The Valorization of Wastes and Byproducts from Cruciferous Vegetables: A Review on the Potential Utilization of Cabbage, Cauliflower, and Broccoli Byproducts.

The management of vegetable waste and byproducts is a global challenge in the agricultural industry. As a commonly consumed vegetable crop, cruciferous vegetables marked higher amounts of wastage during their supply chain processes, with a significant contribution from cabbage, cauliflower, and broccoli. Therefore, the sustainable and resource-efficient utilization of discarded materials is crucial. This review explores potential applications of cruciferous vegetable waste and byproducts, spotlighting cabbage, cauliflower, and broccoli in food, medicinal, and other industries. Their significance of being utilized in value-added applications is addressed, emphasizing important biomolecules, technologies involved in the valorization process, and future aspects of practical applications. Cabbage, cauliflower, and broccoli generate waste and low-processing byproducts, including leaves, stems, stalks, and rot. Most of them contain high-value biomolecules, including bioactive proteins and phytochemicals, glucosinolates, flavonoids, anthocyanins, carotenoids, and tocopherols. Interestingly, isothiocyanates, derived from glucosinolates, exhibit strong anti-inflammatory and anticancer activity through various interactions with cellular molecules and the modulation of key signaling pathways in cells. Therefore, these cruciferous-based residues can be valorized efficiently through various innovative extraction and biotransformation techniques, as well as employing different biorefinery approaches. This not only minimizes environmental impact but also contributes to the development of high-value-added products for food, medicinal, and other related industries.

Curcumin analogue NL04 inhibits spinal cord central sensitization in rats with bone cancer pain by inhibiting NLRP3 inflammasome activation and reducing IL-1ß production.

The management and therapy of bone cancer pain (BCP) remain formidable clinical challenges. Curcumin and its analogues have been shown to have anti-inflammatory and analgesic properties. In the present study, we investigated the efficacy of curcumin analogue NL04 (NL04) in modulating inflammation in spinal dorsal horn (SDH), thereby exploring its potential to reduce central sensitization of BCP in a rat model. Differing doses of NL04 and curcumin were administered intrathecally either once (on day 12 of BCP) or over seven consecutive days (from day 6-12 of BCP). Results indicated that the ED50 for NL04 and curcumin ameliorating BCP-induced mechanical hyperalgesia is 49.08 µg/kg and 489.6 µg/kg, respectively. The analgesic effects at various doses of NL04 lasted between 4 and 8 h, with sustained administration over a week maintaining pain relief for 1-4 days, while also ameliorating locomotor gait via gait analysis and reducing depressive and anxiety-like behaviors via open-field and light-dark transition tests. The analgesic effects at various doses of curcumin lasted 4 h, with sustained administration over a week maintaining pain relief for 0-2 days. ELISA, Western blotting, qPCR, and immunofluorescence assays substantiated that intrathecal administration of NL04 on days 6-12 of BCP dose-dependently lowered spinal IL-1ß and IL-18 levels and significantly reduced the expression of IKKß genes and proteins, as well as the downstream cleavage of the trans-Golgi network (TGN). Whole-cell patch-clamp results demonstrated that NL04 inhibits potassium ion efflux in rat primary spinal neurons. Thus, NL04 exhibits significant analgesic effects in a BCP rat model by downregulating IKKß expression and inhibiting neuronal potassium ion efflux, which, in turn, suppresses the activation of NLRP3 inflammasomes and reduces IL-1ß production, potentially ameliorating pain management in BCP.

Effect of CT-Guided Repeated Pulsed Radiofrequency on Controlling Acute/Subacute Zoster-Associated Pain: A Retrospective Cohort Study.

