The Added Value of a Computer-Aided Diagnosis System in Differential Diagnosis of Breast Lesions by Radiologists With Different Experience.

OBJECTIVES: To evaluate the value of the computer-aided diagnosis system, S-Detect (based on deep learning algorithm), in distinguishing benign and malignant breast masses and reducing unnecessary biopsy based on the experience of radiologists. METHODS: From February 2018 to March 2019, 266 breast masses in 192 women were included in our study. Ultrasound (US) examination, including S-Detect technique, was performed by the radiologist with about 10 years of clinical experience in breast US imaging. US images were analyzed by four other radiologists with different experience in breast imaging (radiologists 1, 2, 3, and 4 with 1, 4, 9, and 20 years, respectively) according to their clinical experience (with and without the results of S-Detect). Diagnostic capabilities and unnecessary biopsy of radiologists and radiologists combined with S-Detect were compared and analyzed. RESULTS: After referring to the results of S-Detect, the changes made by less experienced radiologists were greater than experienced radiologists (benign or malignant, 44 vs 22 vs 14 vs 2; unnecessary biopsy, 34 vs 25 vs 10 vs 5). When combined with S-Detect, less experienced radiologists showed significant improvement in accuracy, specificity, positive predictive value, negative predictive value, and area under curve (P < .05), but not for experienced radiologists (P > .05). Similarly, the unnecessary biopsy rate of less experienced radiologists decreased significantly (44.4% vs 32.7%, P = .006; 36.8% vs 28.2%, P = .033), but not for experienced radiologists (P > .05). CONCLUSIONS: Less experienced radiologists rely more on S-Detect software. And S-Detect can be an effective decision-making tool for breast US, especially for less experienced radiologists.

Bromodomains and Extra-Terminal (BET) Inhibitor JQ1 Suppresses Proliferation of Acute Lymphocytic Leukemia by Inhibiting c-Myc-Mediated Glycolysis.

BACKGROUND Acute lymphocytic leukemia (ALL) is a common blood cancer which induces high mortality in children. Bromodomains and extra-terminal (BET) protein inhibitors, such as JQ1 and ARV-825, are promising cancer therapeutic agents that can be used by targeting c-Myc. A recent work reported that JQ1 effectively attenuates ALL in vitro by suppressing cell proliferation and accelerating apoptosis. The purpose of this research was to probe into the potential mechanism of how JQ1 inhibits ALL cell proliferation in vitro. MATERIAL AND METHODS Cell viability of ALL cells were measured by CTG after treatment by JQ1. Cell cycle analysis was done by EdU and PI staining. Cell apoptosis was assessed by Annexin V/PI staining. Glycolysis was detected using Seahorse and LC-MS kits. The expression of glycolytic rate-limiting enzymes was assessed by RNA-seq, qRT-PCR, and Western blot. RESULTS JQ1 suppressed cell proliferation by arresting the cell cycle and inducing the apoptosis of acute lymphocytic leukemia cells. JQ1 inhibited cell proliferation of B-ALL cells by restraining glycolysis. Conversely, the cell cycle block of B-ALL cells induced by JQ1 was partially abolished after pretreatment with 2-Deoxy-D-glucose (2-DG), an inhibitor of glycolysis. Furthermore, JQ1 restrained the glycolysis of B-ALL cell lines by remarkably downregulating the rate-limiting enzymes of glycolysis, such as hexokinase 2, phosphofructokinase, and lactate dehydrogenase A. Moreover, the cell cycle arrest was reversed in B-ALL cells with overexpressed c-Myc treated by JQ1, which is involved in the enhancement of glycolysis. CONCLUSIONS The BET inhibitor JQ1 suppresses the proliferation of ALL by inhibiting c-Myc-mediated glycolysis, thus providing a new strategy for the treatment of ALL.

Pharmacological Inhibition of TFF3 Enhances Sensitivity of CMS4 Colorectal Carcinoma to 5-Fluorouracil through Inhibition of p44/42 MAPK.

