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Targeting Acinetobacter baumannii lipase by coniferous species through metabolomics supported approach

Abstract The opportunistic pathogen Acinetobacter baumannii is a particularly problematic nosocomial threat worldwide, leading to high morbidity and mortality rates due to its multiple resistance mechanisms, including the production of lipolytic enzymes. Herein, the aerial parts of three coniferous plants, Pinus canariensis C. Sm. (PC), Cupressus lusitanica Mill. (CL), and Cupressus arizonica Greene. (CA), were extracted and fractionated. Among these, the CA extract followed by CL and then PC, exhibited the highest inhibition of bacterial lipase activity, with half-maximal inhibitory concentration (IC50) values of 1117 ± 87, 1278 ± 62, and 1926 ± 104 µg/mL, respectively. The methylene chloride fractions of CA and CL extracts exhibited the highest inhibition of bacterial lipase activity, with IC50 (940 ± 25 µg/mL and 1103 ± 155 µg/mL), respectively. The metabolite profile of the three extracts, along with their most active fractions, were determined using liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry (LC-QTOF-MS/MS). Interestingly, the metabolite profiles of CL extracts were established here for the first time. A total of 99 secondary metabolites from diverse classes were identified across all samples. Among these, four metabolites were isolated: 3,5-di-p-coumaroylquinic acid, epicatechin, cupressuflavone, and rutin. The biflavonoid cupressuflavone showed the lowest IC50 value (3812 ± 450 µg/mL). Additionally, partial least squares was applied to assess the key metabolites contributing to the differentiation of the studied bioactivity. Consequently, this study provides novel insights into the bioactivity potential of coniferous plants, demonstrating their value as a natural source of antivirulence agents against the A. baumannii lipase enzyme.

Author Correction: Foxp3 + Treg-derived IL-10 promotes colorectal cancer-derived lung metastasis

Retraction Note: Overexpression of MAP3K3 promotes tumour growth through activation of the NF-κB signalling pathway in ovarian carcinoma

Dynamic life cycle impact assessment (DLCIA) in a sustainable building planning process

Abstract Building sector significantly contributes to the anthropogenic environmental impacts. To promote sustainable construction, life cycle assessment (LCA) serves as a useful tool to quantify the environmental impacts of a building and suggest improvement solutions. It is widely acknowledged by various regional and international regulations and is mandated for new buildings in the European Union. While the conventional LCA often fails to capture the dynamics in a building’s life cycle, this study enhances the plausibility of building LCA by implementing a dynamic life cycle impact assessment (DLCIA) for a solid masonry building, evaluating improvement solutions across its product and End-of-Life (EoL) phases. Our DLCIA approach, aligned with Intergovernmental Panel on Climate Change Assessment Report (IPCC AR) 6, provides a transparent and clear calculation process of global warming potential (GWP) overtime and a comprehensible comparison with the conventional static calculation. We demonstrate that the dynamic GWP calculations based on the DLCIA approach are consistently 5–7% higher than static counterparts, successfully capturing the continuous decay of GHG emissions in the atmosphere and the environmental impact of each emission event. Applied to improvement solutions, this method guided strategies that achieved a 31.52% reduction in total GWP. Furthermore, integrating a dynamic circular recycling model into the improvement solutions in the EoL phases highlights the potential of combining multiple dynamic factors and critically discusses the concept of circular economy. To promote circular economy in construction, it is essential not only to improve the conversion rate of waste materials into compounds for virgin materials but also to explore cross-material recycling and recycling among multiple building entities. Future dynamic LCA (DLCA) studies should integrate DLCIA with other dynamic factors to enable more comprehensive and systematic assessments.

