Extracellular cold-inducible RNA-binding protein mediated neuroinflammation and neuronal apoptosis after traumatic brain injury.

Background: Extracellular cold-inducible RNA-binding protein (eCIRP) plays a vital role in the inflammatory response during cerebral ischaemia. However, the potential role and regulatory mechanism of eCIRP in traumatic brain injury (TBI) remain unclear. Here, we explored the effect of eCIRP on the development of TBI using a neural-specific CIRP knockout (KO) mouse model to determine the contribution of eCIRP to TBI-induced neuronal injury and to discover novel therapeutic targets for TBI. Methods: TBI animal models were generated in mice using the fluid percussion injury method. Microglia or neuron lines were subjected to different drug interventions. Histological and functional changes were observed by immunofluorescence and neurobehavioural testing. Apoptosis was examined by a TdT-mediated dUTP nick end labelling assay in vivo or by an annexin-V assay in vitro. Ultrastructural alterations in the cells were examined via electron microscopy. Tissue acetylation alterations were identified by non-labelled quantitative acetylation via proteomics. Protein or mRNA expression in cells and tissues was determined by western blot analysis or real-time quantitative polymerase chain reaction. The levels of inflammatory cytokines and mediators in the serum and supernatants were measured via enzyme-linked immunoassay. Results: There were closely positive correlations between eCIRP and inflammatory mediators, and between eCIRP and TBI markers in human and mouse serum. Neural-specific eCIRP KO decreased hemispheric volume loss and neuronal apoptosis and alleviated glial cell activation and neurological function damage after TBI. In contrast, eCIRP treatment resulted in endoplasmic reticulum disruption and ER stress (ERS)-related death of neurons and enhanced inflammatory mediators by glial cells. Mechanistically, we noted that eCIRP-induced neural apoptosis was associated with the activation of the protein kinase RNA-like ER kinase-activating transcription factor 4 (ATF4)-C/EBP homologous protein signalling pathway, and that eCIRP-induced microglial inflammation was associated with histone H3 acetylation and the α7 nicotinic acetylcholine receptor. Conclusions: These results suggest that TBI obviously enhances the secretion of eCIRP, thereby resulting in neural damage and inflammation in TBI. eCIRP may be a biomarker of TBI that can mediate the apoptosis of neuronal cells through the ERS apoptotic pathway and regulate the inflammatory response of microglia via histone modification.

Extended Black Hole Thermodynamics from Extended Iyer-Wald Formalism.

In recent years, there has been significant interest in the field of extended black hole thermodynamics, where the cosmological constant and/or other coupling parameters are treated as thermodynamic variables. Drawing inspiration from the Iyer-Wald formalism, which reveals the intrinsic and universal structure of conventional black hole thermodynamics, we illustrate that a proper extension of this formalism also unveils the underlying theoretical structure of extended black hole thermodynamics. As a remarkable consequence, for any gravitational theory described by a diffeomorphism invariant action, it is always possible to construct a consistent extended thermodynamics using this extended formalism.

The regrouping of Luminal B (HER2 negative), a better discriminator of outcome and recurrence score.

BACKGROUND: Breast cancer (BC) remains the leading cause of cancer-related deaths worldwide. High recurrence risk Luminal BC receives adjuvant chemotherapy in addition to standard hormone therapy. Considering the heterogeneity of Luminal B BC, a more accurate classification model is urgently needed. METHODS: In this study, we retrospectively reviewed the data of 1603 patients who were diagnosed with HER2-negative breast invasive ductal carcinoma. According to the expression level of PR and Ki-67 index, the Luminal B (HER2-negative) BCs were divided into three groups: ER+PR-Ki67low (ER-positive, PR-negative, and Ki-67 index <20%), ER+PR+Ki67high (ER-positive, PR-positive, and Ki-67 index ≥20%), and ER+PR-Ki67high (ER-positive, PR-negative, and Ki-67 index ≥20%). The cox proportional hazards regression model was used to evaluate the correlation between each variable and outcomes. Besides, discriminatory accuracy of the models was compared using the area under the receiver operating characteristic curve and log-rank χ2 value. RESULTS: The analysis results showed that there was a significant correlation between subtypes using this newly defined classification and overall survival (p < 0.001) and disease-free survival (DFS) (p < 0.001). Interestingly, patients in the ER+PR-Ki67high subgroup have the worst survival outcome in Luminal B (HER2-negative) subtype, similar to Triple-negative patients. Besides, the ER+PR+Ki67high has worse 5-year DFS compared with Luminal A group. There was a significant relationship between the regrouping subtype and the recurrence score index (RI) (p < 0.001). Moreover, the results showed that patients in ER+PR-Ki67high subtype were more likely to have high RI for distance recurrence (RI-DR) and local recurrence (RI-LRR). Our newly defined classification has a better discrimination ability to predict survival outcome and recurrence score of Luminal B (HER2-negative) BC patients, which may help in clinical decision-making for individual treatment.

