Machine learning-based identification and validation of immune-related biomarkers for early diagnosis and targeted therapy in diabetic retinopathy.

The early diagnosis of diabetic retinopathy (DR) is challenging, highlighting the urgent need to identify new biomarkers. Immune responses play a crucial role in DR, yet there are currently no reports of machine learning (ML) algorithms being utilized for the development of immune-related molecular markers in DR. Based on the datasets GSE102485 and GSE160306, differentially expressed genes (DEGs) were screened using Weighted Gene Co-expression Network Analysis (WGCNA). Five ML algorithms including Bayesian, Learning Vector Quantization (LVQ), Wrapper (Boruta), Random Forest (RF), and Logistic Regression were employed to select immune-related genes associated with DR (DR.Sig). Seven ML algorithms including Naive Bayes (NB), RF, Support Vector Machine (SVM), AdaBoost Classification Trees (AdaBoost), Boosted Logistic Regressions (LogitBoost), K-Nearest Neighbors (KNN), and Cancerclass were utilized to construct a predictive model for DR. The relationship between DR.Sig genes and immune cells was analyzed using single-sample Gene Set Enrichment Analysis (ssGSEA). Additionally, drug sensitivity prediction of DR.Sig genes and molecular docking were performed. Through the utilization of 5 ML algorithms, 6 immune-related biomarkers closely related to the occurrence of DR were identified, including FCGR2B, CSRP1, EDNRA, SDC2, TEK, and CIITA. The DR predictive model constructed based on these 6 DR.Sig genes using the Cancerclass algorithm demonstrated superior predictive performance compared to 4 previously published DR-related biomarkers. In vivo and in vitro experiments also provided strong validation of the expression of the 6 genes in DR. Positive correlations were observed between these genes and 22 types of immune cells. Molecular docking results revealed that CSRP1, EDNRA, and TEK exhibited the highest affinities with the small molecule compounds etoposide, FR-139317, and camptothecin, respectively. The models constructed based on various ML algorithms can effectively predict the occurrence of DR events and hold potential for targeted drug therapies, providing a basis for the early diagnosis and targeted treatment of DR.

Potent covalent irreversible inhibitor of KRAS G12C IBI351 in patients with advanced solid tumors: First-in-human phase I study.

BACKGROUND: IBI351 is an irreversible and covalent inhibitor of KRAS G12C. Despite FDA approval of two KRAS G12C inhibitors, there are still significant unmet clinical needs in Chinese patients and ongoing concerns about the optimal dosage. Herein, we presented the phase Ia/Ib study of IBI351 monotherapy in Chinese patients with advanced solid tumors harboring KRAS G12C mutation. METHODS: In phase Ia dose escalation, IBI351 at 250/450/700/900 mg once daily and 450/600/750 mg twice daily (BID) were evaluated. Potentially efficacious doses and optimal recommended phase 2 dose (RP2D) were further evaluated in patients with advanced non-small cell lung cancer (NSCLC) in phase Ia dose expansion and phase Ib. Safety, pharmacokinetics, and investigator-assessed tumor response were evaluated. RESULTS: As of June 13, 2023, 176 patients were enrolled. IBI351 was well tolerated with no dose-limiting toxicity reported across all evaluated doses. The RP2D was determined as 600 mg BID by considering safety, efficacy and pharmacokinetics. A total of 168 patients (95.5 %) had at least one treatment-related adverse event (TRAE), and 64 patients (36.4 %) had grade 3 or higher TRAEs, most commonly gamma-glutamyl transferase increased (10.2 %) and anemia (6.8 %). For patients with NSCLC, the confirmed objective response rate (ORR) was 45.5 % across all doses. At 600 mg BID, the confirmed ORR was 46.8 % and median progression-free survival was 9.6 months with a median follow-up of 6.9 months. CONCLUSIONS: IBI351 was well tolerated in patients with advanced solid tumors and showed promising antitumor activity in advanced NSCLC patients with KRAS G12C mutation.

Heterostructured g-C3N4/Bi2WO6 Composites as Highly Efficient Photocatalysts for Selective Atmospheric Oxidation of Thiols to Disulfides.

