A novel Cu(I)-based coordination polymer for efficient photocatalytic oxidation of C(sp3)-H bonds.

A novel coordination polymer CuCl-Pyhc was successfully synthesized, which can catalyze efficient and selective oxidation of C(sp3)-H bonds under mild conditions, exhibiting exceptional stability and remarkable recyclability. Furthermore, CuCl-Pyhc can mimic natural monooxygenases and activate oxygen into singlet oxygen (1O2).

A novel porphyrin MOF catalyst for efficient conversion of CO2 with propargyl amines.

The capture and conversion of carbon dioxide (CO2) into valuable chemical products under mild conditions is an important and challenging approach for contemporary industry. Carboxylic acid ligands are widely used in the development of functionalized metal organic framework materials due to their excellent stability. Herein, a novel mixed-metal organic framework Cu-TCPP(Fe) was assembled from iron-(Fe)-porphyrin ligands, which can efficiently catalyze the reaction of propargylic amines and CO2 to synthesize 2-oxazolidinones.

Parallel CNN-Deep Learning Clinical-Imaging Signature for Assessing Pathologic Grade and Prognosis of Soft Tissue Sarcoma Patients.

BACKGROUND: Traditional biopsies pose risks and may not accurately reflect soft tissue sarcoma (STS) heterogeneity. MRI provides a noninvasive, comprehensive alternative. PURPOSE: To assess the diagnostic accuracy of histological grading and prognosis in STS patients when integrating clinical-imaging parameters with deep learning (DL) features from preoperative MR images. STUDY TYPE: Retrospective/prospective. POPULATION: 354 pathologically confirmed STS patients (226 low-grade, 128 high-grade) from three hospitals and the Cancer Imaging Archive (TCIA), divided into training (n = 185), external test (n = 125), and TCIA cohorts (n = 44). 12 patients (6 low-grade, 6 high-grade) were enrolled into prospective validation cohort. FIELD STRENGTH/SEQUENCE: 1.5 T and 3.0 T/Unenhanced T1-weighted and fat-suppressed-T2-weighted. ASSESSMENT: DL features were extracted from MR images using a parallel ResNet-18 model to construct DL signature. Clinical-imaging characteristics included age, gender, tumor-node-metastasis stage and MRI semantic features (depth, number, heterogeneity at T1WI/FS-T2WI, necrosis, and peritumoral edema). Logistic regression analysis identified significant risk factors for the clinical model. A DL clinical-imaging signature (DLCS) was constructed by incorporating DL signature with risk factors, evaluated for risk stratification, and assessed for progression-free survival (PFS) in retrospective cohorts, with an average follow-up of 23 ± 22 months. STATISTICAL TESTS: Logistic regression, Cox regression, Kaplan-Meier curves, log-rank test, area under the receiver operating characteristic curve (AUC)，and decision curve analysis. A P-value <0.05 was considered significant. RESULTS: The AUC values for DLCS in the external test, TCIA, and prospective test cohorts (0.834, 0.838, 0.819) were superior to clinical model (0.662, 0.685, 0.694). Decision curve analysis showed that the DLCS model provided greater clinical net benefit over the DL and clinical models. Also, the DLCS model was able to risk-stratify patients and assess PFS. DATA CONCLUSION: The DLCS exhibited strong capabilities in histological grading and prognosis assessment for STS patients, and may have potential to aid in the formulation of personalized treatment plans. TECHNICAL EFFICACY: Stage 2.

Tumor-associated NK cells drive MDSC-mediated tumor immune tolerance through the IL-6/STAT3 axis.

