Study on the enhanced efficacy mechanism of vinegar-processed Cyperus rotundus in the treatment of primary dysmenorrhea.

The enhanced efficacy of vinegar-processed Cyperus rotundus (VCR) in treating primary dysmenorrhea (PD) has been observed. However, the active components and potential mechanisms of synergy are still unclear. The objective of this study was to develop a method that combines bionic technology, plant metabolomics and network pharmacology to discover the active components and potential mechanisms underlying the enhanced therapeutic effects of VCR for PD. Vinegar processing alters the flavor of C. rotundus, leading to changes in its properties. The acidic nature of vinegar enhances the selectivity of the medicine toward the liver, thereby improving its ability to soothe the liver, regulate qi and provide pain relief. Through gas chromatography-mass spectrometry and multivariate statistical analysis, 30 key differential components between raw C. rotundus and VCR have been screened and identified. These differential components primarily exert their therapeutic effects in treating PD by modulating targets such as interleukin-6, TNF, TP53 and PTGS2, as well as pathways including the estrogen signaling pathway, ovarian steroidogenesis, the TNF signaling pathway and the HIF-1 signaling pathway. The findings of this study serve as a reference for the application of VCR in compound formulas and clinic practiceal. Furthermore, the methodology employed in this study provides research insights for the processing of other Chinese medicines.

Unconventional superconductivity in chiral molecule-TaS2 hybrid superlattices.

Chiral superconductors, a unique class of unconventional superconductors in which the complex superconducting order parameter winds clockwise or anticlockwise in the momentum space1, represent a topologically non-trivial system with intrinsic time-reversal symmetry breaking (TRSB) and direct implications for topological quantum computing2,3. Intrinsic chiral superconductors are extremely rare, with only a few arguable examples, including UTe2, UPt3 and Sr2RuO4 (refs. 4-7). It has been suggested that chiral superconductivity may exist in non-centrosymmetric superconductors8,9, although such non-centrosymmetry is uncommon in typical solid-state superconductors. Alternatively, chiral molecules with neither mirror nor inversion symmetry have been widely investigated. We suggest that an incorporation of chiral molecules into conventional superconductor lattices could introduce non-centrosymmetry and help realize chiral superconductivity10. Here we explore unconventional superconductivity in chiral molecule intercalated TaS2 hybrid superlattices. Our studies reveal an exceptionally large in-plane upper critical field Bc2,|| well beyond the Pauli paramagnetic limit, a robust π-phase shift in Little-Parks measurements and a field-free superconducting diode effect (SDE). These experimental signatures of unconventional superconductivity suggest that the intriguing interplay between crystalline atomic layers and the self-assembled chiral molecular layers may lead to exotic topological materials. Our study highlights that the hybrid superlattices could lay a versatile path to artificial quantum materials by combining a vast library of layered crystals of rich physical properties with the nearly infinite variations of molecules of designable structural motifs and functional groups11.

Artificial intelligence model system for bone age assessment of preschool children.

BACKGROUD: Our study aimed to assess the impact of inter- and intra-observer variations when utilizing an artificial intelligence (AI) system for bone age assessment (BAA) of preschool children. METHODS: A retrospective study was conducted involving a total sample of 53 female individuals and 41 male individuals aged 3-6 years in China. Radiographs were assessed by four mid-level radiology reviewers using the TW3 and RUS-CHN methods. Bone age (BA) was analyzed in two separate situations, with/without the assistance of AI. Following a 4-week wash-out period, radiographs were reevaluated in the same manner. Accuracy metrics, the correlation coefficient (ICC)and Bland-Altman plots were employed. RESULTS: The accuracy of BAA by the reviewers was significantly improved with AI. The results of RMSE and MAE decreased in both methods (p < 0.001). When comparing inter-observer agreement in both methods and intra-observer reproducibility in two interpretations, the ICC results were improved with AI. The ICC values increased in both two interpretations for both methods and exceeded 0.99 with AI. CONCLUSION: In the assessment of BA for preschool children, AI was found to be capable of reducing inter-observer variability and enhancing intra-observer reproducibility, which can be considered an important tool for clinical work by radiologists. IMPACT: The RUS-CHN method is a special bone age method devised to be suitable for Chinese children. The preschool stage is a critical phase for children, marked by a high degree of variability that renders BA prediction challenging. The accuracy of BAA by the reviewers can be significantly improved with the aid of an AI model system. This study is the first to assess the impact of inter- and intra-observer variations when utilizing an AI model system for BAA of preschool children using both the TW3 and RUS-CHN methods.

