Investigating the inhibition of xanthine oxidase by five catechins: Kinetic studies, spectroscopy, molecular docking, and dynamics simulations.

Catechins compounds from tea have demonstrated significant inhibitory effects on xanthine oxidase (XOD). However, the precise inhibitory mechanisms of the main catechins on XOD remain to be fully elucidated. This study explored the inhibition mechanisms and binding characteristics of five catechins (GC, EGC, EC, EGCG, and ECG) on XOD through a combination of inhibition kinetics, multi-spectroscopy analysis, molecular docking, and dynamics simulations. Among the catechins, EGCG and ECG exhibited the most potent inhibitory activities against XOD. All five catechins were found to exhibit mixed inhibition, affecting the hydrophobic groups and secondary structure of XOD predominantly through hydrophobic interactions and hydrogen bonding. Molecular dynamics simulations revealed that a 3,4,5-trihydroxybenzoic acid moiety at C3 position significantly enhances the binding affinity of EGCG and ECG to XOD. Additionally, the decrease of ß-sheet and random coil induced by EGCG and ECG was found to be crucial for enhancing inhibitory activity of XOD. In vitro cell experiments showed that EGCG and ECG significantly reduced high uric acid levels of BRL-3A cell. This study elucidates the inhibitory mechanisms of catechins on XOD, paving the way for their application as XOD inhibitors to combat hyperuricemia.

Challenges in treating coexisting scrotal apocrine carcinoma and gastric cancer: insights from an elderly patient: a case report and literature review.

BACKGROUND: Apocrine carcinoma associated with Paget's disease is a rare malignancy that typically manifests in elderly individuals, predominantly affecting the geriatric population. It commonly arises in regions rich in apocrine glands and often exhibits an insidious onset, potentially requiring several years to be diagnosed. CASE PRESENTATION: An 80-year-old male was simultaneously diagnosed with scrotal apocrine carcinoma (showing Paget changes) and early-stage gastric cancer. Whole-genome exome sequencing confirmed these as independent malignancies with minimal genetic overlap, indicating that they were two primary tumors. The patient initially underwent successful surgery but experienced recurrence and metastasis. Treatment with capecitabine and paclitaxel showed promising responses, highlighting similarities between breast and apocrine carcinomas. Challenges were noted in the use of genetic testing and drug susceptibility assessments for treatment guidance. Notably, HER-2 expression in metastatic lesions, a trait of apocrine carcinoma, has remained unexplored due to negative HER-2 FISH results and a lack of available targeted therapies in China. CONCLUSION: Elderly patients often exhibit a lesser degree of aggressiveness toward treatment following a diagnosis of malignant tumors. It is imperative to carefully consider how to strike a balance between effective treatment and maintaining a satisfactory quality of life for these patients. This case underscores the complexity of treating coexisting rare cancers in older adults and emphasizes the need for personalized treatments and continued innovation in cancer therapy. The insights gained offer significant value in understanding and managing such rare cancer cases.

Two-Step Noncatalyzed Hydrolysis Mechanism of Imines at the Air-Water Interface.

The hydrolysis of imines has long been assumed to be their main atmospheric fate, based on early studies in the field of organic chemistry. However, the hydrolysis mechanism and kinetics of atmospheric imines remain unclear. Here, an advanced Born-Oppenheimer molecular dynamics method was employed to investigate the noncatalyzed hydrolysis mechanism and kinetics at the air-water interface by selecting CH2NH as a model molecule. The results indicate that CH2NH exhibits a pronounced surface preference. The noncatalyzed hydrolysis of CH2NH follows a unique two-step reaction mechanism involving first proton transfer and then OH- transfer through the water bridge at the air-water interface, in contrast to the traditional one-step mechanism. The calculated reaction rate for the rate-determining step is 3.32 × 105 s-1, which is 2 orders of magnitude greater than that of the bulk phase. In addition, the involvement of the interfacial electric field further enhances the reaction rate by approximately 3 orders of magnitude. The noncatalyzed hydrolysis rate at both the air-water interface and the bulk phase is higher than that of the possible acid-catalyzed one, clarifying noncatalyzed hydrolysis as the dominant mechanism for CH2NH. This study elucidates that the noncatalyzed hydrolysis of atmospheric imines is feasible at the air-water interface and that the revealed unique two-step hydrolysis mechanism has significant implications in atmospheric and water environmental chemistry.