The world’s largest cities under climate change and their adaptive capacity to rising heat

Abstract We quantify future urban heat exposure and adaptation capacity for the 1563 largest global cities, for the first time globally integrating climate projections, urban morphology, and economic capacity. We use high-resolution mean annual temperature (MAT) projections under SSP1-2.6, SSP3-7.0, and SSP5-8.5. These are combined with Local Climate Zone (LCZ) profiles and downscaled socioeconomic data, evaluated consistently within morphological city boundaries. With this framework, we identify cities projected to exceed a 29 °C MAT threshold by 2071–2100. The number of threshold-exceeding cities is projected to rise from 17 (2011–2040) to 217 (2071–2100), exposing up to 320 million residents. Cities with compact built-up forms show higher exposure, while responsiveness to eight expert-curated adaptation measures (e.g., reflective materials, greening, water bodies) and GDP distributions reveal large regional disparities in adaptive capacity. European cities face the steepest relative warming (median + 4 °C under SSP5-8.5), while African and South American cities, despite smaller increases (+2.7 to 3.2  °C), confront higher baseline heat. Our framework demonstrates how morphology- and economy-informed adaptation planning can spatially target measures to safeguard urban habitability in a warming world.

A versatile Lepidium sativum bioassay for use in ecotoxicological studies

Abstract This study presents a straightforward and efficient bioassay with garden cress ( Lepidium sativum L.) for ecotoxicological analyses. Cress seedlings grow upright in hanging plastic bags on chromatography paper soaked with the test substance. Scans of the bags easily allow digital measurement of the length of the seedlings after the growth period. Suitability of this test system was examined by treating cress with different concentrations of several heavy metal compounds (cadmium nitrate, copper sulphate, iron sulphate, lead nitrate, manganese chloride, zinc chloride) and sodium chloride. Germination rate, length of shoot and root, total length, and root-to-shoot ratio of the seedlings were measured. Calculated values for half maximal effective concentration (EC50) showed that the used heavy metal compounds affected root length, total length, and root-to-shoot ratio of cress in the following order of toxicity: copper > cadmium > iron > lead > zinc > manganese. The results of our experiments indicate that the cress bioassay presented is an efficient and suitable approach for future investigations on water-soluble ecotoxicologically relevant substances.

Using UV and FTIR spectroscopy for discrimination among vicia seeds with emphasis on UV based multivariate modelling

Abstract Legume Seeds of Vicia are cultivated and consumed worldwide for their nutritional value and bioactive compounds. Notably, Vicia faba (fava bean) seeds, with their many cultivars or varieties, are deeply rooted in cuisines of the Middle East and across the globe. In this work, simple and fast spectroscopic techniques, including UV and FT-IR spectroscopy, were used in combination with multivariate statistical techniques not only to discriminate among different varieties of fava beans but also to distinguish them from other Vicia legumes, such as Vicia sativa and Vicia monantha . In addition, the total phytochemical phenolics and flavonoids, and in vitro radical scavenging activity were assessed. Preliminary exploratory data analysis using PCA on both UV and FT-IR spectra was capable of distinguishing the seeds of fava bean varieties from other Vicia species. On the other hand, the FT-IR was limited in distinguishing between the varieties of fava beans compared to the UV spectra. Therefore, UV spectra were subjected to unsupervised techniques, PCA and HCA, and supervised classification techniques, SIMCA and PLS-DA, to construct useful discrimination models for eight varieties of fava beans. PCA and HCA successfully segregated the eight fava bean varieties into three informative clusters: the first cluster for the five traditional commercial Egyptian varieties, the second cluster for the two new Egyptian varieties Maryout 2 and 3, and the third cluster for the Spanish variety Luz de Otoño. Furthermore, SIMCA and PLS-DA models demonstrated good separation among these three classes of fava beans, with 100% classification accuracy for the validation set samples. In addition, the varieties of fava beans and other Vicia species showed a diverse content of Phenolics, flavonoids, and radical scavenging capacity, with the traditional Egyptian varieties of Sakha4 and Giza 843, as well as Vicia sativa and Vicia monantha , being the best. In conclusion, for the first time, UV spectroscopy combined with multivariate techniques could serve as a simple and fast method to distinguish between some Vicia seeds. Additionally, Vicia sativa , Vicia monantha , and the fava bean varieties Sakha 4 and Giza 843 might be superior to others in developing functional foods and phytopharmaceuticals.

