Browse Articles
Discover research articles across all indexed journals
Experimental study and geochemical modeling of the effect of asphaltene during smart water flooding in carbonate reservoirs
PLM-interact: extending protein language models to predict protein-protein interactions
Abstract Computational prediction of protein structure from amino acid sequence alone has been achieved with unprecedented accuracy, yet the prediction of protein-protein interactions remains a challenge. Here, we assess the ability of protein language models (PLMs), routinely applied to protein folding, to be retrained for protein-protein interaction prediction. Existing models that exploit PLMs use a pre-trained PLM feature set, ignoring that the proteins are physically interacting. We propose PLM-interact, which goes beyond single proteins by jointly encoding protein pairs to learn their relationships, analogous to the next-sentence prediction task from natural language processing. This approach achieves state-of-the-art performance in a widely adopted cross-species protein-protein interaction prediction benchmark: trained on human data and tested on mouse, fly, worm, E. coli and yeast. In addition, we develop a fine-tuning method for PLM-interact to detect mutation effects on interactions. Finally, we report that the model outperforms existing approaches in predicting virus-host interaction at the protein level. Our work demonstrates that large language models can be extended to learn the intricate relationships among biomolecules from their sequences alone.
Cost effectiveness analysis of low dose computed tomography lung cancer screening in Chinese population
Barcode-free hit discovery from massive libraries enabled by automated small molecule structure annotation
Abstract Affinity-selection platforms are powerful tools in early drug discovery, but current technologies – most notably DNA-encoded libraries (DELs) – are limited by synthesis complexity and incompatibility with nucleic acid-binding targets. We present a barcode-free self-encoded library (SEL) platform that enables direct screening of over half a million small molecules in a single experiment. SELs combine tandem mass spectrometry with custom software for automated structure annotation, eliminating the need for external tags for the identification of screening hits. We develop efficient, high-diversity synthesis protocols for a broad range of chemical scaffolds and benchmark the platform in affinity selections against carbonic anhydrase IX, identifying multiple nanomolar binders. We further apply SELs to flap endonuclease 1 (FEN1) – a disease related DNA-processing enzyme inaccessible to DELs – and discover potent inhibitors. Taken together, screening barcode-free libraries of this scale all at once represents an important development, enables access to novel target classes, and promises substantial impact on both academic and industrial early drug discovery.
Fast highway abandoned object detection via block-based multi-group foreground extraction
Structural basis of drug recognition by human MATE1 transporter
Abstract Human MATE1 (multidrug and toxin extrusion protein 1) is highly expressed in the kidney and liver, where it mediates the final step in the excretion of a broad range of cationic drugs, including the antidiabetic drug metformin, into the urine and bile. This transport process is essential for drug clearance and also affects therapeutic efficacy. To understand the molecular basis of drug recognition by hMATE1, we determined cryo-electron microscopy structures of the transporter in complex with the substrates 1-methyl-4-phenylpyridinium (MPP) and metformin and with the inhibitor cimetidine. The structures reveal a shared binding site located in a negatively charged pocket in the C-lobe of the protein. We functionally validated key interactions using radioactivity-based cellular uptake assays using hMATE1 mutants. Molecular dynamics simulations provide insights into the different binding modes and dynamic behaviour of the ligands within the pocket. Collectively, these findings define the structural basis of hMATE1 substrate specificity and shed light on its role in drug transport and drug-drug interactions.
Effect of field of view variation on CTP assessment of infarct core and penumbra in acute ischemic stroke
Author Correction: Helioseismic inference of the solar radiative opacity
Inferior position of the coracoid process increases the probability of risk factors for rotator cuff tear
Signatures of quantum spin liquid state and unconventional transport in thin film TbInO3
Abstract Quantum spin liquids, where the frustrated magnetic ground state hosts highly entangled spins resisting long-range order to 0 K, are exotic quantum magnets proximate to unconventional superconductivity and candidate platforms for topological quantum computing. Although several quantum spin liquid material candidates have been identified, thin films crucial for device fabrication and further tuning of properties remain elusive. Recently, hexagonal TbInO 3 has emerged as a quantum spin liquid candidate which also hosts improper ferroelectricity and exotic high-temperature carrier transport. Here, we synthesize thin films of TbInO 3 and characterize their magnetic and electronic properties. Our films present a highly frustrated magnetic ground state without long-range order to 0.4 K, consistent with bulk crystals. We further reveal a rich ferroelectric domain structure and unconventional non-local transport near room temperature, suggesting hexagonal TbInO 3 as a promising candidate for realizing exotic magnetic and transport phenomena in epitaxial heterostructures.
