Recognizing high-priority disinfection byproducts based on experimental and predicted endocrine disrupting data: Virtual screening and in vitro study.

So far, about 130 disinfection by-products (DBPs) and several DBPs-groups have had their potential endocrine-disrupting effects tested on some endocrine endpoints. However, it is still not clear which specific DBPs, DBPs-groups/subgroups may be the most toxic substances or groups/subgroups for any given endocrine endpoint. In this study, we attempt to address this issue. First, a list of relevant DBPs was updated, and 1187 DBPs belonging to 4 main-groups (aliphatic, aromatic, alicyclic, heterocyclic) and 84 subgroups were described. Then, the high-priority endocrine endpoints, DBPs-groups/subgroups, and specific DBPs were determined from 18 endpoints, 4 main-groups, 84 subgroups, and 1187 specific DBPs by a virtual-screening method. The results demonstrate that most of DBPs could not disturb the endocrine endpoints in question because the proportion of active compounds associated with the endocrine endpoints ranged from 0 (human thyroid receptor beta) to 32% (human transthyretin (hTTR)). All the endpoints with a proportion of active compounds greater than 10% belonged to the thyroid system, highlighting that the potential disrupting effects of DBPs on the thyroid system should be given more attention. The aromatic and alicyclic DBPs may have higher priority than that of aliphatic and heterocyclic DBPs by considering the activity rate and potential for disrupting effects. There were 2 (halophenols and estrogen DBPs), 12, and 24 subgroups that belonged to high, moderate, and low priority classes, respectively. For individual DBPs, there were 23 (2%), 193 (16%), and 971 (82%) DBPs belonging to the high, moderate, and low priority groups, respectively. Lastly, the hTTR binding affinity of 4 DBPs was determined by an in vitro assay and all the tested DBPs exhibited dose-dependent binding potency with hTTR, which was consistent with the predicted result. Thus, more efforts should be performed to reveal the potential endocrine disruption of those high research-priority main-groups, subgroups, and individual DBPs.

Draft genome sequence of Monascus ruber strain FM39-7.

In China, certain Monascus ruber strains are traditionally used as edible fungi. We sequenced the genome of M. ruber FM39-7 strain, an isolate from fermented rice. The genome is 25.89 Mb with a G + C content of 48.86%, containing 8485 annotated genes.

Disinfection byproducts of iopamidol, iohexol, diatrizoate and their distinct acute toxicity on Scenedesmus sp., Daphnia magna and Danio rerio.

The COVID-19 pandemic resulted in increasing the usage of iodinated contrast media (ICM), and thus an increase in the prevalence of ICM-contaminated wastewater. While ICM is generally safe, this has the potential to be problematic because as medical wastewater is treated and disinfected, various ICM-derived disinfection byproducts (DBPs) may be generated and released into the environment. However, little information was available about whether ICM-derived DBPs are toxic to aquatic organisms. In this study, the degradation of three typical ICM (iopamidol, iohexol, diatrizoate) at initial concentration of 10 µM and 100 µM in chlorination and peracetic acid without or with NH4+ was investigated, and the potential acute toxicity of treated disinfected water containing potential ICM-derived DBPs on Daphnia magna, Scenedesmus sp. and Danio rerio was tested. The degradation results suggested that only iopamidol was significantly degraded (level of degradation >98%) by chlorination, and the degradation rate of iohexol and diatrizoate were significantly increased in chlorination with NH4+. All three ICM were not degraded in peracetic acid. The toxicity analysis results indicate that only the disinfected water of iopamidol and iohexol by chlorination with NH4+ were toxic to at least one aquatic organism. These results highlighted that the potential ecological risk of ICM-contained medical wastewater by chlorination with NH4+ should not be neglected, and peracetic acid may be an environment-friendly alternative for the disinfection of wastewater containing ICM.

Potential Disrupting Effects of Wastewater-Derived Disinfection Byproducts on Chinese Rare Minnow (Gobiocypris rarus) Transthyretin: An In Vitro and In Silico Study.

