Elevated plasma solMER concentrations link ambient PM2.5 and PAHs to myocardial injury and reduced left ventricular systolic function in children.

Exposure to fine particulate matter (PM2.5) and polycyclic aromatic hydrocarbons (PAHs) is known to be associated with the polarization of pro-inflammatory macrophages and the development of various cardiovascular diseases. The pro-inflammatory polarization of resident cardiac macrophages (cMacs) enhances the cleavage of membrane-bound myeloid-epithelial-reproductive receptor tyrosine kinase (MerTK) and promotes the formation of soluble MerTK (solMER). This process influences the involvement of cMacs in cardiac repair, thus leading to an imbalance in cardiac homeostasis, myocardial injury, and reduced cardiac function. However, the relative impacts of PM2.5 and PAHs on human cMacs have yet to be elucidated. In this study, we aimed to investigate the effects of PM2.5 and PAH exposure on solMER in terms of myocardial injury and left ventricular (LV) systolic function in healthy children. A total of 258 children (aged three to six years) were recruited from Guiyu (an area exposed to e-waste) and Haojiang (a reference area). Mean daily PM2.5 concentration data were collected to calculate the individual chronic daily intake (CDI) of PM2.5. We determined concentrations of solMER and creatine kinase MB (CKMB) in plasma, and hydroxylated PAHs (OH-PAHs) in urine. LV systolic function was evaluated by stroke volume (SV). Higher CDI values and OH-PAH concentrations were detected in the exposed group. Plasma solMER and CKMB were higher in the exposed group and were associated with a reduced SV. Elevated CDI and 1-hydroxynaphthalene (1-OHNa) were associated with a higher solMER. Furthermore, increased solMER concentrations were associated with a lower SV and higher CKMB. CDI and 1-OHNa were positively associated with CKMB and mediated by solMER. In conclusion, exposure to PM2.5 and PAHs may lead to the pro-inflammatory polarization of cMacs and increase the risk of myocardial injury and systolic function impairment in children. Furthermore, the pro-inflammatory polarization of cMacs may mediate cardiotoxicity caused by PM2.5 and PAHs.

Review of Sensor-Based Subgrade Distress Identifications.

The attributes of diversity and concealment pose formidable challenges in the accurate detection and efficacious management of distresses within subgrade structures. The onset of subgrade distresses may precipitate structural degradation, thereby amplifying the frequency of traffic incidents and instigating economic ramifications. Accurate and timely detection of subgrade distresses is essential for maintaining and repairing road sections with existing distresses. This helps to prolong the service life of road infrastructure and reduce financial burden. In recent years, the advent of numerous novel technologies and methodologies has propelled significant advancements in subgrade distress detection. Therefore, this review delineates a concentrated examination of subgrade distress detection, methodically consolidating and presenting various techniques while dissecting their respective merits and constraints. By furnishing comprehensive guidance on subgrade distress detection, this review facilitates the expedient identification and targeted treatment of subgrade distresses, thereby fortifying safety and enhancing durability. The pivotal role of this review in bolstering the construction and operational facets of transportation infrastructure is underscored.

Regenerated Graphite Electrodes with Reconstructed Solid Electrolyte Interface and Enclosed Active Lithium Toward >100% Initial Coulombic Efficiency.

Solid electrolyte interface (SEI) is arguably the most important concern in graphite anodes, which determines their achievable Coulombic efficiency (CE) and cycling stability. In spent graphite anodes, there are already-formed (yet loose and/or broken) SEIs and some residual active lithium, which, if can be inherited in the regenerated electrodes, are highly desired to compensate for the lithium loss due to SEI formation. However, current graphite regenerated approaches easily destroy the thin SEIs and residue active lithium, making their reuse impossible. Herein, this work reports a fast-heating strategy (e.g., 1900 K for ≈150 ms) to upcycle degraded graphite via instantly converting the loose original SEI layer (≈100 nm thick) to a compact and mostly inorganic one (≈10-30 nm thick with a 26X higher Young's Modulus) and still retaining the activity of residual lithium. Thanks to the robust SEI and enclosed active lithium, the regenerated graphite exhibited 104.7% initial CE for half-cell and gifted the full cells with LiFePO4 significantly improved initial CE (98.8% versus 83.2%) and energy density (309.4 versus 281.4 Wh kg-1), as compared with commercial graphite. The as-proposed upcycling strategy turns the "waste" graphite into high-value prelithiated ones, along with significant economic and environmental benefits.