Enhancing the in vitro anticancer efficacy of Paclitaxel against triple-negative breast cancer via an exopolysaccharide from a haloalkaliphilic archaeal strain

Abstract Exopolysaccharides (EPSs) produced by haloalkaliphilic archaea exhibit unique properties contributing to varied industrial and medicinal applications. This study explored the anticancer therapeutic potential of an EPS derived from a haloalkaliphilic archaeal strain, which has not been previously isolated from solar salterns on the northwestern Mediterranean Egyptian coast. The selected isolate was identified as Natrialba chahannaoensis BG8. A Plackett–Burman (PB) fractional factorial design determined NaCl as the only significant variable positively affecting EPS production. The partially purified EPS analytical characterization revealed a carbohydrate content of 75.16 ± 2.1%, with Fourier transform infrared (FT-IR) spectroscopy; moreover, GC–MS suggested a heteropolysaccharide nature. For the first time, a neutral red uptake (NRU) assay revealed the anticancer effect of EPS against multiple human cancerous cell lines; A-431 epidermoid cancer (IC50= 8.8 mg/mL), MCF-7 breast cancer (IC50= 12.7 mg/mL), MDA-MB-231 triple-negative breast cancer (TNBC) (IC50= 9.4 mg/mL), and HCT-116 colorectal cancer (IC50= 10.4 mg/mL) cells. Additionally, EPS exhibited previously reported anti-hepatoblastoma activity against HepG-2 cells (IC50= 21.2 mg/mL). The cell cycle analysis results suggested that the antiproliferative effect on MDA-MB-231 cells occurred through S phase arrest. Notably, synergistic interactions between EPS and the anticancer drug paclitaxel (PXL) were recorded in MDA-MB-231 cells via the Chou‒Talalay approach. Furthermore, an unpaired Student’s t test disclosed that EPS induced a significant rise in the apoptosis marker caspase-3 (casp-3). This increase was higher than PXL alone and combined with EPS. However, the combined treatment exceeded PXL in significantly reducing MDA-MB-231 cells’ migratory potentials, as evidenced by wound healing and matrix metalloproteinase-9 (MMP-9) determination assays. It also reduced the levels of the oxidative stress marker malondialdehyde (MDA). The EPS of N. chahannaoensis BG8 displayed a pro-apoptotic action against the TNBC cells MDA-MB-231, surpassing that of PXL. Furthermore, PXL–EPS combination reduced PXL-associated toxicity and increased metastasis control. These findings put EPS as a recommended safe complementary therapy, more effective than PXL monotherapy.

The dynamics of stomatal closure of Arabidopsis thaliana determined by terahertz spectroscopy and a water transport model

Abstract Terahertz (THz) time-domain spectroscopy allows the detection of temporal changes of plant water content in vivo and non-destructively, for example over the course of the day or at the onset of drought stress. By studying a wildtype and a genetically modified variant of Arabidopsis thaliana, we observed significant differences in their dehydration dynamics. For a better understanding of the underlying processes, we modelled this behaviour with a simple rate equation model, compared the results with the experimental data and correlated our model with the biological regulatory mechanisms. In particular, under drought stress, we found an almost three times ( $$2.80\pm {}0.51$$ ) higher maximal stomatal opening in the mutant than in the wildtype. Over the course of the day, the degree of stomatal opening shows an exponential decrease with a half-life $$t_{1/2}$$ of $$12.3\pm {}$$ 2.6 h in the wildtype and $$3.4\pm {}$$ 0.8 h in the mutant.