Molecular Characterization of Plant Volatile Compound Interactions with Cnaphalocrocis medinalis Odorant-Binding Proteins.

Odorant-binding proteins (OBPs) play important roles in the insect olfactory system since they bind external odor molecules to trigger insect olfactory responses. Previous studies have identified some plant-derived volatiles that attract the pervasive insect pest Cnaphalocrocis medinalis (Lepidoptera: Pyralidae), such as phenylacetaldehyde, benzyl acetate, 1-heptanol, and hexanal. To characterize the roles of CmedOBPs in the recognition of these four volatiles, we analyzed the binding abilities of selected CmedOBPs to each of the four compounds, as well as the expression patterns of CmedOBPs in different developmental stages of C. medinalis adult. Antennaes of C. medinalis adults were sensitive to the studied plant volatile combinations. Expression levels of multiple CmedOBPs were significantly increased in the antennae of 2-day-old adults after exposure to volatiles. CmedOBP1, CmedOBP6, CmedPBP1, CmedPBP2, and CmedGOBP2 were significantly up-regulated in the antennae of volatile-stimulated female and male adults when compared to untreated controls. Fluorescence competition assays confirmed that CmedOBP1 could strongly bind 1-heptanol, hexanal, and phenylacetaldehyde; CmedOBP15 strongly bound benzyl acetate and phenylacetaldehyde; and CmedOBP26 could weakly bind 1-heptanol. This study lays a theoretical foundation for further analysis of the mechanisms by which plant volatiles can attract C. medinalis. It also provides a technical basis for the future development of efficient plant volatile attractants of C. medinalis.

Study on Thermomechanical Properties and Morphology of an Epoxy Resin Thermally Conductive Adhesive under Different Curing Conditions.

An epoxy resin thermally conductive adhesive is a type of thermosetting polymer encapsulation material that exhibits comprehensive performance, and the thermomechanical properties of this adhesive vary significantly under different curing conditions. In this paper, spherical alumina was used as a filler for thermal conductivity to prepare an epoxy resin thermal conductivity adhesive using a multistage freezing mixing method. The effects of various curing conditions on the thermal-mechanical properties and fracture morphology of the epoxy resin thermal conductivity adhesive were studied. The results showed that the curing condition of 150 °C/2.5 h significantly improved the performance of the epoxy resin thermally conductive adhesive. Through the shear test of the composite material, the influence of the curing agent on the adhesion of the thermally conductive adhesive under fixed conditions was explored. It was found that the curing agent with a superbranched structure exhibited latent properties and greatly enhanced the toughness of the cured epoxy resin product. Altering the curing conditions increases the shear strength by up to 307%. With the increase in curing temperature and the extension of curing temperature, the glass transition temperature gradually increased from 103.9 to 159.8 °C. The initial decomposition temperature TIDT gradually increased from 295.4 to 310.1 °C, and the temperature at which the fastest decomposition rate occurs (Tmax) gradually increased from 312.48 to 330.33 °C. The thermal stability of the substance increased with both temperature and time. The curing time and curing temperature were increased, and the morphology of the fracture of the epoxy resin thermally conductive adhesive cured sample gradually showed a ductile fracture from a typical brittle fracture. The research results reveal the influence of curing conditions on the thermal conductivity and thermal stability of the epoxy resin thermally conductive adhesive, which has a specific reference value for improving the performance of the epoxy resin thermally conductive adhesive, optimizing its usage conditions, and improving production efficiency.

Individualized atomoxetine response and tolerability in children with ADHD receiving different dosage regimens: the need for CYP2D6 genotyping and therapeutic drug monitoring to dance together.