INTRODUCTION: Zoster-associated pain (ZAP) treatment and management is still inadequate. Repeated intervention protocol is often applied to manage ZAP. This study aimed to retrospectively investigate the effect of repeated applications of pulsed radiofrequency therapy on controlling acute/subacute ZAP. METHODS: From March 2019 to December 2021, 150 patients with acute/subacute ZAP who underwent repeated application of pulsed radiofrequency treatment (R-PRF) and pulsed radiofrequency combined paravertebral block interventions (PRF + PVB) in the Pain Department of the affiliated Hospital of Jiaxing University were enrolled. Patients were grouped by intervention protocol and received at least 12 months of follow-up assessments using the Numerical Rating Scale score (NRSs), Pittsburg Sleep Quality Index (PSQI), Simple McGill Pain Questionnaire-2 score (SF-MPQ-2s), and follow-up interventions. RESULTS: Both groups experienced a reduction in the incidence of clinically meaningful ZAP after the intervention therapy. In the R-PRF group, there were 36 cases of clinically meaningful ZAP within the first month post-treatment, while the PRF + PVB group had 38 cases. The incidence of clinically meaningful ZAP, as determined by multivariable generalized estimating equations, was 42.86% in the R-PRF group and 57.58% in the PRF + PVB group during the first month of follow-up. There was a significant difference in the incidence of clinically meaningful ZAP between the two groups after 1 month of treatment (adjusted odds ratio: 0.40; 95% confidence interval: 0.18-0.91; p = 0.03). CONCLUSIONS: Both R-PRF and PRF + PVB treatments effectively relieve pain in patients with acute/subacute ZAP. However, R-PRF may have superior efficacy compared to PRF + PVB in reducing the incidence of clinically meaningful ZAP 1 month after treatment.

The success rate and associated risk factors of CT-guided percutaneous radiofrequency sympathectomy in the treatment of primary hyperhidrosis: A retrospective observational trial.

PURPOSE: The aim of this study was to investigate the success rate of surgical technique and associated risk factors based on the follow-up of patients who underwent CT-guided percutaneous radiofrequency sympathectomy (RFS) to treat primary hyperhidrosis (PH). METHODS: 370 patients who underwent RFS for PH treatment between January 2018 and April 2022 were enrolled. Patients responded to a questionnaire and telephone follow-up on the effects of treatment and their electronic medical records and imaging findings were reviewed. Logistic regression was performed to identify risk factors related to the success rate of surgical technique. RESULTS: A temperature difference ≥2 °C before and after procedure was defined as a successful surgical technique. Among the 370 patients (740 sides), 637 sides had successful RFS, and the technical success rate was 86.1 %. Immediately after procedure, 636 sides (85.9 %) were completely dry, 64 (8.7 %) were partially dry, and 40 (5.4 %) were still wet. During the longest follow-up period (54 months), 103 patients relapsed. The median hyperhidrosis disease severity scale score on both sides decreased from 4 to 1 after RFS. According to logistic regression analysis, only the pre-post pulse index was associated with the success rate of surgical technique (odds ratio, 1.14; 95 % confidence interval, 1.06-1.23; p = 0.0004). CONCLUSIONS: We observed that the immediate efficiency and success rate of surgical technique after RFS for PH treatment were relatively high, although there is a possibility of recurrence in the long term. In general, RFS is a safe and effective procedure for alleviating the symptoms of patients with hyperhidrosis.

Synergistic Effects of Organic Ligands and Visible Light on the Reductive Dissolution of CeO2 Nanoparticles: Mechanisms and Implications for the Transformation in Plant Surroundings.

Cerium oxide (CeO2) nanoparticles are one of the most important engineered nanomaterials with demonstrated applications in industry. Although numerous studies have reported the plant uptake of CeO2, its fate and transformation pathways and mechanisms in plant-related conditions are still not well understood. This study investigated the stability of CeO2 in the presence of organic ligands (maleic and citric acid) and light irradiation. For the first time, we found that organic ligands and visible light had a synergistic effect on the reductive dissolution of CeO2 with up to 30% Ce releases after 3 days, which is the highest release reported so far under environmental conditions. Moreover, the photoinduced dissolution of CeO2 in the presence of citrate was much higher than that in maleate, which are adsorbed on the surface of CeO2 through inner-sphere and outer-sphere complexation, respectively. A novel ligand-dependent photodissolution mechanism was proposed and highlighted: upon electron-hole separation under light irradiation, the inner-sphere complexed citrate is more capable of consuming the hole, prolonging the life of electrons for the reduction of Ce(IV) to Ce(III). Finally, reoxidation of Ce(III) by oxygen was observed and discussed. This comprehensive work advances our knowledge of the fate and transformation of CeO2 in plant surroundings.

Development and Validation of a Nomogram to Predict Recurrence of Primary Hyperhidrosis after CT-guided Percutaneous Radiofrequency Sympathectomy.

