Can Pretrained Models Really Learn Better Molecular Representations for AI-Aided Drug Discovery?

Self-supervised pretrained models are gaining increasingly more popularity in AI-aided drug discovery, leading to more and more pretrained models with the promise that they can extract better feature representations for molecules. Yet, the quality of learned representations has not been fully explored. In this work, inspired by the two phenomena of Activity Cliffs (ACs) and Scaffold Hopping (SH) in traditional Quantitative Structure-Activity Relationship analysis, we propose a method named Representation-Property Relationship Analysis (RePRA) to evaluate the quality of the representations extracted by the pretrained model and visualize the relationship between the representations and properties. The concepts of ACs and SH are generalized from the structure-activity context to the representation-property context, and the underlying principles of RePRA are analyzed theoretically. Two scores are designed to measure the generalized ACs and SH detected by RePRA, and therefore, the quality of representations can be evaluated. In experiments, representations of molecules from 10 target tasks generated by 7 pretrained models are analyzed. The results indicate that the state-of-the-art pretrained models can overcome some shortcomings of canonical Extended-Connectivity FingerPrints, while the correlation between the basis of the representation space and specific molecular substructures are not explicit. Thus, some representations could be even worse than the canonical fingerprints. Our method enables researchers to evaluate the quality of molecular representations generated by their proposed self-supervised pretrained models. And our findings can guide the community to develop better pretraining techniques to regularize the occurrence of ACs and SH.

The metabolic adaptation of bile acids and cholesterol after biliary atresia in lamprey via transcriptome-based analysis.

Lamprey underwent biliary atresia (BA) at its metamorphosis stage. In contrast to patients with BA who develop progressive disease, lamprey can grow and develop normally, suggesting that lamprey has several adaptations for BA. Here we show that adaptive changes in bile acid and cholesterol metabolism are produced after lamprey BA. Among 1102 differentially expressed genes (DGEs) after BA in lamprey, many are enriched in gene ontology (GO) terms and pathways related to steroid metabolism. We find that among the DGEs related to bile acids and cholesterol metabolism, the expression of cytochrome P450 family 7 subfamily A member 1 (CYP7A1), sodium-dependent taurine cotransport polypeptide (NTCP) are significantly downregulated, whereas nuclear receptor farnesoid X receptor (FXR), multidrug resistance-associated protein 3 (MRP3), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), sterol O-acyltransferase 1 (SOAT1), and ATP binding cassette subfamily A member 1 (ABCA1) are remarkably upregulated. The changes in expression level are also validated by RT-qPCR. Furthermore, the level of high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C) in juvenile serum is higher compared to larvae. Taken together, the findings collectively indicate that after BA, lamprey may maintain bile acids and cholesterol homeostasis in liver tissue by inhibiting bile acids synthesis and uptake, promoting its efflux back to circulation, and enhancing cholesterol esterification for storage as lipid droplets and its egress to form nascent HDL (nHDL). Understanding the possible molecular mechanisms of lamprey metabolic adaptation sheds new light on the understanding of the development and treatment of diseases caused by abnormal bile acid and cholesterol metabolism in humans.

Effects of Coal Metakaolin on the Mechanical Properties and Microstructure of High-belite Sulphoaluminate Cement.

The effects of coal metakaolin on the mechanical properties of high-belite sulphoaluminate cement under compressive loading were investigated. The composition and microstructure of hydration products at different hydration times were analyzed by X-ray diffraction and scanning electronic microscopy. The hydration process of blended cement was studied via electrochemical impedance spectroscopy. In particular, replacing a part of cement with CMK (10%, 20%, and 30%) was found to promote the hydration process, to refine the pore size, and to improve the compressive strength of the composite. The best compressive strength of the cement was achieved at a CMK content of 30% after 28 days hydration, being improved by 20.13 MPa, or 1.44 times relative to that of undoped specimens. Furthermore, the compressive strength is shown to correlate with the impedance parameter RCCP, which allows the latter to be used for nondestructive assessment of the compressive strength of blended cement materials.