Worldwide productivity and research trend of publications concerning glioma-associated macrophage/microglia: A bibliometric study.

Glioma-associated macrophage/microglia (GAM) represents a key player in shaping a unique glioma ecosystem to facilitate tumor progression and therapeutic resistance. Numerous studies have been published concerning GAM, but no relevant bibliometric study has been performed yet. Our bibliometric study aimed to comprehensively summarize and analyze the global scientific output, research hotspots, and trendy topics of publications on GAM over time. Data on publications on GAM were collected using the Web of Science (WoS). The search date was 16 January 2022, and the publications were collected from 2002 to 2021. Totally, 1,224 articles and reviews were incorporated and analyzed in the current study. It showed that the annual publications concerning GAM kept increasing over the past 20 years. The United States had the largest number of publications and total citations. Holland, Kettenmann, and Gutmann were the top three authors in terms of citation frequency. Neuro-oncology represented the most influential journal in GAM studies, with the highest H-index, total citations, and publication numbers. The paper published by Hambardzumyan in 2016 had the highest local citations. Additionally, the analysis of keywords implied that "prognosis," "tumor microenvironment," and "immunotherapy" might become research hotspots. Furthermore, trendy topics in GAM studies suggested that "immune infiltration," "immune microenvironment," "bioinformatics," "prognosis," and "immunotherapy" deserved additional attention. In conclusion, this bibliometric study comprehensively analyzed the publication trend of GAM studies for the past 20 years, in which the research hotspots and trendy topics were also uncovered. This information offered scholars critical references for conducting in-depth studies on GAM in the future.

Black Hole Solutions as Topological Thermodynamic Defects.

In this Letter, employing the generalized off-shell free energy, we treat black hole solutions as defects in the thermodynamic parameter space. The results show that the positive and negative winding numbers corresponding to the defects indicate the local thermodynamical stable and unstable black hole solutions, respectively. The topological number defined as the sum of the winding numbers for all the black hole branches at an arbitrary given temperature is found to be a universal number independent of the black hole parameters. Moreover, this topological number only depends on the thermodynamic asymptotic behaviors of the black hole temperature at small and large black hole limits. Different black hole systems are characterized by three classes via this topological number. This number could help us in better understanding the black hole thermodynamics and, further, shed new light on the fundamental nature of quantum gravity.

Cell Heterogeneity Uncovered by Single-Cell RNA Sequencing Offers Potential Therapeutic Targets for Ischemic Stroke.

Ischemic stroke is a detrimental neurological disease characterized by an irreversible infarct core surrounded by an ischemic penumbra, a salvageable region of brain tissue. Unique roles of distinct brain cell subpopulations within the neurovascular unit and peripheral immune cells during ischemic stroke remain elusive due to the heterogeneity of cells in the brain. Single-cell RNA sequencing (scRNA-seq) allows for an unbiased determination of cellular heterogeneity at high-resolution and identification of cell markers, thereby unveiling the principal brain clusters within the cell-type-specific gene expression patterns as well as cell-specific subclusters and their functions in different pathways underlying ischemic stroke. In this review, we have summarized the changes in differentiation trajectories of distinct cell types and highlighted the specific pathways and genes in brain cells that are impacted by stroke. This review is expected to inspire new research and provide directions for investigating the potential pathological mechanisms and novel treatment strategies for ischemic stroke at the level of a single cell.

Neuroimmune Regulation in Sepsis-Associated Encephalopathy: The Interaction Between the Brain and Peripheral Immunity.