PURPOSE: To evaluate the recurrence rate of primary hyperhidrosis (PH) after computed tomography (CT)-guided radiofrequency sympathectomy (RFS) and identify risk factors associated with recurrence. MATERIALS AND METHODS: A total of 290 patients with PH who underwent CT-guided RFS were included in this retrospective cohort study. The electronic medical record was reviewed for patients' information and procedural parameters. Follow-ups were conducted for recurrence rate, and Hyperhidrosis Disease Severity Scale was used to assess presence or absence of recurrence. Stepwise regression and the least absolute shrinkage and selection operator regression algorithms were used for feature selection. RESULTS: The recurrence rate 1 year after procedure was 17.6%. Male (hazard ratio [HR], 2.35; 95% confidence interval [CI], 1.08-5.15), low postoperative palm or foot temperature (HR, 0.77; 95% CI, 0.60-0.98), high postoperative heart rate (HR, 1.06; 95% CI, 1.02-1.10), low preoperative and postoperative hospital anxiety and depression score difference (HR, 0.59; 95% CI, 0.43-0.80), and the absence of compensatory hyperhidrosis immediately after procedure (HR, 0.46; 95% CI, 0.22-0.98) were established as independent factors affecting prognosis. A nomogram was built accordingly. The C indices of the training and testing sets were 0.773 and 0.659, respectively. CONCLUSIONS: Follow-up results showed that the recurrence rate of PH treated with CT-guided RFS was low. This study constructed and validated a nomogram to predict the recurrence of PH 1 year after CT-guided RFS, which is convenient for interventionalists to evaluate accurately the prognosis of patients postoperatively and to identify high-risk patients who need more active treatment.

Plant antimicrobial peptides: a comprehensive review of their classification, production, mode of action, functions, applications, and challenges.

The emergence of pathogens resistant to conventional antibiotics and the growing interest in developing alternative natural antimicrobial agents have prompted a search for plant-derived antimicrobial peptides (PAMPs) in recent years. PAMPs have unique antimicrobial properties, including broad-spectrum activity, rapid killing, and cell selectivity, making them promising candidates for the treatment of animal and human infections caused by pathogens. PAMPs primarily target cell membranes or intracellular components in a variety of ways, which enables them to effectively kill a wide range of microorganisms and reduce the chance of pathogens developing resistance. This article reviewed the classification of PAMPs and the progress of research on the isolation and purification of PAMPs. In addition, a focus was placed on the mechanisms of action of PAMPs, the potential toxicity of PAMPs and their functions and applications in food, agricultural production, animal feed additives, medical, and other possible fields. Finally, the challenges associated with PAMPs applications have been discussed along with molecular-based delivery and chemical modification strategies to overcome these limitations. This review highlights the potential applications of PAMPs, which will not only help to reduce the misuse of antibiotics, but will also be useful for the development of new antimicrobial agents in the future.

Using less annotation workload to establish a pathological auxiliary diagnosis system for gastric cancer.

Pathological diagnosis of gastric cancer requires pathologists to have extensive clinical experience. To help pathologists improve diagnostic accuracy and efficiency, we collected 1,514 cases of stomach H&E-stained specimens with complete diagnostic information to establish a pathological auxiliary diagnosis system based on deep learning. At the slide level, our system achieves a specificity of 0.8878 while maintaining a high sensitivity close to 1.0 on 269 biopsy specimens (147 malignancies) and 163 surgical specimens (80 malignancies). The classified accuracy of our system is 0.9034 at the slide level for 352 biopsy specimens (201 malignancies) from 50 medical centers. With the help of our system, the pathologists' average false-negative rate and average false-positive rate on 100 biopsy specimens (50 malignancies) are reduced to 1/5 and 1/2 of the original rates, respectively. At the same time, the average uncertainty rate and the average diagnosis time are reduced by approximately 22% and 20%, respectively.

Redispersion Behavior of 2D MoS2 Nanosheets: Unique Dependence on the Intervention Timing of Natural Organic Matter.

The aggregation-redispersion behavior of nanomaterials determines their transport, transformation, and toxicity, which could be largely influenced by the ubiquitous natural organic matter (NOM). Nonetheless, the interaction mechanisms of two-dimensional (2D) MoS2 and NOM and the subsequent influences on the redispersion behavior are not well understood. Herein, we investigated the redispersion of single-layer MoS2 (SL-MoS2) nanosheets as influenced by Suwannee River NOM (SRNOM). It was found that SRNOM played a decisive role on the redispersion of MoS2 2D nanosheets that varied distinctly from the 3D nanoparticles. Compared to the poor redispersion of MoS2 aggregates in the absence or post-addition of SRNOM to the aggregates, co-occurrence of SRNOM in the dispersion could largely enhance the redispersion and mobility of MoS2 by intercalating into the nanosheets. Upon adsorption to SL-MoS2, SRNOM enhanced the hydration force and weakened the van der Waals forces between nanosheets, leading to the redispersion of the aggregates. The SRNOM fractions with higher molecular mass imparted better dispersity due to the preferable sorption of the large molecules onto SL-MoS2 surfaces. This comprehensive study advances current understanding on the transport and fate of nanomaterials in the water system and provides fresh insights into the interaction mechanisms between NOM and 2D nanomaterials.