The available information about whether wastewater-derived disinfection byproducts (DBPs) could elicit potential endocrine-related detrimental effects on aquatic organisms was scarce. Herein, the potential disrupting effects and underlying binding mechanism of 14 wastewater-derived aliphatic and aromatic DBPs and 12 other substances on Chinese rare minnow (Gobiocypris rarus) transthyretin (CrmTTR) were tested and revealed by in vitro and in silico methods. The amino acid sequences of CrmTTR were determined, and the recombinant CrmTTR with a molecular mass of 66.3 kDa was expressed and purified. In vitro assay results indicated that eight selected aromatic DBPs exhibited detectable CrmTTR disrupting ability. Meanwhile, six aliphatic DBPs were not CrmTTR binders. Molecular modeling results implied that hydrophobic hydrogen bonds and/or ionic pair interactions were non-negligible. Four binary classification models with high classification performance were constructed. A significant positive linear relationship was observed for the binding affinity data from CrmTTR and human TTR (n = 18, r = 0.922, p < 0.0001). However, the binding affinity for 13 out of 18 tested compounds with CrmTTR was higher than that with human TTR. All the results highlighted that some wastewater-derived DBPs may be potential disruptors on the aquatic organism endocrine system, and interspecies variation should not be neglected in future determination of the potential endocrine disrupting effects of wastewater-derived DBPs.

Endocrine disrupting effect and reproductive toxicity of the separate exposure and co-exposure of nano-polystyrene and diethylstilbestrol to zebrafish.

The co-occurrence of nanoplastics and other pollutants in the environment has gotten a lot of attention, but information on the biological toxicity of their co-exposure was limited. This study aims to reveal the endocrine disrupting effect and reproductive toxicity of nano-polystyrene (NPS) and diethylstilbestrol (DES) to zebrafish under separate and combined exposure. Results indicated that NPS and DES exposure in isolation reduced the hepatosomatic index and gonadosomatic index, and altered the cell maturity in gonads in both cases. Even worse, the co-exposure of NPS and DES exacerbated the damage to the liver and gonads of fish. The two pollutants individually inhibited the secretion of sex hormones and vitellogenin. The inhibition effect of DES was especially dose-dependent, while NPS had weaker effect than DES. Their combined action on the secretion of sex hormones and vitellogenin exhibited additive effect. However, NPS did not affect the content of thyroid hormones in fish, and also had no significant effect on the reduction of thyroid hormone caused by DES exposure. Furthermore, their co-exposure decreased the cumulative eggs from 1031 to 306, and the spawning number from 12 to 8. The fertilization rate and hatchability rete of eggs were reduced by 30.9% and 40.4%, respectively. The abnormality rate of embryos was 65.0%, significantly higher than in separate DES and NPS groups (55.7% and 30.8% respectively). The abnormal development of offspring was mainly pericardial cyst, spinal curvature, and growth retardation.

Effect of Hydrogel Contact Angle on Wall Thickness of Artificial Blood Vessel.

Vascular replacement is one of the most effective tools to solve cardiovascular diseases, but due to the limitations of autologous transplantation, size mismatch, etc., the blood vessels for replacement are often in short supply. The emergence of artificial blood vessels with 3D bioprinting has been expected to solve this problem. Blood vessel prosthesis plays an important role in the field of cardiovascular medical materials. However, a small-diameter blood vessel prosthesis (diameter < 6 mm) is still unable to achieve wide clinical application. In this paper, a response surface analysis was firstly utilized to obtain the relationship between the contact angle and the gelatin/sodium alginate mixed hydrogel solution at different temperatures and mass percentages. Then, the self-developed 3D bioprinter was used to obtain the optimal printing spacing under different conditions through row spacing, printing, and verifying the relationship between the contact angle and the printing thickness. Finally, the relationship between the blood vessel wall thickness and the contact angle was obtained by biofabrication with 3D bioprinting, which can also confirm the controllability of the vascular membrane thickness molding. It lays a foundation for the following study of the small caliber blood vessel printing molding experiment.