Sepsis-associated encephalopathy (SAE), the most popular cause of coma in the intensive care unit (ICU), is the diffuse cerebral damage caused by the septic challenge. SAE is closely related to high mortality and extended cognitive impairment in patients in septic shock. At present, many studies have demonstrated that SAE might be mainly associated with blood-brain barrier damage, abnormal neurotransmitter secretion, oxidative stress, and neuroimmune dysfunction. Nevertheless, the precise mechanism which initiates SAE and contributes to the long-term cognitive impairment remains largely unknown. Recently, a growing body of evidence has indicated that there is close crosstalk between SAE and peripheral immunity. The excessive migration of peripheral immune cells to the brain, the activation of glia, and resulting dysfunction of the central immune system are the main causes of septic nerve damage. This study reviews the update on the pathogenesis of septic encephalopathy, focusing on the over-activation of immune cells in the central nervous system (CNS) and the "neurocentral-endocrine-immune" networks in the development of SAE, aiming to further understand the potential mechanism of SAE and provide new targets for diagnosis and management of septic complications.

Small RNA and Degradome Sequencing Reveal Important MicroRNA Function in Nicotiana tabacum Response to Bemisia tabaci.

MicroRNAs (miRNAs), a class of small non-coding regulatory RNAs, are key molecules in many biological and metabolic processes of plant growth, development and stress response via targeting mRNAs. The phloem-feeding insect whitefly Bemisia tabaci (Hemiptera, Aleyrodidae) is a serious pest that causes devastating harm to agricultural production worldwide. However, the function of host miRNAs in the response to whitefly infestation remains unclear. Here, we sequenced the small RNA and degradome of tobacco (Nicotiana tabacum L.), after and before infestation by B. tabaci. We identified 1291 miRNAs belonging to 138 miRNA families including 706 known miRNAs and 585 novel miRNAs. A total of 47 miRNAs were differentially expressed, of which 30 were upregulated and 17 were downregulated by whitefly exposure. Then, computational analysis showed that the target genes of differential miRNAs were involved in R gene regulation, plant innate immunity, plant pathogen defense, the plant hormone signal pathway and abiotic stress tolerance. Furthermore, degradome analysis demonstrated that 253 mRNAs were cleaved by 66 miRNAs. Among them, the targets cleaved by upregulated miR6025, miR160, miR171, miR166 and miR168 are consistent with our prediction, suggesting that pathogen-related miRNAs may function in plant defense against whitefly. Moreover, our results show that plant miRNA response and miRNA-mediated post-transcriptional regulation for phloem-feeding insect infestation are similar to pathogen invasion. Our study provides additional data to further elucidate how host plants respond and defend the phloem-feeding insects.

Primary Exploration of the Clinical Application of 3D-Printed Complete Dentures.

PURPOSE: To explore the applications of 3D scanning and 3D printing techniques in the restorative treatment of edentulous patients. MATERIALS AND METHODS: A total of 30 edentulous patients (Atwood classes 1 to 4) who visited The 960th Hospital of the People's Liberation Army, Jinan, China, from March 1, 2018 to May 1, 2020 were selected, and the patients were randomly divided into two groups: a traditional complete denture group (group A) and a 3D-printed complete denture group (group B). Each group comprised 15 patients. In group A, the traditional method was used to fabricate complete dentures. In group B, 3D scanning, computer-aided design (CAD), 3D printing, and the duplicate denture technique were used to fabricate the dentures. A single-blinded method was used. Patient satisfaction was measured with a 0-10 visual analog scale (VAS) at four time points: immediately and 1 month, 3 months, and 6 months after denture delivery. SPSS version 22.0 software was used to analyze the data. RESULTS: The ability to speak, ability to chew, and comfort in the two groups gradually improved at the first three time points. VAS scores increased to a satisfactory level after 3 months. The esthetics and stability of the two groups were scored high after the initial delivery. The VAS scores of the two groups regarding esthetics, ability to speak, ability to chew, stability, and comfort were not significantly different (P > .05) at any time point. The number of visits in the 3D-printed complete denture group were significantly decreased in comparison to the traditional group. CONCLUSION: The use of 3D printing for manufacturing complete dentures can rapidly restore edentulous patients and meet patient demands regarding esthetics and function.

[Biological functions of CREB/ATF bZIP transcription factor in metabolism and cell growth].