Prognostic biomarker GSTK1 in head and neck squamous cell carcinoma and its correlation with immune infiltration and DNA methylation.

Background: Glutathione S-transferase kappa 1 (GSTK1) is critical in sarcoma and breast cancer (BRCA) development. However, the clinical significance of GSTK1 in head and neck squamous cell carcinoma (HNSC) remains unclear. This study is the first investigation into the role of GSTK1 in HNSC. Methods: All original data were downloaded from the Cancer Genome Atlas (TCGA) dataset and verified by R Base Package 4.2.0. The expression of GSTK1 in various cancers was explored with TIMER and TCGA databases. Prognostic value of GSTK1 was analyzed via survival module of Kaplan-Meier plotter and Human Protein Atlas database and Cox regression analysis. The association between GSTK1 and clinical features was evaluated by Wilcoxon signed-rank test and logistic regression analysis. The relationship between GSTK1 and immune infiltration and methylation level was further explored. The expression of GSTK1 and its correlation with immune cell infiltration was verified by Immunohistochemical staining (IHC). Results: GSTK1 was lower in HNSC, BRCA, Lung squamous cell carcinoma, and Thyroid carcinoma than in para-carcinoma. Low GSTK1 expression was associated with worse overall survival in Bladder urothelial carcinoma, Kidney renal papillary cell carcinoma, BRCA, and HNSC. However, only in BRCA and HNSC, GSTK1 expression in tumors was lower than that in normal tissues. Cox regression analyses confirmed that GSKT1 was an independent prognostic factor of overall survival in HNSC patients. The decrease in GSTK1 expression in HNSC was significantly correlated with high T stage and smoker history. IHC showed that the expression level of GSTK1 in HNSC was lower than that in para-carcinoma. In addition, GSEA showed that three pathways related to immune infiltration were positively correlated, while two pathways related to DNA methylation were negatively correlated with expression of GSTK1. Further analysis showed that GSTK1 was moderately positively correlated with the infiltration level of T cells and Cytotoxic cells, which was further confirmed by IHC. The methylation level of GSTK1 was associated with prognosis in patients with HNSC. Conclusion: Low GSTK1 expression may be a potential molecular marker for poor prognosis in HNSC and provide new insight for the development of diagnostic marker or therapeutic target.

Theoretical and experimental bases for the equivalent circuit model for interpretation of silty soil at different temperatures.

The exploitation of underground space is accompanied by complex geotechnical problems. The development of electromagnetic exploration technology provides a new perspective for preventing and avoiding these problems. In this work, electrochemical impedance spectroscopy (EIS) was used to test the single-phase and mixed-phase medium. Based on the unsaturated soil theory and the dual-water conductivity theory, an equivalent circuit model to describe the electrochemical characteristics and microstructure of silty soil with temperature changes through comparative research. The results indicate that the resistance of near-water layer is not affected by temperature, the resistance of silty soil increases mainly results from the influence of the far-water layer until which increases significantly after freezing. The capacitance change of silty soil is mainly affected by the slowing down of the orientation movement of polar molecules in the far-water layer. Based on the fitting data, a mathematical model for calculating the unfrozen water content of frozen soil was proposed, which reasonably verified the relationship between the unfrozen water content and electrical resistance. By improving the testing conditions of electrochemical impedance spectroscopy, this method may provide new insights for future research of soil electromagnetic testing technology.

The effect of thermodynamic changes in the cooling of saline soils on the corrosion system of carbon steels.

In this experiment, Q235 and X80 carbon steels, which are widely used in oil and gas pipelines and ancillary facilities, were selected to study the changes in the corrosion behaviour and mechanism of carbon steels in the process of natural saline soil cooling to a freezing state through electrochemical testing. The equivalent circuit model of carbon steel before and after the freezing phase transformation in the soil was determined. Based on the corrosion kinetic parameters and soil thermodynamic changes, the influencing factors of steel corrosion during the cooling process were systematically analysed. It was found that temperature mainly affected carbon steel corrosion by changing the properties of the solution. The main factors affecting the corrosion behaviour of the carbon steel were the thermal motion of molecules, ions, and electrons in solution, oxygen dissolution and diffusion, ion adsorption, diffusion mass transfer, and unfrozen water content change during the cooling process.