Prediction of Surface Roughness in Gas-Solid Two-Phase Abrasive Flow Machining Based on Multivariate Linear Equation.

The main purpose of this study is to explore a surface roughness prediction model of Gas-Solid Two-Phase Abrasive Flow Machining. In order to achieve the above purpose, an orthogonal experiment was carried out. Q235 steel as processing material and white corundum with different particle sizes as abrasive particles were used in the experiment. Shape and spindle speed were the main reference factors. The range method and factor trend graph are used to comprehensively analyze the experimental results of different processing stages of the detection point, and the optimal parameter combination of A3B2C1D2 was obtained. According to the experimental results, a multiple linear regression equation was established to predict the surface roughness, and the experimental results were solved and significantly analyzed by software to obtain a highly reliable prediction model. Through experiments, modeling and verification, it is known that the maximum error between the obtained model and the actual value is 0.339 µm and the average error is 0.00844 µm, which can better predict the surface roughness of the gas-solid two-phase flow abrasive pool.

Research Progress of the Endocrine-Disrupting Effects of Disinfection Byproducts.

Since 1974, more than 800 disinfection byproducts (DBPs) have been identified from disinfected drinking water, swimming pool water, wastewaters, etc. Some DBPs are recognized as contaminants of high environmental concern because they may induce many detrimental health (e.g., cancer, cytotoxicity, and genotoxicity) and/or ecological (e.g., acute toxicity and development toxicity on alga, crustacean, and fish) effects. However, the information on whether DBPs may elicit potential endocrine-disrupting effects in human and wildlife is scarce. It is the major objective of this paper to summarize the reported potential endocrine-disrupting effects of the identified DBPs in the view of adverse outcome pathways (AOPs). In this regard, we introduce the potential molecular initiating events (MIEs), key events (KEs), and adverse outcomes (AOs) associated with exposure to specific DBPs. The present evidence indicates that the endocrine system of organism can be perturbed by certain DBPs through some MIEs, including hormone receptor-mediated mechanisms and non-receptor-mediated mechanisms (e.g., hormone transport protein). Lastly, the gaps in our knowledge of the endocrine-disrupting effects of DBPs are highlighted, and critical directions for future studies are proposed.

Study on Wear Mechanism of Helical Gear by Three-Body Abrasive Based on Impact Load.

This study aimed to explore the wear characteristics and evolution mechanisms of large-scale wind power gears under the impact load of particles of the three-body abrasive Al2O3 (0.2 mg/mL) from four aspects: oil analysis, vibration analysis, amount of gear wear, and tooth-surface-wear profile analysis. A magnetic powder brake was used to simulate the actual working conditions. Combined with the abrasive particle monitoring and the morphology analysis of the tooth-surface-wear scar, by setting quantitative hard particles in the lubricating oil, the gears are mainly operated in the abrasive wear state, and wear monitoring and wear degree analysis are carried out for the whole life cycle of the gears. Oil samples were observed and qualitatively analyzed using a particle counter, a single ferrograph, a metallographic microscope, and a scanning electron microscope. The experiments demonstrate that the initial hard particles have a greater impact in the early wear stage of the gears (<20 h), and abrasive particle concentration increases by 30%. This means that Al2O3 particles accelerate the gear wear during the running-in period. The loading method of the impact load on the oblique gear exacerbates the abrasion particle wear and expands the stress concentration, which reduces the surface of large milling particles on the surface, and reduces the width of the tooth (the part above the pitch line is severely worn), which causes the gear to break into failure. The research provides help for analyzing the mechanism of abrasive wear of gears and predicting wear life.

Aquatic toxicity and aquatic ecological risk assessment of wastewater-derived halogenated phenolic disinfection byproducts.