Increased expression of trefoil factor 3 (TFF3) has been reported in colorectal carcinoma (CRC), being correlated with distant metastasis and poor clinical outcomes. Amongst the CRC subtypes, mesenchymal (CMS4) CRC is associated with the worst survival outcome. Herein, the functional roles of TFF3 and the pharmacological inhibition of TFF3 by a novel specific small molecule TFF3 inhibitor-2-amino-4-(4-(6-fluoro-5-methylpyridin-3-yl)phenyl)-5-oxo-4H,5H-pyrano[3,2-c]chromene-3-carbonitrile (AMPC) in CMS4 CRC was explored. Forced expression of TFF3 in CMS4 CRC cells promoted cell proliferation, cell survival, foci formation, invasion, migration, cancer stem cell like behaviour and growth in 3D Matrigel. In contrast, siRNA-mediated depletion of TFF3 or AMPC inhibition of TFF3 in CMS4 CRC cells decreased oncogenic behaviour as indicated by the above cell function assays. AMPC also inhibited tumour growth in vivo. The TFF3-stimulated oncogenic behaviour of CMS4 CRC cells was dependent on TFF3 activation of the p44/42 MAPK (ERK1/2) pathway. Furthermore, the forced expression of TFF3 decreased the sensitivity of CMS4 CRC cells to 5-fluorouracil (5-FU); while depleted TFF3 expression enhanced 5-FU sensitivity in CMS4 CRC cells. 5-FU treatment induced TFF3 expression in CMS4 CRC cells. AMPC, when used in combination with 5-FU in CMS4 CRC cells exhibited a synergistic inhibitory effect. In summary, this study provides functional evidence for TFF3 as a therapeutic target in CMS4 CRC.

[Progress on in situ cell transdifferentiation in central nervous system].

Central nervous system injury leads to irreversible neuronal loss and glial scar formation, which ultimately results in persistent neurological dysfunction. Regenerative medicine suggests that replenishing missing neurons may be an ideal approach to repair the damage. Recent researches showed that many mature cells could be transdifferentiated into functional neurons by reprogramming. Therefore, reprogramming endogenous glia in situ to produce functional neurons shows great potential and unique advantage for repairing neuronal damage and treating neurodegenerative diseases. The present review summarized the current research progress on in situ transdifferentiation in the central nervous system, focusing on the cell types, characteristics and research progress of glial cells that could be transdifferentiated in situ, in order to provide theoretical basis for the development of new therapeutic strategies of neuronal injury and further clinical application.

Cytoplasmic glutamine synthetase gene expression regulates larval development in Bactrocera dorsalis (Hendel).

In insects, glutamine synthetase (GS), a key enzyme in the synthesis of glutamine, has been reported to be associated with embryonic development, heat shock response, and fecundity regulation. However, little is known about the influence of GS on postembryonic development. In this study, we demonstrate that blocking the activity of GS in the oriental fruit fly (Bactrocera dorsalis) with use of a GS-specific inhibitor (L-methionine S-sulfoximine), led to a significant delay in larval development, pupal weight loss, and inhibition of pupation. We further identify cloned and characterized two GS genes (BdGS-c and BdGS-m) from B. dorsalis. The two GS genes identified in B. dorsalis were predicted to be located in the cytosol (BdGS-c) and mitochondria (BdGS-m), and homology analysis indicated that both genes were similar to homologs from other Dipterans, such as Drosophila melanogaster and Aedes aegypti. BdGS-c was highly expressed in the larval stages, suggesting that cytosolic GS plays a predominant role in larval development. Furthermore, RNA interference experiments against BdGS-c, to specifically decrease the expression of cytosolic GS, resulted in delay in larval development as well as pupal weight loss. This study presents the prominent role played by BdGS-c in regulating larval development and suggests that the observed effect could have been modulated through ecdysteroid synthesis, agreeing with the reduced expression of the halloween gene spook. Also, the direct effects of BdGS-c silencing on B. dorsalis, such as larval lethality, delayed pupation, and late emergence, can be further exploited as novel insecticide target in the context of pest management.

Comparative Proteomic Profiling Reveals Molecular Characteristics Associated with Oogenesis and Oocyte Maturation during Ovarian Development of Bactrocera dorsalis (Hendel).