Integrating CYP2D6 genotyping and therapeutic drug monitoring (TDM) is crucial for guiding individualized atomoxetine therapy in children with attention-deficit/hyperactivity disorder (ADHD). The aim of this retrospective study was (1) to investigate the link between the efficacy and tolerability of atomoxetine in children with ADHD and plasma atomoxetine concentrations based on their CYP2D6 genotypes; (2) to offer TDM reference range recommendations for atomoxetine based on the CYP2D6 genotypes of children receiving different dosage regimens. This retrospective study covered children and adolescents with ADHD between the ages of 6 and <18, who visited the psychological and behavioral clinic of Children's Hospital of Nanjing Medical University from June 1, 2021, to January 31, 2023. The demographic information and laboratory examination data, including CYP2D6 genotype tests and routine TDM of atomoxetine were obtained from the hospital information system. We used univariate analysis, Mann-Whitney U nonparametric test, Kruskal-Wallis test, and the receiver operating characteristic (ROC) curve to investigate outcomes of interest. 515 plasma atomoxetine concentrations of 385 children (325 boys and 60 girls) with ADHD between 6 and 16 years of age were included for statistical analysis in this study. Based on genotyping results, >60% of enrolled children belonged to the CYP2D6 extensive metabolizer (EM), while <40% fell into the intermediate metabolizer (IM). CYP2D6 IMs exhibited higher dose-corrected plasma atomoxetine concentrations by 1.4-2.2 folds than those CYP2D6 EMs. Moreover, CYP2D6 IMs exhibited a higher response rate compare to EMs (93.55% vs 85.71%, P = 0.0132), with higher peak plasma atomoxetine concentrations by 1.67 times than those of EMs. Further ROC analysis revealed that individuals under once daily in the morning (q.m.) dosing regimen exhibited a more effective response to atomoxetine when their levels were ≥ 268 ng/mL (AUC = 0.710, P < 0.001). In addition, CYP2D6 IMs receiving q.m. dosing of atomoxetine were more likely to experience adverse reactions in the central nervous system and gastrointestinal system when plasma atomoxetine concentrations reach 465 and 509 ng/mL, respectively. The findings in this study provided promising treatment strategy for Chinese children with ADHD based on their CYP2D6 genotypes and plasma atomoxetine concentration monitoring. A peak plasma atomoxetine concentration higher than 268 ng/mL might be requisite for q.m. dosing. Assuredly, to validate and reinforce these initial findings, it is necessary to collect further data in controlled studies with a larger sample size.

Hierarchical CoWO4/NixFeyS microspheres bearing crystalline-amorphous interface as a multifunctional platform for outperformed water splitting and sensitive hydrazine sensing.

Highly efficient and multifunctional electrocatalysts are of high value in energy transformation and electrochemical sensing. Herein, hierarchically architectured cobalt tungstate/nickel iron sulfide (CoWO4/NixFeyS) microspheres with a crystalline-amorphous interface have been prepared on bimetallic substrate of nickel-iron foam (NIF) by a two-step hydrothermal method. Electrochemical characterization shows that CoWO4/NixFeyS microspheres can boost the electrocatalytic activity effectively through the synergistic effect on the crystalline-amorphous interface. When the CoWO4/NixFeyS is applied as the electrocatalysts for oxygen evolution reaction (OER) and the hydrogen evolution reaction (HER), the overpotentials at a high current density of 500 mA cm-2 are only 322.8 mV and 306.5 mV, respectively. The overall water splitting device composed of CoWO4/NixFeyS/NIF couple only needs a cell voltage of 1.80 V to reach a current density of 100 mA cm-2, and 2.19 V to reach 500 mA cm-2. The CoWO4/NixFeyS/NIF can be also utilized as an effective electrochemical platform for the sensing of toxic hydrazine in a wide range from 50 µM to 17.3 mM, with a detection limit of 46.4 µM. All these results display that the CoWO4/NixFeyS/NIF can be a high-performance multifunctional material for energy transformation and environmental pollutant monitoring.

SEIR-diffusion modeling and stability analysis of supply chain finance based on blockchain technology.

Inadequate information sharing and difficult information diffusion are the main factors that cause upstream and downstream enterprises to default on supply chain finance. Blockchain technology, which exploits distributed storage and a consensus mechanism, can provide effective solutions to overcome these problems such as information sharing. When blockchain technology is adopted by the enterprises that comprise the supply chain finance business, this technology shows a diffusion trend. As a result, the decision pertaining to the application of novel technologies is affected. Therefore, to investigate the diffusion mechanism pertaining to the blockchain technology that is applied in supply chain finance, the study exploited the idea of a class of SEIR infectious disease models, and built a blockchain model that considers the supply chain financial system. Besides, the study verifies the stability of the model by constructing a Lyapunov function. The results indicate that the basic reproduction number determines the proliferation of the blockchain technology. When the basic reproduction number is less than 1, the proliferation of the blockchain technology that is applied in supply chain finance system would terminate. By contrast, when the basic reproduction number is greater than 1, during the average infection period, the number of non-adopting enterprises that accept the blockchain technology becomes greater than 1, which can maintain a continuous impact on supply chain finance system. Over time, the number of enterprises that accept blockchain technology tends to be stable. Through numerical simulations that consider the influencing parameters pertaining to the basic regeneration number, which has important effect on blockchain technology diffusion, we enlarge the diffusion efficiency and increase the transfer rate of potential on-chain enterprises or decrease the default exit rate. As a result, we facilitate the diffusion of blockchain technology in the system.