Improving the transmission and separation efficiency of light carriers is considered an effective method to enhance the catalytic performance of semiconductor photocatalysis. Herein, we report the synthesis and application of g-C3N4/Bi2WO6 heterostructure nanosheets for the photocatalytic coupling of thiols to disulfides under visible light irradiation. The heterojunction exhibits significant photocatalytic performance compared to the bare catalyst, which dramatically enhances the separation and transfer of photogenerated charge carriers due to the remarkable hole-trapping ability of g-C3N4. Various functional symmetrical and asymmetrical disulfides have been effectively prepared by employing this heterostructure photocatalytic system, which features excellent photocatalytic activity and cycling stability. The outstanding photocatalytic activity of the semiconductor heterojunction catalyst provides an economical, sustainable, and thus green process for producing disulfides.

Preparation and antitumor activity of selenium nanocomposite stabilized by AAGL from Agerocybe aegerita.

Selenium nanoparticles (SeNPs) have limited bioavailability because of their poor stability in aqueous solutions. AAGL, a naturally active protein, extracted from Agrocybe aegerita has strong antitumor activity. However, AAGL has been used to stabilize SeNPs, and whether it exerts anti-lung cancer effects remains unknown. In this study, a novel nanocomposite, AAGL-SeNPs, was prepared using AAGL-encapsulated SeNPs. The particle size of the AAGL-SeNPs was approximately 206.1 nm, which was uniform and well dispersed in aqueous solution and showed satisfactory stability. AAGL-SeNPs was non-toxic and reduced the hepatotoxicity of AAGL in mice. Importantly, AAGL-SeNPs inhibited the proliferation of lung cancer cells and suppressed tumor growth in tumor-bearing mice. AAGL-SeNPs enhanced the cytotoxic effects on lung cancer cells by stimulating immune cells. In addition, the combination of AAGL-SeNPs and osimertinib inhibited lung cancer, and AAGL-SeNPs reversed osimertinib resistance in H1975 cells. Mechanistically, Krüppel-like transcriptional factor 4 (KLF4) was identified by data-independent acquisition mass spectrometry (DIA-MS), and its expression levels in lung cancer increased after AAGL-SeNPs treatment. This study demonstrated that nanocomposite AAGL-SeNPs is stable, safe, and has excellent antitumor efficacy, which will be a potential therapeutic drug for lung cancer treatment.

Clinical phenotyping of septic shock with latent profile analysis: A retrospective multicenter study.

BACKGROUND: Septic shock (SS) is a highly fatal and heterogeneous syndrome. Identifying distinct clinical phenotypes provides valuable insights into the underlying pathophysiological mechanisms and may help to propose precise clinical management strategies. METHODS: Latent profile analysis (LPA), a model-based unsupervised method, was used for phenotyping in the MIMIC cohort, and the model was externally independently validated in the eICU and AUMC cohorts. RESULTS: Three phenotypes, labeled phenotype I, II, and III, were derived. These phenotypes varied in demographics, clinical features, comorbidities, patterns of organ dysfunction, organ support, and prognosis. Phenotype I, characterized by the most severe organ dysfunction (especially liver), the youngest age, and the highest BMI, had the highest mortality (p < 0.001). Phenotype II, with moderate mortality, was characterized by severe renal injury. In contrast, phenotype III, associated with the oldest age and the fewest comorbidities, exhibited significantly lower mortality. Phenotype I patients had the steepest survival curves and demonstrated an ultra-high risk of death, particularly within the first few days after SS onset. CONCLUSIONS: The individualized identification of phenotypes is well suited to clinical practice. The three SS phenotypes differed significantly in pathophysiological and clinical outcomes, which are crucial for informing management decisions and prognosis.

SON controls mouse early embryonic development by regulating RNA splicing and histone methylation.

Thousands of genes are activated in late 2-cell embryos, which means that numerous pre-mRNAs are generated during this time. These pre-mRNAs must be accurately spliced to ensure that the mature mRNAs are translated to functional proteins. However, little is known about the roles of pre-mRNA splicing and cellular factors modulating pre-mRNA splicing during early embryonic development. Here, we report that downregulation of SON, a large Ser/Arg (SR)-related protein, reduced embryonic development and caused deficient blastomere cleavage. These embryonic developmental defects result from dysregulated nuclear speckle organization and pre-mRNA splicing of a set of cell cycle-related genes. Furthermore, SON downregulation disrupted the transcriptome (2128 upregulated and 1399 downregulated) in 4-cell embryos. Increased H3K4me3, H3K9me3 and H3K27me3 levels were detected in 4-cell embryos after SON downregulation. Taken together, these results demonstrate that accurate pre-mRNA splicing is essential for early embryonic development and that SON plays important roles in nuclear speckle organization, pre-mRNA splicing, transcriptome establishment and histone methylation reprogramming during early embryonic development.