Increasing number of wastewater-derived aliphatic and phenolic disinfection byproducts (DBPs) were discharged into aquatic environment with the discharge of disinfected wastewater. However, the currently available aquatic toxicity data and the aquatic ecological risk information of them are limited, especially for wastewater-derived phenolic DBPs. In this study, we investigated the acute toxicity of 7 phenolic DBPs that selected from the typical five groups of phenolic DBPs (2,4,6-trihalo-phenols, 2,6-dihalo-4-nitrophenols, 3,5-dihalo-4-hydroxybenzaldehydes, 3,5-dihalo-4-hydroxybenzoic acids and halo-salicylic acids) and 4 aliphatic DBPs to Gobiocypris rarus and also assessed their potential aquatic ecological risk. Experimental results indicated that the half lethal concentration (LC50) values of 2,4,6-trihalo-phenols and 2,6-dihalo-4-nitrophenols ranged from 1 to 10 mg/L; While that of 3,5-dihalo-4-hydroxybenzaldehydes was between 10 and 100 mg/L, and 3,5-dihalo-4-hydroxybenzoic acids and halo-salicylic acids was >100 mg/L. The toxicity mode of action (MOA) identification results from three methods suggested that no clear and consistent MOA were obtained for those 11 DBPs currently. The species-specific aquatic toxicity analysis results highlighted that no aquatic species would be considered as the most sensitive species for all 11 DBPs. However, crustacean and fish were more sensitive than that of algae for most of tested compounds. Lastly, the aquatic ecological risk assessment results of those 11 DBPs revealed that all 7 phenolic and 2 aliphatic DBPs (2-bromoacetamide and bromodichloromethane) had low aquatic ecological risk, while dichloroacetic acid and dibromoacetonitrile had high aquatic ecological risk. The low environmental concentration was the main reason why high toxic phenolic DBPs (2,4,6-trihalo-phenols and 2,6-dihalo-4-nitrophenols) exhibited low ecological risk. Their ecological risk may increase with the increases of corresponding environmental concentration. Thus, more efforts should be made to determine other potential harmful effects of those high toxic phenolic DBPs and to minimize their potential ecological risk by taking appropriate measures.

Theoretical and Experimental Research on Multi-Layer Vessel-like Structure Printing Based on 3D Bio-Printing Technology.

Cardiovascular disease is the leading cause of death worldwide. Traditional autologous transplantation has become a severe issue due to insufficient donors. Artificial blood vessel is an effective method for the treatment of major vascular diseases, such as heart and peripheral blood vessel diseases. However, the traditional single-material printing technology has been unable to meet the users' demand for product functional complexity, which is not only reflected in the field of industrial manufacturing, but also in the field of functional vessel-like structure regeneration. In order to achieve the printing and forming of multi-layer vessel-like structures, this paper carries out theoretical and experimental research on the printing and forming of a multi-layer vessel-like structure based on multi-material 3D bioprinting technology. Firstly, theoretical analysis has been explored to research the relationship among the different parameters in the process of vessel forming, and further confirm the synchronous relationship among the extrusion rate of material, the tangential speed of the rotating rod, and the movement speed of the platform. Secondly, sodium alginate and gelatin have been used as the experimental materials to manufacture the vessel-like structure, and the corrected parameter of the theoretical analysis is further verified. Finally, the cell-loaded materials have been printed and analyzed, and cell viability is more than 90%, which provides support for the research of multi-layer vessel-like structure printing.

Modeling, Validation, and Performance of Two Tandem Cylinder Piezoelectric Energy Harvesters in Water Flow.