Nutrient overload-caused deregulation of glucose and lipid metabolism leads to insulin resistance and metabolic disorders, which increases the risk of several types of cancers. CREB/ATF bZIP transcription factor (CREBZF), a novel transcription factor of the ATF/CREB family, has emerged as a critical mechanism bridging the gap between metabolism and cell growth. CREBZF forms a heterodimer with other proteins and functions as a coregulator for gene expression. CREBZF deficiency in the liver attenuates hepatic steatosis in high fat diet-induced insulin-resistant mice, while the expression levels of CREBZF are increased in the livers of obese mice and humans with hepatic steatosis. Intriguingly, CREBZF also regulates cell proliferation and apoptosis via interaction with several transcription factors including STAT3, p53 and HCF-1. Knockout of CREBZF in hepatocytes results in enhanced cell cycle progression and proliferation capacity in mice. Here we highlight how the CREBZF signaling network contributes to the deregulation of metabolism and cell growth, and discuss the potential of targeting these molecules for the treatment of insulin resistance, diabetes, fatty liver disease and cancer.

SCSit: A high-efficiency preprocessing tool for single-cell sequencing data from SPLiT-seq.

SPLiT-seq provides a low-cost platform to generate single-cell data by labeling the cellular origin of RNA through four rounds of combinatorial barcoding. However, an automatic and rapid method for preprocessing and classifying single-cell sequencing (SCS) data from SPLiT-seq, which directly identified and labeled combinatorial barcoding reads and distinguished special cell sequencing data, is currently lacking. Here, we develop a high-efficiency preprocessing tool for single-cell sequencing data from SPLiT-seq (SCSit), which can directly identify combinatorial barcodes and UMI of cell types and obtain more labeled reads, and remarkably enhance the retained data from SCS due to the exact alignment of insertion and deletion. Compared with the original method used in SPLiT-seq, the consistency of identified reads from SCSit increases to 97%, and mapped reads are twice than the original. Furthermore, the runtime of SCSit is less than 10% of the original. It can accurately and rapidly analyze SPLiT-seq raw data and obtain labeled reads, as well as effectively improve the single-cell data from SPLiT-seq platform. The data and source of SCSit are available on the GitHub website https://github.com/shang-qian/SCSit.

Lipid accumulation and novel insight into vascular smooth muscle cells in atherosclerosis.

Atherosclerosis is a chronic and progressive process. It is the most important pathological basis of cardiovascular disease and stroke. Vascular smooth muscle cells (VSMCs) are an essential cell type in atherosclerosis. Previous studies have revealed that VSMCs undergo phenotypic transformation in atherosclerosis to participate in the retention of atherogenic lipoproteins as well as the formation of the fibrous cap and the underlying necrotic core in plaques. The emergence of lineage-tracing studies indicates that the function and number of VSMCs in plaques have been greatly underestimated. In addition, recent studies have revealed that VSMCs make up at least 50% of the foam cell population in human and mouse atherosclerotic lesions. Therefore, understanding the formation of lipid-loaded VSMCs and their regulatory mechanisms is critical to elucidate the pathogenesis of atherosclerosis and to explore potential therapeutic targets. Moreover, combination of many complementary technologies such as lineage tracing, single-cell RNA sequencing (scRNA-seq), flow cytometry, and mass cytometry (CyTOF) with immunostaining has been performed to further understand the complex VSMC function. Correct identification of detrimental and beneficial processes may reveal successful therapeutic treatments targeting VSMCs and their derivatives during atherosclerosis. The purpose of this review is to summarize the process of lipid-loaded VSMC formation in atherosclerosis and to describe novel insight into VSMCs gained by using multiple advanced methods.

Repulsive Interactions and Universal Properties of Charged Anti-de Sitter Black Hole Microstructures.

The Ruppeiner geometry of thermodynamic fluctuations provides a powerful diagnostic of black hole microstructures. We investigate this for charged anti-de Sitter black holes and find that, while an attractive microstructure interaction dominates for most parameter ranges, a weak repulsive interaction dominates for small black holes of high temperature. This unique property distinguishes the black hole system from that of a van der Waals fluid, where only attractive microstructure interactions are found. We also find two other novel universal properties for charged black holes. One is that the repulsive interaction is independent of the black hole charge and temperature. The other is that the behavior of the Ruppeiner curvature scalar near criticality is characterized by a dimensionless constant that is identical to that for a van der Waals fluid, providing us with new insight into black hole microstructures.

CIRP regulates BEV-induced cell migration in gliomas.