Apart from their killer identity, natural killer (NK) cells have integral roles in shaping the tumor microenvironment. Through immune gene deconvolution, the present study revealed an interplay between NK cells and myeloid-derived suppressor cells (MDSCs) in nonresponders of immune checkpoint therapy. Given that the mechanisms governing the outcome of NK cell-to-myeloid cell interactions remain largely unknown, we sought to investigate the cross-talk between NK cells and suppressive myeloid cells. Upon contact with tumor-experienced NK cells, monocytes and neutrophils displayed increased expression of MDSC-related suppressive factors along with increased capacities to suppress T cells. These changes were accompanied by impaired antigen presentation by monocytes and increased ER stress response by neutrophils. In a cohort of patients with sarcoma and breast cancer, the production of interleukin-6 (IL-6) by tumor-infiltrating NK cells correlated with S100A8/9 and arginase-1 expression by MDSCs. At the same time, NK cell-derived IL-6 was associated with tumors with higher major histocompatibility complex class I expression, which we further validated with b2m-knockout (KO) tumor mice models. Similarly in syngeneic wild-type and IL-6 KO mouse models, we then demonstrated that the accumulation of MDSCs was influenced by the presence of such regulatory NK cells. Inhibition of the IL-6/signal transducer and activator of transcription 3 (STAT3) axis alleviated suppression of T cell responses, resulting in reduced tumor growth and metastatic dissemination. Together, these results characterize a critical NK cell-mediated mechanism that drives the development of MDSCs during tumor immune escape.

Multi-frequency electromagnetic radiation induces anxiety in mice via inflammation in the cerebral cortex.

Modern life is filled with radiofrequency electromagnetic radiation (RF-EMR) in various frequency bands, while the health risks are not clear. In this study, mice were whole-body exposed to 0.9/1.5/2.65 GHz radiofrequency radiation at 4 W/kg for 2 h per day for 4 weeks to investigate the emotional effects. It was found that the mice showed anxiety but no severe depression. The ELISA results showed a significant decrease in amino acid neurotransmitters (GABA, DA, 5-HT), although acetylcholine (ACH) levels were not significantly altered. Furthermore, Western blot results showed that BDNF, TrkB, and CREB levels were increased in the cerebral cortex, while NF-κB levels were decreased. In addition, pro-inflammatory factors (IL-6, IL-1ß, TNF-α) were significantly elevated, and anti-inflammatory factors (IL-4, IL-10) tended to decrease. In conclusion, multi-frequency electromagnetic radiation induces an inflammatory response through the CREB-BDNF-TrkB and NF-κB pathways in the cerebral cortex and causes a decrease in excitatory neurotransmitters, which ultimately causes anxiety in mice.

High-throughput semi-automated emulsive liquid-liquid microextraction for detecting SDHI fungicides in water, juice, and alcoholic beverage samples via UHPLC-MS/MS.

Herein, a High-Throughput Semi-automated Emulsive Liquid-Liquid Microextraction (HTSA-ELLME) method was developed to detect Succinate Dehydrogenase Inhibitor (SDHI) fungicides in food samples via UHPLC-MS/MS. The Oil-in-Water (O/W) emulsion comprising a hydrophobic extractant and water was dilutable with the aqueous sample solution. Upon injecting the primary emulsion into the sample solution, a secondary O/W emulsion was formed, allowing SDHI fungicides to be extracted. Subsequently, a NaCl-saturated solution was injected in the secondary O/W emulsion as a demulsifier to rapidly separate the extractant, eliminating the need for centrifugation. A 12-channel electronic micropipette was used to achieve a high-throughput semi-automation of the novel sample pretreatment. The linear range was 0.003-0.3 µg L-1 with R2 > 0.998. The limit of detection was 0.001 µg L-1. The HTSA-ELLME method successfully detected SDHI fungicides in water, juice, and alcoholic beverage samples, with recoveries and relative standard deviations of 82.6-106.9% and 0.8-5.8%, respectively. Unlike previously reported liquid-liquid microextraction approaches, the HTSA-ELLME method is the first to be both high-throughput and semi-automated and may aid in designing pesticide pretreatment processes in food samples.

Compare deep learning model and conventional logistic regression model for the identification of unstable saccular intracranial aneurysms in computed tomography angiography.