Landscape of DILI-related adverse drug reaction in China Mainland.

Drug-induced liver injury (DILI) is a type of bizarre adverse drug reaction (ADR) damaging liver (L-ADR) which may lead to substantial hospitalizations and mortality. Due to the general low incidence, detection of L-ADR remains an unsolved public health challenge. Therefore, we used the data of 6.673 million of ADR reports from January 1st, 2012 to December 31st, 2016 in China National ADR Monitoring System to establish a new database of L-ADR reports for future investigation. Results showed that totally 114,357 ADR reports were retrieved by keywords searching of liver-related injuries from the original heterogeneous system. By cleaning and standardizing the data fields by the dictionary of synonyms and English translation, we resulted 94,593 ADR records reported to liver injury and then created a new database ready for computer mining. The reporting status of L-ADR showed a persistent 1.62-fold change over the past five years. The national population-adjusted reporting numbers of L-ADR manifested an upward trend with age increasing and more evident in men. The annual reporting rate of L-ADR in age group over 80 years old strikingly exceeded the annual DILI incidence rate in general population, despite known underreporting situation in spontaneous ADR reporting system. The percentage of herbal and traditional medicines (H/TM) L-ADR reports in the whole number was 4.5%, while 80.60% of the H/TM reports were new findings. There was great geographical disparity of reported agents, i.e. more cardiovascular and antineoplastic agents were reported in higher socio-demographic index (SDI) regions and more antimicrobials, especially antitubercular agents, were reported in lower SDI regions. In conclusion, this study presented a large-scale, unbiased, unified, and computer-minable L-ADR database for further investigation. Age-, sex- and SDI-related risks of L-ADR incidence warrant to emphasize the precise pharmacovigilance policies within China or other regions in the world.

Establishment of a Nomogram-Based Prognostic Model (LASSO-COX Regression) for Predicting Progression-Free Survival of Primary Non-Small Cell Lung Cancer Patients Treated with Adjuvant Chinese Herbal Medicines Therapy: A Retrospective Study of Case Series.

Nowadays, Jin-Fu-Kang oral liquid (JFK), one of Chinese herbal medicines (CHMs) preparations, has been widely used as an adjuvant therapy for primary non-small cell lung cancer (PNSCLC) patients with the syndrome of deficiency of both Qi and Yin (Qi-Yin deficiency pattern) based on Traditional Chinese Medicine (TCM) theory. However, we found insufficient evidence of how long-term CHM treatment influence PNSCLC patients' progression-free survival (PFS). Thus, using electronic medical records, we established a nomograph-based prognostic model for predicting PNSCLC patients' PFS involved with JFK supplementary formulas (JFK-SFs) over 6 months, in order to preliminarily investigate potential predictors highly related to adjuvant CHMs therapies in theoretical epidemiology. In our retrospective study, a series of 197 PNSCLC cases from Long Hua Hospital were enrolled by non-probability sampling and divided into 2 datasets at the ratio of 5:4 by Kennard-Stone algorithm, as a result of 109 in training dataset and 88 in validation dataset. Besides, TNM stage, operation history, sIL-2R, and CA724 were considered as 4 highly correlated predictors for modeling based on LASSO-Cox regression. Additionally, we respectively used training dataset and validation dataset for establishment including internal validation and external validation, and the prediction performance of model was measured by concordance index (C-index), integrated discrimination improvement, and net reclassification indices (NRI). Moreover, we found that the model containing clinical characteristics and bio-features presented the best performance by pairwise comparison. Next, the result of sensitivity analysis proved its stability. Then, for preliminarily examination of its discriminative power, all eligible cases were divided into high-risk or low-risk progression by the cut-off value of 57, in the light of predicted nomogram scores. Ultimately, a completed TRIPOD checklist was used for self-assessment of normativity and integrity in modeling. In conclusion, our model might offer crude probability of uncertainly individualized PFS with long-term CHMs therapy in the real-world setting, which could discern the individuals implicated with worse prognosis from the better ones. Nevertheless, our findings were prone to unmeasured bias caused by confounding factors, owing to retrospective cases series.