Time-dependent expression of proteins in ovary is important to understand oogenesis in insects. Here, we profiled the proteomes of developing ovaries from Bactrocera dorsalis (Hendel) to obtain information about ovarian development with particular emphasis on differentially expressed proteins (DEPs) involved in oogenesis. A total of 4838 proteins were identified with an average peptide number of 8.15 and sequence coverage of 20.79%. Quantitative proteomic analysis showed that a total of 612 and 196 proteins were differentially expressed in developing and mature ovaries, respectively. Furthermore, 153, 196 and 59 potential target proteins were highly expressed in early, vitellogenic and mature ovaries and most tested DEPs had the similar trends consistent with the respective transcriptional profiles. These proteins were abundantly expressed in pre-vitellogenic and vitellogenic stages, including tropomyosin, vitellogenin, eukaryotic translation initiation factor, heat shock protein, importin protein, vitelline membrane protein, and chorion protein. Several hormone and signal pathway related proteins were also identified during ovarian development including piRNA, notch, insulin, juvenile, and ecdysone hormone signal pathways. This is the first report of a global ovary proteome of a tephritid fruit fly, and may contribute to understanding the complicate processes of ovarian development and exploring the potentially novel pest control targets.

Proteo-genomic characterization of cirrhosis-associated liver cancers reveals potential subtypes and therapeutic targets.

BACKGROUND: This study aimed to identify potential subtypes of hepatocellular carcinoma (HCC) associated with cirrhosis and to investigate key markers using bioinformatic analysis of gene expression datasets-0. METHODS: Three data sets (GSE17548, GSE56140, and GSE87630) were extracted from the Gene Expression Omnibus (GEO) database and normalized using the Limma package in R. Principal component analysis (PCA) and cluster analysis was performed to examine data distribution and identify subtypes. Differential gene expression analysis was performed using the Limma software package. Protein-protein interaction analysis and functional annotation were performed using the STRING database and Cytoscape software. Important signaling pathways and processes were identified using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway Analysis. RESULTS: The analysis revealed different subtypes of HCC associated with cirrhosis and identified several key genes, including CCNB2, MCM4, and CDC20, with strong binding power and prognostic value. Functional annotation indicated involvement in cell cycle regulation and metabolic pathways. ROC analysis showed high sensitivity and specificity of these genes in predicting HCC prognosis. CONCLUSION: These results suggest that CCNB2, MCM4, and CDC20 may serve as potential biomarkers for predicting HCC prognosis in patients with cirrhosis and provide insights into the molecular mechanisms of HCC progression.

Ligand dose-dependent activation of signaling pathways through the gustatory receptor NlGr11 linked to feeding efficacy in Nilaparvata lugens.

Insects often face both conditions with sufficient nutrients and conditions of undernutrition in the field. Through gustatory receptors, insects sense nutrients and regulate their physiological functions such as feeding and reproduction. However, it remains unclear whether signaling pathways activated by gustatory receptors depend on the concentration of nutrients and whether the difference in signaling pathways directly affects insects' physiological functions. Herein, we found that a sugar gustatory receptor, NlGr11, from the brown planthopper (BPH), Nilaparvata lugens, activated G protein-coupled signaling and ionotropic pathways when bound to high galactose concentration. BPHs subsequently demonstrated longer feeding times, feeding loads, and higher vitellogenin (NlVg) expression than BPHs exposed to high galactose concentrations, which only activated the ionotropic pathway. For the first time, our findings link plant nutrient conditions, signaling pathways activated by nutrients, and their gustatory receptors, and nutrient dose-dependent feeding efficacy and vitellogenin (Vg) expression in an insect. This will help us to better understand the molecular mechanism for insect feeding strategies on plants at different stages of nutritional conditions.

Chronic hypotony management using endoscopy-assisted vitrectomy after severe ocular trauma or vitrectomy.

AIM: To report outcomes of endoscopy-assisted vitrectomy (EAV) in patients with chronic hypotony following severe ocular trauma or vitrectomy. METHODS: This was a retrospective, noncomparative case series. Ciliary bodies were evaluated using ultrasound biomicroscopy pre-operatively and direct visualisation intraoperatively. All selected individuals (seven patients/seven eyes) underwent EAV. Removal of ciliary membrane and traction, gas/silicone oil tamponade (GT/SOT), and scleral buckling (SB) were performed in selected eyes. Outcome measurements mainly included intraocular pressure (IOP) and best-corrected visual acuity (BCVA). RESULTS: Seven eyes from 7 male aphakic patients with a mean age of 45 (range, 20-68)y were included in this study; the average follow-up time was 12 (9-15)mo. GT was performed in 2 eyes; membrane peeling (MP) and SOT in 2 eyes; and MP, SOT, and SB in 3 eyes. The mean pre- and post-operative IOP were 4.5 (range, 4.0±0.11 to 4.8±0.2) mm Hg and 9.9 (range, 5.6±0.17 to 12.1±0.2) mm Hg at 52wk (12mo), respectively. BCVA improved in six eyes; one eye still showed light perception, and no bulbi phthisis was observed. CONCLUSION: Endoscopy offers improved judgment and recognition and has an improved prognosis for chronic hypotony. Therefore, endoscopy can be an effective and promising operative technique for chronic traumatic hypotony management.

