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Hydropower station is vital for the stable growth of the national economy. How to timely warn the possible faults of hydropower stations has become an increasingly popular research topic. The traditional detection model is difficult to detect the small abnormal changes in the data, and these abnormal changes are often the precursor of faults. To improve the sensitivity of the traditional detection model, this study introduced a weight factor into the traditional LSTM detection model. By using the correction mechanism, the LSTM correction model makes the prediction model never deviate from the normal track following the appearance of abnormal data. This ensures that the model can generate large residuals after abnormal data occur so that we can detect these abnormal data in time. Finally, this paper puts forward two factors related to equipment health and integrates these two factors to form a health index. The results show that the LSTM correction model based on the health index can not only detect small changes that cannot be detected by traditional detection models but also knows the wear and tear of equipment during operation based on the changes in health indicators. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effect and mechanism of methylcrotonyl-CoA carboxylase subunit 1 (MCCA) on multidrug resistance in multiple myeloma (MM). The apoptosis kit and CCK-8 reagent were used to detect drug-induced cell apoptosis and viability. Immunoprecipitation, immunofluorescence staining, and protein structural simulation were used to detect the interaction between MCCA and Bad. Immunodeficient mice were injected with ARD cells and treated with bortezomib. Changes in tumor burden were recorded by bioluminescence imaging, and κ light chain content in the blood of mice was detected by enzyme-linked immunoassay. Patients with high MCCA expression from a primary MM dataset had superior overall survival. After treatment with different anti-MM drugs, MCCA knockdown MM (MCCA-KD) cells had higher survival rates than control knockdown (CTR-KD) cells (p < 0.05). Mechanistic studies have revealed that MCCA-KD cells had dysfunctional mitochondria with decreased Bax and Bad levels and increased Bcl-xl and Mcl-1 levels. Furthermore, that MCCA and Bad demonstrated protein–protein interactions. The half-life of Bad in MCCA-KD cells is significantly shorter than that in CTR-KD cells (7.34 vs. 2.42 h, p < 0.05). In a human MM xenograft mouse model, we confirmed that MCCA-KD tumors had a poor response to anti-MM drugs in vivo. Finally, we showed that MCCA might contribute to multidrug resistance in different human cancers, particularly in solid tumors. Our findings demonstrated a novel function of MCCA in multidrug resistance. The lack of MCCA expression promoted antiapoptotic cell signaling in MM cells. [ABSTRACT FROM AUTHOR]

Summary: To study glycolysis/glycogenesis‐related genes expression in childhood B‐cell acute lymphoblastic leukaemia (B‐ALL), we performed a microarray‐based analysis using published gene expression profiles. We found that SLC2A5, which encodes solute carrier family 2 member 5 (SLC2A5, previously termed GLUT5) that facilitates cell fructose uptake, was up‐regulated in Philadelphia chromosome‐positive ALL (Ph+ALL). Microarray‐based analyses also suggested that SLC2A5 expression was significantly down‐regulated in childhood B‐ALL with t(1;19) or 11q23 mutation. High SLC2A5 expression was found in patients who had disease recurrence within 3 years, early relapse, shortened complete remission duration and positive minimal residue disease (MRD) status after treatment. SLC2A5 overexpression at both the mRNA and protein level in Ph+ALL was confirmed in a validation cohort of childhood B‐ALL. We also validated the correlation of SLC2A5 expression and MRD status. A mechanistic study using a human Ph+ALL cell line showed that BCR‐ABL1 kinase might regulate SLC2A5 expression via MYC. The tyrosine kinase inhibitors (TKIs) imatinib and dasatinib repressed SLC2A5 expression and the cell uptake of fructose. Fructose protected the tumour cells from nutrition deficiency and drug‐induced cell death. Overall, our findings showed that SLC2A5 was up‐regulated in childhood Ph+ALL. SLC2A5 expression correlated with childhood B‐ALL clinical factors, such as MRD status. Given that TKIs could inhibit SLC2A5 expression, repression of fructose utility after TKI treatment contributes to TKI‐induced Ph+ALL cytotoxicity. Targeting SLC2A5 might be promising in B‐ALL treatment, especially for Ph+ALL patients with high SLC2A5 expression. [ABSTRACT FROM AUTHOR]