Stature prediction using anthropometric measurements of the hand in a sample of adult Egyptian, Arab, and Malaysian populations

Abstract Among the major parameters of any biological profile, stature holds particular significance in forensic investigations. It may be problematic to have the hands of the victim in an integral form at different crime scenes. This study aimed to predict stature using different hand, fingers, and phalanges measurements in a sample of Egyptians, Arabs from the Gulf area and Malaysians. The present cross-sectional study included 300 adult, male and female healthy subjects (100 Egyptians, 100 Arabs from the Gulf area, and 100 Malaysians). Measurements included hand length, hand breadth, each finger length, and each phalanx length from the right hands of the study participants using a digital vernier calliper. Significant differences among the three studied populations regarding stature, together with hand, finger, and phalanx measurements. Males had significantly higher values than females in the three studied groups (Egyptians, Arabs and Malaysians), according to stature and all studied hand measurements. The multiple regression models obtained were population- and sex-specific, and they had higher estimates of reliability than the simple regression models. It is worth noting that simple linear regression models can be more useful when only part of a damaged hand is found at the crime scene. This scenario is more common than we might think, especially in mass disasters or murders, making the research on these models highly relevant.

Investigation of different LSTM-based encoder-decoder neural networks for vehicle speed prediction

Abstract In this work, different Long Short-Term Memory (LSTM) encoder-decoder artificial neural networks are investigated. These networks differ in their complexity. The aim of this work is to evaluate whether complex networks are necessary for vehicle speed predictions or whether simple and less computing power intensive networks can handle this task also with sufficient accuracy. For this task, simulatively generated data is used, which is created with a Simulation of Urban Mobility (sumo) traffic simulation from an urban traffic scenario from the city center of Darmstadt, Germany. The data generating process is described as well as the data handling and processing. For the investigated network architectures, grid searches are executed to investigate the sensitivity to four main hyperparameters, the mini batch size, the learning rate, the weight decay and the number of LSTM cells within each layer. The results are then evaluated based on their accuracy regarding a test data set and based on the computing power required for training. The results presented in this work indicate that also less complex models can handle the task of speed predictions and, at least for these applications, simple models should be considered in order to save computing power and, as a consequence, also energy.

Triglyceride-glucose index combined with estimated pulse wave velocity improves stroke risk stratification in the CHARLS cohort

<i>Drosophila</i> Ahcy is a redox sensor that modulates gene expression to protect against light stress–induced retinal degeneration

One-carbon metabolism influences gene expression by providing methyl units for DNA, RNA, and histone methylation. Robust methylation requires rapid hydrolysis of the methylation by-product S -adenosylhomocysteine (SAH) by S -adenosylhomocysteinase (Ahcy). Ahcy is essential for maintaining methylation potential; however, the mechanisms governing its enzymatic activity, particularly in response to cellular stress, remain largely uncharacterized. Here, we show Ahcy is a redox-sensitive enzyme that is inhibited by oxidation of a conserved cysteine, C195, in vitro resulting in elevated SAH levels upon oxidative stress in vivo. We leveraged High-Throughput Desorption Electrospray Ionization Mass Spectrometry to directly quantify Ahcy enzymatic activity and observed that H 2 O 2 -induced oxidation significantly reduced its catalytic efficiency. Notably, while C195 is essential for enzymatic activity in Drosophila melanogaster and humans, this residue is not conserved in Caenorhabditis elegans Ahcy that is also insensitive to H 2 O 2 . Structural analysis revealed that C195 is positioned near NAD + in the active site, close to a second cysteine residue that is also lacking in C. elegans Ahcy. Ahcy oxidation is neuroprotective in a Drosophila light stress model that increases oxidative stress. Moreover, Ahcy knockdown suppresses light stress–induced gene expression changes in photoreceptors, although this response is uncoupled from changes in H3K4me3 and H3K27me3 levels, which were previously reported to alter in response to Ahcy knockdown in cultured cells. Thus, the one-carbon metabolism enzyme Ahcy senses changes in cellular redox homeostasis through a conserved cysteine residue that alters its activity, enabling rapid changes in gene expression that enable a neuroprotective response.

