthermore, the conversion coating exhibited improved corrosion resistance when evaluated using the immersion test. Therefore, these findings demonstrate the feasibility of the potentiostatic method for creating nearly crack‐free CeCC on Mg alloys, unlike conventional conversion coatings. Moreover, this approach holds great potential for effectively mitigating the corrosion issues in Mg alloys.
Regularity results for Hölder minimizers to functionals with non‐standard growth
Authors: Grimaldi Antonio Giuseppe , Ipocoana Erica 
Published: May 2024

AbstractWe study the regularity properties of Hölder continuous minimizers to non‐autonomous functionals satisfying ‐growth conditions, under Besov assumptions on the coefficients. In particular, we are able to prove higher integrability and higher differentiability results for solutions to our minimum problem.
Alkaliptosis induction counteracts paclitaxel‐resistant ovarian cancer cells via ATP6V0D1‐mediated ABCB1 inhibition
Authors: Chen Fangquan , Lin Junhao , Kang Rui , Tang Daolin , Liu Jiao 
Published: May 2024

AbstractPaclitaxel serves as the cornerstone chemotherapy for ovarian cancer, yet its prolonged administration frequently culminates in drug resistance, presenting a substantial challenge. Here we reported that inducing alkaliptosis, rather than apoptosis or ferroptosis, effectively overcomes paclitaxel resistance. Mechanistically, ATPase H+ transporting V0 subunit D1 (ATP6V0D1), a key regulator of alkaliptosis, plays a pivotal role by mediating the downregulation of ATP‐binding cassette subfamily B member 1 (ABCB1), a multidrug resistance protein. Both ATP6V0D1 overexpression through gene transfection and pharmacological enhancement of ATP6V0D1 protein stability using JTC801 effectively inhibit ABCB1 upregulation, resulting in growth inhibition in drug‐resistant cells. Additionally, increasing intracellular pH to alkaline (pH 8.5) via sodium hydroxide application suppresses ABCB1 expression, whereas reducing the pH to acidic conditions (pH 6.5) with hydrochloric acid amplifies ABCB1 expression in drug‐resistant cells. Collectively, these results indicate a potentially effective therapeutic strategy for targeting paclitaxel‐resistant ovarian cancer by inducing ATP6V0D1‐dependent alkaliptosis.
The role of information sources as a driver of innovation
Authors: Quiroz‐Rojas Paula , Teruel Mercedes 
Published: May 2024

AbstractAn extensive empirical literature shows the important role that information sources have on firm innovation. However, there is scarce evidence on the different typologies of between technological and non‐technological innovations and their expectations. We investigate how the wide number of information sources affect the propensity to innovate and its future expectations. At the methodological level, we apply a multivariate Probit to the Innovation Survey of Chilean companies (2013–2016). Our results show that internal information sources, suppliers, clients and the Internet are significantly associated with the development of technological and non‐technological innovations. Social innovations are affected only by internal and by market (primarily from consultancy firms) sources of information. Finally, internal information sources and the Internet affect firms' expectations to innovate. Our results indicate the importance of different information flows and how they may drive the generation of innovations.
Bivalent and bitopic ligands of the opioid receptors: The prospects of a dual approach
Authors: Hovah Marie Emilie , Holzgrabe Ulrike 
Published: May 2024

AbstractOpioid receptors belonging to the class A G‐protein coupled receptors (GPCRs) are the targets of choice in the treatment of acute and chronic pain. However, their on‐target side effects such as respiratory depression, tolerance and addiction have led to the advent of the ‘opioid crisis’. In the search for safer analgesics, bivalent and more recently, bitopic ligands have emerged as valuable tool compounds to probe these receptors. The activity of bivalent and bitopic ligands rely greatly on the allosteric nature of the GPCRs. Bivalent ligands consist of two pharmacophores, each binding to the individual orthosteric binding site (OBS) of the monomers within a dimer. Bitopic or dualsteric ligands bridge the gap between the OBS and the spatially distinct, less conserved allosteric binding site (ABS) through the simultaneous occupation of these two sites. Bivalent and bitopic ligands stabilize distinct conformations of the receptors which ultimately translates into unique signalling and pharmacological profiles. Some of the interesting properties shown by these ligands include improved affinity and/or efficacy, subtype and/or functional selectivity and reduced side effects. This review aims at providing an overview of some of the bivalent and bitopic ligands of the opioid receptors and, their pharmacology in the hope of inspiring the design and discovery of the next generation of opioid analgesics.