The Plant Volatile-Sensing Mechanism of Insects and Its Utilization.

Plants and insects are engaged in a tight relationship, with phytophagous insects often utilizing volatile organic substances released by host plants to find food and egg-laying sites. Using plant volatiles as attractants for integrated pest management is vital due to its high efficacy and low environmental toxicity. Using naturally occurring plant volatiles combined with insect olfactory mechanisms to select volatile molecules for screening has proved an effective method for developing plant volatile-based attractant technologies. However, the widespread adoption of this technique is still limited by the lack of a complete understanding of molecular insect olfactory pathways. This paper first describes the nature of plant volatiles and the mechanisms of plant volatile perception by insects. Then, the attraction mechanism of plant volatiles to insects is introduced with the example of Cnaphalocrocis medinalis. Next, the progress of the development and utilization of plant volatiles to manage pests is presented. Finally, the functions played by the olfactory system of insects in recognizing plant volatiles and the application prospects of utilizing volatiles for green pest control are discussed. Understanding the sensing mechanism of insects to plant volatiles and its utilization will be critical for pest management in agriculture.

Efr3b is essential for social recognition by modulating the excitability of CA2 pyramidal neurons.

CA2 pyramidal neurons (PNs) are associated with social behaviors. The mechanisms, however, remain to be fully investigated. Here, we report that Efr3b, a protein essential for phospholipid metabolism at the plasma membrane, is widely expressed in the brain, especially in the hippocampal CA2/CA3 areas. To assess the functional significance of Efr3b in the brain, we generated Efr3bf/f mice and crossed them with Nestin-cre mice to delete Efr3b specifically in the brain. We find that Efr3b deficiency in the brain leads to deficits of social novelty recognition and hypoexcitability of CA2 PNs. We then knocked down the expression of Efr3b specifically in CA2 PNs of C57BL/6J mice, and our results showed that reducing Efr3b in CA2 PNs also resulted in deficits of social novelty recognition and hypoexcitability of CA2 PNs. More interestingly, restoring the expression of Efr3b in CA2 PNs enhances their excitability and improves social novelty recognition in Efr3b-deficient mice. Furthermore, direct activation of CA2 PNs with chemogenetics improves social behaviors in Efr3b-deficient mice. Together, our data suggest that Efr3b is essential for social novelty by modulating the excitability of CA2 PNs.

Broadband 1.0†µm emission in Nd3+/Yb3+ co-doped phosphate glasses and fibers for photonic applications.

In this work, the spectroscopic properties of 1.0 µm emission in Nd3+/Yb3+ co-doped phosphate glasses were systematically investigated under 808 nm excitation. Notably, broadband 1.0 µm emission with a full width at half maximum (FWHM) of 96 nm was obtained in the phosphate glass doped with 2 mol.% Nd2O3 and 1 mol.% Yb2O3. In addition, the energy transfer microscopic parameter and transfer efficiency were analyzed. What is more, multimaterial fibers with Nd3+/Yb3+ co-doped phosphate glass core and silicate cladding were successfully drawn by using the molten core method. An intense 1.0 µm amplified spontaneous emission (ASE) can be realized in a 3 cm long multimaterial fiber. More importantly, the FWHM of the ASE can reach as large as 60 nm when excited at 976 nm. These results demonstrate that the Nd3+/Yb3+ co-doped phosphate glasses and fibers are promising gain materials for amplifier and laser applications in photonics.

Effect of the alumina micro-particle sizes on the thermal conductivity and dynamic mechanical property of epoxy resin.

