UniMAP: Universal SMILES-Graph Representation Learning

Molecular representation learning is fundamental for many drug related applications. Most existing molecular pre-training models are limited in using single molecular modality, either SMILES or graph representation. To effectively leverage both modalities, we argue that it is critical to capture the fine-grained 'semantics' between SMILES and graph, because subtle sequence/graph differences may lead to contrary molecular properties. In this paper, we propose a universal SMILE-graph representation learning model, namely UniMAP. Firstly, an embedding layer is employed to obtain the token and node/edge representation in SMILES and graph, respectively. A multi-layer Transformer is then utilized to conduct deep cross-modality fusion. Specially, four kinds of pre-training tasks are designed for UniMAP, including Multi-Level Cross-Modality Masking (CMM), SMILES-Graph Matching (SGM), Fragment-Level Alignment (FLA), and Domain Knowledge Learning (DKL). In this way, both global (i.e. SGM and DKL) and local (i.e. CMM and FLA) alignments are integrated to achieve comprehensive cross-modality fusion. We evaluate UniMAP on various downstream tasks, i.e. molecular property prediction, drug-target affinity prediction and drug-drug interaction. Experimental results show that UniMAP outperforms current state-of-the-art pre-training methods.We also visualize the learned representations to demonstrate the effect of multi-modality integration

Protein-ligand binding representation learning from fine-grained interactions

The binding between proteins and ligands plays a crucial role in the realm of drug discovery. Previous deep learning approaches have shown promising results over traditional computationally intensive methods, but resulting in poor generalization due to limited supervised data. In this paper, we propose to learn protein-ligand binding representation in a self-supervised learning manner. Different from existing pre-training approaches which treat proteins and ligands individually, we emphasize to discern the intricate binding patterns from fine-grained interactions. Specifically, this self-supervised learning problem is formulated as a prediction of the conclusive binding complex structure given a pocket and ligand with a Transformer based interaction module, which naturally emulates the binding process. To ensure the representation of rich binding information, we introduce two pre-training tasks, i.e.~atomic pairwise distance map prediction and mask ligand reconstruction, which comprehensively model the fine-grained interactions from both structure and feature space. Extensive experiments have demonstrated the superiority of our method across various binding tasks, including protein-ligand affinity prediction, virtual screening and protein-ligand docking

Simulation and Seasonal Characteristics of the Intra-Annual Heat Exchange Process in a Shallow Ice-Covered Lake

The intra-annual heat exchange process has a considerable influence on the energy circulation, material metabolism, and ecological succession of lakes. The input and output of heat in an ice-covered lake provide the basic dynamic force driving changes in the biochemical state of the lake. Based on the heat balance between the lake surface and the atmosphere, we established a thermodynamic model for calculating the thermodynamic factors of shallow inland lakes during the ice and open seasons. The data of the Ulansuhai Lake, Inner Mongolia, from two years (2012 and 2013) are used to analyze the seasonal characteristics and associated influences of the heat budget on the ecosystem. The results indicated that the monthly mean lake temperature over the past 10 years was 1.7–2.2 °C lower than in the previous 50 years. The absorbed solar radiation reached up to 210 W/m2 in 2012 and 179 W/m2 in 2013, and there were clear differences in the heat budget between the ice-covered and open seasons. The mean net heat fluxes in the ice season were −33.8 and −38.5 W/m2 in 2012 and 2013, respectively; while in the open season water, these fluxes were 62.5 and 19.1 W/m2. In the simulations, the wind was an important factor for intensive evaporation in summer and the main driver of the ice cover formation patterns in winter, involving the transmission and diffusion of material and energy in the lake. The results provide a theoretical foundation for simulating ice cover growth and ablation processes in shallow lakes. They also present data on the ecological evolution in these lacustrine environments

Utilization of cotton byproduct-derived biochar : A review on soil remediation and carbon sequestration

Biochar can improve soil health and fix CO2 by altering soil microenvironment, thus impacting the global carbon cycle and the change of soil ecological environment. Recent studies show that cotton byproduct-derived biochar is a potential effective amendment for soil improvement so that it could play an important role in agricultural and environmental conservation. In this work, research topics on cotton byproduct-derived biochar in soil in last decade and so are systematically reviewed for better understanding of the progresses of cotton byproduct-derived biochar in (i) the morphologic and physicochemical characterization, (ii) latest research hotspots and trends, (iii) the roles in soil reclamation, and (iv) relevant carbon sequestration mechanisms. Finally, the future research directions regarding cotton byproduct-derived biochar mingled to soil environment are discussed. Insight derived from this work would provide scientific basis for promoting more applications of cotton byproduct-derived biochar in soil ecological restoration and carbon fixation