Objective Osteolytic lesion (OL) and bone damage are common complications in multiple myeloma (MM). This study aimed to analyze the occurrence of OL in MM patient groups of different ages and genders. Patients and methods We performed a retrospective study of 762 MM patients admitted to West China Hospital from 2009 to 2014 to investigate the association between OL occurrence with patients' ages and genders. The presence or absence of OL was confirmed by X-ray, computed tomography (CT) or magnetic resonance imaging (MRI) examination. We also downloaded MM patients' published gene expression profiles and performed microarray-based analyses to identify differentially regulated genes and signaling pathways. Finally, we examined target gene expressions in MM bone marrow (BM) biopsies through immunohistochemistry (IHC). Results We calculated the frequency of OL in female and male MM patients with different age cut-offs. From West China Hospital data, we found that in young female MM patients aged under 55, the frequency of OL was 16.67%, significantly lower than the frequencies in other groups of patients (young males: 34.38%; old males: 31.04%; old females: 29.24%; p  < .05). The same was true in another independent MM cohort. Microarray-based analyses showed that Microtubule Associated Serine/Threonine Kinase Family Member 4 ( MAST4 ), an estrogen-responsive gene, expression was up-regulated in MM patients without OL and in young female MM patients ( p  < .05). The expression of MAST4 in MM BM was confirmed by IHC. The perspective of cell signaling network suggested that MAST4 might interact with phosphatase and tensin homolog (PTEN) and control the expression of a panel of osteoclast-regulatory cytokines, such as TNFSF11 and CCL2. Conclusions Young female (<55 years) MM patients have significantly lower OL frequency than other groups. MAST4 gene expression is thought to be associated with this phenomenon. [ABSTRACT FROM AUTHOR]

Overexpression of survivin is observed in various hematological malignancies, including acute myeloid leukemia (AML). Studies show that elevated expression of survivin correlates with a worse clinic outcome in AML patients. It remains unclear whether inhibition of survivin may alter the efficacy of chemotherapy against AML. Here, we evaluate the effects of specific knockdown of survivin on AML cells' sensitivity to chemotherapy, and investigate the therapeutic potential of the transcription inhibitor of survivin YM155 either alone or in combination with chemotherapeutic agents. We found Kasumi-1 and HL-60 cells had relatively higher expression levels of survivin among all AML cell lines tested. Specific knockdown of survivin in Kasumi-1 and HL-60 cells resulted in: inhibition of cell proliferation; cell cycle G2/M arrest; induction of DNA damage response and apoptosis. Downregulation of survivin enhanced etoposide- or doxorubicin-induced anti-proliferative/anti-survival activity in AML cells. The small molecule inhibitor YM155 reduced survivin in a dose- and time-dependent manner and trigged apoptosis in Kasumi-1 and HL-60 cells. The combinatorial effects of YM155 and chemotherapeutics were either synergetic or antagonistic, depending upon the drugs used for combination and the type of AML cells being treated. Collectively, our data demonstrate that survivin plays an important role in the maintenance and proliferation of AML cells. While specific knockdown of survivin enhances chemosensitivity, the combinations of YM155 and chemotherapeutic agents exhibit synergetic or antagonistic effects on AML cells. Our findings provide a rationale for further assessment of survivin-targeted therapy in the treatment of patients with AML. [ABSTRACT FROM AUTHOR]

[Display omitted] Acute myeloid leukemia (AML) with FLT3 internal tandem duplication (FLT3 -ITD) has a dismal prognosis. FLT3 inhibitors have been developed to treat patients with FLT3 -ITD AML; however, when used alone, their efficacy is insufficient. FLT3 inhibitors combined with chemotherapy may be a promising treatment for FLT3 -ITD AML. Homoharringtonine (HHT) is a classical anti-leukaemia drug with high sensitivity to FLT3 -ITD AML cells. Here, we showed that HHT synergizes with a selective next-generation FLT3 inhibitor, quizartinib, to inhibit cell growth/viability and induce cell-cycle arrest and apoptosis in FLT3 -ITD AML cells in vitro, significantly inhibit acute myeloid leukemia progression in vivo, and substantially prolong survival of mice-bearing human FLT3 -ITD AML. Mechanistically, HHT and quizartinib cooperatively inhibit FLT3-AKT and its downstream targets GSK3β, c-Myc, and cyclin D1, cooperatively up-regulate the pro-apoptosis proteins Bim and Bax, and down-regulate the anti-apoptosis protein Mcl1. Most strikingly, HHT and quizartinib cooperatively reduce the numbers of side-population (SP) and aldehyde dehydrogenase (ALDH)-positive cells, which reportedly are rich in LSCs. In conclusion, HHT combined with quizartinib may be a promising treatment strategy for patients with FLT3 -ITD AML. [ABSTRACT FROM AUTHOR]

