Browse Articles

Novel adaptive immune systems in pristine Antarctic soils

Abstract Antarctic environments are dominated by microorganisms, which are vulnerable to viral infection. Although several studies have investigated the phylogenetic repertoire of bacteria and viruses in these poly-extreme environments with freezing temperatures, high ultra violet irradiation levels, low moisture availability and hyper-oligotrophy, the evolutionary mechanisms governing microbial immunity remain poorly understood. Using genome-resolved metagenomics, we test the hypothesis that Antarctic poly-extreme high-latitude microbiomes harbour diverse adaptive immune systems. Our analysis reveals the prevalence of prophages in bacterial genomes (Bacteroidota and Verrucomicrobiota), suggesting the significance of lysogenic infection strategies in Antarctic soils. Furthermore, we demonstrate the presence of diverse CRISPR-Cas arrays, including Class 1 arrays (Types I-B, I-C, and I-E), alongside systems exhibiting novel gene architecture among their effector cas genes. Notably, a Class 2 system featuring type V variants lacks CRISPR arrays, encodes Cas1 and Cas2 adaptation module genes. Phylogenetic analysis of Cas12 effector proteins hints at divergent evolutionary histories compared to classified type V effectors and indicates that TnpB is likely the ancestor of Cas12 nucleases. Our findings suggest substantial novelty in Antarctic cas sequences, likely driven by strong selective pressures. These results underscore the role of viral infection as a key evolutionary driver shaping polar microbiomes.

A metal-trap tests and refines blueprints to engineer cellular protein metalation with different elements

Abstract It has been challenging to test how proteins acquire specific metals in cells. The speciation of metalation is thought to depend on the preferences of proteins for different metals competing at intracellular metal-availabilities. This implies mis-metalation may occur if proteins become mis-matched to metal-availabilities in heterologous cells. Here we use a cyanobacterial Mn II -cupin (MncA) as a metal trap, to test predictions of metalation. By re-folding MncA in buffered competing metals, metal-preferences are determined. Relating metal-preferences to metal-availabilities estimated using cellular metal sensors, predicts mis-metalation of MncA with Fe II in E. coli . After expression in E. coli , predominantly Fe II -bound MncA is isolated experimentally. It is predicted that in metal-supplemented viable cells metal-MncA speciation should switch. Mn II -, Co II -, or Ni II -MncA are recovered from the respective metal-supplemented cells. Differences between observed and predicted metal-MncA speciation are used to refine estimated metal availabilities. Values are provided as blueprints to guide engineering biological protein metalation.

Development and assessment of a mortality risk prediction nomogram model for pneumocystis disease in ICU within 28 days

Enhanced CH4 emissions from global wildfires likely due to undetected small fires

Abstract Monitoring methane (CH4) emissions from terrestrial ecosystems is essential for assessing the relative contributions of natural and anthropogenic factors leading to climate change and shaping global climate goals. Fires are a significant source of atmospheric CH4, with the increasing frequency of megafires amplifying their impact. Global fire emissions exhibit large spatiotemporal variations, making the magnitude and dynamics difficult to characterize accurately. In this study, we reconstruct global fire CH4 emissions by integrating satellite carbon monoxide (CO)-based atmospheric inversion with well-constrained fire CH4 to CO emission ratio maps. Here we show that global fire CH4 emissions averaged 24.0 (17.7–30.4) Tg yr−1 from 2003 to 2020, approximately 27% higher (equivalent to 5.1 Tg yr−1) than average estimates from four widely used fire emission models. This discrepancy likely stems from undetected small fires and underrepresented emission intensities in coarse-resolution data. Our study highlights the value of atmospheric inversion based on fire tracers like CO to track fire-carbon-climate feedback.

Machine learning approach for predicting tramp elements in the basic oxygen furnace based on the compiled steel scrap mix

Abstract In the blast furnace and basic oxygen furnace route, pig iron and steel scrap are used as resources for steel production. The scrap content can consist of many different types of scrap varying in origin and composition. This makes it difficult to compile the scrap mix and predict the future chemical analysis in the converter. When compiling the scrap mix, steel manufacturers often rely on experience and trials. In this paper, we present a machine learning approach based on XGBoost to predict the chemical element content in the converter. Data from around 115000 heats were analyzed and a model was developed to better predict the content of the tramp elements copper, chromium, molybdenum, phosphorus, nickel, tin and sulphur at the end of the basic oxygen furnace process. The study shows that it is possible to predict the chemical element content for tramp elements in the converter based solely on data available in advance and routinely collected without the necessity of additional sensors or analysis of input material. Given the nature of scrap classifications for (external) scrap types, this is non-trivial. Furthermore, an online model was implemented, accessible via a defined synchronous interface, which allows to optimize the use of different scrap types by predicting the chemical content at the end of the basic oxygen furnace process and simulating with new combinations of input material. Not all types of steel scrap are always available. With the model developed, new scrap input constellations can now be created to ensure that the quality of the melt is maintained. However, for very accurate predictions, the data from the upstream processes must be of high quality and quantity. Efficient scrap management, monitoring of the scrap input and confusion checks.