Molecular mechanisms of ferroptosis and its roles in leukemia

Cell death is a complex process required to maintain homeostasis and occurs when cells are damage or reach end of life. As research progresses, it is apparent that necrosis and apoptosis do not fully explain the whole phenomenon of cell death. Therefore, new death modalities such as autophagic cell death, and ferroptosis have been proposed. In recent years, ferroptosis, a new type of non-apoptotic cell death characterized by iron-dependent lipid peroxidation and reactive oxygen species (ROS) accumulation, has been receiving increasing attention. Ferroptosis can be involved in the pathological processes of many disorders, such as ischemia-reperfusion injury, nervous system diseases, and blood diseases. However, the specific mechanisms by which ferroptosis participates in the occurrence and development of leukemia still need to be more fully and deeply studied. In this review, we present the research progress on the mechanism of ferroptosis and its role in leukemia, to provide new theoretical basis and strategies for the diagnosis and treatment of clinical hematological diseases

Exosomes and cancer immunotherapy: A review of recent cancer research

As phospholipid extracellular vesicles (EVs) secreted by various cells, exosomes contain non-coding RNA (ncRNA), mRNA, DNA fragments, lipids, and proteins, which are essential for intercellular communication. Several types of cells can secrete exosomes that contribute to cancer initiation and progression. Cancer cells and the immune microenvironment interact and restrict each other. Tumor-derived exosomes (TDEs) have become essential players in this balance because they carry information from the original cancer cells and express complexes of MHC class I/II epitopes and costimulatory molecules. In the present study, we aimed to identify potential targets for exosome therapy by examining the specific expression and mechanism of exosomes derived from cancer cells. We introduced TDEs and explored their role in different tumor immune microenvironment (TIME), with a particular emphasis on gastrointestinal cancers, before briefly describing the therapeutic strategies of exosomes in cancer immune-related therapy

Single cell atlas for 11 non-model mammals, reptiles and birds.

The availability of viral entry factors is a prerequisite for the cross-species transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Large-scale single-cell screening of animal cells could reveal the expression patterns of viral entry genes in different hosts. However, such exploration for SARS-CoV-2 remains limited. Here, we perform single-nucleus RNA sequencing for 11 non-model species, including pets (cat, dog, hamster, and lizard), livestock (goat and rabbit), poultry (duck and pigeon), and wildlife (pangolin, tiger, and deer), and investigated the co-expression of ACE2 and TMPRSS2. Furthermore, cross-species analysis of the lung cell atlas of the studied mammals, reptiles, and birds reveals core developmental programs, critical connectomes, and conserved regulatory circuits among these evolutionarily distant species. Overall, our work provides a compendium of gene expression profiles for non-model animals, which could be employed to identify potential SARS-CoV-2 target cells and putative zoonotic reservoirs

Expériences de corrosion sous contrainte de verres borosilicates de sodium à séparation de phases