Summary Multiple myeloma (MM) is an incurable plasma cell cancer in the bone marrow. Immunomodulatory drugs, such as lenalidomide (LEN) and pomalidomide, are backbone agents in MM treatment, and LEN resistance is commonly seen in the MM clinic. In this study, we presented that heterogeneous nuclear ribonucleoprotein U (hnRNPU) affected MM resistance to LEN via the regulation of target mRNA translation. hnRNPULow MM cells exhibited upregulated CRBN and IKZF1 proteins, stringent IKZF1/3 protein degradation upon LEN addition and increased sensitivity to LEN. RNA pulldown assays and RNA electrophoretic mobility shift assays revealed that hnRNPU bound to the 3′‐untranslated region of CRBN and IKZF1 mRNA. A sucrose gradient assay suggested that hnRNPU specifically regulated CRBN and IKZF1 mRNA translation. The competition of hnRNPU binding to its target mRNAs by small RNAs with hnRNPU‐binding sites restored MM sensitivity to LEN. hnRNPU function in vivo was confirmed in an immunocompetent MM mouse model constructed by the inoculation of Crbn‐humanized murine 5TGM1 cells into CrbnI391V/+ mice. Overall, this study suggests a novel mechanism of LEN sensitivity in which hnRNPU represses CRBN and IKZF1 mRNA translation. [ABSTRACT FROM AUTHOR]

Background: The HER3 receptor functions as a major cause of drug resistance in cancer treatment. It is believed that therapeutic targeting of HER3 is required to improve patient outcomes. It is not clear whether a novel strategy with two functional cooperative miRNAs would effectively inhibit erbB3 expression and potentiate the anti-proliferative/anti-survival effects of a HER2-targeted therapy (trastuzumab) and chemotherapy (paclitaxel) on HER2-overexpressing breast cancer cells. Results: Combination of miR-125a and miR-205, as compared to either miRNA alone, potently inhibited expression of HER3 in HER2-overexpressing breast cancer BT474 cells. Co-expression of the two miRNAs not only reduced the levels of phosphorylated erbB3 (P-erbB3), Akt (P-Akt), and Src (P-Src), it also inhibited cell proliferation and increased cells at G1 phase. A multi-miRNA lentiviral vector - the cluster of miR-125a and miR-205 - was constructed to simultaneously express the two miRNAs in HER2-overexpressing breast cancer cells. Concurrent expression of miR-125a and miR-205 via the miRNA cluster transfection significantly enhanced trastuzumab-mediated growth inhibition and cell cycle G1 arrest in BT474 cells and markedly increased paclitaxel-induced apoptosis in another HER2-overexpressing breast cancer cell line HCC1954. Conclusions: Here, we showed that functional cooperative miRNAs effectively suppressed erbB3 expression. This novel approach targeting of HER3 was able to enhance the therapeutic efficacy of trastuzumab and paclitaxel against HER2-overexpressing breast cancer. [ABSTRACT FROM AUTHOR]

Elevated expression of HER3, which interacts with HER2 in breast cancer cells, confers chemoresistance via phosphoinositide 3-kinase (PI-3K)/Akt-dependent upregulation of Survivin. However, the underlying mechanism is not clear. Ectopic expression or specific knockdown of HER3 in HER2-overexpressing breast cancer cells did not alter Survivin mRNA levels and Survivin protein stability, supporting the notion that HER3 signaling may regulate specific miRNAs that target Survivin to alter its protein translation. Here we showed that overexpression and specific knockdown of HER3 reduced and enhanced expression of two Survivin-targeting miRNAs, miR-203 and miR-542-3p, in breast cancer cells, respectively. While the specific inhibitor of either miR-203 or miR-542-3p attenuated an anti-HER3 antibody-induced downregulation of Survivin, inhibition of miR-542-3p exhibited a better efficacy than miR-203 inhibition did. Consistently, miR-542-3p mimic was much more effective than miR-203 mimic not only in inhibition of Survivin, but also in enhancement of paclitaxel-induced apoptosis in HER2-overexpressing breast cancer cells. Moreover, the combination of miR-542-3p mimic and paclitaxel, as compared with either agent alone, significantly inhibited in vivo tumor growth of HER2-overexpressing breast cancer cells. Collectively, our data indicated that the HER3/PI-3K/Akt signaling upregulates Survivin via suppression of miR-203 and miR-542-3p. Because miR-542-3p has three binding sites on the 3'-UTR of Survivin mRNA, its mimic was able to effectively downregulate Survivin in vitro and in vivo. Thus, miR-542-3p-replacement therapy is an excellent approach to overcome HER3-mediated paclitaxel resistance and significantly enhances the antitumor activity of paclitaxel against HER2-overexpressing breast cancer. [ABSTRACT FROM AUTHOR]