Multicenter evaluation of a simple and sensitive nucleic acid self-testing for SARS-CoV-2.

A rapid and accurate COVID-19 diagnosis is a prerequisite for blocking the source of infection as soon as possible and taking the appropriate medical action. Herein, we developed GeneClick, a device for nucleic acid self-testing of SARS-CoV-2, consisting of three modules: a sampling kit, a microfluidic chip-based disposable cartridge, and an amplification reader. In addition, we evaluated the clinical performance of GeneClick using 2162 nasal swabs collected at three medical institutions, using three commercial RT-qPCR kits and an antigen self-test as references. Compared to RT-qPCR, the sensitivity and specificity of the GeneClick assay were 97.93% and 99.72%, respectively, with a kappa value of 0.979 (P â€‹< â€‹0.01). Of the 2162 samples, 2076 were also tested for SARS-CoV-2 antigens. Among the 314 positive samples identified by GeneClick assay, 63 samples were undetected by antigen tests. Overall, the GeneClick nucleic acid self-test demonstrated higher accuracy than the antigen-based detection. Based on the additional features, including simple operation, affordable price, portable device, and reliability of smartphone APP-driven sampling and result reporting, GeneClick offers a powerful tool for field-based SARS-CoV-2 detection in primary healthcare institutions or at-home use.

Comprehensive analysis of competitive endogenous RNA network in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. Growing evidence supports a role for noncoding RNAs (ncRNAs) in CRC. In particular, they form competitive endogenous RNA (ceRNA) networks involved in the regulation of mRNA expression. However, the role of these networks in the pathogenesis of CRC is not fully understood. The aim of this study was to elucidate the role of circRNA/lncRNA-miRNA-mRNA systems in CRC pathogenesis based on the construction of a ceRNA network. METHODS: RNA expression profiles were obtained from public datasets in the Gene Expression Omnibus (GEO) database and used for further analysis by online databases and tools. RESULTS: In total, 245 circRNAs, 1,666 lncRNAs, 5 miRNAs, and 934 mRNAs were differentially expressed in CRC samples. Functional enrichment analysis identified altered biological functions related to the mRNAs in the ceRNA network, and it was found that the oxytocin signaling pathway was significantly enriched (P<0.05) in genes with differential expression in CRC. Additionally, we established a protein-protein interaction (PPI) network and identified 10 hub genes for the construction of circRNA/lncRNA-miRNA-hub gene regulatory modules. CONCLUSIONS: We identified several ncRNAs with a possible pathogenetic role in CRC and built a CRC-specific ceRNA network. The results of our study provide novel insights into the molecular events implicated in CRC.

The value of S-Detect in improving the diagnostic performance of radiologists for the differential diagnosis of thyroid nodules.

AIMS: To compare the diagnostic value of S-Detect (a computer aided diagnosis system using deep learning) in differentiating thyroid nodules in radiologists with different experience and to assess if S-Detect can improve the diagnostic performance of radiologists. MATERIALS AND METHODS: Between February 2018 and October 2019, 204 thyroid nodules in 181 patients were included. An experienced radiologist performed ultrasound for thyroid nodules and obtained the result of S-Detect. Four radiologists with different experience on thyroid ultrasound (Radiologist 1, 2, 3, 4 with 1, 4, 9, 20 years, respectively) analyzed the conventional ultrasound images of each thyroid nodule and made a diagnosis of "benign" or "malignant" based on the TI-RADS category. After referring to S-Detect results, they re-evaluated the diagnoses. The diagnostic performance of radiologists was analyzed before and after referring to the results of S-Detect. RESULTS: The accuracy, sensitivity, specificity, positive predictive value and negative predictive value of S-Detect were 77.0, 91.3, 65.2, 68.3 and 90.1%, respectively. In comparison with the less experienced radiologists (radiologist 1 and 2), S-Detect had a higher area under receiver operating characteristic curve (AUC), accuracy and specificity (p <0.05). In comparison with the most experienced radiologist, the diagnostic accuracy and AUC were lower (p<0.05). In the less experienced radiologists, the diagnostic accuracy, specificity and AUC were significantly improved when combined with S-Detect (p<0.05), but not for experienced radiologists (radiologist 3 and 4) (p>0.05). CONCLUSIONS: S-Detect may become an additional diagnostic method for the diagnosis of thyroid nodules and improve the diagnostic performance of less experienced radiologists.