Intelligent optimization based prestack inversion method for high resolution estimation of elastic parameters
Proximity-induced nodal metal in an extremely underdoped CuO2 plane in triple-layer cuprates
BRD2 phase separation activates super-enhancer-driven ATG7 transcription to promote ferritinophagy in depression
Confinement-enhanced valorization of contaminants in electrified hydrogenation membranes for water purification
Abstract Electrocatalytic hydrogenation offers an environmentally benign approach for contaminant valorization, but suffers from sluggish mass and electron transfer. Electrified membranes (EMs) represent an effective strategy to address these challenges, yet their structure-performance relationship remains inadequately understood. Here, we develop EMs featuring atomically dispersed Ru sites, enabling the efficient hydrogenation of nitrate, trichloroacetic acid, and phenol. A volcano-shaped relationship is observed between electrocatalytic activity and pore size. The EM with a pore size of 7 μm (EM 7 ) achieves 94% nitrate removal within 55 s, exhibiting over 97% selectivity towards ammonium and a 2.5 times higher kinetic constant (2.7 min −1 ) than that of EM with 80 μm pores (EM 80 ). However, further reducing the pore diameter to 4 μm diminishes performance. Multiphysics simulations reveal that smaller pores enhance mass transfer but worsen current distribution uniformity. Elucidating this spatial confinement effect offers a guiding design principle of cost-effective electrodes for sustainable wastewater treatment.
Multi-scenario simulation of land use change based on the objectives of cultivated land, ecological protection, and economic development in Yunnan Province, China
Endothelial RNF20 suppresses endothelial-to-mesenchymal transition and safeguards physiological angiocrine signaling to prevent congenital heart disease
Abstract Heart morphogenesis and function rely on intricate communication among distinct cardiac cell types. How their co-development and crosstalk are coordinated is largely unexplored. Our study unveils key functions of the histone H2B ubiquitin (H2Bub1) ligase RNF20 in second heart field development and cardiac endothelial cells. We demonstrate that RNF20 promotes Nrg1 expression through a RNF20-H2Bub1-dependent mechanism and restrains TGF-β signaling by influencing RNA polymerase II pause release at TGF-β target genes in endothelial cells. While heightened TGF-β signaling following RNF20 loss results endothelial-to-mesenchymal transition (EndMT), both impaired Nrg1 signaling and elevated TGF-β activity contribute to abnormal cardiomyocyte proliferation and contractility. Importantly, RNF20 expression is significantly reduced in cardiac endothelial cells from congenital heart disease patients showing a positive correlation with oxygen saturation and a negative correlation with key components and downstream effectors of TGF-β signaling. In summary, our work identifies a crucial role for RNF20 in safeguarding endothelial identity and physiological angiocrine signaling, thereby ensuring proper heart development and function.
Allostatic load and risk of prostate cancer in UK Biobank
Abstract Allostatic load (AL), a biomarker of chronic stress, has been implicated in the carcinogenesis of various types of cancers. However, its role in the etiology of prostate cancer is unclear. Utilizing valuable resources from the UK Biobank, we analyzed the association between AL and subsequent risk of prostate cancer in a total of 161,964 men. Levels of AL were higher in cases than in non-cancer controls (3.47 vs. 3.35, P < 0.001). In the univariate analysis, one unit increase in AL was associated with a 5% increased risk of prostate cancer (hazard ratio (HR) = 1.05, 95% Confidence Interval (CI) 1.03, 1.06). In the multivariate Cox regression analysis, the significant association was only observed among men younger than 58 years old. The significant association was further confirmed in the categorical analysis, and compared to men with AL of 0, those with AL of 1, 2, 3, 4, 5, and ≥ 6 had a statistically significantly increased risk of prostate cancer, respectively. Additionally, we observed a more than additive joint effect between AL and polygenic risk score (PRS) of prostate cancer among younger men (< 58 years old). In summary, those findings have shown that higher AL was associated with an increased prostate cancer risk in younger men.