Abstract: Bendamustine, a hybrid molecule of purine analog and alkylator, induces cell death by activation of apoptosis, DNA damage response, and mitotic catastrophe. Entinostat, a selective class I inhibitor of histone deacetylase (HDAC), exerts anti-tumor activity in various cancer types, including multiple myeloma (MM). We sought to determine the combinatorial effects of bendamustine and entinostat on MM cells. Cell growth assays showed that bendamustine or entinostat inhibited proliferation in a dose-dependent manner, and their combinations synergistically induced growth inhibition in all MM cells tested. An apoptotic-ELISA and western blot assays on PARP cleavage and caspase-8 and caspase-3 revealed that bendamustine in combination with entinostat exhibited a much more potent activity than either agent alone to promote the MM cells undergoing apoptosis in a dose-dependent manner. Flow cytometric analysis found that entinostat exhibited distinct effects on cell cycle progression in different lines and bendamustine mainly arrested the cells at S phase, whereas their combinations dramatically blocked the S cells entering G2/M phase. Furthermore, studies on DNA damage response indicated that phospho-histone H2A.X (P-H2A.X), a hall marker of DNA double strand break, along with phosphorylated CHK2 (P-CHK2) was significantly enhanced by the combinations of bendamustine and entinostat as compared to either agent alone. These molecular changes were correlated with the increases in mitotic catastrophe. Collectively, our data demonstrate that bendamustine in combination with entinostat exhibit potent anti-proliferative/anti-survival activity in MM cells via induction of apoptosis and DNA damage response. Regimens consisting of bendamustine and/or entinostat may represent novel therapeutic strategies against MM. [Copyright &y& Elsevier]

Multiple myeloma (MM) is an incurable haematological cancer. Selinexor is the first-in-class selective inhibitor of nuclear export (SINE) and was newly approved for the treatment of MM. Until now, very few studies have investigated selinexor resistance in MM. Heterogeneous nuclear ribonucleoprotein U (hnRNPU) is an RNA-binding protein and a component of hnRNP complexes. Here we found that hnRNPU regulates MM sensitivity to selinexor. Cell apoptosis assays were performed to compare selinexor-induced cell death in control knockdown (CTR-KD) and hnRNPU knockdown (hnR-KD) MM cells. HnRNPU knockdown-induced nuclear protein retention was examined by proteomics array. HnRNPU-conferred mRNA translation regulation was evaluated by sucrose gradient assay, RNA electrophoresis mobility shift assay, and RNA pull-down assay. We found that hnR-KD MM cells were more sensitive to selinexor-induced cell death in vitro and in mouse model. MM patients who responded to selinexor had relatively low hnRNPU expression. In brief, hnRNPU comprehensively regulated MM sensitivity to selinexor by affecting the localization of LTV1 and NMD3, and mRNA translation of MDM2 and RAN, which were involved in XPO1-mediated nuclear export of ribosome subunits and tumor suppressors. Our discoveries indicate that hnRNPU might be a possible marker to categorize MM patients for the use of Selinexor. • HnRNPUHigh MM cells were resistant to selinexor-induced cell death in vitro and in vivo. • HnRNPU distinguished nuclear protein retention including p53, NMD3 and LTV1. • HnRNPU bound to RAN and MDM2 mRNAs and regulated their translation. • HnRNPU regulated the factors involved in the XPO1-mediated nuclear export of ribosome subunits or cancer suppressors. • A possible approach to categorize MM patients for the use of Selinexor. [ABSTRACT FROM AUTHOR]