A Deep Learning Quantification Algorithm for HER2 Scoring of Gastric Cancer.

Gastric cancer is the third most common cause of cancer-related death in the world. Human epidermal growth factor receptor 2 (HER2) positive is an important subtype of gastric cancer, which can provide significant diagnostic information for gastric cancer pathologists. However, pathologists usually use a semi-quantitative assessment method to assign HER2 scores for gastric cancer by repeatedly comparing hematoxylin and eosin (H&E) whole slide images (WSIs) with their HER2 immunohistochemical WSIs one by one under the microscope. It is a repetitive, tedious, and highly subjective process. Additionally, WSIs have billions of pixels in an image, which poses computational challenges to Computer-Aided Diagnosis (CAD) systems. This study proposed a deep learning algorithm for HER2 quantification evaluation of gastric cancer. Different from other studies that use convolutional neural networks for extracting feature maps or pre-processing on WSIs, we proposed a novel automatic HER2 scoring framework in this study. In order to accelerate the computational process, we proposed to use the re-parameterization scheme to separate the training model from the deployment model, which significantly speedup the inference process. To the best of our knowledge, this is the first study to provide a deep learning quantification algorithm for HER2 scoring of gastric cancer to assist the pathologist's diagnosis. Experiment results have demonstrated the effectiveness of our proposed method with an accuracy of 0.94 for the HER2 scoring prediction.

O-Net: A Novel Framework With Deep Fusion of CNN and Transformer for Simultaneous Segmentation and Classification.

The application of deep learning in the medical field has continuously made huge breakthroughs in recent years. Based on convolutional neural network (CNN), the U-Net framework has become the benchmark of the medical image segmentation task. However, this framework cannot fully learn global information and remote semantic information. The transformer structure has been demonstrated to capture global information relatively better than the U-Net, but the ability to learn local information is not as good as CNN. Therefore, we propose a novel network referred to as the O-Net, which combines the advantages of CNN and transformer to fully use both the global and the local information for improving medical image segmentation and classification. In the encoder part of our proposed O-Net framework, we combine the CNN and the Swin Transformer to acquire both global and local contextual features. In the decoder part, the results of the Swin Transformer and the CNN blocks are fused to get the final results. We have evaluated the proposed network on the synapse multi-organ CT dataset and the ISIC 2017 challenge dataset for the segmentation task. The classification network is simultaneously trained by using the encoder weights of the segmentation network. The experimental results show that our proposed O-Net achieves superior segmentation performance than state-of-the-art approaches, and the segmentation results are beneficial for improving the accuracy of the classification task. The codes and models of this study are available at https://github.com/ortonwang/O-Net.

Landscape of Hepatobiliary Adverse Drug Reactions Related to Preparations Containing Psoraleae Fructus and Its Application in Pharmacovigilance.

OBJECTIVE: To analyze clinical feature and information of medication to explore the risk signals of preparations containing Psoraleae Fructus (BGZP) related with hepatobiliary adverse drug reactions (ADR), in order to reinforce pharmacovigilance. METHODS: A retrospective study was conducted based on hepatobiliary ADR related with BGZP from the China Adverse Drug Reaction Monitoring System in years from January 2012 to December 2016. Serious and general ADRs were analyzed and assessed. RESULTS: There were 355 cases of hepatobiliary ADR related to BGZP. Both the amount of cases and the proportion of serious ADR showed an increasing growth by years (P<0.05). It was found that 10.43% of 355 cases may be involved with irrational drug use, including overdose, repeated medication, and combination of multiple drugs. There were 190 cases which used BGZP (non-combination), and they were mainly for common in diseases caused by abnormal immune activation (accounting for 40.53% of the total cases). Especially at the age group with the most cases with age of 41-50 years, the cases associated with immunological diseases of female were obviously more than that of male (P<0.05). The latency of hepatobiliary ADR related to BGZP ranged from 1 to 386 days, and the median latency was 27.5 days, along with the range of cumulative dose (0.45-520.02 g) as well as the daily dose (0.09-2.64 g/d) after the conversion. CONCLUSIONS: Cases of hepatobiliary ADR related to BGZP showed significant individual differences, and there was no correlation between drug usage duration and dosage and the occurrence of hepatobiliary ADR. It may be similar with idiosyncratic drug-induced liver injury, and recommended that BGZP should be used with more caution under monitoring liver function, especially in female patients with immunological diseases.