This paper studies a novel enhanced energy-harvesting method to harvest water flow-induced vibration with a tandem arrangement of two piezoelectric energy harvesters (PEHs) in the direction of flowing water, through simulation modeling and experimental validation. A mathematical model is established by two individual-equivalent single-degree-of-freedom models, coupled with the hydrodynamic force obtained by computational fluid dynamics. Through the simulation analysis, the variation rules of vibration frequency, vibration amplitude, power generation and the distribution of flow field are obtained. And experimental tests are performed to verify the numerical calculation. The experimental and simulation results show that the upstream piezoelectric energy harvester (UPEH) is excited by the vortex-induced vibration, and the maximum value of performance is achieved when the UPEH and the vibration are resonant. As the vortex falls off from the UPEH, the downstream piezoelectric energy harvester (DPEH) generates a responsive beat frequency vibration. Energy-harvesting performance of the DPEH is better than that of the UPEH, especially at high speed flows. The maximum output power of the DPEH (371.7 µW) is 2.56 times of that of the UPEH (145.4 µW), at a specific spacing between the UPEN and the DPEH. Thereupon, the total output power of the two tandem piezoelectric energy harvester systems is significantly greater than that of the common single PEH, which provides a good foreground for further exploration of multiple piezoelectric energy harvesters system.

Human transthyretin binding affinity of halogenated thiophenols and halogenated phenols: An in vitro and in silico study.

Serious harmful effects have been reported for thiophenols, which are widely used industrial materials. To date, little information is available on whether such chemicals can elicit endocrine-related detrimental effects. Herein the potential binding affinity and underlying mechanism of action between human transthyretin (hTTR) and seven halogenated-thiophenols were examined experimentally and computationally. Experimental results indicated that the halogenated-thiophenols, except for pentafluorothiophenol, were powerful hTTR binders. The differentiated hTTR binding affinity of halogenated-thiophenols and halogenated-phenols were observed. The hTTR binding affinity of mono- and di-halo-thiophenols was higher than that of corresponding phenols; while the opposite relationship was observed for tri- and penta-halo-thiophenols and phenols. Our results also confirmed that the binding interactions were influenced by the degree of ligand dissociation. Molecular modeling results implied that the dominant noncovalent interactions in the molecular recognition processes between hTTR and halogenated-thiophenols were ionic pair, hydrogen bonds and hydrophobic interactions. Finally, a model with acceptable predictive ability was developed, which can be used to computationally predict the potential hTTR binding affinity of other halogenated-thiophenols and phenols. Taken together, our results highlighted that more research is needed to determine their potential endocrine-related harmful effects and appropriate management actions should be taken to promote their sustainable use.

Polarizability and aromaticity index govern AhR-mediated potencies of PAHs: A QSAR with consideration of freely dissolved concentrations.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants associated with adverse human effects including cancer, and the aryl hydrocarbon receptor (AhR) is a key ligand-activated transcription factor mediating their toxicity. However, there is presently a lack of data on AhR potencies of PAHs. Simple, transparent, interpretable and predictive quantitative structure-activity relationship (QSAR) models are helpful, especially with the consideration of freely dissolved concentrations linked to bioavailability. Here, QSAR models on AhR-mediated luciferase activity of PAHs were developed with nominal median effect concentrations (EC50, nom) and freely dissolved concentration (EC50, free) as endpoints, and quantum chemical and Dragon descriptors as predictor variables. Results indicated that only the EC50, free model met the acceptable criteria of QSAR model (determination coefficient (R2) > 0.600, leave-one-out cross validation (QLOO2) > 0.500, and external validation coefficient (QEXT2) > 0.500), implying that it has good goodness-of-fit, robustness and external predictive power. Molecular polarizability and aromaticity index reflecting the partition behavior and intermolecular interactions can effectively predict AhR-mediated potencies of PAHs. The results highlight the necessity of adoption of the freely dissolved concentration in the QSAR modeling and more in silico models need to be further developed for different animal models (in vivo or in vitro).

Enhanced toxicity of triphenyl phosphate to zebrafish in the presence of micro- and nano-plastics.