Purpose: Acute myeloid leukemia (AML) is a heterogenous disease and the survival of AML patients is largely attributed to the improvement of supportive treatment. Wilms' tumor 1-associated protein (WTAP) is a nuclear protein functions in many physiological and pathological processes. Although its expression and function in many malignant diseases have been reported, its prognostic and epigenetic roles in AML are largely unknown. Methods: Peripheral blood or bone marrow samples were collected from AML patients. The WTAP expression was detected by western blot. WTAP expression level and patients clinical features were analyzed using statistical methods. WTAP knockdown AML cells were constructed. The experiments on proliferation, tumorigenic ability, cell cycle, and apoptosis were performed. Transcriptome sequencing was performed and analyzed. M6A methylation level was measured and m6A-RIP was performed to quantify m6A methylation level of MYC mRNA. RNA stability assay was performed to measure the half-life of mRNA. Results: WTAP was overexpressed in AML patients and was an independent poor-risk factor in AML (p = 0.0140). Moreover, we found that WTAP regulated proliferation, tumorigenesis, cell cycle, and differentiation of AML cells. Furthermore, WTAP made AML cells resistant to daunorubicin. In further investigations, m6A methylation level was downregulated when knocking down WTAP, and c-Myc was upregulated due to the decreased m6A methylation of MYC mRNA. Conclusion: High WTAP expression predicts poor prognosis in AML and WTAP plays an epigenetic role in AML. [ABSTRACT FROM AUTHOR]

Purpose: Acute myeloid leukemia (AML) is associated with a poor overall prognosis. PIM family genes, including PIM1, PIM2, and PIM3, are proto-oncogenes that are aberrantly overexpressed in different types of human cancers. In this study, we aimed to explore and clarify the function of PIM3 in AML. Patients and Methods: The expression of the three PIM genes in AML was detected using the Gene Expression Omnibus. The expression of PIM3 and PIM3 in patient samples and AML cell lines was measured using quantitative real-time polymerase chain reaction or Western blot analyses. The cellular behaviors of PIM3-overexpressing AML cell lines were detected using a CCK-8 assay, flow cytometry, Western blotting, immunofluorescence staining, and a cell migration assay. The interactions between PIM3 and phosphorylated CXCR4 (pCXCR4) were explored via immunoprecipitation. Results: Higher PIM3 expression was detected in primary AML cells than in healthy donor cells. Second, PIM3 overexpression promoted AML cell proliferation and protected against spontaneous apoptosis by phosphorylating BAD (pBAD) at Ser112. Furthermore, PIM3 overexpression might promote the migration of AML cells via CXCR4. PIM3-overexpressing AML cell lines exhibited increased CXCR4 phosphorylation at Ser339, and pCXCR4 interacted with PIM3. Conclusion: Our findings suggest that PIM3 regulates the proliferation, survival, and chemotaxis of AML cell lines. Moreover, pCXCR4 might mediate the regulation of PIM3-induced chemotaxis. Therefore, the inhibition of PIM3 expression may be a promising therapeutic target in AML. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is an incurable malignancy of plasma cells. Ivermectin is a US Food and Drug Administration-approved drug for antiparasitic use. Here, we showed that ivermectin exerted anti-MM effects and significantly synergized with proteasome inhibitors in vitro and in vivo. Ivermectin alone exhibited mild anti-MM activity in vitro. Further investigation suggested that ivermectin inhibited proteasome activity in the nucleus by repressing the nuclear import of proteasome subunits, such as PSMB5-7 and PSMA3-4. Therefore, ivermectin treatment caused the accumulation of ubiquitylated proteins and the activation of the UPR pathway in MM cells. Furthermore, ivermectin treatment caused DNA damage and DNA damage response (DDR) signaling pathway activation in MM cells. Ivermectin and bortezomib exhibited synergized anti-MM activity in vitro. The dual-drug treatment resulted in synergistic inhibition of proteasome activity and increased DNA damage. An in vivo study using a human MM cell line xenograft mouse model showed that ivermectin and bortezomib efficiently repressed MM tumor growth in vivo, while the dual-drug treatment was well tolerated by experimental animals. Overall, our results demonstrated that ivermectin alone or cotreated with bortezomib might be promising in MM treatment. • Ivermectin, a mature macrolide drug, exerts antimyeloma effects. • Ivermectin targeted multiple myeloma cells via inhibiting nuclear proteasome activity and inducing DNA damage. • Ivermectin significantly synergized with proteasome inhibitors in vitro and in vivo. • The combination of ivermectin with bortezomib was well tolerated by experimental animals. [ABSTRACT FROM AUTHOR]