Background: It is crucial to distinguish unstable from stable intracranial aneurysms (IAs) as early as possible to derive optimal clinical decision-making for further treatment or follow-up. The aim of this study was to investigate the value of a deep learning model (DLM) in identifying unstable IAs from computed tomography angiography (CTA) images and to compare its discriminatory ability with that of a conventional logistic regression model (LRM). Methods: From August 2011 to May 2021, a total of 1,049 patients with 681 unstable IAs and 556 stable IAs were retrospectively analyzed. IAs were randomly divided into training (64%), internal validation (16%), and test sets (20%). Convolutional neural network (CNN) analysis and conventional logistic regression (LR) were used to predict which IAs were unstable. The area under the curve (AUC), sensitivity, specificity and accuracy were calculated to evaluate the discriminating ability of the models. One hundred and ninety-seven patients with 229 IAs from Banan Hospital were used for external validation sets. Results: The conventional LRM showed 11 unstable risk factors, including clinical and IA characteristics. The LRM had an AUC of 0.963 [95% confidence interval (CI): 0.941-0.986], a sensitivity, specificity and accuracy on the external validation set of 0.922, 0.906, and 0.913, respectively, in predicting unstable IAs. In predicting unstable IAs, the DLM had an AUC of 0.771 (95% CI: 0.582-0.960), a sensitivity, specificity and accuracy on the external validation set of 0.694, 0.929, and 0.782, respectively. Conclusions: The CNN-based DLM applied to CTA images did not outperform the conventional LRM in predicting unstable IAs. The patient clinical and IA morphological parameters remain critical factors for ensuring IA stability. Further studies are needed to enhance the diagnostic accuracy.

Engineering NH2-Cu-NH2 Triple-atom Sites in Defective MOFs for Selective Overall Photoreduction of CO2 into CH3COCH3.

Selective photoreduction of CO2 to multicarbon products, is an important but challenging task, due to high CO2 activation barriers and insufficient catalytic sites for C-C coupling. Herein, a defect engineering strategy for incorporating copper sites into the connected nodes of defective metal-organic framework UiO-66-NH2 for selective overall photo-reduction of CO2 into acetone. The Cu2+ site in well-modified CuN2O2 units served as a trapping site to capture electrons via efficient electron-hole separation, forming the active Cu+ site for CO2 reduction. Two NH2 groups in CuN2O2 unit adsorb CO2 and cooperated with copper ion to functionalize as a triple atom catalytic site, each interacting with one CO2 molecule to strengthen the binding of *CO intermediate to the catalytic site. The deoxygenated *CO attached to the Cu site interacted with *CH3 fixed at one amino group to form the key intermediate CO*-CH3, which interacted with the third reduction intermediate on another amino group to produce acetone. Our photocatalyst realizes efficient overall CO2 reduction to C3 product acetone CH3COCH3 with an evolution rate of 70.9 µmol gcat -1 h-1 and a selectivity up to 97 % without any adducts, offering a promising avenue for designing triple-atomic sites to producing C3 product from photosynthesis with water.

Association of serum albumin with heart failure mortality with NYHA class IV in Chinese patients: Insights from PhysioNet database (version 1.3).

BACKGROUND: Studies have proved that low albumin level is associated with increased mortality in most diseases, such as chronic kidney disease and hepatic cirrhosis. However, the relationship between albumin and all-cause death in heart failure patients in China is still unclear. OBJECTIVES: We aimed to investigate the association between albumin level and 28-day mortality in Chinese hospitalized patients with NYHA IV heart failure. METHODS: A total of 2008 Chinese patients were included. The correlation between serum albumin level and mortality was tested using a cox proportional hazards regression model. The smooth curve fitting was used to identify non-linear relationships between serum albumin and mortality. The Forest plot analysis was used to assess the association between albumin and 28-day mortality in different groups. RESULTS: Compared with patients with NYHA II-III, patients with NYHA IV had lower albumin level and higher mortality within 28 days. The albumin on admission was independently and inversely associated with the endpoint risk, which remained significant (hazard ratio: 0.80; 95 % confidence interval: 0.66 to 0.96; p = 0.0196) after multivariable adjustment. The smooth curve fitting showed with the increase of albumin, the mortality within 28 days would decrease. A subgroup analysis found that the inverse association between the albumin level and risk of the mortality was consistent across the subgroup stratified by possible influence factors. CONCLUSION: Serum albumin level is negatively associated with 28-day mortality in hospitalized heart failure patients within NYHA IV in China, which can be used as an independent predictor.