Synthesis and evaluation of neuroactive steroids with novel pharmacophore at C-21 let identify a compound with advantageous PK profile and higher EC50 and Emax as PAM on GABAA receptor.

Zuranolone (SAGE-217) is a neuroactive steroid (γ-aminobutyric acid)A (GABAA) receptor positive allosteric modulator (PAM) as the first oral drug approved by the FDA in 2023, which is used to treat patients with postpartum depression (PPD). SAGE-217 has a "black box" warning with impairing ability to drive or engage in other potentially hazardous activities. In addition, SAGE-217 can cause CNS depressant effects such as somnolence and confusion, suicidal thoughts and behavior and embryo-fetal toxicity. Based on the structure-activity relationship (SAR) of SAGE-217, a total of 28 neuroactive steroids with novel pharmacophore at C-21 modulated SAGE-217 derivatives were designed and synthesized. The biological activities were evaluated by both synaptic α1ß2γ2 GABAA receptor and extrasynaptic α4ß3δ GABAA receptor cell assays. The optimal compound S28 exhibited much more potent potency and similar efficacy at extrasynaptic GABAA receptor than SAGE-217. Different from above, compound S28 exhibited similar potency and lower efficacy at synaptic GABAA receptor than SAGE-217, which were consistent with the analysis of molecular docking and dynamics simulation results. The appropriate lower efficacy at synaptic GABAA receptor of compound S28 might contribute to reduce the side effects of excessive sedation. Furthermore, compound S28 was demonstrated to have excellent in vivo pharmacokinetic (PK) parameters, robust in vivo pharmacodynamic (PD) effects and good safety profiles. Therefore, compound S28 represents a potentially promising treatment of PPD candidate that warrants further investigation.

2', 3', 5'-tri-O-acetyl-N6-(3-hydroxyphenyl) adenosine alleviates diet-induced hyperlipidemia by modulating intestinal gene expression profiles and metabolic pathway.

There is a growing body of evidence suggesting that the composition of intestinal flora plays a significant role in regulating lipid metabolism. 2', 3', 5'-tri-O-acetyl-N6-(3-hydroxyphenyl) adenosine (IMMH007) is a new candidate compound for regulating blood cholesterol and other lipids. In this study, we conducted metagenomic and metabolomic analyses on samples from high-fat diet-fed (HFD) hamsters treated with IMMH007. Our findings revealed that IMM-H007 reversed the imbalance of gut microbiota caused by a high-fat diet. Additionally, it activated adiponectin receptor and pantothenate and CoA biosynthesis pathway-related genes, which are known to regulate lipid and glucose metabolism. Furthermore, IMM-H007 promotes cholesterol metabolism by reducing the abundance of genes and species associated with 7α-dehydroxylation and bile salt hydrolase (BSH). Metabolomics and pharmacological studies have shown that IMM-H007 effectively improved glucose and lipid metabolism disorders caused by HFD, reduced the aggregation of secondary bile acids (SBAs), significantly increased the content of hyodeoxycholic acid (HDCA), and also activated the expression of VDR in the small intestine. As a result, there was a reduction in the leakage of diamine oxidase (DAO) into the bloodstream in hamsters, accompanied by an upregulation of ZO-1 expression in the small intestine. The results suggested that IMM-H007 regulated glucose and lipid metabolism, promoted cholesterol metabolism through activating the expression of VDR, inhibiting inflammatory and improving the permeability of the intestinal barrier. Thus, our study provides new understanding of how IMM-H007 interacts with intestinal function, microbiota, and relevant targets, shedding light on its mechanism of action.

Recent progress of metal halide perovskite materials in heterogeneous photocatalytic organic reactions.

Photocatalytic technology is widely regarded as an important way to utilize solar energy and achieve carbon neutrality, which has attracted considerable attentions in various fields over the past decades. Metal halide perovskites (MHPs) are recognized as "superstar" materials due to their exceptional photoelectric properties, readily accessible and tunable structure, which made them intensively studied in solar cells, light-emitting diodes, and solar energy conversion fields. Since 2018, increased attention has been focused on applying the MHPs as a heterogeneous visible light photocatalyst in catalyzing organic synthesis reactions. In this review, we present an overview of photocatalytic technology and principles of heterogeneous photocatalysis before delving into the structural characteristics, stability, and classifications of MHPs. We then focus on recent developments of MHPs in photocatalyzing various organic synthesis reactions, such as oxidation, cyclization, C-C coupling etc., based on their classifications and reported reaction types. Finally, we discuss the main limitations and prospects regarding the application of metal halide perovskites in organic synthesis.