Self-expanding metal stent for relieving the stricture after endoscopic injection for esophageal varices.

BACKGROUND: Esophageal stricture is one of the complications after esophageal varices sclerotherapy injection (ESI), and the incidence rate is between 2%-10%. AIM: To explore the efficacy of self-expanding metal stent (SEMS) for the stricture after endoscopic injection with cyanoacrylate (CYA) and sclerotherapy for esophageal varices. METHODS: We retrospectively analyzed the efficacy of SEMS to improve the stricture after endoscopic injection with CYA and sclerotherapy for esophageal varices in 4 patients from February 2023 to June 2023. RESULTS: The strictures were improved in four patients after stenting. The stent was removed after two weeks because of chest pain with embedding into esophageal mucosa in one patient. The stent was removed after one month, however, the stent was reinserted because of the strictures happening again in two patients. The stent was removed after three months, however, the stent was reinserted because of the strictures happening again in one patient. The stent embedded into esophageal mucosa in three patients. There were 3 patients suffered reflux esophagitis, and the acid reflux was relieved by taking hydrotalcite. There was no other complication of esophageal perforation, bleeding from varices or infection. CONCLUSION: SEMS may relieve the stricture which happened after endoscopic injection with CYA and sclerotherapy for esophageal varices. However, when we should remove the stent still needs to be explored.

Glymphatic system dysfunction and risk of clinical milestones in patients with Parkinson disease.

BACKGROUND AND PURPOSE: Glymphatic dysfunction may play a significant role in the development of neurodegenerative diseases. We aimed to evaluate the association between glymphatic dysfunction and the risk of malignant event/clinical milestones in Parkinson disease (PD). METHODS: This study included 236 patients from August 2014 to December 2020. Diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index was calculated as an approximate measure of glymphatic function. The primary outcomes were four clinical milestones including recurrent falls, wheelchair dependence, dementia, and placement in residential or nursing home care. The associations of DTI-ALPS with the risk of clinical milestones were examined using multivariate Cox proportional hazards regression models. Then, logistic regression was repeated using clinical variables and DTI-ALPS index individually and in combination of the two to explore the ability to distinguish patients who reached clinical milestones within a 5-year period. RESULTS: A total of 175 PD patients with baseline DTI-ALPS index and follow-up clinical assessments were included. A lower DTI-ALPS was independently associated with increased risk of recurrent falls, wheelchair dependence, and dementia. Additionally, in 103 patients monitored over 5 years, a logistic regression model combining clinical variables and DTI-ALPS index showed better performance for predicting wheelchair dependence within 5 years than a model using clinical variables or DTI-ALPS index alone. CONCLUSIONS: Glymphatic dysfunction, as measured by the DTI-ALPS index, was associated with increased risk of clinical milestones in patients with PD. This finding implies that therapy targeting the glymphatic system may serve as a viable strategy for slowing down the progression of PD.

Increased rainfall frequency enhances dry seasonal soil mineral-associated organic carbon in a subtropical forest.

