Browse Articles
Discover research articles across all indexed journals
Crossover dynamics of non-Fickian ionic diffusion in solids
Genome analysis of Channel millet reveals a wild dodecaploid shaped by environmental variability
Optimized spatial planning offers a dual solution for managing urban heat and air pollution in humid subtropical climates
Multi-ancestry transcriptome-wide association studies uncover insights into breast cancer genetics and biology
A labile sulfur ligand in a three-cysteine-coordinated [2Fe−2S] cluster mediates sulfide sensing in NreB
Structure-based screening and a conformational biosensor identify a GPR183 inverse agonist and an activation switch
Abstract GPR183 is a chemotactic GPCR involved in immune cell migration. Using AI-driven virtual screening and biophysical assays, we identify inverse agonists. From 70 compounds and a subsequent hit expansion, compound 78 emerges as a potent inhibitor of constitutive and agonist-induced Gi signaling as well as β-arrestin2 recruitment. Binding within the receptor core is confirmed by a conformational biosensor, molecular dynamics simulations, and mutagenesis. The compound also blocks agonist-driven migration of peripheral blood mononuclear cells ex vivo with very high potency. Additionally, our analyses reveal key features of GPR183 activation, highlighting tyrosine 260 (Y260 6.51 ) in transmembrane helix 6 as critical. Mutation of this residue alters compound 78 efficacy as well as induces receptor signaling bias, indicating a switch mechanism. Overall, this study provides tools to probe GPR183 function, identifies a chemical scaffold, and advances understanding of receptor activation, supporting therapeutic targeting in inflammatory, autoimmune, and cancer-related diseases.
Beyond petrochemicals: challenges and opportunities in industrial-scale biomanufacturing
Identification and characterisation of an elusive bacterial enzyme system for chloromethane dehalogenation
Abstract Chloromethane, a toxic gas primarily produced naturally, contributes to stratospheric ozone destruction. The anaerobic acetogen Acetobacterium dehalogenans can utilise chloromethane as a carbon and energy source, but the associated dehalogenase/methyltransferase has remained elusive. Through comparative transcriptomics we identify a gene cluster, cdmBCA , which encodes a corrinoid-dependent methyltransferase system distinct from the characterised Cmu system used for chloromethane degradation in aerobic methylotrophs. Biochemical characterisation reveals that the Cdm system reacts with other haloalkanes, but not with methoxylated aromatics, unlike closely related O -demethylases. X-ray structural analysis of the protein CdmB shows a hydrophobic channelling system directing haloalkanes towards cobalamin-dependent activation. Homologous proteins are found in anaerobic prokaryotes, particularly within the phyla Bacillota and Asgardarchaeota, suggesting previously unidentified microbial transformation of chloromethane in the environment. Discovery of the Cdm dehalogenation/methyltransferase system sheds light on the microbial contribution to the global chloromethane cycle.
The spatial proteome of the Plasmodium falciparum schizont illuminates the composition and evolutionary trajectories of its organelles
Abstract Malaria is caused by apicomplexan parasites of the genus Plasmodium , with all malaria symptoms and pathology caused by parasite stages that develop within, or transit between, host erythrocytes. The ability of Plasmodium cells to parasitise erythrocytes depends on distinctive intracellular compartments associated with invasion, as well as the development of unique cellular niches within the infected host cell. However, our understanding of the biology of the malaria parasite is limited by the fact that a large proportion of the parasite’s proteome has no known cellular location or function. To address this problem, we have generated comprehensive high-resolution maps of protein subcellular localisation for the invasive stage of the erythrocytic life cycle of Plasmodium falciparum , the major cause of malaria mortality. Using the spatial proteomics technique hyperplexed Localisation of Organelle Proteins by Isotopic Tagging (hyperLOPIT) we generated data for 3000 P. falciparum proteins expressed in late schizont stages. Our hyperLOPIT data resolve 24 distinct cellular niches, and using supervised machine-learning we can classify 1646 proteins into one of these compartments including exported sites within the host cell. Through comparative genomic analyses our data resolve the spatial patterns of cell evolution that have shaped the development of Plasmodium species and ongoing adaptive pressures and responses that challenge our efforts to manage these major disease-causing organisms.
An implantable mechano-electro cascade platform synchronizes neuro-muscle repair
Tunable gene control via RNA splicing with a clinically approved small molecule
Emergent and controllable behaviors of Janus swarmalator collectives
A universal scaling law for active diffusion in complex media
Fmp30p is a mitochondrial phosphatidylinositol hydrolase that modulates CoQ biosynthesis
Abstract Organellar membranes feature bespoke lipid compositions; however, the enzymes that craft these compositions and the functional implications these lipids exert on membrane protein organization and activity are insufficiently understood. Here, we discover that the inner mitochondrial membrane protein Fmp30p, a member of the metallo-β-lactamase superfamily, displays phospholipase type D activity toward phosphatidylinositol (PI)—a notable mitochondrial membrane component with unclear functional roles. FMP30 deletion caused substantial and specific elevation of PI species in purified mitochondria. Augmenting mitochondrial PI levels in this way, or by targeting established PI-modifying enzymes to the organelle, increased coenzyme Q (CoQ) biosynthesis concomitant with elevated expression of CoQ-related enzymes and enhanced CoQ metabolon formation. Collectively, our work establishes Fmp30p as a mitochondrial PI phospholipase related to CoQ biology and reveals the broader importance of inner membrane PI in regulating mitochondrial function.