Metaplastic regeneration in the mouse stomach requires a reactive oxygen species pathway.

In pyloric metaplasia, mature gastric chief cells reprogram via an evolutionarily conserved process termed paligenosis to re-enter the cell cycle and become spasmolytic polypeptide-expressing metaplasia (SPEM) cells. Here, we use single-cell RNA sequencing (scRNA-seq) following injury to the murine stomach to analyze mechanisms governing paligenosis at high resolution. Injury causes induced reactive oxygen species (ROS) with coordinated changes in mitochondrial activity and cellular metabolism, requiring the transcriptional mitochondrial regulator Ppargc1a (Pgc1α) and ROS regulator Nf2el2 (Nrf2). Loss of the ROS and mitochondrial control in Ppargc1a-/- mice causes the death of paligenotic cells through ferroptosis. Blocking the cystine transporter SLC7A11(xCT), which is critical in lipid radical detoxification through glutathione peroxidase 4 (GPX4), also increases ferroptosis. Finally, we show that PGC1α-mediated ROS and mitochondrial changes also underlie the paligenosis of pancreatic acinar cells. Altogether, the results detail how metabolic and mitochondrial changes are necessary for injury response, regeneration, and metaplasia in the stomach.

Fatty Acid Oxidation Supports Lymph Node Metastasis of Cervical Cancer via Acetyl-CoA-Mediated Stemness.

Accumulating evidence indicates that metabolic reprogramming of cancer cells supports the energy and metabolic demands during tumor metastasis. However, the metabolic alterations underlying lymph node metastasis (LNM) of cervical cancer (CCa) have not been well recognized. In the present study, it is found that lymphatic metastatic CCa cells have reduced dependency on glucose and glycolysis but increased fatty acid oxidation (FAO). Inhibition of carnitine palmitoyl transferase 1A (CPT1A) significantly compromises palmitate-induced cell stemness. Mechanistically, FAO-derived acetyl-CoA enhances H3K27 acetylation (H3K27Ac) modification level in the promoter of stemness genes, increasing stemness and nodal metastasis in the lipid-rich nodal environment. Genetic and pharmacological loss of CPT1A function markedly suppresses the metastatic colonization of CCa cells in tumor-draining lymph nodes. Together, these findings propose an effective method of cancer therapy by targeting FAO in patients with CCa and lymph node metastasis.

Interface fluid syndrome caused by the corneal perforation injury after small incision lenticule extraction: a case report.

BACKGROUND: To report a case of interface fluid syndrome (IFS) following traumatic corneal perforation repair after small incision lenticule extraction (SMILE). CASE PRESENTATION: A 23-year-old woman, with a past history of SMILE, was struck in the left eye with a barbecue prod and subsequently underwent corneal perforation repair at local hospital. Primary wound repaired with a single 10 - 0 nylon suture at the area of leakage. After the surgery, her best corrected visual acuity (BCVA) was 20/30. Four days later, she presented at our hospital with blurred vision, and interface fluid syndrome (IFS) was diagnosed. Intraoperative optical coherence tomography (iOCT) was used to guide the resuturing of the corneal perforation in the left eye, followed by anterior chamber gas injection. At the first postoperative month, the BCVA was 20/25. The corneal cap adhered closely to the stroma, the surface became smooth. CONCLUSIONS: This case illustrates that any corneal perforation following lamellar surgery, including SMILE, may lead to IFS. It is crucial to consider the depth of corneal perforation, and intraoperative optical coherence tomography (iOCT) plays a unique role in the repair procedure.

CircMAST1 inhibits cervical cancer progression by hindering the N4-acetylcytidine modification of YAP mRNA.