Climate models predict longer and more severe droughts, and alterations in the frequency and intensity of rainfall events. However, how changing precipitation patterns affect soil organic carbon (SOC), particulate organic carbon (POC), and mineral-associated organic carbon (MAOC) remains unclear. Here, we conducted a three-year rainfall manipulation experiment with ambient rainfall as the control, removal of half the total rainfall amount with unaltered frequency (DRA), and increased rainfall frequency with the total amounts unchanged (IRF) in a subtropical forest. The results showed that the rainfall treatments did not change SOC content or fractions during the wet season. In the dry season, DRA significantly increased topsoil POC but did not change SOC or MAOC. IRF significantly increased POC and MAOC levels. The increased MAOC was associated with the newly formed binary complexes of Fe3+, Al3+, and Ca2+, and the adsorption/precipitation of reduced short-range-ordered Fe oxides, likely derived from the enhanced reductive dissolution in the IRF treatment. Our results suggest that changes in rainfall frequency affect organo-mineral interactions more profoundly relative to the rainfall amount and that these effects are season-dependent. Therefore, moisture-sensitive geochemical processes play an essential role in SOC stabilization in subtropical forests.

Joint probabilistic risk of organic micropollutants in the aquaculture seawater around Liaodong Peninsula.

The limited number of organic micropollutants (OMPs) investigated in aquaculture seawater may underestimate the risk to marine organisms. It is critical to comprehensively investigate the occurrence of diverse OMPs in mariculture area and assess their joint risks to coastal marine organisms. Herein, the joint risks caused by multiple substances were assessed based on the screened results of approximately 1300 non-polar to polar OMPs in the seawater of mariculture ponds and raft culture areas around Liaodong Peninsula. In this study, 48 out of 886 non-polar to low-polar OMPs were detected at least once in 36 seawater samples, including 16 alkanes, 6 phthalate esters, 6 pesticides, 5 polycyclic aromatic hydrocarbons, etc. For 99 detected OMPs from both this study and our previously reported study, their aquatic toxicity data were comprehensively collected to assess the probabilistic risk. For 14 OMPs with sufficient toxicity data, their species sensitivity distribution curves were established. The results show that only three pollutants - ametryn, atrazine and diuron - alone adversely affect >5 % of coastal marine organisms. However, for the joint risks, up to 15.2 % of coastal marine organisms were affected by 14 OMPs under long-term exposure, suggesting that the OMP mixtures could enhance adverse effects. Although the ecological risks for most of compounds were acceptable, the joint risks of co-pollution by various OMPs cannot be ignored. The findings could support risk management of pollutants in aquaculture seawater, thereby contributing to the conservation of coastal marine biodiversity.

Mental programming of spatial sequences in working memory in the macaque frontal cortex.

How the brain mentally sorts a series of items in a specific order within working memory (WM) remains largely unknown. We investigated mental sorting using high-throughput electrophysiological recordings in the frontal cortex of macaque monkeys, who memorized and sorted spatial sequences in forward or backward orders according to visual cues. We discovered that items at each ordinal rank in WM were encoded in separate rank-WM subspaces and then, depending on cues, were maintained or reordered between the subspaces, accompanied by two extra temporary subspaces in two operation steps. Furthermore, the cue activity served as an indexical signal to trigger sorting processes. Thus, we propose a complete conceptual framework, where the neural landscape transitions in frontal neural states underlie the symbolic system for mental programming of sequence WM.

Perspectives on Advancing Multimodal Learning in Environmental Science and Engineering Studies.

The environment faces increasing anthropogenic impacts, resulting in a rapid increase in environmental issues that undermine the natural capital essential for human wellbeing. These issues are complex and often influenced by various factors represented by data with different modalities. While machine learning (ML) provides data-driven tools for addressing the environmental issues, the current ML models in environmental science and engineering (ES&E) often neglect the utilization of multimodal data. With the advancement in deep learning, multimodal learning (MML) holds promise for comprehensive descriptions of the environmental issues by harnessing data from diverse modalities. This advancement has the potential to significantly elevate the accuracy and robustness of prediction models in ES&E studies, providing enhanced solutions for various environmental modeling tasks. This perspective summarizes MML methodologies and proposes potential applications of MML models in ES&E studies, including environmental quality assessment, prediction of chemical hazards, and optimization of pollution control techniques. Additionally, we discuss the challenges associated with implementing MML in ES&E and propose future research directions in this domain.

The Estimation of Knee Medial Force with Substitution Parameters during Walking and Turning.