Co-occurrence of microplastics and chemicals was a complex environmental issue, whereas little concerned on the effect of microplastics on the toxicity of chemicals. In this study, we studied the changes of toxicity of triphenyl phosphate (TPhP) to zebrafish, in the presence of micro-polystyrene (MPS, 5.8 µm) and nano-polystyrene (NPS, 46 nm). Results indicated that separate MPS and NPS had no acute toxicity and little reproductive toxicity on zebrafish. TPhP alone was a highly toxic substance with a median lethal concentration (LC50) of 976 µg/L, the presence of MPS and NPS did not have significant effect on the acute toxicity of TPhP. TPhP alone stimulated the enlargement of liver and gonad of fish (except the testis) by 1.25-2.12 fold, and the presence of NPS further aggravated this stimulation by 1.23-2.84 fold, while MPS did not. The gonadal histology indicated that comparing with TPhP alone, the addition of MPS and NPS further inhibited the process of spermatogenesis and oogenesis, even causing obvious lacunas in testis and atretic follicles oocytes in ovary. Meanwhile, TPhP did not significantly disturb the hormone homeostasis (E2/T) and vitellogenin (Vtg) content in fish, but the presence of NPS increased the E2/T ratio and Vtg content in male fish, while slightly decreased those in female fish, which implying that effects of PS was sex-dependent. As a result, the egg production, the fertilization rate and hatchability of eggs significantly reduced after combined TPhP+PS exposure, demonstrating that co-occurrence of TPhP and PS, especially NPS, could greatly impaired the reproductive performance of zebrafish.

Simulation Analysis of the Influence of Nozzle Structure Parameters on Material Controllability.

With the evolution of three-dimensional (3D) printing, many restrictive factors of 3D printing have been explored to upgrade the feasibility of 3D printing technology, such as nozzle structure, print resolution, cell viability, etc., which has attracted extensive attention due to its possibility of curing disease in tissue engineering and organ regeneration. In this paper, we have developed a novel nozzle for 3D printing, numerical simulation, and finite element analysis have been used to optimize the nozzle structure and further clarified the influence of nozzle structure parameters on material controllability. Using novel nozzle structure, we firstly adopt ANSYS-FLUENT to analyze material controllability under the different inner cavity diameter, outer cavity diameter and lead length. Secondly, the orthogonal experiments with the novel nozzle are carried out in order to verify the influence law of inner cavity diameter, outer cavity diameter, and lead length under all sorts of conditions. The experiment results show that the material P diameter can be controlled by changing the parameters. The influence degree of parameters on material P diameter is shown that lead length > inner cavity diameter > outer cavity diameter. Finally, the optimized parameters of nozzle structure have been adjusted to estimate the material P diameter in 3D printing.

Changes of the acute and chronic toxicity of three antimicrobial agents to Daphnia magna in the presence/absence of micro-polystyrene.

The effects of microplastics on aquatic organisms are drawing growing attention, but little has been focused on their effects on the toxicity of other chemicals. In this study, we examined the acute and chronic toxicity of micro-polystyrene (5.8 µm dia.), and its effects on the toxicity of three antimicrobial agents (triclosan, triclocarban and methyl-triclosan) to Daphnia magna. Results indicated that polystyrene had a low acute toxicity with an EC50 of 36.5 mg/L. The presence of polystyrene (1 mg/L) did not produce significant effect on the acute toxicity of three chemicals, because the 95% confidence intervals of their EC50 values had a large overlap of 11.3%-48.3%. For the 21 day chronic toxicity, polystyrene alone had significant toxicity with concentrations of at least 2 mg/L, which prolonged the time of the first brood, limited the number of broods, and reduced the total number of neonates. Compared with the chemicals alone, the addition of polystyrene enhanced their reproduction toxicity. Based on the various reproduction indicators, an intrinsic rate of natural increase (rm) was calculated to assess the rate of population growth. Results suggested that the rm values of three chemicals decreased in the presence of PS, and further decreased with increasing PS concentrations. Among the three chemicals, methyl-triclosan was the most affected. These results suggested that the presence of microplastics would exacerbate the detrimental influence of pollutants on Daphnia magna.

Development of quantitative structure-property relationship model for predicting the field sampling rate (Rs) of Chemcatcher passive sampler.