BACKGROUND: Cervical cancer (CCa) is the fourth most common cancer among females, with high incidence and mortality rates. Circular RNAs (circRNAs) are key regulators of various biological processes in cancer. However, the biological role of circRNAs in cervical cancer (CCa) remains largely unknown. This study aimed to elucidate the role of circMAST1 in CCa. METHODS: CircRNAs related to CCa progression were identified via a circRNA microarray. The relationship between circMAST1 levels and clinicopathological features of CCa was evaluated using the clinical specimens and data of 131 patients with CCa. In vivo and in vitro experiments, including xenograft animal models, cell proliferation assay, transwell assay, RNA pull-down assay, whole-transcriptome sequencing, RIP assay, and RNA-FISH, were performed to investigate the effects of circMAST1 on the malignant behavior of CCa. RESULTS: CircMAST1 was significantly downregulated in CCa tissues, and low expression of CircMAST1 was correlated with a poor prognosis. Moreover, our results demonstrated that circMAST1 inhibited tumor growth and lymph node metastasis of CCa. Mechanistically, circMAST1 competitively sequestered N-acetyltransferase 10 (NAT10) and hindered Yes-associated protein (YAP) mRNA ac4C modification to promote its degradation and inhibit tumor progression in CCa. CONCLUSIONS: CircMAST1 plays a major suppressive role in the tumor growth and metastasis of CCa. In particular, circMAST1 can serve as a potential biomarker and novel target for CCa.

Modifying the Oxidative Potentials of Imines in a Dye Loaded Capsule for Photocatalytic Cyclization with Hydrogen Evolution.

Modifying redox potential of substrates and intermediates to balance pairs of redox steps are important stages for multistep photosynthesis but faced marked challenges. Through co-clathration of iridium photosensitizer and imine substrate within one packet of a metal-organic capsule to shift the redox potentials of substrate, herein, we reported a multiphoton enzymatic strategy for the generation of heterocycles by intramolecular C-X hydrogen evolution cross-couplings. The cage facilitated a pre-equilibrium substrate-involving clathrate that cathodic shifts the oxidation potential of the substrate-dye-host ternary complex and configuration inversion of substrate via spatial constraints in the confined space. The new two photon excitation strategy enabled the precise control of the multistep electron transfer between each pair (photosensitizer, substrate and the capsule), endowing the catalytic system proceeding smoothly with an enzymatic fashion. Three kinds of 2-subsituted (-OH, -NH2 , and -SH) imines and N-aryl enamines all give the corresponding cyclization products efficiently under visible light irradiation, demonstrating the promising of the microenvironment driven thermodynamic activation in the host-dye-substrate ternary for synergistic combination of multistep photocatalytic transformations.

Self-powered molecularly imprinted photoelectrochemical sensor based on Ppy/QD/HOF heterojunction for the detection of bisphenol A.

As an emerging porous material, hydrogen-bonded organic framework materials (HOFs) still pose application challenges. In this work, the designed type "I + II" heterojunction extracted hot electrons from HOFs using quantum dots (QDs) and polypyrrole (Ppy), improving the stability and photoelectrochemical performance of materials. In addition to serving as a potential well, electropolymerized Ppy was used as a recognition element for bisphenol A (BPA), and a novel self-powered molecularly imprinted photoelectrochemical (MIP-PEC) sensor was designed. The sensing platform showed a linear relationship from 1 × 10-10 to 1 × 10-7 mol∙L-1 and from 1 × 10-7 to 1 mol∙L-1 with an acceptable detection limit of 4.2 × 10-11 mol∙L-1. This is the first application of HOFs in constructing MIP-PEC sensors and a new attempt to improve the stability of HOFs for the application of porous crystal materials in the sensing field.

Gastric intestinal metaplasia: progress and remaining challenges.

