3D Printable Polymeric Composite Material with Enhanced Conductivity Achieved by Affinity Matching.

Polymer-based conductive composites are lightweight, low-cost, and easily processable materials with important applications in various fields. However, achieving highly conductive and 3D printable polymer-based conductive composites remains challenging. In this study, we successfully developed a highly conductive composite suitable for direct ink writing 3D printing using unsaturated polyester resin as the polymer matrix and graphene nanosheets as conductive fillers and rheological modifiers. Due to the well-matched affinity between graphene nanosheets and unsaturated polyester, the graphene nanosheets aggregate within the unsaturated polyester, forming a 3D conductive network. Moreover, the shearing force during direct ink writing 3D printing induces the orientation of the 2D graphene nanosheets, significantly enhancing their conductivity along the printing direction. At room temperature, the unsaturated polyester resin/graphene composite shows a high conductivity of 69.9 S m-1 while maintaining excellent 3D printability. Structures printed using this material exhibit improved heat dissipation and electromagnetic shielding performance. The reported unsaturated polyester resin/graphene nanosheet composites demonstrate outstanding electrical and heat conductivity and excellent processability, making them promising candidates for applications in electromagnetic shielding, printed electronics, and other fields.

Modulation of audiovisual integration in the left and right sides: effects of side and spatial coherency.

BACKGROUND: Using event-related potentials (ERPs), we aimed to investigate audiovisual integration neural mechanisms during a letter identification task in the left and right sides. Unimodal (A,V) and bimodal (AV) stimuli were presented on either side, with ERPs from unimodal (A,V) stimuli on the same side being compared to those from simultaneous bimodal stimuli (AV). Non-zero results of the AV-(A + V) difference waveforms indicated audiovisual integration on the left/right side. RESULTS: When spatially coherent AV stimuli were presented on the right side, two significant ERP components in the integrated differential wave were noted. The N134 and N262, present in the first 300 ms of the AV-(A + V) integration difference wave, indicated significant audiovisual integration effects. However, when these stimuli were presented on the left side, there were no significant integration components. This audiovisual integration difference may stem from left/right asymmetry of cerebral hemisphere language processing. CONCLUSIONS: Audiovisual letter information presented on the right side was easier to integrate, process, and represent. Additionally, only one significant integrative component peaked at 140 ms in the parietal cortex for spatially non-coherent AV stimuli and provided audiovisual multisensory integration, which could be attributed to some integrative neural processes that depend on the spatial congruity of the auditory and visual stimuli.

Grafting Carbon Fibers with Graphene via a One-Pot Aryl Diazonium Reaction to Refine the Interface Performance of T1100-Grade CF/BMI Composites.

In this study, a one-pot aryl diazonium reaction was used as a simple and mild method to graft graphene onto the smooth and inert surface of T1100-grade carbon fiber (CF) through covalent bonding without any damage on CF, to refine the interface performance of CF/bismaleimide (BMI) composites. XPS, SEM, AFM, and dynamic contact angle testing (DCAT) were used to characterize chemical activity, morphologies, and wettability on untreated and grafted CF surfaces. Meanwhile, the impact of the graft method on the tensile strength of CF was also examined using the monofilament tensile test. IFSS between CF grafted with graphene and BMI resin achieved 104.2 MPa after modification, increasing from 85.5 MPa by 21.8%, while the tensile strength did not decrease compared to the pristine CF. The mechanism of this interface enhancement might be better chemical bonding and mechanical interlock between CF grafted with graphene and BMI resin, which is generated from the high surface chemical activity and rough structure of graphene. This study may propose a simple and mild method to functionalize the CF surface and enhance the interface performance of composites without compromising the tensile properties of T1100-grade CF.

High internal phase emulsions gel ink for direct-ink-writing 3D printing of liquid metal.

3D printing of liquid metal remains a big challenge due to its low viscosity and large surface tension. In this study, we use Carbopol hydrogel and liquid gallium-indium alloy to prepare a liquid metal high internal phase emulsion gel ink, which can be used for direct-ink-writing 3D printing. The high volume fraction (up to 82.5%) of the liquid metal dispersed phase gives the ink excellent elastic properties, while the Carbopol hydrogel, as the continuous phase, provides lubrication for the liquid metal droplets, ensuring smooth flow of the ink during shear extrusion. These enable high-resolution and shape-stable 3D printing of three-dimensional structures. Moreover, the liquid metal droplets exhibit an electrocapillary phenomenon in the Carbopol hydrogel, which allows for demulsification by an electric field and enables electrical connectivity between droplets. We have also achieved the printing of ink on flexible, non-planar structures, and demonstrated the potential for alternating printing with various materials.