Tailoring atomic 1T phase CrTe2forin situfabrication.

Controllable tailoring and understanding the phase-structure relationship of the 1T phase two-dimensional (2D) materials are critical for their applications in nanodevices. Thein situtransmission electron microscope (TEM) could regulate and monitor the evolution process of the nanostructure of 2D material with atomic resolution. In this work, a controllably tailoring 1T-CrTe2nanopore is carried out by thein situTEM. A preferred formation of the 1T-CrTe2border structure and nanopore healing process are studied at the atomic scale. The controllable tailoring of the 1T phase nanopore could be achieved by regulating the transformation of two types of low indices of crystal faces {101¯0} and {112¯0} at the nanopore border. Machine learning is applied to automatically process the TEM images with high efficiency. By adopting the deep-learning-based image segmentation method and augmenting the TEM images specifically, the nanopore of the TEM image could be automatically identified and the evaluation result of DICE metric reaches 93.17% on test set. This work presents the unique structure evolution of 1T phase 2D material and the computer aided high efficiency TEM data analysis based on deep learning. The techniques applied in this work could be generalized to other materials for controlled nanostructure regulation and automatic TEM image analyzation.

Evaluation of mining capacity of mines using the combination weighting approach: A case study in Shenmu Mining Area in Shaanxi Province, China.

Aiming at the low mining rate in mines, Xingelao, Dabianyao, and Dongliang Coal Mines in Shenmu Mining Area, Shaanxi Province, China were taken as research objects. Based on this, this study constructed an evaluation index system for the mining capacity of the mines from the perspectives of geological factors, mechanical equipment, humans, and mining design. Moreover, the factors influencing the mining capacity of the mines were evaluated using a combination weighting approach based on an improved analytic hierarchy process and an entropy weight method. A standard cloud was generated based on the mapping standards of each index and a comprehensive cloud was obtained according to comprehensive weight and a backward cloud algorithm. Finally, by combining the comprehensive cloud with local and overall scores of the mines, the mining capacities of the mines were evaluated. The research results demonstrate that the key factor restricting the mining capacity of the mines is the geological environment and five major third-grade indexes affecting mining capacity are igneous rock intrusion, collapse column, scouring zone of the ancient river bed, mechanization level and coal pillar width. In addition, the corresponding suggestions and measures were put forward according to the main factors influencing the mining rate of the mines. In accordance with the weights and scores of each index, the overall scores of the mines were calculated. Dongliang, Dabianyao, and Xingelao Coal Mines were ranked in order based on scores. The research results provide a theoretical basis for improving the mining capacity of the mines under similar geological conditions.

Increased intestinal permeability with elevated peripheral blood endotoxin and inflammatory indices for e-waste lead exposure in children.

Lead (Pb) entering the body through different channels can damage the function of intestinal mucosal barrier and cause the body stressful inflammatory response to enhance. This study conducted a cross-sectional study to investigate the effects of Pb exposure on intestinal permeability in children by measuring the level of bacterial endotoxin and index of inflammatory cell types in peripheral blood. From November to December 2018, we recruited 187 participants aged 3-6 years by stratified randomization, from an electronic-waste-exposed group (n = 82) and a referent group (n = 105). General demographic information, past history of the digestive system in child, and family situation were informed by children's guardians with questionnaires. Children in the exposed group showed lower weight, height, and body mass index while more diarrhea in a month. Blood Pb and plasma endotoxin were elevated in exposed children than referent children and the positive relationship between them was shown in all children [B (95% CI): 0.072 (0.008, 0.137), P = 0.033]. Peripheral monocyte counts and leukotriene B4 (LTB4) levels were significantly increased in the exposed group. Endotoxin levels were positively correlated with neutrophils, monocytes, and LTB4 [B (95% CI): 0.054 (0.015, 0.093), 0.018 (0.005, 0.031), and 0.049 (0.011, 0.087), respectively, P < 0.05]. To sum up, the exposed children showed lower physical growth levels, poorer gut health, and increased intestinal permeability, which was related to high blood Pb and peripheral inflammatory indices. These results suggest the possible adverse impact of environmental Pb exposure on the intestinal health of children.