Epoxy thermal conductive adhesives with high thermal conductivity and dynamic mechanical properties are important thermally conductive materials for fabricating highly integrated electronic devices. In this paper, micro-Al2O3 is used as a thermally conductive filler for the epoxy resin composite and investigated the effect of micron-sized alumina particle size on the thermal conductivity and dynamic mechanical property of epoxy resin by the transient planar hot plate method and DMA (Dynamic mechanical analysis). The experimental results show that with the same amount of alumina filling, the thermal conductivity and Tg (glass transition temperature) of epoxy/Al2O3 composite material decrease with the increase of alumina particle size. The maximum thermal conductivity of the composite material is 0.679 (W/mK), while the energy storage modulus of epoxy/Al2O3 composite material increases with the increase of alumina particle size, and the maximum energy storage modulus of the composite material is 160MPa. Compared with pure epoxy resin, the thermal conductivity and energy storage modulus have increased by 2.7 and 3.2 times, respectively. The epoxy/Al2O3 composite was applied to the COB (Chips On Board) type LED package, and the substrate temperature of the LED dropped to the lowest after 1.5 hours of operation using EP-A5 composite, and the temperature was stabilized at 38.2°C, indicating that the addition of 5-micron alumina composite has the best heat dissipation in the COB type LED package. These results are critical for the implementation of particulate-filled polymer composites in practical applications because relaxed material specifications and handling procedures can be incorporated in production environments to improve efficiency.

Broadband near-infrared amplified spontaneous emission of Er3+-doped germanate glass fiber.

Er3+-doped glass and fiber are very attractive for near-infrared (NIR) lasers and photonic applications. In this work, the full width at half maximum (FWHM) of NIR fluorescence emission of the Er3+-doped germanate glass can be broadened from 72 to 99 nm when Al2O3 was added. In addition, the spectroscopic properties, including absorption and emission spectra, Judd-Ofelt intensity parameters, absorption and emission cross sections, gain coefficient, and fluorescence lifetime, of the Al2O3-modified germanate glass were systematically investigated. What is more, silicate-clad heavily Er3+-doped germanate core multimaterial fibers were successfully drawn by a rod-in-tube method. Notably, broadband NIR amplified spontaneous emission (ASE) with an FWHM of 120 nm was achieved in this new fiber. To the best of our knowledge, this is the largest FWHM reported for Er3+-doped germanate glass fibers. These results suggest that the as-drawn Er3+-doped germanate glass fiber with superior performances is a promising candidate for broadband optical amplification.

Ion channels in cancer-induced bone pain: from molecular mechanisms to clinical applications.

Cancer-induced bone pain (CIBP) caused by bone metastasis is one of the most prevalent diseases, and current treatments rely primarily on opioids, which have significant side effects. However, recent developments in pharmaceutical science have identified several new mechanisms for CIBP, including the targeted modification of certain ion channels and receptors. Ion channels are transmembrane proteins, which are situated on biological cell membranes, which facilitate passive transport of inorganic ions across membranes. They are involved in various physiological processes, including transmission of pain signals in the nervous system. In recent years, there has been an increasing interest in the role of ion channels in chronic pain, including CIBP. Therefore, in this review, we summarize the current literature on ion channels, related receptors, and drugs and explore the mechanism of CIBP. Targeting ion channels and regulating their activity might be key to treating pain associated with bone cancer and offer new treatment avenues.

Identification of quality markers for Cyanotis arachnoidea and analysis of its physiological mechanism based on chemical pattern recognition, network pharmacology, and experimental validation.

Cyanotis arachnoidea C. B. Clarke is a traditional Chinese medicinal herb that has a limited clinical use in the treatment of diabetes mellitus (DM) in minority areas of Guizhou in China. However, few prior reports are available on the quality control of Cyanotis arachnoidea, and its quality markers and hypoglycemic mechanism are still unclear. The purpose of this study is to explore the quality markers (Q-markers) of Cyanotis arachnoidea and predict its hypoglycemic mechanism. In this study, ultra-high-performance liquid chromatography (UHPLC) fingerprint combined with chemical pattern recognition were performed, and four differential components were screened out as quality markers, including 20-Hydroxyecdysone, 3-O-acetyl-20-hydroxyecdysone, Ajugasterone C, and 2-O-acetyl-20-hydroxyecdysone. Network pharmacology analysis revealed 107 therapeutic target genes of Cyanotis arachnoidea in DM treatment, and the key targets were Akt1, TNF, IL-6, MAPK3, and JUN. The hypoglycemic mode of action of Cyanotis arachnoidea may be mediated by tumor necrosis factor (TNF) signaling, cancer, insulin resistance, and JAK-STAT pathways. Molecular docking analysis disclosed that the foregoing quality markers effectively bound their key target genes. An in vitro experiment conducted on pancreatic islet ß-cells indicated that the forenamed active components of Cyanotis arachnoidea had hypoglycemic efficacy by promoting PI3K/Akt and inhibiting MAPK signaling. UHPLC also accurately quantified the quality markers. The identification and analysis of quality markers for Cyanotis arachnoidea is expected to provide references for the establishment of a quality control evaluation system and clarify the material basis and hypoglycemic mechanisms of this traditional Chinese medicine (TCM).