Cross-trait multivariate GWAS confirms health implications of pubertal timing

Abstract Pubertal timing is highly variable and is associated with long-term health outcomes. Phenotypes associated with pubertal timing include age at menarche, age at voice break, age at first facial hair and growth spurt, and pubertal timing seems to have a shared genetic architecture between the sexes. However, puberty phenotypes have primarily been assessed separately, failing to account for shared genetics, which limits the reliability of the purported health implications. Here, we model the common genetic architecture for puberty timing using a multivariate GWAS, with an effective population of 514,750 European participants. We find 266 independent variants in 197 loci, including 18 novel variants. Transcriptomic, proteome imputation and fine-mapping analyses reveal genes causal for pubertal timing, including KDM4C, LEPR, CCNC, ACP1, and PCSK1. Linkage disequilibrium score regression and Mendelian randomisation analysis establish causal associations between earlier puberty and both accelerated ageing and the risk of developing cardiovascular disease and osteoporosis. We find that alanine aminotransferase, glycated haemoglobin, high-density lipoprotein cholesterol and Parabacteroides levels are mediators of these relationships, and establish that controlling oily fish and retinol intake may be beneficial for promoting healthy pubertal development.

The effects of intermittent fasting on antioxidant and inflammatory markers and liver enzymes in postmenopausal, overweight and obese women with rheumatoid arthritis: a randomized controlled trial

Undoped ruthenium oxide as a stable catalyst for the acidic oxygen evolution reaction

Practice and application of learning curve theory in improving prescription review skills in standardized training for pharmacists in medical institutions

Schlieren texture and topography induced confinement in an organic exciton-polariton laser

Abstract Non-linearities in organic exciton-polariton microcavities represent an attractive platform for quantum devices. However, progress in this area hinges on the development of material platforms for high-performance polariton lasing, scalable and sustainable fabrication, and ultimately strategies for electrical pumping. Here, we show how introducing Schlieren texturing and a rough intra-cavity topography in a liquid crystalline conjugated polymer enables strong in-plane confinement of polaritons and drastic enhancement of the lasing properties. In high-Q distributed Bragg reflector microcavities, polariton lasing was observed at unprecedented thresholds of 136 fJ per pulse. Morphology tuning also permitted polariton lasing in more lossy metallic microcavities while maintaining a competitive lasing threshold. The facile fabrication of these cavities will drastically reduce the complexity of integrating polariton lasers with other structures and the high conductivity of metallic mirrors may provide a route to electrical pumping.

A machine learning framework for short-term prediction of chronic obstructive pulmonary disease exacerbations using personal air quality monitors and lifestyle data

Design of antiferroelectric polarization configuration for ultrahigh capacitive energy storage via increasing entropy

Anti-inflammatory and antioxidant properties of Camellia sinensis L. extract as a potential therapeutic for atopic dermatitis through NF-κB pathway inhibition

Abstract Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by immune dysregulation and excessive cytokine production. This study aimed to explore the potential of Camellia sinensis L. water extract (CSE) as a treatment for AD by the impact of CSE on inflammatory responses in keratinocytes, particularly concerning the production of inflammatory cytokines and the modulation of signaling pathways relevant to AD pathogenesis. CSE was obtained via hot water extraction from Camellia sinensis L. Ultra-high-performance liquid chromatography (UPLC) analyzed catechin and caffeine content. Cell viability was assessed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), polyphenol and flavonoid content were determined. 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay measured antioxidant activity. Enzyme-Linked Immunosorbent Assay (ELISA), western blotting, and Immunofluorescence (IF) assays examined cytokines, pathways, and protein localization, respectively. Molecular docking assessed compound binding with inflammation-related proteins. UPLC identified six CSE components including epigallocatechin (EGC) epicatechin (EC), caffeine (CF), catechin (C), epigallocatechin gallate (EGCG), and epicatechin gallate (ECG). CSE demonstrated a significant reduction in the production of inflammatory cytokines interleukin (IL)-2 and IL-6 in TNF-α/IFN-γ activated keratinocytes. Treatment with CSE inhibited the mitogen-activated protein kinase (MAPK) pathway, which resulted in decreased phosphorylation of p38, Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK). Exposure of TNF-α/IFN-γ- stimulated human keratinocytes (HaCaT) cells to CSE resulted in a 200 µg/mL dependent inhibition of p65 and signal transducer and activator of transcription 1 (STAT-1) translocation from the cytosol to the nucleus, as confirmed through immunofluorescence (IF) staining. Molecular docking simulations provided insights into the underlying mechanisms of CSE action, which supported its potential as a therapeutic agent for AD. CSE might be a potential candidate for its therapeutic efficacy for inflammatory skin conditions like AD. Thus, based on this evidence, the authors suggest that CSE should be studied further for its anti-inflammatory activities and topical application in the treatment of AD.