E-waste polycyclic aromatic hydrocarbon (PAH) exposure leads to child gut-mucosal inflammation and adaptive immune response.

Polycyclic aromatic hydrocarbon (PAH) exposure alters immunological responses. Research concerning PAH exposure on intestinal immunity of children in electronic waste (e-waste) areas is scarce. The aim of this study was to evaluate the effects of polycyclic aromatic hydrocarbon (PAH) pollutants on intestinal mucosal immunity of children in e-waste areas. Results showed higher hydroxylated PAH (OH-PAH) concentrations in e-waste-exposed children, accompanied with higher sialyl Lewis A (SLA) level, absolute lymphocyte and monocyte counts, decreased of percentage of CD4+ T cells, and had a higher risk of diarrhea. OH-PAH concentrations were negative with child growth. 1-OHNap mediated through WBCs, along with 1-OHPyr, was correlated with an increase SLA concentration. 2-OHFlu, 1-OHPhe, 2-OHPhe, 1-OHPyr, and 6-OHChr were positively correlated with secretory immunoglobulin A (sIgA) concentration. Our results indicated that PAH pollutants caused inflammation, affected the intestinal epithelium, and led to transformation of microfold cell (M cell). M cells initiating mucosal immune responses and the subsequent increasing sIgA production might be an adaptive immune respond of children in the e-waste areas. To our knowledge, this is the first study of PAH exposure on children intestinal immunity in e-waste area, showing that PAH exposure plays a negative role in child growth and impairs the intestinal immune function.

Prognostic role of Wnt and Fzd gene families in acute myeloid leukaemia.

Wnt-Fzd signalling pathway plays a critical role in acute myeloid leukaemia (AML) progression and oncogenicity. There is no study to investigate the prognostic value of Wnt and Fzd gene families in AML. Our study screened 84 AML patients receiving chemotherapy only and 71 also undergoing allogeneic haematopoietic stem cell transplantation (allo-HSCT) from the Cancer Genome Atlas (TCGA) database. We found that some Wnt and Fzd genes had significant positive correlations. The expression levels of Fzd gene family were independent of survival in AML patients. In the chemotherapy group, AML patients with high Wnt2B or Wnt11 expression had significantly shorter event-free survival (EFS) and overall survival (OS); high Wnt10A expressers had significantly longer OS than the low expressers (all P < .05), whereas, in the allo-HSCT group, the expression levels of Wnt gene family were independent of survival. We further found that high expression of Wnt10A and Wnt11 had independent prognostic value, and the patients with high Wnt10A and low Wnt11 expression had the longest EFS and OS in the chemotherapy group. Pathway enrichment analysis showed that genes related to Wnt10A, Wnt11 and Wnt 2B were mainly enriched in 'cell morphogenesis involved in differentiation', 'haematopoietic cell lineage', 'platelet activation, signalling and aggregation' and 'mitochondrial RNA metabolic process' signalling pathways. Our results indicate that high Wnt2B and Wnt11 expression predict poor prognosis, and high Wnt10A expression predicts favourable prognosis in AML, but their prognostic effects could be neutralized by allo-HSCT. Combined Wnt10A and Wnt11 may be a novel prognostic marker in AML.

Prognostic value of HMGN family expression in acute myeloid leukemia.