PURPOSE: A better understanding of the underlying molecular mechanisms in treatment failure of bevacizumab (BEV) for malignant glioma would contribute to overcome therapeutic resistance. METHODS: Here, we used a quantitative proteomic method to identify molecular signatures of glioblastoma cell after BEV treatment by two-dimensional liquid chromatography-tandem mass spectrometry analysis and 6-plex iTRAQ quantification. Next, the function of cold-inducible RNA-binding protein (CIRP), one of the most significantly affected proteins by drug treatment, was evaluated in drug resistance of glioma cells by invasion assays and animal xenograft assays. Target molecules bound by CIRP were determined using RNA-binding protein immunoprecipitation and microarray analysis. Then, these mRNAs were identified by quantitative real-time PCR. RESULTS: Eighty-seven proteins were identified with significant fold changes. The biological functional analysis indicated that most of the proteins were involved in the process of cellular signal transduction, cell adhesion, and protein transport. The expression of CIRP greatly decreased after BEV treatment, and ectopic expression of CIRP abolished cell migration in BEV-treated glioma cells. In addition, CIRP could bind mRNA of CXCL12 and inhibit BEV-induced increase of CXCL12 in glioma cells. CONCLUSION: These data suggested that CIRP may take part in BEV-induced migration of gliomas by binding of migration-relative RNAs.

Highly efficient conversion of 1-cyanocycloalkaneacetonitrile using a "super nitrilase mutant".

Nitrilase is the member of carbon-nitrogen hydrogen hydrolase superfamily, which has been widely used for the hydrolysis of nitriles into corresponding carboxylic acids. But most nitrilases are plagued by product inhibition in the industrial application. In this study, a "super nitrilase mutant" of nitrilase with high activity, thermostability and improved product tolerance from Acidovorax facilis ZJB09122 was characterized. Then, an efficient process was developed by employing the whole cell of recombinant E. coli for the conversion of high concentration of 1-cyanocyclohexylacetonitrile-to-1-cyanocyclohexaneacetic acid, an important intermediate of gabapentin. Under the optimized conditions, the higher substrate concentrations such as 1.3 M, 1.5 M and 1.8 M could be hydrolyzed by 13.58 g DCW/L with outstanding productivity (> 740 g/L/day). This study developed a highly efficient bioprocess for the preparation of 1-cyanocyclohexaneacetic acid which has the great potential for industrial application.

Delivery of bevacizumab by intracranial injection: assessment in glioma model.

BACKGROUND: Many reports have indicated that the intravenous administration of bevacizumab produces a number of systemic side effects. Therefore, we investigated the therapeutic effects of intratumoral bevacizumab administration using a glioma animal model. METHODS: The glioma cell lines U251 and U87 that carried luciferase were implanted into the brains of mice to develop glioma models. Glioma-bearing mice were treated with bevacizumab intravenously or intratumorally by Alzet micro-osmotic pumps, and the survival time of mice was monitored. Tumor volumes and location were observed by fluorescence imaging and histological analysis. Levels of microvessel marker, cancer stem cell marker as well as angiogenesis-, invasion-, and inflammation-related factors in tumors were examined by immunohistochemical staining. RESULTS: Mice treated with intratumoral low-dose bevacizumab had smaller tumor volumes, longer survival time, lower microvessel density, and fewer cancer stem cells as compared with untreated and intravenously treated mice. Furthermore, expression levels of inflammation-related factors increased signifiwhereas that of angiogenesis- and invasion-related factors decreased in intratumorally treated animals, compared with intravenously treated mice. CONCLUSION: These results implied bevacizumab delivery by intratumoral injection via Alzet micro-osmotic pumps may be a more effective and safer protocol for treating gliomas.

Effects of Four Different Crown Materials on the Peri-Implant Clinical Parameters and Composition of Peri-Implant Crevicular Fluid.