Discovery of Oral AMP-Activated Protein Kinase Activators for Treating Hyperlipidemia.

Activation of AMP-activated protein kinase (AMPK) is proposed to alleviate hyperlipidemia. With cordycepin and N6-(2-hydroxyethyl) adenosine (HEA) as lead compounds, a series of adenosine-based derivatives were designed, synthesized, and evaluated on activation of AMPK. Finally, compound V1 was identified as a potent AMPK activator with the lipid-lowering effect. Molecular docking and circular dichroism indicated that V1 exerted its activity by binding to the γ subunit of AMPK. V1 markedly decreased the serum low-density lipoprotein cholesterol levels in C57BL/6 mice, golden hamsters, and rhesus monkeys. V1 was selected as the clinical compound and concluded Phase 1 clinical trials. A single dose of V1 (2000 mg) increased AMPK activation in human erythrocytes after 5 and 12 h of treatment. RNA sequencing data suggested that V1 downregulated expression of genes involved in regulation of apoptotic process, lipid metabolism, endoplasmic reticulum stress, and inflammatory response in liver by activating AMPK.

Three-dimensional chromatin landscapes in somatotroph tumour.

BACKGROUND: The three-dimensional (3D) genome architecture plays a critical role inregulating gene expression. However, the specific alterations in thisarchitecture within somatotroph tumors and their implications for gene expression remain largely unexplored. METHODS: We employed Hi-C and RNA-seq analyses to compare the 3D genomic structures of somatotroph tumors with normal pituitary tissue. This comprehensive approachenabled the characterization of A/B compartments, topologically associateddomains (TADs), and chromatin loops, integrating these with gene expression patterns. RESULTS: We observed a decrease in both the frequency of chromosomal interactions andthe size of TADs in tumor tissue compared to normal tissue. Conversely, the number of TADs and chromatin loops was found to be increased in tumors. Integrated analysis of Hi-C and RNA-seq data demonstrated that changes inhigher-order chromat in structure were associated with alterations in gene expression. Specifically, genes in A compartments showed higher density and increased expression relative to those in B compartments. Moreover, the weakand enhanced insulation boundaries were identified, and the associated genes were enriched in the Wnt/ß-Catenin signaling pathway. We identified the gainedand lost loops in tumor and integrated these differences with transcriptional changes to examine the functional relevance of the identified loops. Notably, we observed an enhanced insulation boundary and a greater number of loops in the TCF7L2 gene region within tumors, which was accompanied by an upregulation of TCF7L2 expression. Subsequently, TCF7L2 expression was confirmed through qRT-PCR, and upregulated TCF7L2 prompted cell proliferation and growth hormone (GH) secretion in vitro. CONCLUSION: Our results provide comprehensive 3D chromatin architecture maps of somatotroph tumors and offer a valuable resource for furthering the understanding of the underlying biology and mechanisms of gene expression regulation.

TNF-α can promote membrane invasion by activating the MAPK/MMP9 signaling pathway through autocrine in bone-invasive pituitary adenoma.

AIMS: A bone-invasive pituitary adenoma exhibits aggressive behavior, leading to a worse prognosis. We have found that TNF-α promotes bone invasion by facilitating the differentiation of osteoclasts, however, before bone-invasive pituitary adenoma invades bone tissue, it needs to penetrate the dura mater, and this mechanism is not yet clear. METHODS: We performed transcriptome microarrays on specimens of bone-invasive pituitary adenomas (BIPAs) and noninvasive pituitary adenomas (NIPAs) and conducted differential expressed gene analysis and enrichment analysis. We altered the expression of TNF-α through plasmids, then validated the effects of TNF-α on GH3 cells and verified the efficacy of the TNF-α inhibitor SPD304. Finally, the effects of TNF-α were validated in in vivo experiments. RESULTS: Pathway act work showed that the MAPK pathway was significantly implicated in the pathway network. The expression of TNF-α, MMP9, and p-p38 is higher in BIPAs than in NIPAs. Overexpression of TNF-α elevated the expression of MAPK pathway proteins and MMP9 in GH3 cells, as well as promoted proliferation, migration, and invasion of GH3 cells. Flow cytometry indicated that TNF-α overexpression increased the G2 phase ratio in GH3 cells and inhibited apoptosis. The expression of MMP9 was reduced after blocking the P38 MAPK pathway; overexpression of MMP9 promoted invasion of GH3 cells. In vivo experiments confirm that the TNF-α overexpression group has larger tumor volumes. SPD304 was able to suppress the effects caused by TNF-α overexpression. CONCLUSION: Bone-invasive pituitary adenoma secretes higher levels of TNF-α, which then acts on itself in an autocrine manner, activating the MAPK pathway and promoting the expression of MMP9, thereby accelerating the membrane invasion process. SPD304 significantly inhibits the effect of TNF-α and may be applied in the clinical treatment of bone-invasive pituitary adenoma.