Reduced Glutamine Synthetase Activity Alters the Fecundity of Female Bactrocera dorsalis (Hendel).

Glutamine synthetase (GS) is a key enzyme in glutamine synthesis and is associated with multiple physiological processes in insects, such as embryonic development, heat shock response, and fecundity regulation. However, little is known about the influence of GS on female fecundity in the oriental fruit fly, Bactrocera dorsalis. Based on the cloning of BdGSs, mitochondrial BdGSm and cytoplasmic BdGSc, we determined their expressions in the tissues of adult B. dorsalis. BdGSm was highly expressed in the fat body, while BdGSc was highly expressed in the head and midgut. Gene silencing by RNA interference against two BdGSs isoforms suppressed target gene expression at the transcriptional level, leading to a reduced ovarian size and lower egg production. The specific inhibitor L-methionine S-sulfoximine suppressed enzyme activity, but only the gene expression of BdGSm was suppressed. A similar phenotype of delayed ovarian development occurred in the inhibitor bioassay. Significantly lower expression of vitellogenin and vitellogenin receptor was observed when GS enzyme activity was suppressed. These data illustrate the effects of two GS genes on adult fecundity by regulating vitellogenin synthesis in different ways.

Blocking ATM-dependent NF-κB pathway overcomes niche protection and improves chemotherapy response in acute lymphoblastic leukemia.

Bone marrow (BM) niche responds to chemotherapy-induced cytokines secreted from acute lymphoblastic leukemia (ALL) cells and protects the residual cells from chemotherapeutics in vivo. However, the underlying molecular mechanisms for the induction of cytokines by chemotherapy remain unknown. Here, we found that chemotherapeutic drugs (e.g., Ara-C, DNR, 6-MP) induced the expression of niche-protecting cytokines (GDF15, CCL3 and CCL4) in both ALL cell lines and primary cells in vitro. The ATM and NF-κB pathways were activated after chemotherapy treatment, and the pharmacological or genetic inhibition of these pathways significantly reversed the cytokine upregulation. Besides, chemotherapy-induced NF-κB activation was dependent on ATM-TRAF6 signaling, and NF-κB transcription factor p65 directly regulated the cytokines expression. Furthermore, we found that both pharmacological and genetic perturbation of ATM and p65 significantly decreased the residual ALL cells after Ara-C treatment in ALL xenograft mouse models. Together, these results demonstrated that ATM-dependent NF-κB activation mediated the cytokines induction by chemotherapy and ALL resistance to chemotherapeutics. Inhibition of ATM-dependent NF-κB pathway can sensitize ALL to chemotherapeutics, providing a new strategy to eradicate residual chemo-resistant ALL cells.

Label-free based quantitative proteomic analysis identifies proteins involved in the testis maturation of Bactrocera dorsalis (Hendel).

Complex structural and biochemical processes take place in insect testis maturation, but the mechanisms by which functional proteins induce and regulate male fertility are unknown. Proteomics has been widely used to identify functional proteins involved in such complex physiological processes. In this study, we performed a label-free based quantitative proteomic analysis of developing testis of Bactrocera dorsalis with the aim of shedding light on spermatogenesis, sperm formation and also tissue development. A total of 1912 reliable proteins were identified, including 1589, 1705 and 1723 proteins in 1-, 5- and 9-d-old testis, respectively. Most of these proteins (76.68%) were identified by two to ten peptides, and the mean number of peptides was 7.46 with an average sequence coverage of 30.71%. Quantitative proteomic analysis showed that there were 141 and 111 proteins which were abundant in the 5- and 9-d-old testis, respectively. The Gene Ontology (GO) and Clusters of Orthologous Groups (COG) analyses showed that many of these proteins function in cellular and metabolic processes, including binding and catalytic activities in molecular function analysis, and energy production, cell division, and cell motility in COG analysis. Potential functional proteins, such as heat shock proteins, glutathione S-transferase, transferrin, metalloproteinase and energy metabolism-related proteins, were found to be abundant in the intermediate and sexual maturity stages of testis. The findings in this study help us to better understand the molecular mechanisms behind testis development and spermatogenesis, which is essential for manipulating male fertility for ecological regulation and potential control of this species.