Electrochemical response of solidification Cu2+ contaminated soil influenced by red mud/fly ash ratio.

The main purpose of this work was to study a new method for evaluating the solidification of contaminated soil based on electrochemical impedance spectroscopy (EIS). To explore how the EIS parameters were affected by the pore structure and mesostructure of the cured system, the physical and mechanical properties, leaching toxicity, microstructure, and EIS of the stabilized contaminated soil were tested after 7, 28, 60, and 90 days of curing. Based on the EIS results, a physical and equivalent circuit model of the stabilized contaminated soil's impedance response was established to reveal the mechanism of binder-heavy metal ion-soil interaction. The results showed that as the red mud (RM)-fly ash (FA) mass ratio and curing age increased, the strength and structural compactness of the solidified body also increased. The best curing effect was achieved with an RM-FA mass ratio of 7:3 after curing for 90 days. The equivalent circuit model of the solidified body obtained by EIS was Rs (Q1 (Rct1W) Q2Rct2). The pore solution resistance Rs, solid-liquid interface ion transfer resistance Rct 1, and unconfined compressive strength (UCS) qu all showed an increasing trend with increasing RM-FA mass ratio and increasing curing time. Fitting the model demonstrated that both Rs and Rct1 were closely correlated with the strength of the solidified bodies. These conclusions were further verified by scanning electron microscope (SEM) experiments. Overall, this work demonstrates that the strength characteristics of solidified bodies can be evaluated by EIS and reveals the microscopic mechanism of the solidification of Cu2+-contaminated soil.

Electrochemical corrosion behaviour of four low-carbon steels in saline soil.

In this paper, the electrochemical corrosion behaviour of Q235, X65, X70, and X80 low-carbon steel was systematically studied by a variety of test techniques using natural saline soil containing 1.1% salt under laboratory conditions. The electrochemical corrosion behaviour, macro-micro corrosion morphology, and corrosion product composition of these four low-carbon steels in saline soil were studied to explore their salt corrosion resistance and reveal their corrosion mechanisms. The research results showed that oxygen absorption corrosion occurred in all four low-carbon steels in the saline soil, and the corrosion types were all localised corrosion. The corrosion process of Q235 steel was controlled by mass transfer, while the corrosion processes of X65, X70, and X80 steel were controlled by charge transfer. The corrosion rates of these four low-carbon steels in saline soil followed the order Q235 > X65 ≈ X70 > X80. Variation in elemental composition was the main reason for this difference in corrosion behaviour. Finally, microscopic test results showed that local corrosion pits were present on the surface of the steel sheet specimens, and the uniformity and compactness of the corrosion product accumulation were poor.

Micellar Ratiometric Fluorescent Blood pH Probe Based on Triplet-Sensitized Upconversion and Energy-Transfer Behaviors.

The measurement of pH is greatly significant in monitoring physiological and biochemical states. In this work, a novel micellar ratiometric fluorescent probe featuring sophisticated energy-transfer (ET) behaviors with p-nitrophenol (PNP) as the energy acceptor and a triplet-triplet annihilation upconversion (TTA-UC) system as the energy donor was designed. The pH-induced molecular configuration of PNP determined the process for the transfer of energy from TTA-UC to PNP. The introduction of the TTA-UC system enabled probe excitation under a long wavelength and afforded a ratiometric signal for pH detection with excellent reliability over diverse interfering factors. This TTA-UC/ET pH probe demonstrated a high sensitivity to hydronium below nanomolar concentrations and an excellent anti-interference ability in serum samples, which provided a novel significant strategy for rapid and accurate detection of blood pH in vitro.

EIS analysis of the electrochemical characteristics of the metal-water interface under the effect of temperature.