Comparison of progestin-primed ovarian stimulation regimen and antagonist regimen in women aged 35 years or older with diminished ovarian reserve: A propensity score-matched study.

OBJECTIVE: Diminished ovarian reserve (DOR) has been a major challenge in infertility treatment. The present study aimed to compare the efficacy of progestin-primed ovarian stimulation (PPOS) regimen and antagonist regimen in infertile patients aged 35 years or older with DOR. METHODS: A retrospective study of 289 in vitro fertilization (IVF) cycles from April 2016 to June 2022 was performed. Propensity score matching (PSM) was used to balance the baseline characteristics between the two groups at a ratio of 1:1. RESULTS: After matching, there were 87 cycles in the PPOS group and 87 cycles in the antagonist group. The primary outcome measures included the incidence of premature LH surge, the number of retrieved oocytes, and the number of mature oocytes, which were comparable between the two groups (all P values >0.05). There were no significant differences in laboratory indicators and final clinical outcomes between the two groups (all P values >0.05). CONCLUSIONS: For DOR patients aged 35 years or older, the number of retrieved oocytes and the number of mature oocytes were comparable between the PPOS and antagonist groups. Moreover, the two regimens showed no difference in the inhibition of premature LH surge.

Nicotinamide Mononucleotide improves oocyte maturation of mice with type 1 diabetes.

BACKGROUND: The number of patients with type 1 diabetes rises rapidly around the world in recent years. Maternal diabetes has a detrimental effect on reproductive outcomes due to decreased oocyte quality. However, the strategies to improve the oocyte quality and artificial reproductive technology (ART) efficiency of infertile females suffering from diabetes have not been fully studied. In this study, we aimed to examine the effects of nicotinamide mononucleotide (NMN) on oocyte maturation of mouse with type 1 diabetes mouse and explore the underlying mechanisms of NMN's effect. METHODS: Streptozotocin (STZ) was used to establish the mouse models with type 1 diabetes. The successful establishment of the models was confirmed by the results of body weight test, fasting blood glucose test and haematoxylin and eosin (H&E) staining. The in vitro maturation (IVM) rate of oocytes from diabetic mice was examined. Immunofluorescence staining (IF) was performed to examine the reactive oxygen species (ROS) level, spindle/chromosome structure, mitochondrial function, actin dynamics, DNA damage and histone modification of oocytes, which are potential factors affecting the oocyte quality. The quantitative reverse transcription PCR (RT-qPCR) was used to detect the mRNA levels of Sod1, Opa1, Mfn2, Drp1, Sirt1 and Sirt3 in oocytes. RESULTS: The NMN supplementation increased the oocyte maturation rate of the mice with diabetes. Furthermore, NMN supplementation improved the oocyte quality by rescuing the actin dynamics, reversing meiotic defects, improving the mitochondrial function, reducing ROS level, suppressing DNA damage and restoring changes in histone modifications of oocytes collected from the mice with diabetes. CONCLUSION: NMN could improve the maturation rate and quality of oocytes in STZ-induced diabetic mice, which provides a significant clue for the treatment of infertility of the patients with diabetes.

Lead-free Cs2AgBiBr6 double perovskite microcrystals for effective visible-light photocatalytic thio/selenocyanation.

Lead-free perovskite microcrystals (MCs) have been regarded as promising potential photocatalysts, owing to their high molar extinction coefficient, low economic cost, adjustable light absorption range, and ample surface-active sites. Herein, C-3 thio/selenocyanation of indoles is demonstrated in high selectivity and yield by using lead-free double perovskite Cs2AgBiBr6 MCs under visible light irradiation. Moreover, the photocatalyst can be recycled at least 5 times without a significant decrease in catalytic activity.

Mouse Round Spermatid Injection.