Epigenetic characterization of sarcopenia-associated genes based on machine learning and network screening.

To screen characteristic genes related to sarcopenia by bioinformatics and machine learning, and to verify the accuracy of characteristic genes in the diagnosis of sarcopenia. Download myopia-related data sets from geo public database, find the differential genes through R language limma package after merging, STRING database to build protein interaction network, and do Go analysis and GSEA analysis to understand the functions and molecular signal pathways that may be affected by the differential genes. Further screen the characteristic genes through LASSO and SVM-RFE machine algorithms, make the ROC curve of the characteristic genes, and obtain the AUC value. 10 differential genes were obtained from the data set, including 7 upregulated genes and 3 downregulated genes. Eight characteristic genes were screened by a machine learning algorithm, and the AUC value of characteristic genes exceeded 0.7. In patients with sarcopenia, the expression of TPPP3, C1QA, LGR5, MYH8, and CDKN1A genes are upregulated, and the expression of SLC38A1, SERPINA5, and HOXB2 genes are downregulated. The above genes have high accuracy in the diagnosis of sarcopenia. The research results provide new ideas for the diagnosis and mechanism research of sarcopenia.

Preparation and Validation of a Longitudinally and Transversely Stiffened Panel Based on Hybrid RTM Composite Materials.

In the face of the difficulty in achieving high-quality integrated molding of longitudinally and transversely stiffened panels for helicopters by resin-matrix composite materials, we combine the prepreg process and the resin transfer molding (RTM) process to propose a hybrid resin transfer molding (HRTM) for composite stiffened panel structures. The HRTM process uses a mixture of prepreg and dry fabric to lay up a hybrid fiber preform, and involves injecting liquid resin technology. Using this process, a longitudinally and transversely stiffened panel structure is prepared, and the failure modes under compressive load are explored. The results show that at the injection temperature of the RTM resin, the prepreg resin dissolves slightly and has little effect on the viscosity of the RTM resin. Both resins have good miscibility at the curing temperature, which allows for the overall curing of the resin. A removable box core mold for the HRTM molding is designed, which makes it convenient for the mold to be removed after molding and is suitable for the overall molding of the composite stiffened panel. Ultrasonic C-scan results show that the internal quality of the composite laminates prepared using the HRTM process is good. A compression test proves that the composite stiffened panel undergoes sequential buckling deformation in different areas under compressive load, followed by localized debonding and delamination of the skin, and finally failure due to the fracture of the longitudinal reinforcement ribs on both sides. The compressive performance of the test specimen is in good agreement with the finite element simulation results. The verification results show that the HRTM process can achieve high-quality integrated molding of the composite longitudinally and transversely stiffened panel structure.

Aspergillus niger Fermentation Broth Promotes Maize Germination and Alleviates Low Phosphorus Stress.

Aspergillus niger is a type of soil fungus with the ability to dissolve insoluble phosphate and secrete organic metabolites such as citric acid. However, whether cell-free Aspergillus niger fermentation broth (AFB) promotes maize growth and alleviates low-phosphorus stress has not been reported. In this study, we explored their relationship through a hydroponics system. The results indicated that either too low or too high concentrations of AFB may inhibit seed germination potential and germination rate. Under low phosphorus conditions, all physiological indexes (biomass, soluble sugar content, root length, etc.) increased after AFB was applied. A qRT-PCR analysis revealed that the expression of the EXPB4 and KRP1 genes, which are involved in root development, was upregulated, while the expression of the CAT2 and SOD9 genes, which are keys to the synthesis of antioxidant enzymes, was downregulated. The expression of LOX3, a key gene in lipid peroxidation, was down-regulated, consistent with changes in the corresponding enzyme activity. These results indicate that the application of AFB may alleviate the oxidative stress in maize seedlings, reduce the oxidative damage caused by low P stress, and enhance the resistance to low P stress in maize seedlings. In addition, it reveals the potential of A. niger to promote growth and provides new avenues for research on beneficial plant-fungal interactions.