[Analysis of epidemiological characteristics of drug induced liver injury associated with Baixianpi Preparations].

A retrospective study was performed in drug-induced liver injury(DILI) cases associated with Dictamni Cortex(Baixianpi,BXP) Preparations,which were treated at grade Ⅲ class A liver disease hospitals from 2008 to 2016 and spontaneously reported for adverse reactions between 2012 and 2016 at HILI Cloud(hilicloud.net). The results showed 25 DLII cases associated with BXP Preparations treated at grade Ⅲ class A liver disease hospitals during the 9 years,including only 14 cases in line with the clinical diagnostic criteria of Guidelines for the Diagnosis and Treatment of Herb-Induced Liver Injury. And 74 DILI cases associated with BXP Preparations spontaneously reports adverse reactions,and 18. 92% of them had unreasonable medication,including polypharmacy(21. 43%),overdose(28. 57%) and repeated dosage(50%). And 47 DILI cases used BXP Preparations to treat psoriasis and vitiligo(a total of59. 57%). The time range of taking BXP Preparations until liver injury occurred was 1-366 d,with the median of 18 d. The dose of BXP Preparations was estimated to be 0. 09-12 g·d-1. And the cumulative dosage of taking drugs until liver injury occurred was 1. 1-336 g. Obvious associations with time-toxicity as well as quantity-toxicity could not be found based on the wide range of time-toxicity relations and quantity-toxicity relations. On the basis of the study,we found that DILI cases associated with BXP Preparations commonly occurred in patients with immune diseases,such as psoriasis and vitiligo,indicating specific individual differences. The results suggested that DILI cases associated with BXP Preparations would be correlated with the property of idiosyncratic drug-induced liver injury. In conclusion,the risk of liver injury clinically caused by BXP Preparations should be paid more attention,and the studies on the mechanism of idiosyncratic drug-induced liver injury must be enhanced,and those on risk factors,like irrational drug use,should be strengthened. Moreover,the evaluation of the risk-to-benefit ratio is supposed to be performed for the sake of improving the risk prevention and control standards for BXP preparations,and ensuring safe and rational clinical application of BXP Preparations.

Susceptibility-Related Factor and Biomarkers of Dietary Supplement Polygonum multiflorum-Induced Liver Injury in Rats.

Polygonum multiflorum [PM, synonym Reynoutria multiflora (Thunb.) Moldenke.], a well-known and commonly used Traditional Chinese Medicine and herbal dietary supplement for nourishing the kidney and liver, etc., has aroused wide concern for its reported potential hepatotoxicity. Previous clinical cases and experimental studies have suggested that mild immune stress (MIS) may be one of the susceptibility-related factors of idiosyncratic drug-induced liver injury (IDILI) caused by PM. In this paper, we found that the same dose of PM caused abnormal liver biochemical indicators and liver tissue damage in MIS model rats, while it did not result in liver injury in normal rats, further confirming that MIS is a susceptibility factor for PM-IDILI. Plasma chemokine/cytokine profiling indicated that the MIS model group was significantly different from the other groups, showing a significant upregulation of plasma chemokines, while the MIS/PM group showed upregulated expression of chemokines or pro-inflammatory cytokines. Liver histopathological examination indicated a small amount of inflammatory cytokine infiltration in the MIS group, but no hepatocyte injury, consistent with the plasma profiles of increased chemokines and unchanged inflammatory cytokines. Notably, metabolomics characterization showed that MIS caused reprogramming of these metabolic pathways (such as phenylalanine and glutamate pathways), which was associated with acute phase reactions and inflammatory responses. These results suggested that MIS may promote an immune response to the initial cellular injury induced by PM in the liver, and MIS-induced upregulation of chemokines and metabolic reprogramming may an important mechanism that mediates the susceptibility to PM-IDILI. Furthermore, via receiver operating characteristic (ROC) curves analysis, we identified 12 plasma cytokines (e.g., IP-10, MCP-1 and MIP-1α) and nine metabolomics biomarkers (e.g., L-Phenylalanine, Creatinine, and L-glutamine) with differential capabilities (all ROC AUC > 0.9) of identifying susceptibility model animals from normal ones, which might be of referable value for the clinical recognition of PM-IDILI susceptible individuals.