Round spermatids, characterized by their haploid genetic content, represent the precursor cells to mature spermatozoa. Through the innovative technique of round spermatid injection (ROSI), oocytes can be successfully fertilized and developed into viable fetuses. In a groundbreaking milestone achieved in 1995, the first mouse fetus was born through ROSI technology. ROSI has since emerged as a pivotal tool for unraveling the intricate mechanisms governing embryonic development and holds significant potential in various applications, including the acceleration of mouse generation and the production of genetically modified mice. In 1996, a milestone was reached when the first human fetus was born through ROSI technology. However, the clinical applications of this method have shown a fluctuating pattern of success and failure. To date, ROSI technology has not found widespread application in clinical practice, primarily due to its low birth efficiency and insufficient validation of fetal safety. This article provides a comprehensive account of the precise methods of performing ROSI in mice, aiming to shed new light on basic research and its potential clinical applications.

Multi-centers experience using therapeutic plasma exchange for corticosteroid/tocilizumab-refractory cytokine release syndrome following CAR-T therapy.

The chimeric antigen receptor T (CAR-T) cell therapy significantly enhances the prognosis of various hematologic malignancies; however, the systemic expansion of CAR-T cells also gives rise to severe cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS). Despite the successful application of corticosteroids and tocilizumab in alleviating severe CRS in most patients, there are still individuals who experience life-threatening CRS without responding to the aforementioned therapies. In our retrospective cohort, we conducted an analysis of clinical and laboratory parameters, including inflammatory cytokines, in 17 patients from three centers who underwent therapeutic plasma exchange (TPE) for refractory CRS with or without ICANS following CAR-T products treatment. Our findings demonstrate a significant improvement in both clinical symptoms and laboratory parameters subsequent to TPE treatment. The rapid decrease in temperature and levels of inflammatory indexes indicates the remarkable scavenging efficacy of TPE against cytokine storm following CAR-T therapy. In conclusion, TPE may serve as a valuable and safe adjunct to corticosteroids and tocilizumab in the management of severe CRS resulting from CAR-T cell infusion. We eagerly await further prospective studies to validate this finding.

Neutral nickel-catalyzed dehydrosulfonylation of unactivated allylic alcohols under mild conditions.

Allyl sulfones are important sulfur-containing compounds that have widespread applications in organic synthesis, medicinal chemistry and materials science. Herein, nickel-catalysed dehydrosulfonylation of unactivated allyl alcohols with aryl sulfonyl hydrazides without additional active agents under mild conditions was developed. A variety of functional allyl sulfones could be efficiently synthesized in the presence of air-stable Ni(acac)2 as the catalyst and 1,1'-bis(diphenylphosphino)ferrocene (DPPF) as the ligand.

Modified EASIX scores predict severe CRS/ICANS in patients with acute myeloid leukemia following CLL1 CAR-T cell therapy.

Chimeric antigen receptor T (CAR-T) cell therapy targeting CLL1 has been considered a potent weapon for patients with acute myeloid leukemia (AML). This study aims to evaluate the efficacy and toxicity of CLL1 CAR-T cell therapy in a larger cohort, with particular attention to cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Among the 32 patients assessed for efficacy, complete remission occurred in 71.88% (23/32) of cases and undetectable minimal residual disease in 14 patients. The CRS developed in all patients, with 8 individuals experiencing ICANS. Severe CRS and ICANS were observed in 11 and 2 patients, respectively. Furthermore, the Endothelial Activation and Stress Index (EASIX) and its derivatives measured before and after CLL1 CAR-T cell infusion were employed for predicting the severe complications. Significant differences were observed in EASIX scores on the day before lymphodepletion (Day BL, P = 0.023), -1 (P < 0.001), +1 (P < 0.001), and +3(P = 0.014); sEASIX scores on Day BL (P = 0.007), -1 (P < 0.001), +1 (P < 0.001), and +3 (P < 0.001); and mEASIX score on Day -1 (P = 0.004) between patients with mild and severe CRS/ICANS. Additionally, there was a significant difference in mEASIX scores between responders and non-responders on Day BL (P = 0.004) and Day -1 (P = 0.044). Our findings indicate that pre- and post-infusion assessments of EASIX/mEASIX/sEASIX scores serve as reliable prognostic indicators for severe CRS/ICANS and treatment response following CLL1 CAR-T cell therapy, which can assist physicians in implementing preemptive treatment strategies for potential severe complications and screening patients who are suitable candidates for CLL1 CAR-T cell therapy. EASIX/mEASIX/sEASIX scores serve as reliable prognostic indicators for severe CRS/ICANS following CLL1 CAR-T cell therapy. The preinfusion mEASIX scores of CLL1 CAR-T cells can effectively predict treatment response.