Most gastric cancers arise in the setting of chronic inflammation which alters gland organization, such that acid-pumping parietal cells are lost, and remaining cells undergo metaplastic change in differentiation patterns. From a basic science perspective, recent progress has been made in understanding how atrophy and initial pyloric metaplasia occur. However, pathologists and cancer biologists have long been focused on the development of intestinal metaplasia patterns in this setting. Arguably, much less progress has been made in understanding the mechanisms that lead to the intestinalization seen in chronic atrophic gastritis and pyloric metaplasia. One plausible explanation for this disparity lies in the notable absence of reliable and reproducible small animal models within the field, which would facilitate the investigation of the mechanisms underlying the development of gastric intestinal metaplasia (GIM). This review offers an in-depth exploration of the current state of research in GIM, shedding light on its pivotal role in tumorigenesis. We delve into the histological subtypes of GIM and explore their respective associations with tumor formation. We present the current repertoire of biomarkers utilized to delineate the origins and progression of GIM and provide a comprehensive survey of the available, albeit limited, mouse lines employed for modeling GIM and engage in a discussion regarding potential cell lineages that serve as the origins of GIM. Finally, we expound upon the myriad signaling pathways recognized for their activity in GIM and posit on their potential overlap and interactions that contribute to the ultimate manifestation of the disease phenotype. Through our exhaustive review of the progression from gastric disease to GIM, we aim to establish the groundwork for future research endeavors dedicated to elucidating the etiology of GIM and developing strategies for its prevention and treatment, considering its potential precancerous nature.

Relationship between the impacted mandibular third molar and adjacent second molar' external root resorption by conebean computed tomography analysi / Relación entre la reabsorción de la raíz externa del tercer molar mandibular impactado y el segundo molar adyacente mediante análisis de tomografía computarizada de cono

Background: The relationship between the impacted mandibular third molar (IMTM) and the external root re-sorption (ERR) of the mandibular second molar (MSM) was analysed with cone-beam computed tomography(CBCT). The risk factors affecting the ERR of the MSM were examined to provide a reference.Material and Methods: A total of 327 patients (total: 578 teeth) admitted to the Affiliated Hospital of YanbianUniversity for IMTM extraction from January 2017 to December 2019 was chosen and divided according togender and age. The correlation between the IMTM and ERR of MSM was analysed, including inclination angle,impaction direction and depth. The relationship of mandibular ascending ramus classification with ERR of MSMwas also analysed. In addition, the correlation between the MTM impaction type and the severity of ERR wasanalysed.Results: The incidence of ERR of MSM in male patients was higher than in females (27.9% vs.17.6%, p = 0.018).The occurrence and the site of ERR showed statistical differences in the inclination angle [(≤20°, 3.6%) vs. (21°-40°, 27.1%) vs. (41°-60°, 27.6%) vs. (61°-80°, 25.6%) vs. (>80°, 31.7%), p <0.001], impaction direction [(Vertical,1.1%) vs. (Mesial, 32.7%) vs. (Horizontal, 25.3%), p <0.001] and depth of MTM [(Low position, 38.6%) vs. (Medi-an position, 32.0%) vs. (High position, 13.7%), p <0.001]. Also, there was a significant difference in the mandib-ular ascending ramus type [(Class I, 17.4%) vs. (Class II, 32.3%) vs. (Class III, 44.9%), p <0.001]. In addition, theseverity of ERR showed statistical differences in the mesial (40.9%, p<0.05), lower impaction (54.5%, p<0.05)depth of MTM and type III of mandibular ascending ramus (63.6%, p<0.05).Conclusions: The inclination angle, impaction direction, and depth of MTM were the influencing factors for theoccurrence and site of ERR.(AU)

Determination of chiral prothioconazole and its chiral metabolite in water, juice, tea, and vinegar using emulsive liquid-liquid microextraction combined with ultra-high performance liquid chromatography.

Emulsive liquid-liquid microextraction (ELLME), a simple, rapid, and environmentally friendly technique, was established to identify chiral prothioconazole and its chiral metabolite in water, juice, tea, and vinegar using ultra-high-performance liquid chromatography (UPLC). Environmentally friendly extractant was mixed with pure water to prepare a high-concentration emulsion, which was added to samples to complete the emulsification and extraction in 1 s. Afterward, an electrolyte solution was added to complete the demulsification without centrifugation. ELLME did not use dispersants compared to the familiar dispersive liquid-liquid microextraction (DLLME), thus reducing the use of toxic solvents and avoiding the effect of dispersants on the partition coefficient. The linear range was from 0.01 to 1 mg/L. The limit of detection was 0.003 mg/L. The extraction recoveries ranged from 82.4 % to 101.6 %, with relative standard deviations of 0.7-5.2 %. The ELLME method developed has the potential to serve as an alternative to DLLME.