PURPOSE: Knee adduction, flexion moment, and adduction angle are often used as surrogate parameters of knee medial force. To verify whether these parameters are suitable as surrogates under different walking states, we investigated the correlation between knee medial loading with the surrogates during walking and turning. METHODS: Sixteen healthy subjects were recruited to complete straight walk (SW), step turn (ST), and crossover turn (CT). Knee joint moments were obtained using inverse dynamics, and knee medial force was computed using a previously validated musculoskeletal model, Freebody. Linear regression was used to predict the peak of knee medial force with the peaks of the surrogate parameters and walking speed. RESULTS: There was no significant difference in walking speed among these three tasks. The peak knee adduction moment (pKAM) was a significant predictor of the peak knee medial force (pKMF) for SW, ST, and CT (p < 0.001), while the peak knee flexion moment (pKFM) was only a significant predictor of the pKMF for SW (p = 0.034). The statistical analysis showed that the pKMF increased, while the pKFM and the peak knee adduction angle (pKAA) decreased significantly during CT compared to those of SW and ST (p < 0.001). The correlation analysis indicated that the knee parameters during SW and ST were quite similar. CONCLUSIONS: This study investigated the relationship between knee medial force and some surrogate parameters during walking and turning. KAM was still the best surrogate parameter for SW, ST, and CT. It is necessary to consider the type of movement when comparing the surrogate predictors of knee medial force, as the prediction equations differ significantly among movement types.

Cortical microstructural alterations in different stages of Parkinson's disease.

To explore the cortical microstructural alterations in Parkinson's disease (PD) at different stages. 149 PD patients and 76 healthy controls were included. PD patients were divided into early stage PD (EPD) (Hoehn-Yahr stage ≤ 2) and moderate-to-late stage PD (MLPD) (Hoehn-Yahr stage ≥ 2.5) according to their Hoehn-Yahr stages. All participants underwent two-shell diffusion MRI and the images were fitted to Neurite Orientation Dispersion and Density Imaging (NODDI) model to obtain the neurite density index (NDI) and orientation dispersion index (ODI) to reflect the cortical microstructure. We used gray matter-based spatial statistics method to compare the voxel-wise cortical NODDI metrics between groups. Partial correlation was used to correlate the NODDI metrics and global composite outcome in PD patients. Compared with healthy controls, EPD patients showed lower ODI in widespread regions, covering bilateral frontal, temporal, parietal and occipital cortices, as well as regional lower NDI in bilateral cingulate and frontal lobes. Compared with healthy controls, MLPD patients showed lower ODI and NDI in more widespread regions. Compared with EPD patients, MLPD patients showed lower ODI in bilateral temporal, parietal and occipital cortices, where the ODI values were negatively correlated with global composite outcome in PD patients. PD patients showed widespread cortical microstructural degeneration, characterized by reduced neurite density and orientation dispersion, and the cortical neuritic microstructure exhibit progressive degeneration during the progression of PD.

Flexible control of sequence working memory in the macaque frontal cortex.

To memorize a sequence, one must serially bind each item to its rank order. How the brain controls a given input to bind its associated order in sequence working memory (SWM) remains unexplored. Here, we investigated the neural representations underlying SWM control using electrophysiological recordings in the frontal cortex of macaque monkeys performing forward and backward SWM tasks. Separate and generalizable low-dimensional subspaces for sensory and memory information were found within the same frontal circuitry, and SWM control was reflected in these neural subspaces' organized dynamics. Each item at each rank was sequentially entered into a common sensory subspace and, depending on forward or backward task requirement, flexibly and timely sent into rank-selective SWM subspaces. Neural activity in these SWM subspaces faithfully predicted the recalled item and order information in single error trials. Thus, compositional neural population codes with well-orchestrated dynamics in frontal cortex support the flexible control of SWM.

Distinct Species-Specific and Toxigenic Metabolic Profiles for 6PPD and 6PPD Quinone by P450 Enzymes: Insights from In Vitro and In Silico Studies.