Aim: The objective of this work was to investigate the prognostic role of the HMGN family in acute myeloid leukemia (AML). Methods: A total of 155 AML patients with HMGN1-5 expression data from the Cancer Genome Atlas database were enrolled in this study. Results: In the chemotherapy-only group, patients with high HMGN2 expression had significantly longer event-free survival (EFS) and overall survival (OS) than those with low expression (all p < 0.05), whereas high HMGN5 expressers had shorter EFS and OS than the low expressers (all p < 0.05). Multivariate analysis identified that high HMGN2 expression was an independent favorable prognostic factor for patients who only received chemotherapy (all p < 0.05). HMGN family expression had no impact on EFS and OS in AML patients receiving allogeneic hematopoietic stem cell transplantation. Conclusion: High HMGN2/5 expression is a potential prognostic indicator for AML.

Relations of blood lead levels to echocardiographic left ventricular structure and function in preschool children.

Lead (Pb) has been proved to exert adverse effect on human cardiovascular system. However, the cardiotoxicity of Pb on children is still unclear. The aim of this study was to evaluate left ventricular (LV) structure and function, by using echocardiographic indices, in order to elucidate the effect of Pb on low-grade inflammation related to left ventricle in healthy preschool children. We recruited a total of 486 preschool children, 310 from Guiyu (e-waste-exposed area) and 176 from Haojiang (reference area). Blood Pb levels, complete blood counts, and LV parameters were evaluated. Associations between blood Pb levels and LV parameters and peripheral leukocyte counts were analyzed using linear regression models. The median blood level of Pb and the counts of white blood cells (WBCs), monocytes, and neutrophils were higher in exposed group. In addition, the exposed group showed smaller left ventricle (including interventricular septum, LV posterior wall, and LV mass index) and impaired LV systolic function (including LV fractional shortening and LV ejection fraction) regardless gender. After adjustment for confounding factors, elevated blood Pb levels were significantly associated with higher counts of WBCs and neutrophils, and lower levels of LV parameters. Furthermore, counts of WBCs, monocytes, and neutrophils were negatively correlated with LV parameters. Taken together, smaller left ventricle and impaired systolic function were found in e-waste-exposed children and associated with chronic low-grade inflammation and elevated blood Pb levels. It indicates that the heart health of e-waste-exposed children is at risk due to the long-term environmental chemical insults.

Prognostic significance of Spinster homolog gene family in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a clonal and heterogeneous disease characterized by proliferation of immature myeloid cells, with impaired differentiation and maturation. Spinster homolog (SPNS) is a widely distributed transmembrane transporter, which assists sphingolipids in playing their roles through the cell membrane. However, the expression and clinical implication of the SPNS family has not been investigated in AML. From the Cancer Genome Atlas database, a total of 155 AML patients with complete clinical characteristics and SPNS1-3 expression data were contained in our study. In patients who received chemotherapy only, high expressions of SPNS2 and SPNS3 had adverse effects on event-free survival (EFS) and overall survival (OS) (all P<0.05). However, in the allogeneic hematopoietic stem cell transplantation (allo-HSCT) group, we only found a significant difference in OS between the high and low SPNS3 expression groups (P=0.001), while other SPNS members showed no effect on survival. Multivariate analysis indicated that high SPNS2 expression was an independent risk factor for both EFS and OS in chemotherapy patients. The results confirmed that high expression of SPNS2 and SPNS3 were poor prognostic factors, and the effect of SPNS2 can be neutralized by allo-HSCT.

Early-life exposure to widespread environmental toxicants and maternal-fetal health risk: A focus on metabolomic biomarkers.