The role of glucose metabolism reprogramming and its targeted therapeutic agents in inflammation-related diseases / 药学学报

Cells undergo glucose metabolism reprogramming under the influence of the inflammatory microenvironment, changing their primary mode of energy supply from oxidative phosphorylation to aerobic glycolysis. This process is involved in all stages of inflammation-related diseases development. Glucose metabolism reprogramming not only changes the metabolic pattern of individual cells, but also disrupts the metabolic homeostasis of the body microenvironment, which further promotes aerobic glycolysis and provides favourable conditions for the malignant progression of inflammation-related diseases. The metabolic enzymes, transporter proteins, and metabolites of aerobic glycolysis are all key signalling molecules, and drugs can inhibit aerobic glycolysis by targeting these specific key molecules to exert therapeutic effects. This paper reviews the impact of glucose metabolism reprogramming on the development of inflammation-related diseases such as inflammation-related tumours, rheumatoid arthritis and Alzheimer's disease, and the therapeutic effects of drugs targeting glucose metabolism reprogramming on these diseases.

Development of an in vitro screening method for idiosyncratic hepatotoxic components in traditional Chinese medicine: a case study with Epimedii Folium and Psoraleae Fructus / 药学学报

Idiosyncratic drug-induced liver injury (IDILI) has long posed a challenging and pivotal concern in pharmaceutical research. The complex composition of traditional Chinese medicine (TCM) has introduced a bottleneck in current research, hindering the elucidation of the component basis associated with IDILI in TCM. Using Epimedii Folium (EF) and Psoraleae Fructus (PF) as illustrative examples, this study endeavors to establish an in vitro evaluation model, providing a high-throughput and preliminary assessment method for screening components related to TCM-induced IDILI. A TNF-α-mediated HepG2 susceptible model was first established in this study, with the focus on the index components present in EF and PF. The release of lactate dehydrogenase (LDH) in the cell supernatant served as the detection index. A concentration-toxicity response curve was constructed, and the hepatotoxic components of EF and PF were identified utilizing the synergistic toxicity index. The LDH results unveiled the hepatotoxic effects of bavachin, backuchiol, isobavachin, neobavaisoflavone, psoralidin, isobavachalcone, icarisid I, and icarisid II on both normal and susceptible cells, categorizing these 8 components as both direct hepatotoxicity components and idiosyncratic hepatotoxicity components. Bavachin and neobavaisoflavone exhibited no hepatotoxicity on normal cells but demonstrated significant effects on susceptible cells, designating them as potential idiosyncratic susceptible hepatotoxicity components. The study further delineated that 10 EF components and 3 PF components were direct immune-promoting hepatotoxicity components. Additionally, 14 idiosyncratic immune-promoting hepatotoxicity components were identified, encompassing 10 EF components and 4 PF components, with neobavaisoflavone, bavachinin, and isobavachin being potential idiosyncratic susceptible immune-promoting hepatotoxicity components. Synergistic toxicity index results indicated that 13 idiosyncratic immune-promoting hepatotoxicity components (except anhydroicaritin) combined with bavachin demonstrated synergistic hepatotoxicity on susceptible cells. Notably, 3 idiosyncratic susceptible immune-promoting hepatotoxicity components combined with bavachin exhibited synergistic hepatotoxicity, with neobavaisoflavone displaying the highest synergistic toxicity index and bavachinin the lowest. In summary, this methodology successfully screens hepatotoxic and immune-promoting hepatotoxic components in EF and PF, distinguishing the types of components inducing hepatotoxicity, evaluating the hepatotoxicity degree of each component, and elucidating the synergistic relationships among them. Importantly, these findings align with the characteristics of IDILI. The method provides an effective model tool for the fundamental research of TCM-related IDILI components.