The tire rubber antioxidant N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) and its quinone product (6PPDQ) are prevalent emerging contaminants, yet their biotransformation profiles remain poorly understood, hampering the assessment of environmental and health risks. This study investigated the phase-I metabolism of 6PPD and 6PPDQ across aquatic and mammalian species through in vitro liver microsome (LM) incubations and in silico simulations. A total of 40 metabolites from seven pathways were identified using the highly sensitive nano-electrospray ionization mass spectrometry. Notably, 6PPDQ was consistently detected as a 6PPD metabolite with an approximate 2% yield, highlighting biotransformation as a neglected indirect exposure pathway for 6PPDQ in organisms. 6PPDQ was calculated to form through a facile two-step phenyl hydroxylation of 6PPD, catalyzed by cytochrome P450 enzymes. Distinct species-specific metabolic kinetics were observed, with fish LM demonstrating retarded biotransformation rates for 6PPD and 6PPDQ compared to mammalian LM, suggesting the vulnerability of aquatic vertebrates to these contaminants. Intriguingly, two novel coupled metabolites were identified for 6PPD, which were predicted to exhibit elevated toxicity compared to 6PPDQ and result from C-N oxidative coupling by P450s. These unveiled metabolic profiles offer valuable insights for the risk assessment of 6PPD and 6PPDQ, which may inform future studies and regulatory actions.

Psychometric evaluation of the Chinese version of the Academic Resilience Scale-30 (C-ARS-30) in college students.

Background: Amidst the expansion of student enrollment in higher education, the well-being and retention rates of students have emerged as important concerns. Resilience, especially academic resilience, a multidimensional construct that can lead to academic success in adversity, is pivotal in enabling students to successfully cope with academic challenges. While the Academic Resilience Scale-30 (ARS-30) has been validated as an effective instrument in various languages, its applicability for Chinese students in higher education remains unexplored. Objective: This study aims to translate and validate the ARS-30 in Chinese, assessing its reliability and validity among Chinese college students in higher education. Methods: A convenience sample of 1,542 students participated in this study. The inventory included the demographic form, Chinese version of ARS-30 (C-ARS-30), 10-item Connor Davidson Resilience Scale (CD-RISC-10), and General Self-Efficacy Scale (GSES). The assessment of validity was conducted by analyzing content validity, construct validity, convergent and discriminant validity, as well as criterion-related validity. Construct validity was evaluated through Confirmatory Factor Analysis (CFA), Exploratory Factor Analysis (EFA) and Exploratory Structural Equation Modeling (ESEM). Reliability analysis was performed using Cronbach's alpha and test-retest reliability. Results: The C-ARS-30 demonstrated commendable content validity, with the CVI value of items ranging from 0.833 to 1.000, and a total scale CVI of 0.986. ESEM analysis revealed a solid four-factor structure, maintaining the scale's 30 items with excellent fit indices (χ2/df = 2.647, CFI = 0.937, TLI = 0.915, RMSEA = 0.057, SRMR = 0.027). The total score of C-ARS-30 exhibited positive correlations with the CD-RISC-10 (r = 0.542) and the GSES (r = 0.488). The scale demonstrated high internal consistency (Cronbach's α = 0.930) and test-retest reliability (0.794, p < 0.01). Conclusion: The C-ARS-30 is a reliable and valid instrument for assessing academic resilience among Chinese college students, offering a valuable tool for educational and psychological evaluations.

Sensitive SWIR Organic Photodetectors with Spectral Response Reaching 1.5 µm.