Genome-wide identification, phylogenetic analysis, and expression profiles of ATP-binding cassette transporter genes in the oriental fruit fly, Bactrocera dorsalis (Hendel) (Diptera: Tephritidae).

The ATP-binding cassette (ABC) is the largest transporter gene family and the genes play key roles in xenobiotic resistance, metabolism, and development of all phyla. However, the specific functions of ABC gene families in insects is unclear. We report a genome-wide identification, phylogenetic, and transcriptional analysis of the ABC genes in the oriental fruit fly, Bactrocera dorsalis (Hendel). We identified a total of 47 ABC genes (BdABCs) from the transcriptomic and genomic databases of B. dorsalis and classified these genes into eight subfamilies (A-H), including 7 ABCAs, 7 ABCBs, 9 ABCCs, 2 ABCDs, 1 ABCE, 3 ABCFs, 15 ABCGs, and 3 ABCHs. Comparative phylogenetic analysis of the ABCs suggests an orthologous relationship between B. dorsalis and other insect species in which these genes have been related to pesticide resistance and essential biological processes. Comparison of transcriptome and relative expression patterns of BdABCs indicated diverse multifunctions within different B. dorsalis tissues. The expression of 4, 10, and 14 BdABCs from 18 BdABCs was significantly upregulated after exposure to LD50s of malathion, avermectin, and beta-cypermethrin, respectively. The maximum expression level of most BdABCs (including BdABCFs, BdABCGs, and BdABCHs) occurred at 48h post exposures, whereas BdABCEs peaked at 24h after treatment. Furthermore, RNA interference-mediated suppression of BdABCB7 resulted in increased toxicity of malathion against B. dorsalis. These data suggest that ABC transporter genes might play key roles in xenobiotic metabolism and biosynthesis in B. dorsalis.

Chemotherapy-induced niche perturbs hematopoietic reconstitution in B-cell acute lymphoblastic leukemia.

BACKGROUND: Considerable efforts have been devoted toward the uncovering of the molecular mechanisms underlying the maintenance of hematopoietic stem cells (HSCs) by the normal bone marrow (BM) niche. Previously, we demonstrated that a chemotherapy-induced niche, which is mainly composed of mesenchymal stem cells (MSCs), protects the residual B-cell acute lymphoblastic leukemia (B-ALL) cells from the insult of chemotherapeutic drugs. However, the roles of chemotherapy-induced niche on HSCs functions in B-ALL remain unclear. METHODS: We established an oncogenic N-MYC-driven B-ALL mouse model, which were subsequently treated with common chemotherapy drug cytarabine (Ara-C) and daunorubicin (DNR). After treatment, the structures of the BM niche were imaged by immunofluorescence staining. Then, the self-renewal and differentiation capability of the MSCs in the BM after Ara-C and DNR treatment were studied by ex vivo culture and gene expression analysis with RNA-seq and qRT-PCR. The effects of chemotherapy-induced niche on the hematopoietic reconstitution of HSCs were determined with series transplantation assay. Furthermore, the cell cycle, ROS level, mitochondrial membrane potential and cell apoptosis of HSCs were detected by flow cytometry. RESULTS: The MSCs, which is the main component of chemotherapy-induced BM niche, have decreased self-renewal capability and are prone to differentiate into adipocytes and chondrocytes. The results of gene expression analysis with RNA-seq showed that the MSCs have reduced levels of cytokines, including SCF, CXCL12, ANGPT1, VCAM1, and IL7. Furthermore, the chemotherapy-induced niche perturbed the hematopoietic reconstitution of HSCs in our N-MYC-driven B-ALL mouse model by promoting HSCs to enter cell cycle and increasing intracellular ROS levels and mitochondrial membrane potential of HSCs, which lead to the cell apoptosis of HSCs. CONCLUSIONS: Chemotherapy-induced BM niche perturbs the hematopoietic reconstitution of HSCs by increasing intracellular ROS level and inducing cell apoptosis.