Effects of Surface Properties of Fiber on Interface Properties of Carbon Fiber/Epoxy Resin and Its Graphene Oxide Modified Hybrid Composites.

In the present study, surface properties of three types of carbon fibers (CCF300, CCM40J, and CCF800H) on the interface properties of carbon fiber/epoxy resin (CF/EP) were analyzed. The composites are further modified by graphene oxide (GO) to obtain GO/CF/EP hybrid composites. Meanwhile, the effect of the surface properties of CFs and the additive graphene oxide on the interlaminar shear properties and dynamic thermomechanical properties of GO/CF/EP hybrid composites are also analyzed. The results show that the higher surface oxygen-carbon ratio of carbon fiber (CCF300) has a positive effect on improving the glass transition temperature (Tg) of the CF/EP composites. The Tg of CCF300/EP is 184.4 °C, while the Tg of CCM40J/EP and CCF800/EP are only 177.1 °C and 177.4 °C, respectively. Furthermore, deeper and more dense grooves on the fiber surface (CCF800H and CCM40J) are more conducive to improving the interlaminar shear performance of the CF/EP composites. The interlaminar shear strength (ILSS) of CCF300/EP is 59.7 MPa, and that of CCM40J/EP and CCF800H/EP are 80.1 MPa and 83.5 MPa, respectively. For the GO/CF/EP hybrid composites, graphene oxide with abundant oxygen-containing groups is beneficial to improve the interfacial interaction. Graphene oxide can significantly improve the glass transition temperature and interlamellar shear strength of GO/CCF300/EP composites fabricated by CCF300 with a higher surface oxygen-carbon ratio. For the CCM40J and CCF800H with lower surface oxygen-carbon ratio, graphene oxide has a better modification effect on the glass transition temperature and interlamellar shear strength of GO/CCM40J/EP composites fabricated by CCM40J with deeper and finer surface grooves. Regardless of the type of carbon fiber, the GO/CF/EP hybrid composites with 0.1% graphene oxide have the optimized interlaminar shear strength, and the GO/CF/EP hybrid composites with 0.5% graphene oxide have the maximum glass transition temperature.

Self-Compositing: A Efficient Method of Improving the Electrical Conductivity of Graphene Nanoplatelet/Thermosetting Resin Composites.

Conductive composites based on thermosetting resins have broad applications in various fields. In this paper, a new self-compositing strategy is developed for improving the conductivity of graphene nanoplatelet/thermosetting resin composites by optimizing the transport channels. To implement this strategy, conventional graphene nanoplatelet/thermosetting resin is crushed into micron-sized composite powders, which are mixed with graphene nanoplatelets to form novel complex fillers to prepare the self-composited materials with thermosetting resins. A highly conductive compact graphene layer is formed on the surface of the crushed composite powders, while the addition of the micron-sized powder induces the orientation of graphene nanoplatelets in the resin matrix. Therefore, a highly conductive network is constructed inside the self-composited material, significantly enhancing the electrical conductivity. The composite materials based on epoxy resin, cyanate resin, and unsaturated polyester are prepared with this method, reflecting that the method is universal for preparing composites based on thermosetting resins. The highest electrical conductivity of the self-composited material based on unsaturated polyester is as high as 25.9 S m-1 . This self-compositing strategy is simple, efficient, and compatible with large-scale industrial production, thus it is a promising and general way to enhance the conductivity of thermosetting resin matrix composites.

The Value of Immunocytochemical Staining for the HPV E7 Protein in the Diagnosis of Cervical Lesions.

Purpose: To investigate the value of immunocytochemical (ICC) staining for human papillomavirus (HPV) E7 protein (E7-ICC staining) as a new-generation immunological method in the cytological diagnosis of cervical lesions. Methods: The exfoliated cervical cell samples of 690 women were subjected to a liquid-based cytology test (LCT), high-risk HPV (HR-HPV) test, E7-ICC staining, and cervical biopsy for pathological diagnosis. Results: E7-ICC staining as a preliminary screening scheme for cervical precancerous lesions was comparable to the HR-HPV test in sensitivity and to the LCT in specificity. E7-ICC staining was advantageous in facilitating the secondary triage of HR-HPV-positive patients; therefore, this method can be used as an auxiliary scheme to routine LCT for diagnostic grading to improve the accuracy of cervical cytology. Conclusion: E7-ICC staining as a primary or auxiliary cytological screening scheme can effectively reduce the colposcopy referral rate.