Aggregation-induced emission luminogen in ternary organic bulk-heterojunction for efficient perovskite-organic tandem solar cells
Abstract Perovskite-organic tandem solar cells (TSCs) have recently garnered significant attention due to their potential for high power conversion efficiency (PCE) and excellent stability. However, their development has been significantly hindered by the large open-circuit voltage ( V OC ) deficit in organic sub-cells, primarily caused by severe non-radiative recombination, which is closely related to the electroluminescence quantum efficiency (EQE EL ) and the photoluminescence quantum yield (PLQY). However, mainstream non-fullerene molecules exhibit low PLQY due to the aggregation-caused quenching (ACQ) effect. In this study, an aggregation-induced emission (AIE)-active molecule (TPE-BTA3) featuring a three-dimensional rotor-stereo configuration is rationally designed with an exceptional PLQY of 68%. When TPE-BTA3 is introduced into binary Organic solar cells (OSCs), it not only dramatically enhances the PLQY of alloy-acceptor but also strengthens the utilization of near-infrared photons, leading to a significant increase in V OC and short-circuit current ( J SC ). By integrated above optimized ternary organic bulk-heterojunction with a wide-bandgap (1.85 eV) perovskite, the constructed perovskite-organic TSCs achieve a surprising PCE of 26.5% (certified as 25.8%). This work establishes a conceptual bridge between high-efficiency photovoltaics and AIE molecular design paradigms.
Machine learning-driven image encryption using SVM for enhanced security and computational efficiency
Machine learning and SHAP interpretation for predicting coronary heart disease-diabetes comorbidity with dietary antioxidants
A state-adaptive booby optimization algorithm for engineering design and medical data applications
Abstract Balancing global exploration and local exploitation remains a central challenge in metaheuristic optimization, particularly for high-dimensional, nonlinear, and constrained problems encountered in engineering design and medical data analysis. This paper proposes the Booby Optimization Algorithm (BOA), a state-adaptive population-based metaheuristic inspired by avian dive-foraging behavior but formulated entirely through mathematical and computational mechanisms. BOA employs an adaptive state variable to regulate step magnitude and dynamically control transitions between global exploratory search and local exploitative refinement, augmented by nonlinear motion dynamics, stochastic perturbations, and a recovery strategy for diversity preservation. The algorithm is extensively evaluated on CEC benchmark functions with dimensionalities up to 100, four classical constrained engineering design problems, and feature selection and classification tasks on 14 real-world medical datasets using BOA-based hybrid models. Experimental results demonstrate that BOA consistently outperforms several state-of-the-art metaheuristics in terms of convergence speed, solution accuracy, and robustness, achieving near-optimal or best-known solutions with significantly reduced mean error and variance. In medical classification tasks, BOA-based feature selection attains a mean accuracy of 96.20% ± 1.05, alongside high sensitivity and specificity while effectively reducing feature dimensionality. These improvements are supported by rigorous statistical validation using Friedman, Nemenyi, and Wilcoxon tests ( p < 0.001). Overall, the results establish BOA as an efficient and robust adaptive optimization framework suitable for complex engineering optimization and medical decision-support applications.
Cold SiO2-rich slabs reaching the CMB revealed by the seifertite phase boundary
Abstract A cold silica (SiO 2 )-rich subducted slab creates notable heterogeneity above the core-mantle boundary (CMB), influencing the evolution of the Earth’s mantle. This slab may exhibit characteristic anomalies in the longitudinal and shear wave seismic velocity above the CMB, attributed to the SiO 2 phase transition into its dense polymorph, seifertite. However, the transition depth remains unclear due to the often-observed metastable phases in experiments. To address this long-standing challenge, we conducted laser-heated diamond anvil cell experiments with synchronised rapid X-ray diffraction measurements alongside theoretical calculations. The slope of the seifertite phase boundary was less steep than previously estimated, and consequently, the temperature profile of the slab crosses the boundary twice, like the post-perovskite transition. We observed a decrease in shear wave velocity beneath Hawaii and Central America, and we found anti-correlation in seismic wave velocities matching the depth range of the seifertite transition in a cold slab beneath Central America. This may provide evidence that a cold SiO 2 -rich slab descends towards the CMB.