Background: The umbilical cord blood (UCB) has been widely accepted as an alternative source of hematopoietic stem/progenitor cells (HSPCs) for transplantation, and its use in adults is still restricted because of low absolute numbers. To overcome this obstacle, expansion of UCB-HSPCs under feeder cell-based coculture is a promising possibility. In this study, we explored UCB-CD34+ cells ex vivo expansion using Wharton's jelly mesenchymal stem cells (WJ-MSCs) or umbilical vein endothelial cells (UVECs) as feeder layer-based serum-free coculture system with a cocktail of cytokines. Methods: UCB-CD34+ cells were cultured in five different coculture conditions composed of umbilical cord stromal cells (WJ-MSCs or UVECs) with or without a cocktail of cytokines (SCF, FLT3L, and TPO). The cultured cells were harvested at day 10 and analyzed for phenotypes and functionalities, including total nuclear cells (TNCs), CD34+ cells, CD34+CD38− cells, colony-forming unit (CFU) for committed progenitors, and long-term culture initiating cells (LTC-ICs) for HSPCs. Results: Our work showed the numbers of TNC cells, CD34+ cells, and CD34+CD38− cells were expanded under five coculture conditions, and the feeder layer-based cocultures further promoted the expansion. The numbers of colonies of CFU-GM, CFU-E/BFU-E, and CFU-GEMM in the cocultures with cytokines were significantly higher than their counterparts at day 0 (p < 0.05), while no significant difference (p > 0.05) in those without the addition of cytokines. The numbers of LTC-ICs were increased both under the WJ-MSCs and UVECs with cytokine cocultures, but only in the UVECs group showed a significant difference (p < 0.05), and were decreased under conditions without cytokine (p < 0.05). Conclusion: Our data demonstrate that both WJ-MSCs and UVECs as feeder layer could efficiently support the expansion of UCB-CD34+ cells in synergy with SCF, FLT3L, and TPO under serum-free culture condition. The UVECs combined with the 3GF cytokine cocktail could maintain the growth of LTC-ICs derived from UCB-CD34+ cells and even expand to some extent. [ABSTRACT FROM AUTHOR]

Background: The physiological approach suggests that an environment associating mesenchymal stromal cells with low O2 concentration would be most favorable for the maintenance of hematopoietic stem/progenitor cells (HSPCs). To test this hypothesis, we performed a coculture of cord blood CD34+ cells with Wharton's jelly mesenchymal stem cells (WJ-MSCs) under different O2 concentration to simulate the growth of HSPCs in vivo, and assessed the impacts on stemness maintenance and proliferation of cord blood HSPCs in vitro. Methods: CD34+ cells derived from cord blood were isolated and cocultured under 1%, 3%, or 20% O2 concentrations with irradiated WJ-MSCs without adding exogenous cytokines for 7 days. The cultured cells were harvested and analyzed for phenotype and functionality, including total nuclear cells (TNC), CD34+Lin− cells, colony forming unit (CFU) for committed progenitors, and long-term culture initiating cells (LTC-ICs) for HSPCs. The cytokine levels in the medium were detected with Luminex liquid chips, and the mRNA expression of hypoxia inducible factor (HIF) genes and stem cell signal pathway (Notch, Hedgehog, and Wnt/β-catenin) downstream genes in cord blood HSPCs were confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). Results: Our results showed that the number of TNC cells, CD34+Lin− cells, and CFU were higher or similar with 20% O2 (normoxia) in coculture and compared with 1% O2 (hypoxia). Interestingly, a 1% O2 concentration ensured better percentages of CD34+Lin− cells and LTC-IC cells. The hypoxia tension (1% O2) significantly increased vascular endothelial growth factor (VEGF) secretion and decreased interleukin (IL)-6, IL-7, stem cell factor (SCF), and thrombopoietin (TPO) secretion of WJ-MSCs, and selectively activated the Notch, Wnt/β-catenin, and Hedgehog signaling pathway of cord blood HSPCs by HIF-related factors, which may play an important role in stemness preservation and for sustaining HSPC quiescence. Conclusions: Our data demonstrate that cord blood HSPCs maintain stemness better under hypoxia than normoxia with WJ-MSC coculture, partially due to the increased secretion of VEGF, decreased secretion of IL-6 by WJ-MSCs, and selective activation of stem cell signal pathways in HSPCs. This suggests that the oxygenation may not only be a physiological regulatory factor but also a cell engineering tool in HSPC research, and this may have important translational and clinical implications. [ABSTRACT FROM AUTHOR]