High-strength and machinable load-bearing integrated electrochemical capacitors based on polymeric solid electrolyte.

Load bearing/energy storage integrated devices (LEIDs) allow using structural parts to store energy, and thus become a promising solution to boost the overall energy density of mobile energy storage systems, such as electric cars and drones. Herein, with a new high-strength solid electrolyte, we prepare a practical high-performance load-bearing/energy storage integrated electrochemical capacitors with excellent mechanical strength (flexural modulus: 18.1 GPa, flexural strength: 160.0 MPa) and high energy storage ability (specific capacitance: 32.4 mF cm-2, energy density: 0.13 Wh m-2, maximum power density: 1.3 W m-2). We design and compare two basic types of multilayered structures for LEID, which significantly enhance the practical bearing ability and working flexibility of the device. Besides, we also demonstrate the excellent processability of the LEID, by forming them into curved shapes, and secondarily machining and assembling them into complex structures without affecting their energy storage ability.

Evolution of Transient Luminescent Assemblies Regulated by Trace Water in Organic Solvents.

Trace water in organic solvents can play a crucial role in the construction of supramolecular assemblies, which has not gained enough attention until very recent years. Herein, we demonstrate that residual water in organic solvents plays a decisive role in the regulation of the evolution of assembled structures and their functionality. By adding Mg(ClO4)2 into a multi-component organic solution containing terpyridine-based ligand 3Tpy and monodentate imidazole-based ligand M2, the system underwent an unexpected kinetic evolution. Metallo-supramolecular polymers (MSP) formed first by the coordination of 3Tpy and Mg2+, but they subsequently decomposed due to the interference of M2, resulting in a transient MSP system. Further investigation revealed that this occurred because residual water in the solvent and M2 cooperatively coordinated with Mg2+. This allowed M2 to capture Mg2+ from MSP, which led to depolymerization. However, owing to the slow reaction between trace water/M2/Mg2+, the formation of MSP still occurred first. Therefore, water regulated both the thermodynamics and kinetics of the system and was the key factor for constructing the transient MSP. Fine-tuning the water content and other assembly motifs regulated the assembly evolution pathway, tuned the MSP lifetime, and made the luminescent color of the system undergo intriguing transition processes over time.

The Preforming of an Interlaminar Toughened Carbon Fiber/Bismaleimide Resin Composite by a Benzoxazine-Based Tackifier.

When thermoplastic resin-toughened carbon fiber (CF) composites are formed by liquid resin transfer molding (RTM), the conventional methods cannot be used to set the fabric preform, which affects the overall mechanical properties of the composites. To address this challenge, the benzoxazine-based tackifier BT5501A was designed, a preforming-toughening bifunctional CF fabric was fabricated by employing thermoplastic polyaryletherketone (PEK-C), and an aviation RTM-grade bismaleimide (BMI) resin was used as the matrix to study the effect of the benzoxazine-based tackifier on the thermal curing property and heat resistance of the resin matrix. Furthermore, the preforming and toughening effects on the bifunctional CF fabric reinforced the BMI resin composites. The tackifier BT5501A has good process operability. The application of this tackifier can advance the thermal curing temperature of the BMI resin matrix and decrease the glass transition temperature of the resin, compared to that of the pure BMI resin. Furthermore, when the tackifier was added into the CF/PEK-C/BMI composites, the obtained CF/BT5501A/PEK-C/BMI composites had comparable compression strength after impact, pit depth, and damage area, compared to the CF/PEK-C/BMI composites, while the tackifier endowed the fabric preform with an excellent preforming effect.

Effects of the Interlayer Toughening Agent Structure on the Flow Behavior during the z-RTM Process.