A high-performance GRAB sensor reveals differences in the dynamics and molecular regulation between neuropeptide and neurotransmitter release

Proteomic analysis of spinal dorsal horn in prior exercise protection against neuropathic pain

Enantioselective construction of silicon-stereogenic vinylsilanes from simple alkenes

Advanced IoT-integrated parking systems with automated license plate recognition and payment management

Abstract Urban parking management is a growing challenge with increasing vehicle numbers and limited parking space. Traditional methods often fail during peak hours, leading to inefficiencies, unauthorized usage, and revenue losses. For instance, a parking lot designed for 300 vehicles often exceeds 90% occupancy during peak times, creating congestion and billing inaccuracies. This research proposes an automated system integrating sensors, image processing, and database management to address these issues. A single camera monitors multiple parking slots, with predefined coordinates linked to IR sensors for dual verification. Image processing algorithms, including Optical Character Recognition (OCR), enable accurate license plate recognition. Testing under real-world conditions showed 95% accuracy in daylight, 90% in low light, and 93% for plates at 45-degree angles. Detection accuracy reached 88% at distances of 1.5–3 m, ensuring reliable operation even at the camera’s range limits. Occupancy tracking achieved less than a 5% error margin compared to manual methods, while the fare calculation module reduced billing errors by 90%, enhancing efficiency and revenue. The system’s scalable design supports applications in parking management, toll collection, and traffic monitoring. By improving vehicle detection, occupancy tracking, and billing accuracy, this solution addresses critical challenges in urban parking and contributes to smarter city infrastructure.

Electro-driven direct lithium extraction from geothermal brines to generate battery-grade lithium hydroxide

Association between herpes simplex virus infection and Alzheimer’s disease biomarkers: analysis within the MAPT trial

Abstract In vitro and animal studies have suggested that inoculation with herpes simplex virus 1 (HSV-1) can lead to amyloid deposits, hyperphosphorylation of tau, and/or neuronal loss. Here, we studied the association between HSV-1 and Alzheimer’s disease biomarkers in humans. Our sample included 182 participants at risk of cognitive decline from the Multidomain Alzheimer Preventive Trial who had HSV-1 plasma serology and an amyloid PET scan. Plasma Aβ42/40 ratio, neurofilament light chain and p-tau181 were also available for a sub-sample of participants. Multivariate linear regressions were performed and stratified by APOE4 genotype. The median age was 74.0 years, 85.2% were infected with HSV-1. Infected participants tended to have a lower cortical amyloid load than uninfected participants (β = -0.08, p = 0.06), especially those suspected of reactivating HSV-1 most frequently (i.e. with a high anti-HSV-1 IgG level; n = 58, β = -0.09 p = 0.04). After stratification, the association was only significant in APOE4 carriers (n = 43, β = -0.21 p = 0.01). No association was found with the plasma biomarkers. The trend toward lower cortical amyloid load in HSV-1-infected participants was unexpected given the pre-existing literature and may be explained either by a modified immune response in HSV-1 infected subjects which could favour the clearance of amyloid deposits or by a selection bias.

The clinical-stage drug BTZ-043 accumulates in murine tuberculosis lesions and efficiently acts against Mycobacterium tuberculosis

Abstract The development of granulomas with central necrosis harboring Mycobacterium tuberculosis (Mtb) is the hallmark of human tuberculosis (TB). New anti-TB therapies need to effectively penetrate the cellular and necrotic compartments of these lesions and reach sufficient concentrations to eliminate Mtb. BTZ-043 is a novel antibiotic showing good bactericidal activity in humans in a phase IIa trial. Here, we report on lesional BTZ-043 concentrations severalfold above the minimal-inhibitory-concentration and the substantial local efficacy of BTZ-043 in interleukin-13-overexpressing mice, which mimic human TB pathology of granuloma necrosis. High-resolution MALDI imaging further reveals that BTZ-043 diffuses and accumulates in the cellular compartment, and fully penetrates the necrotic center. This is the first study that visualizes an efficient penetration and accumulation of a clinical-stage TB drug in human-like centrally necrotizing granulomas and that also determines its lesional activity. Our results most likely predict a substantial bactericidal effect of BTZ-043 at these hard-to-reach sites in TB patients.