The corrosion performance of metals is closely related to their durability. Available studies on metal corrosion have seldom focused on the interfacial reaction behaviour influenced by a conductive medium under different temperatures. In this work, a laboratory corrosion simulation environment has been designed for EIS measurements to investigate the electrochemical behaviour of copper immersed in distilled water in different temperature environments. The relationship between the mathematical model of impedance response and the equivalent circuit model is determined based on electrochemical kinetics theory. The complex process of the dielectric properties of distilled water affected by temperature is analysed, and a simple method for calculating the kinetic parameters is presented. The experimental and model results have a good fit, and the analysis results indicate that the semicircle in the high-frequency region of the complex impedance curve represents the charge transfer process of the conductive medium. The decrease in temperature is the major factor that inhibits the rate of dissolution and passivation, resulting in the change rate of surface coverage slowing down, until the attenuation of the mass transfer process of the conductive medium dominates the full range of AC frequencies. This model provides an improved approach for determining physical parameters based on electrochemical impedance spectroscopy to characterize the electrochemical properties of materials.

Electrochemical Corrosion Behaviour of X70 Steel under the Action of Capillary Water in Saline Soils.

In this paper, the electrochemical corrosion behavior of X70 steel in saline soil under capillary water was simulated by a Geo-experts one-dimensional soil column instrument. A volumetric water content sensor and conductivity test were used to study the migration mechanism of water and salt (sodium chloride) under the capillary water. The electrochemical corrosion behavior of the X70 steel in the corrosion system was analyzed by electrochemical testing as well as the macroscopic and microscopic corrosion morphology of the steel. The test results showed that the corrosion behavior of X70 steel was significantly influenced by the rise of capillary water. In particular, the wetting front during the capillary water rise meant that the X70 steel was located at the three-phase solid/liquid/gas interface at a certain location, which worsened its corrosion behavior. In addition, after the capillary water was stabilized, the salts were transported with the capillary water to the top of the soil column. This resulted in the highest salt content in the soil environment and the most severe corrosion of the X70 steel at this location.

High-performance anti-haze window screen based on multiscale structured polyvinylidene fluoride nanofibers.

Indoor air quality (IAQ) has assumed new significance given the extensive amount of time spent indoor due to the coronavirus pandemic and particulate matter (PM) pollution. Accordingly, the development of window air filters to effectively intercept PM from outdoor air under natural ventilation conditions is an important research topic. However, most existing filters inevitably suffer from the compromise among filtration capability, transparency, and air permeability. In this study, we fabricate a high-performance transparent air filter to improve IAQ via natural ventilation. polyvinylidene fluoride (PVDF) superfine nanofibers of size 20-35 nm are prepared using extremely dilute solution electrospinning; a multi-scale nanofiber structure is then designed. By adjusting the ratio of PVDF superfine nanofibers (SNs) to PVDF coarse fibers (CNs), we balance the structure-performance relationship. Benefiting from the multiscale structural features that include a small pore size (0.72 µm) and high porosity (92.22%), the resulting filters exhibit excellent performance including high interception efficiency (99.92%) for PM0.3, low air resistance (69 Pa), high transparency (∼80%) and stable filtration after 100 h of UV irradiation. This work describes a new strategy for the fabrication of nanofibers with true-nanoscale diameters and the design of high-performance air filters.

Biodegradable and high-performance multiscale structured nanofiber membrane as mask filter media via poly(lactic acid) electrospinning.