In this paper, interlayer toughening composites were prepared by the z-directional injection RTM process (z-RTM), which has the advantage of increasing the interlaminar toughness and shortening the filling time and completely impregnating the fibers. The nonwoven fabrics and dot matrix structure material were used as ex situ interlayer toughening agents. The effect of the interlayer toughening agent structure on the resin flow behavior during the z-RTM process was investigated. The macro-flowing and micro-infiltration behaviors of the resin inside the preforms were deduced. The permeability of the fabric preforms with different toughening agents was investigated. The results show that the introduction of the nonwoven structure toughening agent makes the macro flow slow, and the flow front more uniform. The toughening agent with a dot matrix structure promotes the resin macro flow in the preforms, and shortens the injection time. The z-directional permeability of the preform with a dot matrix structural toughening agent is one order of magnitude lower than that of the non-toughened preform, while being higher than the preform toughened by the nonwoven fabric preforms, which is helpful for the further applicability of the z-RTM process. Furthermore, the mode II interlaminar fracture toughness of composites was evaluated.

Covalent Protein Modification: An Unignorable Factor for Bisphenol A-Induced Hepatotoxicity.

Covalent modification of proteins by reactive pollutants/metabolites might trigger various toxicities resulting from the disruption of protein structures and/or functions, which is critical for understanding the mechanism of pollutants-induced toxicity. However, this mechanism has rarely been touched on due to the lack of a methodology. In this research, the protein modification of bisphenol A (BPA) in rats was characterized using a series of liquid chromatography-tandem mass spectrometry (LC-MS) approaches. BPA-modified cysteine (Cys1) was first released from proteins via enzymatic hydrolysis and identified using LC-MS. Moreover, the positive correlation between Cys1 and hepatotoxicity indicated the involvement of protein modification in BPA toxicity. Then, in vitro incubation of BPA with amino acids and protein confirmed that BPA could specifically modify cysteine residues of proteins after bioactivation and provided four additional modification patterns. Finally, 24 BPA-modified proteins were identified from the liver of BPA-exposed rats using proteomic analysis, and they were mainly enriched in oxidative stress-related pathways. The modification on superoxide dismutases, catalase, and glutathione S-transferases disrupted their enzymatic functions, leading to oxidative damage. These results revealed that the covalent protein modification is an unignorable factor for BPA hepatotoxicity. Moreover, the workflow can be applied to identify protein adducts of other emerging contaminants and possible risk.

Dual roles of drug or its metabolite-protein conjugate: Cutting-edge strategy of drug discovery using shotgun proteomics.

Many drugs can bind directly to proteins or be bioactivated by metabolizing enzymes to form reactive metabolites (RMs) that rapidly bind to proteins to form drug-protein conjugates or metabolite-protein conjugates (DMPCs). The close relationship between DMPCs and idiosyncratic adverse drug reactions (IADRs) has been recognized; drug discovery teams tend to avoid covalent interactions in drug discovery projects. Covalent interactions in DMPCs can provide high potency and long action duration and conquer the intractable targets, inspiring drug design, and development. This forms the dual role feature of DMPCs. Understanding the functional implications of DMPCs in IADR control and therapeutic applications requires precise identification of these conjugates from complex biological samples. While classical biochemical methods have contributed significantly to DMPC detection in the past decades, the low abundance and low coverage of DMPCs have become a bottleneck in this field. An emerging transformation toward shotgun proteomics is on the rise. The evolving shotgun proteomics techniques offer improved reproducibility, throughput, specificity, operability, and standardization. Here, we review recent progress in the systematic discovery of DMPCs using shotgun proteomics. Furthermore, the applications of shotgun proteomics supporting drug development, toxicity mechanism investigation, and drug repurposing processes are also reviewed and prospected.

Three-Dimensional Printing and Recycling of Multifunctional Composite Material Based on Commercial Epoxy Resin and Graphene Nanoplatelet.

3D printing of commercial thermosetting epoxy resin is of great significance for the rapid and low-cost construction of high-strength objects with complex structures. Meanwhile, recycling these commercial epoxy resins is essential for environmental protection and sustainable development. This paper reports direct ink writing 3D printing of a multifunctional composite material based on commercial bisphenol A epoxy resin and a 3D printing compatible technique to recycle the printed composite material. Graphene nanoplatelet is designed as an efficient functional thixotropic additive that turns the liquid epoxy resin prepolymer shear-thinning and suitable for direct ink printing. Composite materials with high resolution and high mechanical strength are printed with epoxy resin/graphene nanoplatelet inks, and they also show high thermal and electrical conductivity and fast thermo-induced shape memory response. The printed objects can be recycled by comminuting them into micropowders, which are then used as a thixotropic agent to prepare recycled DIW ink. The physical properties of the materials printed with recycled inks maintain unchanged for successive four recycling cycles. The graphene nanoplatelets at the surface of recycled comminuted powder are found to modulate the surface energy of the powder, thus making the powder able to serve as a thixotropic agent for the recycled inks. The method here provides a new solution to process commercial epoxy resin and opens a new direction to the more sustainable use of thermosetting plastics.