Production of L-Malic Acid by Metabolically Engineered Aspergillus nidulans Based on Efficient CRISPR-Cas9 and Cre-loxP Systems.

Aspergillus nidulans has been more extensively characterized than other Aspergillus species considering its morphology, physiology, metabolic pathways, and genetic regulation. As it has a rapid growth rate accompanied by simple nutritional requirements and a high tolerance to extreme cultural conditions, A. nidulans is a promising microbial cell factory to biosynthesize various products in industry. However, it remains unclear for whether it is also a suitable host for synthesizing abundant L-malic acid. In this study, we developed a convenient and efficient double-gene-editing system in A. nidulans strain TN02A7 based on the CRISPR-Cas9 and Cre-loxP systems. Using this gene-editing system, we made a L-malic acid-producing strain, ZQ07, derived from TN02A7, by deleting or overexpressing five genes (encoding Pyc, pyruvate carboxylase; OahA, oxaloacetate acetylhydrolase; MdhC, malate dehydrogenase; DctA, C4-dicarboxylic acid transporter; and CexA, citric acid transporter). The L-malic acid yield in ZQ07 increased to approximately 9.6 times higher (up to 30.7 g/L titer) than that of the original unedited strain TN02A7, in which the production of L-malic acid was originally very low. The findings in this study not only demonstrate that A. nidulans could be used as a potential host for biosynthesizing organic acids, but also provide a highly efficient gene-editing strategy in filamentous fungi.

Highly Efficient and Simultaneous Analysis of Three Common Fluorotelomer Alcohols in Vegetables and Soils.

Fluorotelomer alcohols (FTOHs), as precursors of perfluoroalkyl carboxylic acids, are difficult to analyze due to their high volatility and matrix interference. A method based on single-factor experiments and response surface methodology design was developed for simultaneous analysis of three common FTOHs in vegetables and soils, using single extraction, dispersive solid phase extraction cleanup, and gas chromatography-mass spectrometry in negative chemical ionization. The method improved the extraction efficiency up to ∼40 folds and showed a commendable linearity range (1-100 ng/mL, R2 > 0.991), low limit of detection (0.025-0.897 ng/g, dry weight (dw)), and high accuracy and precision (83 ± 7.2-117 ± 6.0% recoveries at 2-20 ng/g fortification levels). It was successfully applied to determine the FTOHs in real vegetables and soils, demonstrating its feasibility for routine analysis. Concentrations of the FTOHs ranged from 3.5 to 37.9 ng/g (dw) and from 6.5 to 141.0 ng/g (dw), respectively, in the vegetables and soils collected nearby fluorochemical factories, which warrants further investigations on FTOH pollution and food safety concerns for which the developed method will be useful.

Metabolism-guided development of Ko143 analogs as ABCG2 inhibitors.

ATP-binding cassette subfamily G member 2 (ABCG2), an efflux transporter, is involved in multiple pathological processes. Ko143 is a potent ABCG2 inhibitor; however, it is quickly metabolized through carboxylesterase 1-mediated hydrolysis of its t-butyl ester moiety. The current work aimed to develop more metabolically stable ABCG2 inhibitors. Novel Ko143 analogs were designed and synthesized by replacing the unstable t-butyl ester moiety in Ko143 with an amide group. The synthesized Ko143 analogs were evaluated for their ABCG2 inhibitory activity, binding mode with ABCG2, cytotoxicity, and metabolic stability. We found that the amide modification of Ko143 led to metabolically stable ABCG2 inhibitors. Among these Ko143 analogs, K2 and K34 are promising candidates with favorable oral pharmacokinetic profiles in mice. In summary, we synthesized novel Ko143 analogs with improved metabolic stability, which can potentially be used as lead compounds for the future development of ABCG2 inhibitors.