This study aimed to identify the preferred crown material by measuring the peri-implant clinical parameters and the concentrations of receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), and calcium in peri-implant crevicular fluid (PICF) with 4 different crown materials. A total of 196 patients with a single missing posterior tooth received crown restoration with cobalt-chromium (Co-Cr) porcelain-fused-to-metal (PFM; n = 50), aurum platinum (Au-Pt) PFM (n = 48), titanium (Ti) PFM (n = 52), or zirconia (Zi) all-ceramic crown (n = 46). Fifty-one natural counterpart teeth served as controls. Before and 12 months after restoration, the PICF was collected, and the concentrations of RANKL, OPG, and calcium were quantified. The peri-implant clinical parameters (plaque index, bleeding on probing, and probing depth [PD]) and gingival crevicular fluid (GCF) volumes were assessed. Twelve months after restoration, the PD and GCF volumes for the 4 experimental groups were significantly greater than those for the control group and before restoration. The Co-Cr group showed the greatest PD, GCF volume, RANKL/OPG, RANKL, and calcium ion concentration, followed by the Au-Pt group. The Ti group had the highest OPG concentration, followed by the Zi group. The RANKL and calcium ion concentrations of the Ti and Zi groups were the smallest. The Ti group had the smallest RANKL/OPG ratio, followed by the Zi group. Different crown materials differentially affected the PD, volume, RANKL/OPG ratio, OPG, RANKL, and calcium concentration. Among the 4 tested crown materials, Zi and Ti are preferred. However, some limitations of the present study should be considered.

Immunogenicity and Protective Efficacy of a Fusion Protein Tuberculosis Vaccine Combining Five Esx Family Proteins.

One strategy to develop the next generation of tuberculosis vaccines is to construct subunit vaccines based on T cell antigens. In this study, we have evaluated the vaccine potential of a fusion protein combining EsxB, EsxD, EsxG, EsxU, and EsxM of Mycobacterium tuberculosis (M. tb). This recombinant protein, named BM, was expressed in and purified from Escherichia coli. Immunization of C57BL/6 mice with purified BM protein formulated in Freund's incomplete adjuvant induced the production of Th1 cytokines (IFN-γ, TNF, and IL-2) and multifunctional CD4+ T cells. Vaccination of BALB/c mice with BM protein followed by intravenous challenge with Mycobacterium bovis BCG resulted in better levels of protection than the two leading antigens, Ag85A and PPE18. Taken together, these results indicate that BM is a protective antigen. Future studies to combine BM with other antigens and evaluate its effectiveness as a booster of BCG or as a therapeutic vaccine are warranted.

MiR-124-3p/B4GALT1 axis plays an important role in SOCS3-regulated growth and chemo-sensitivity of CML.

BACKGROUND: Abnormal expression of SOCS3 has been implicated in myeloproliferative neoplasms, but the role of SOCS3 in the pathogenesis of leukemia remains largely unknown. Here, we examined the function of SOCS3 in the growth and chemo-sensitivity of chronic myeloid leukemia (CML) and explored the involved mechanisms. METHODS: Expression levels of SOCS3 in several leukemia cell lines and bone marrow mononuclear cells (BMNCs) from CML patients were determined using quantitative real-time PCR (qPCR) and Western blotting (WB). The roles of SOCS3 in the proliferation, apoptosis, and drug resistance of CML cells were examined by clonogenic progenitor cell assay, flow cytometry, and CCK-8 assay. A detailed analysis of the underlying mechanism of SOCS3 in K562 cells was performed using the Human HT-12 v4 Expression BeadChip, which has more than 48000 gene probes including 600 microRNAs (miRNA) probes. The correlation between the mRNA expression of SOCS3 and miR-124-3p in BMNCs from 30 CML patients was tested by qPCR and analyzed by Pearson correlation and linear regression analysis. The potential target of miR-124-3p in CML cells was explored using the luciferase reporter assay, qPCR, and WB. The effect of SOCS3 on the miR-124-3p/B4GALT1 axis was investigated by qPCR, WB, CCK-8 assay, and tumorigenicity assays in nude mice. RESULTS: SOCS3 was down-regulated in CML cell lines and most of BMNCs from CML patients, and the expression level of SOCS3 was associated with the inhibition of cell proliferation and drug resistance of CML cells. Over-expression of SOCS3 in K562 cells inhibited the expression of leukemia-specific genes and promoted the expression of some miRNAs, among which miR-124-3p was the highest. SOCS3 over-expression enhanced the expression of miR-124-3p and vice versa. The mRNA expression of miR-124-3p and SOCS3 in BMNCs from 30 CML patients was positively correlated. Consistently, the tumor suppressing effects of SOCS3 were partially neutralized by the miR-124-3p inhibitor. B4GALT1 was downstream of miR-124-3p and regulated by SOCS3/miR-124-3p in vitro. Furthermore, SOCS3 over-expression could inhibit the growth and B4GALT expression of K562 cells in vivo. CONCLUSIONS: SOCS3/miR-124-3p/B4GALT1 axis plays an important role in the pathogenesis of CML.