The performance of organic photodetectors (OPDs) sensitive to the short-wavelength infrared (SWIR) light lags behind commercial indium gallium arsenide (InGaAs) photodetectors primarily due to the scarcity of organic semiconductors with efficient photoelectric responses exceeding 1.3 µm. Limited by the Energy-gap law, ultralow-bandgap organic semiconductors usually suffer from severe non-radiative transitions, resulting in low external quantum efficiency (EQE). Herein, a difluoro-substituted quinoid terminal group (QC-2F) with exceptionally strong electron-negativity is developed for constructing a new non-fullerene acceptor (NFA), Y-QC4F with an ultralow bandgap of 0.83 eV. This subtle structural modification significantly enhances intermolecular packing order and density, enabling an absorption onset up to 1.5 µm while suppressing non-radiation recombination in Y-QC4F films. SWIR OPDs based on Y-QC4F achieve an impressive detectivity (D*) over 1011 Jones from 0.4 to 1.5 µm under 0 V bias, with a maximum of 1.68 × 1012 Jones at 1.16 µm. Furthermore, the resulting OPDs demonstrate competitive performance with commercial photodetectors for high-quality SWIR imaging even under 1.4 µm irradiation.

Non-covalent interaction between lactoferrin and theaflavin: Focused on the structural changes, binding mechanism, and functional properties.

In this study, non-covalent binding mechanism of lactoferrin (LaF)-theaflavin (TF) complex and its functional properties were investigated. Multi-spectroscopic analyses showed that the secondary structure of LaF was altered with increasing TF concentration. The non-covalent binding of TF to LaF resulted in a reduction in the content of the α-helix and ß-sheet, as well as a decrease in the fluorescence intensity of LaF. DSC result showed that non-covalent binding of TF improved thermal stability of LaF. Molecular dynamics simulations confirmed that the stable binding of LaF-TF was driven by hydrogen bonding and hydrophobic interactions. Additionally, non-covalent binding of TF increased the antioxidant capacity and emulsifying properties of LaF. Dynamic interfacial tension indicated that the strong interaction between LaF and TF reduced the interfacial tension, but improved the rheological properties of LaF. The functional characteristics of the non-covalent complex was effectively enhanced, paving the way for its potential use in the food industry.

CRYAB Promotes Colorectal Cancer Progression by Inhibiting Ferroptosis Through Blocking TRIM55-Mediated ß-Catenin Ubiquitination and Degradation.

BACKGROUND: α-Crystallin B (CRYAB) is a chaperone member of the HSPs family that protects proteins with which it interacts from degradation. This study aims to investigate the effect of CRYAB on the progression of colorectal cancer (CRC) and its underlying mechanism. METHODS: CRYAB expression was evaluated in CRC tissues. Cell growth was tested by CCK-8 kit. Lipid reactive oxygen species (ROS) assays, lipid peroxidation assays, glutathione assays were used to assess the degree of cellular lipid peroxidation of CRC cells. The potential signal pathways of CRYAB were analyzed and verified by Western blot (WB) and immunoprecipitation (Co-IP). RESULTS: CRYAB expression was elevated in CRC tissues and exhibited sensitivity and specificity in predicting CRC. Functionally, knockdown of CRYAB induced ferroptosis in CRC cells. Mechanistically, CRYAB binding prevented from ß-catenin interacting with TRIM55, leading to an increase in ß-catenin protein stability, which desensitized CRC cells to ferroptosis and ultimately accelerated cancer progression. CONCLUSIONS: Targeting CRYAB might be a promising strategy to enhance ferroptosis and improve the efficacy of CRC therapy.

Trace of delirium after robotic lower abdominal tumor resection at different end-tidal carbon dioxide: a RCT trial.