Active billiards: Engineering boundaries for the spatial control of confined active particles

Unlike gas molecules at equilibrium, the spatial organization of self-propelled particles can be very sensitive to what happens at the boundaries of their container. Understanding the link between boundary phenomena and bulk stationary distributions could enable the design of optimized container shapes for the geometric control of confined active particles. Here, we propose a boundary method based on the flux transfer formalism typical of radiometry problems, where surface elements transmit and receive “rays” of active particles with infinite persistence length. We demonstrate the power of this boundary method in the case of the swimming microalgae Euglena gracilis trapped in light-defined billiard geometries. Quite surprisingly, we found that Euglena scatters with a nearly Lambertian cosine law, resembling the behavior of blackbody radiation and consequently resulting in nearly uniform distributions inside simple cavity geometries. Nevertheless, leveraging our boundary method, we were able to design a stacked multistage billiard geometry, with a connection scheme between subunits that breaks spatial symmetry and achieves an exponential amplification of cell concentration between its two ends. Our method can be applied to confined active matter in contexts ranging from spatial control and sorting of microorganisms to the design of efficient navigation strategies for microscopic and macroscopic robots.

Correction for Tobias et al., Biodiversity conservation requires integration of species-centric and process-based strategies

Historical and experimental evidence that inherent properties are overweighted in early scientific explanation

Scientific explanation is one of the most sophisticated forms of human reasoning. Nevertheless, here we hypothesize that scientific explanation is susceptible to some of the same biases that influence everyday thinking—particularly during the initial stages of theory building, when scientists are first grappling with complex phenomena and are thus more likely to rely on explanatory “guesses.” Specifically, we investigated whether scientific explanation exhibits an inherence bias—a tendency to explain phenomena through inherent or intrinsic features rather than extrinsic factors such as context or relations. Consistent with this hypothesis, a comprehensive analysis of major explanatory transitions across the history of Western science revealed that initial scientific explanations systematically favored inherent properties, while subsequent explanations incorporated extrinsic factors more consistently. Seven experiments with lay participants (both adults and children; N = 1,673) and two experiments with practicing scientists from top departments worldwide ( N = 275) provided converging evidence for this bias and identified the psychological mechanisms involved. When explaining unfamiliar phenomena, even leading scientists showed a robust tendency to overweight inherent properties and underweight extrinsic factors relative to established scientific understanding. This bias appears rooted in basic cognitive constraints on attention and memory that excessively narrow the space of hypotheses initially considered. These findings advance our understanding of both the psychology of explanation and the development of scientific knowledge, while suggesting specific ways to improve scientific training and education.

Rootworm resistance to Bt associated with increased injury to corn pyramids combining Bt proteins and RNA interference

Crops genetically engineered to produce insecticidal proteins from the bacterium Bacillus thuringiensis (Bt) have revolutionized pest management, but their benefits have been reduced by evolution of practical resistance in at least 31 cases. To delay evolution of resistance, farmers have shifted from crops producing one Bt protein to crops called pyramids that produce two or more Bt proteins or other traits targeting each pest. Here, we focus on resistance to transgenic corn pyramids in the western corn rootworm ( Diabrotica virgifera virgifera ) and northern corn rootworm ( Diabrotica barberi ), which cost farmers in the United States $2 billion yearly in yield losses. We analyzed 998 relevant data values for 2005 to 2023 from 12 published field studies. The results support the hypothesis that rootworm resistance to Bt proteins Cry3Bb and Gpp34/Tpp35Ab reduces the efficacy of pyramids that produce one or both of these proteins and an RNA interference trait (DvSnf7) targeting rootworms, despite no apparent strong cross-resistance between the Bt proteins and DvSnf7. The reduced efficacy of pyramids producing Bt proteins and DvSnf7 entails increased root injury and emergence of adult beetles. Efficacy of DvSnf7 was substantially lower for reducing root injury than emergence. Because root injury decreases yield, the increased root injury has immediate practical consequences. More sustainable control may be achieved by deploying pyramids with traits that are each highly effective against rootworms, increasing the abundance of host plants that do not target rootworms, and combining transgenic corn with crop rotation and other control tactics in integrated pest management programs.