Passive sampling technology has been considered as a promising tool to measure the concentration of environmental contaminants. With this technology, sampling rate (Rs) is an important parameter. However, as experimental methods employed to obtain the Rs value of a given compound were time-consuming, laborious, and expensive. A cost-effective method for deriving Rs is urgent. In addition, considering the great dependence of Rs value on water matrix properties, the laboratory measured Rs may not be a good alternative for field Rs. Thus, obtaining the field Rs is very necessary. In this study, a multiparameter quantitative structure-property relationship (QSPR) model was constructed for predicting the field Rs of 91 polar to semi-polar organic compounds. The determination coefficient (R2Train), leave-one-out cross-validated coefficient (Q2LOO), bootstrap coefficient (Q2BOOT), and root mean square error (RMSETrain) of the training set were 0.772, 0.706, 0.769, and 0.230, respectively, while the external validation coefficient (Q2EXT) and RMSEEXT of the validation set were 0.641 and 0.253, respectively. According to the acceptable criteria (Q2 > 0.600, R2 > 0.700), the model had good robustness, goodness-of-fit, and predictive performances. Therefore, we could use the model to fill the data gap for substances within the applicability domain on their missing Rs value.

Binding interactions of halo-benzoic acids, halo-benzenesulfonic acids and halo-phenylboronic acids with human transthyretin.

The anionic form-dependent binding interaction of halo-phenolic substances with human transthyretin (hTTR) has been observed previously. This indicates that ionizable compounds should be the primary focus in screening potential hTTR disruptors. Here, the potential binding potency of halo-benzoic acids, halo-benzenesulfonic acids/sulfates and halo-phenylboronic acids with hTTR was determined and analyzed by competitive fluorescence displacement assay integrated with computational methods. The laboratorial results indicated that the three test groups of model compounds exhibited a distinct binding affinity to hTTR. All the tested halo-phenylboronic acids, some of the tested halo-benzoic acids and halo-benzenesulfonic acids/sulfates were shown to be inactive with hTTR. Other halo-benzoic acids and halo-benzenesulfonic acids/sulfates were moderate and/or weak hTTR binders. The binding affinity of halo-benzoic acids and halo-benzenesulfonic acids/sulfates with hTTR was similar. The low distribution ability of the model compounds from water to hTTR may be the reason why they exhibited the binding potency observed with hTTR. By introducing other highly hydrophobic compounds, we observed that the binding affinity between compounds and hTTR increased with increasing molecular hydrophobicity. Those results indicated that the highly hydrophobic halo-benzoic acids and halo-benzenesulfonic acids/sulfates may be high-priority hTTR disruptors. Finally, a binary classification model was constructed employing three predictive variables. The sensitivity (Sn), specificity (Sp), predictive accuracy (Q) values of the training set and validation set were >0.83, indicating that the model had good classification performance. Thus, the binary classification model developed here could be used to distinguish whether a given ionizable compound is a potential hTTR binder or not.

Cutting Performance Evaluation of the Coated Tools in High-Speed Milling of AISI 4340 Steel.

The cutting performance of cutting tools in high-speed machining (HSM) is an important factor restricting the machined surface integrity of the workpiece. The HSM of AISI 4340 is carried out by using coated tools with TiN/TiCN/TiAlN multi-coating, TiAlN + TiN coating, TiCN + NbC coating, and AlTiN coating, respectively. The cutting performance evaluation of the coated tools is revealed by the chip morphology, cutting force, cutting temperature, and tool wear. The results show that the serration and shear slip of the chips become more clear with the cutting speed. The lower cutting force and cutting temperature are achieved by the TiN/TiCN/TiAlN multi-coated tool. The flank wear was the dominant wear form in the milling process of AISI 4340. The dominant wear mechanisms of the coated tools include the crater wear, coating chipping, adhesion, abrasion, and diffusion. In general, a TiN/TiCN/TiAlN multi-coated tool is the most suitable tool for high-speed milling of AISI 4340, due to the lower cutting force, the lower cutting temperature, and the high resistance of the element diffusion.