The usage of single-use face masks (SFMs) has increased since the outbreak of the coronavirus pandemic. However, non-degradability and mismanagement of SFMs have raised serious environmental concerns. Moreover, both melt-blown and nanofiber-based mask filters inevitably suffer from poor filtration performance, like a continuous decrease in the removal efficiency for particulate matter (PM) and weak breathability. Herein, we report a new method to create biodegradable and reusable fibrous mask filters. The filter consists of a true nanoscale bio-based poly(lactic acid) (PLA) fiber (an average size of 37 ± 4 nm) that is fabricated via electrospinning of an extremely dilute solution. Furthermore, we designed a multiscale structure with integrated features, such as low basis weight (0.91 g m-2), small pore size (0.73 µm), and high porosity (91.72%), formed by electrospinning deposition of true nanoscale fibers on large pore of 3D scaffold nanofiber membranes. The resultant mask filter exhibited a high filtration efficiency (PM0.3-99.996%) and low pressure drop (104 Pa) superior to the commercial N95 filter. Importantly, this filter has a durable filtering efficiency for PM and natural biodegradability based on PLA. Therefore, this study offers an innovative strategy for the preparation of PLA nanofibers and provides a new design for high-performance nanofiber filters.

Corrosion behavior and mechanism of X80 steel in silty soil under the combined effect of salt and temperature.

In this study, X80 pipeline steel was embedded in silty soil with different salinities and subjected to corrosion at a constant temperature for 24 h before electrochemical testing. The effect of soil medium, temperature, and salt content on the kinetics of corrosion behavior of X80 steel was analyzed. Furthermore, the compositions and structures of the corrosion products were analyzed by X-ray photoelectron spectroscopy and scanning electron microscopy. Based on the results, the anodic dissolution reaction mechanism of X80 steel in silty soil was determined, the differences in the corrosion process caused by different soil systems were comprehensively contrasted, and the impact of the migration process of heterogeneous silty soil on corrosion behavior under different conditions was systematically explored. Comparative analysis revealed that chloride ions possess strong adsorption ability at temperatures above freezing point and that more oxidized substances are present in the deposited layer on the surface of corroded steel, which facilitates the occurrence of corrosion under deposition. At temperatures below freezing point, the sulfate ions present in the pore solution contribute to crystallization-induced expansion and lead to swelling and deformation of the soil, rendering the X80 steel more prone to corrosion in sulfate corrosion environments.

Preparation and application of solid-state upconversion materials based on sodium polyacrylate.

By loading a microemulsion containing both sensitizer and emitter into porous sodium polyacrylate (PAAS), a water-absorbent resin (WAR) upconversion (UC) material was fabricated for photocatalysis applications. This WAR UC material showed a highly efficient UC process in the ambient environment owing to its liquid/solid encapsulation structure. In the application measurement, the UC emission from WAR UC materials can excite the catalyst Pt/WO3 to produce hydroxyl radicals, yielding 7-hydroxycoumarin by reacting with coumarin. In another case, since the band gap of ZnCdS matches the energy of UC emission, hole-electron pairs can be obtained under the UC irradiation and capture electrons from rhodamine B, leading to the degradation of rhodamine B. The maximum of the photocatalysis efficiency can be up to 97%. This work solves the oxygen quenching problem by preparing a triplet-triplet annihilation upconversion (TTA-UC) O/W microemulsion and loading it into PAAS WAR, and opens a new avenue to solid-state devices for TTA-UC. The applications of photocatalytic synthesis and photocatalytic degradation lay a foundation for future practical applications for TTA-UC materials.

A stimuli responsive triplet-triplet annihilation upconversion system and its application as a ratiometric sensor for Fe3+ ions.

A ratiometric fluorescent sensor for the detection of Fe3+ ions is achieved based on triplet-triplet annihilation upconversion (TTA-UC) luminescence. A new anthracene derivative (named as DHTPA) is designed and synthesized and reveals similar optical properties to 9,10-diphenylanthracene (DPA) and is used as a stimuli responsive annihilator in a TTA-UC system due to its complexation ability. As a result, the UC emission can be significantly quenched by Fe3+ ions, while the phosphorescence (PL) emission of sensitizer palladium(ii) octaetylporphyrin (PdOEP) remains nearly constant, which makes the PL signal an appropriate internal reference for the UC signal. The UC and ratio signals (I UC/I PL) both reveal a good linear relationship with Fe3+ ion concentration, which for the first time makes the TTA-UC system a perfect ratiometric sensor for Fe3+ ion detection. This sensing method will open a novel avenue to achieve ratiometric sensors in chemical and biological fields.