BACKGROUND: Postoperative delirium (POD) often occurs in oncology patients, further increasing the medical and financial burden. Robotic technology in lower abdominal tumors resection reduces surgical trauma but increases risks such as carbon dioxide (CO2) absorption. This study aimed to investigate the differences in their occurrence of POD at different end-tidal CO2 levels. METHOD: This study was approved by the Ethics Committee of Affiliated Hospital of He Bei University (HDFY-LL-2022-169). The study was registered with the Chinese Clinical Trials Registry on URL: http://www.chictr.org.cn , Registry Number: ChiCTR2200056019 (Registry Date: 27/08/2022). In patients scheduled robotic lower abdominal tumor resection from September 1, 2022 to December 31, 2022, a comprehensive delirium assessment was performed three days postoperatively using the CAM scale with clinical review records. Intraoperative administration of different etCO2 was performed depending on the randomized grouping after intubation. Group L received lower level etCO2 management (31-40mmHg), and Group H maintained the higher level(41-50mmHg) during pneumoperitoneum. Data were analyzed using Pearson Chi-Square or Wilcoxon Rank Sum tests and multiple logistic regression. Preoperative mental status score, alcohol impairment score, nicotine dependence score, history of hypertension and diabetes, duration of surgery and worst pain score were included in the regression model along with basic patient information for covariate correction analysis. RESULTS: Among the 103 enrolled patients, 19 (18.4%) developed postoperative delirium. The incidence of delirium in different etCO2 groups was 21.6% in Group L and 15.4% in Group H, respectively, with no statistical differences. In adjusted multivariate analysis, age and during of surgery were statistically significant predictors of postoperative delirium. The breath-hold test was significantly lower postoperatively, but no statistical differences were found between two groups. CONCLUSION: With robotic assistant, the incidence of postoperative delirium in patients undergoing lower abdominal tumor resection was not modified by different end-tidal carbon dioxide management, however, age and duration of surgery were positively associated risk factors.

IL-2, IL-17A and TNF-α hold potential as biomarkers for predicting acute mountain sickness prior to ascent.

BACKGROUND: Acute mountain sickness (AMS) is the most prevalent condition resulting from hypobaric hypoxia (HH) at high altitudes. Although evidence suggests the involvement of inflammatory cytokines in AMS development, there is currently a lack of reports on variations in cytokine levels between individuals susceptible to AMS and those resistant to AMS prior to ascending to high altitude. Thus our current study aims to assess the predictive capability for AMS occurrence by evaluating differences in cytokine levels at low altitudes. METHODS: The present study recruited 48 participants, who ascended from low altitude to middle high-altitude (3700 m) and further to extreme high-altitude (5000 m). Based on Lake Louise Score (LLS) at the two high altitudes, participants were categorized into severe AMS-susceptible (sAMS), moderate AMS-susceptible (mAMS), and non-AMS groups. The Bio-Plex MAGPIX System was employed to measure plasma levels of 11 inflammatory cytokines. Cytokines at low altitude and middle high-altitude were analyzed through receiver operating characteristic (ROC) analysis to obtain area under the ROC curve (AUROC), sensitivity, and specificity. RESULTS: Based on LLS at 3700 m, we initially categorized the study subjects into the sAMS group (n = 8) and the Non-AMS group (n = 40). Among individuals in the non-AMS group (n = 40) at the altitude of 3700 m, those who developed AMS at the altitude of 5000 m were assigned to the mAMS group (n = 17), whereas those who did not experience AMS were included into the non-AMS group (n = 23). The concentration of TNF-α at low altitude exhibited robust predictive performance for predicting AMS occurrence at the altitude of 3700 m. Among the non-AMS group at the altitude of 3700 m, we identified that the concentration of IL-2 and IL-17A demonstrated high efficacy in predicting the onset of AMS following ascent to 5000 m. In addition, differentially expressed cytokines including IL-17A, TNF-α and IL-2 at low altitude possessed discriminatory potential among the three groups at 5000 m.. CONCLUSION: We posited that the levels of TNF-α, IL-2, IL-17A in serum of low altitude could be considered as potential biomarkers to predict the occurrence of AMS at high altitude. NEW & NOTEWORTHY: Through the two comparisons at different two altitudes (baseline level and 3700 m), we provided a model to progressively screen individuals who are susceptible and resistant to different high altitudes (3700 m and 5000 m). TNF-α could firstly screen out the AMS susceptible individuals at the altitude of 3700 m. And through its combination with IL-2 and IL-17A, we could further screen out AMS susceptible individuals at the altitude of 5000 m.