Research on Clamping Force Control of CVT for Electric Vehicles Based on Slip Characteristics.

The low mechanical efficiency of metal belt's continuously variable transmission (CVT) limits its application in new energy vehicles. To further improve CVT efficiency and reduce the energy consumption of electric vehicles (EVs) with CVT, this paper proposes a pure electric CVT configuration and a clamping force control strategy. The slip characteristics of CVT are obtained through a bench test, the dynamic model of CVT slip is established, and a clamping force fuzzy control strategy is designed. The strategy is studied by simulation under extreme conditions and standard driving cycles. The simulation results show that the proposed clamping force control strategy has good adaptability. Under extreme conditions, this strategy can ensure that CVT does not undergo macro slip, while reducing the clamping force by 12.86-21.65%. Energy consumption per 100 km is 14.90 kWh in NEDC, which is 6.67% lower compared with the traditional strategy. CVT average efficiency and average transmission efficiency increased by 3.71% and 6.40%. The research results demonstrate that adjusting the CVT clamping force through fuzzy control based on the slip rate can improve the CVT efficiency and energy economy of EVs, which provides a certain reference for CVT clamping force control strategy development and the application of CVT on EVs.

Antioxidant and anticancer potentials of edible flowers: where do we stand?

Edible flowers are attracting special therapeutic attention and their administration is on the rise. Edible flowers play pivotal modulatory roles on oxidative stress and related interconnected apoptotic/inflammatory pathways toward the treatment of cancer. In this review, we highlighted the phytochemical content and therapeutic applications of edible flowers, as well as their modulatory potential on the oxidative stress pathways and apoptotic/inflammatory mediators, resulting in anticancer effects. Edible flowers are promising sources of phytochemicals (e.g., phenolic compounds, carotenoids, terpenoids) with several therapeutic effects. They possess anti-inflammatory, anti-diabetic, anti-microbial, anti-depressant, anxiolytic, anti-obesity, cardioprotective, and neuroprotective effects. Edible flowers potentially modulate oxidative stress by targeting erythroid nuclear transcription factor-2/extracellular signal-regulated kinase/mitogen-activated protein kinase (Nrf2/ERK/MAPK), reactive oxygen species (ROS), nitric oxide (NO), malondialdehyde (MDA) and antioxidant response elements (AREs). As the interconnected pathways to oxidative stress, inflammatory mediators, including tumor necrosis factor (TNF)-α, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), interleukins (ILs) as well as apoptotic pathways such as Bcl-2-associated X protein (Bax), Bcl-2, caspase and cytochrome C are critical targets of edible flowers in combating cancer. In this regard, edible flowers could play promising anticancer effects by targeting oxidative stress and downstream dysregulated pathways.

Quantification of Osimertinib and Metabolite-Protein Modification Reveals Its High Potency and Long Duration of Effects on Target Organs.

Covalent drugs are newly developed and proved to be successful therapies in past decades. However, the pharmacokinetics (PK) and pharmacodynamic (PD) studies of covalent drugs now ignore the drug and metabolite-protein modification. The low abundance of modified proteins also prevents its investigation. Herein, a simple, selective, and sensitive liquid chromatography-mass spectrometry (LC-MS)/MS quantitative method was established based on the mechanism of a drug and its metabolite-protein adducts using osimertinib as an example. Five metabolites with covalent modification potential were identified. The drug and its metabolite-cysteine adducts released from modified proteins by a mixed hydrolysis method were developed to characterize the level of the modified proteins. This turned the quantitative objects from proteins or peptides to small molecules, which increased the sensitivity and throughput of the quantitative approach. Accumulation of protein adducts formed by osimertinib and its metabolites in target organs was observed in vivo and long-lasting modifications were noted. These results interpreted the long duration of the covalent drugs' effect from the perspective of both parent and the metabolites. In addition, the established method could also be applied in blood testing as noninvasive monitoring. This newly developed approach showed great feasibility for PK and PD studies of covalent drugs.