Stress-induced preference for antioxidants by <i>Drosophila</i>

In an ever-changing environment, animals make optimal decisions to ensure their well-being. Faced with limited food sources, they often seek foods that provide the nutrients they require to maintain homeostasis. Under extreme circumstances (e.g., infection), they may exhibit ingestive behaviors, such as seeking out substances (e.g., toxins) that suggest self-medication. Few studies, however, have investigated the mechanisms that ensue self-medication. Here, we report the selective intake of antioxidants by Drosophila melanogaster during a period of heat stress or sleep deprivation. This preference was alleviated by prefeeding them vitamin C or dehydroascorbic acid (DHA) before exposure to stress. Heat stress led to an increase in reactive oxygen species (ROS) levels in the gut, which was alleviated by the intake of vitamin C. Heat stress reduced vitamin C in hemolymph, whereas the consumption of vitamin C or DHA increased it. Furthermore, the intake of vitamin C ameliorated the intestinal barrier dysfunction and extended the survival of flies that had been exposed to chronic heat stress. The heat-induced preference for vitamin C appears to develop independently of the known peripheral chemosensory receptors for this micronutrient. We propose that fruit flies possess an interoceptive mechanism that mediates the detection of vitamin C to overcome environmental challenges.

Divergent sustainability profiles of molnupiravir synthesis routes are governed by solvent use and process design

This study presents a comparative cradle-to-gate environmental and economic evaluation of nine synthetic routes for Molnupiravir (EIDD-2801), a broad-spectrum antiviral drug. Integrating Life Cycle Assessment (LCA) with Life Cycle Costing (LCC), we quantified the environmental impacts alongside capital and operational costs, net present costs, and break-even prices of each route. The results reveal significant variation across the schemes, with Schemes #1 and #2 exhibiting the highest impacts and costs due to intensive use of chloroform and diethyl ether, while Scheme #8 demonstrated the lowest impacts and costs, benefitting from higher batch output, greener solvents, and process intensification. Scenario analyses showed that solvent recovery improves sustainability only when high recovery rates are combined with clean electricity; otherwise, the additional energy demand may offset benefits. Scale-up analysis confirmed that higher production scales substantially reduce per-gram impacts and costs, supporting economies of scale. These findings highlight the critical role of solvent management, energy sourcing, the use of sustainability assessment at the earliest stages of innovation, and process design in aligning green chemistry with economic viability. The proposed integrated LCA-LCC framework provides transferable insights to guide sustainable pharmaceutical manufacturing and supports the development of evidence-based policy for greener antiviral drug production.

A model for boundary-driven tissue morphogenesis

Tissue deformations during morphogenesis can be active, driven by internal processes, or passive, resulting from stresses applied at their boundaries. Here, we introduce the Drosophila hindgut primordium as a model for studying boundary-driven tissue morphogenesis. We characterize its deformations and show that its complex shape changes can be a passive consequence of the deformations of the active regions of the embryo that surround it. First, we find an intermediate characteristic “triangular keyhole” shape in the 3D deformations of the hindgut. We construct a minimal model of the hindgut primordium as an elastic ring deformed by active midgut invagination and germ band extension on an ellipsoidal surface, which robustly captures the symmetry-breaking into this triangular keyhole shape. We then quantify the 3D kinematics of the tissue by a set of contours and find that the hindgut deforms in two stages: An initial translation on the curved embryo surface followed by a rapid breaking of shape symmetry. We extend our model to show that the contour kinematics in both stages are consistent with our passive picture. Our results suggest that the role of in-plane deformations during hindgut morphogenesis is to translate the tissue to a region with anisotropic embryonic curvature and show that uniform boundary conditions are sufficient to generate the observed nonuniform shape change. Our work thus provides a possible explanation for the various characteristic shapes of blastopore-equivalents in different organisms and a framework for the mechanical emergence of global morphologies in complex developmental systems.