Les verres borosilicates de sodium (SBN) sont l’objet de nombreuses recherches car les trois oxydes qui les composent (SiO₂, Na₂O, et B₂O₃) font partie des principaux oxydes présents dans les verres industriels. Or il existe, dans le diagramme de phase ternaire des verres SBN, une zone où le phénomène de démixtion (ou séparation de phase amorphe) joue un rôle important. Par ailleurs, la démixtion des verres est un phénomène exploitée dans plusieurs procédés industriels, par exemple pour obtenir des verres résistants à l'écrasement, des verres poreux ou des vitrocéramiques. Les théories, simulations et expériences révèlent le plus souvent une séparation en deux phases dans les verres SBN. Il a été par ailleurs supposé qu’il pouvait exister, pour certaines compositions chimiques, une démixtion en trois phases. Cette démixtion entraîne une structure du verre à l'échelle nanométrique complexe et hétérogène, ce qui peut avoir un impact sur leur propriétés physiques et mécaniques. Pourtant, le lien entre la structure des verres à séparation de phase et leurs propriétés reste difficile à interpréter, en particulier en ce qui concerne leur comportement sous fissuration en corrosion sous contrainte (CSC). L’objectif de ma thèse a été d'étudier les effets de la structure des verres à séparation de phase sur leur comportement en CSC. Mes recherches se sont concentrées sur les verres SBN, supposés avoir une démixtion en trois phases amorphes. Des traitements thermiques adéquats appliqués sur les verres parents ont permis d’engendrer cette démixtion. Plusieurs techniques ont ensuite été utilisées pour caractériser l’évolution de la structure à courte et moyenne distance qui en résulte. Par exemple, des images prises par microscopie à force atomique ont permis de révéler une décomposition spinodale dans ces verres après traitement thermique, et la croissance de cette structure avec le temps et la température du traitement thermique. Pour une température fixée, la taille caractéristique des phases varie comme la racine cubique du temps de traitement. En outre, la structure à courte distance des verres après séparation de phase a été caractérisée par spectroscopie en Résonance Magnétique Nucléaire (RMN) et Raman. On observe une augmentation des anneaux BO₃ dans les verres à séparation de phase et cela confirme la formation d’une phase enrichie en bore.Sodium borosilicate (SBN) glasses concern an important research topic, as the three components (SiO₂, Na₂O, and B₂O₃) are the principal oxides of many industrial glasses. Within in the ternary SBN oxide glass system, there is a region where amorphous phase separation (APS) is a dominant feature. Moreover, APS has industrial relevance for crush resistant glasses, porous glasses and glass ceramics. Theory, simulations, and experiments clearly reveal two-phases. Additionally, it is hypothesized that three-phase exists for certain chemical compositions. APS inside the glasses induces complex heterogeneous structures at the nano-scale, which alter the glasses' physical and mechanical/fracture properties. However, the connection between the structure of APS glasses and their properties remains poorly understood, especially the stress corrosion cracking (SCC) behavior. Hence, in my PhD, I aim at studying the effects of APS structure on SBN glass SCC behavior. My research focuses on SBN glasses with compositions falling within the hypothesized three-phase APS zone. Annealing pristine (as-fabricated) glasses induces APS. Various techniques were used to capture the evolution of the short- and medium-range order of the glass structure with APS. For example, Atomic Force Microscopy (AFM) images evidence spinodal decomposition in the structure, and its growth with annealing temperature and duration. The evolution of phase size is found to be proportional to the cubic root of annealing time for the fix annealing temperature. Additionally, NMR and Raman spectra help in understanding the short-range structure of the APS glasses. An increase in the fraction of BO₃-ring structural units was observed, confirming the formation of boron-rich phases. The SCC behavior in APS glasses was characterized via an in-house experimental setup designed during my thesis. This experimental setup permits me to capture the propagation of the crack front in a well-controlled environment (T=19±1 ℃ and RH=40.0±0.5 %). From images captured, the crack front velocity as a function of the stress intensity factor can be rendered. These results show the inherent meso-scale structure (~APS size) plays on the environmental limit along with Region I SCC parameters. Interestingly, small size APS makes the glasses more susceptible to SCC. However, larger APS structures tends to re-enhance the SCC resistance, and in some instances, the APS glass outperforms their pristine counterparts. After SCC experiments, AFM imaging provides high-resolution topographical images of the fracture surfaces. Post-mortem analysis reveal that the roughness increases with the phase sizes. Additionally, the fracture surfaces of all the samples were found to fit the structure function models. These are the first results proving the reliability of structure function models with experimental fracture surfaces

Countermeasures to Decrease Water Cut and Increase Oil Recovery from High Water Cut, Narrow-Channel Reservoirs in Bohai Sea

Most multilayer sandstone reservoirs in the Bohai Sea have already entered the middle or high water cut production stage with large amounts of remaining oil being scattered distributed. Therefore, there is an urgent need to find a suitable countermeasure to reduce water cut and increase oil recovery. In this study, taking the narrow-channel reservoirs in the M oilfield as an example, we qualitatively described the sand body scale and the contact relationships between different sand bodies, in addition to carefully analyzing the material base and remaining oil distribution characteristics. Accordingly, we proposed a countermeasure based on the injection-production structural adjustment to reduce water cut and increase oil recovery from high water cut, narrow-channel reservoirs. Herein, three optimization strategies were developed based on the proposed development mode: a seepage field optimization strategy was developed based on the quantified injection-production index; a well pattern optimization strategy for narrow-channel reservoirs was developed to overcome the production energy refueling problem; an injection-production measure optimization strategy was developed to tap the different types of remaining oil. Additionally, the well pattern optimization and injection-production optimization strategies were integrated to optimize and adjust the seepage field system. The findings reported herein this paper help understand the development of similar offshore oilfields with a high water cut