Prenatal exposure to widespread environmental toxicants is detrimental to maternal health and fetal development. The effects of environmental toxicants on maternal and fetal metabolic profile changes have not yet been summarized. This systematic review aims to summarize the current studies exploring the association between prenatal exposure to environmental toxicants and metabolic profile alterations in mother and fetus. We searched the MEDLINE (PubMed) electronic database for relevant literature conducted up to September 18, 2019 with some key terms. From the initial 155 articles, 15 articles met the inclusion and exclusion criteria, and consist of highly heterogeneous research methods. Seven studies assessed the effects of multiple environmental pollutants (metals, organic pollutants, nicotine, air pollutants) on the maternal urine and blood metabolomic profile; five studies evaluated the effects of arsenic, polychlorinated biphenyls (PCBs), nicotine, and ambient fine particulate matter (PM2.5) on the cord blood metabolomic profile; and one study assessed the effects of smoking exposure on the amniotic fluid metabolomic profile. The alteration of metabolic pathways in these studies mainly involve energy metabolism, hormone metabolism, oxidative stress and inflammation. No population study investigated the association between environmental toxicants and placental metabolomics. This systematic review provides evidence that prenatal exposure to a variety of environmental pollutants can affect maternal and fetal metabolomic characteristics. Integration of environmental toxicant exposure and metabolomics data in maternal-fetal samples is helpful to understand the interaction between toxicants and metabolites, so as to reveal the pathogenesis of fetal disease or diseases of fetal origin.

Elevated expression of AhR and NLRP3 link polycyclic aromatic hydrocarbon exposure to cytokine storm in preschool children.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs), as a group of persistent organic pollutants, are linked to impaired immune function and low-grade inflammation in adults and children. However, the potential of PAHs to lead to a cytokine storm associated with AhR (aryl hydrocarbon receptor) and NLRP3 (NLR family pyrin domain containing 3) in humans has been poorly studied. OBJECTIVES: We aimed to investigate the associations between PAH exposure, AhR and NLRP3 expression, and cytokines associated with a cytokine storm in healthy preschoolers. METHODS: Basic demographic surveys and physical examinations were conducted on 248 preschoolers from an electronic waste (e-waste) recycling area (Guiyu, n = 121) and a reference area (Haojiang, n = 127). Ten urinary PAH metabolite (OH-PAH) concentrations were measured. We also measured the expression levels of AhR and NLRP3 and seventeen serum cytokine levels. RESULTS: The concentrations of multiple OH-PAHs were significantly higher in the exposed group than those in the reference group, especially 1-hydroxynaphthalene (1-OH-Nap) and 2-hydroxynaphthalene (2-OH-Nap). PAH exposure was closely related to a child's living environment and hygiene habits. Expression levels of AhR and NLRP3 were significantly higher in the exposed group than in the reference group. Similarly, serum IL-1ß, IL-4, IL-5, IL-10, IL-12p70, IL-13, IL-17A, IL-18, IL-22, IL-23, and IFN-γ levels were notably higher in the e-waste-exposed children than in the reference children. After adjusting for age, gender, BMI, family income, parental education level, and second-hand smoke exposure, we found that increased PAH exposure was associated with higher AhR and NLRP3 expression and elevated IL-4, IL-10, IL-12p70, IL-18, IL-22, IL-23, TNF-α, and IFN-γ levels. The associations between PAH exposure and IL-1ß, IL-18, IFN-γ, and TNF-ß were mediated by NLRP3 expression, and the relationships between PAH exposure and IL-4, IL-10, IL-12p70, IL-22, IL-23, and TNF-α were mediated by AhR expression. CONCLUSIONS: Our findings suggest that the association between PAH exposure and a cytokine storm may be mediated by AhR and NLRP3 expression among preschoolers.

Upregulation of Glutamic-Oxaloacetic Transaminase 1 Predicts Poor Prognosis in Acute Myeloid Leukemia.

One of the key features of acute myeloid leukemia (AML), a group of very aggressive myeloid malignancies, is their strikingly heterogenous outcomes. Accurate biomarkers are needed to improve prognostic assessment. Glutamate oxaloacetate transaminase 1 (GOT1) is essential for cell proliferation and apoptosis by regulating cell's metabolic dependency on glucose. It is unclear whether the expression level of GOT1 has clinical implications in AML. Therefore, we analyzed the data of 155 AML patients with GOT1 expression information from The Cancer Genome Atlas (TCGA) database. Among them, 84 patients were treated with chemotherapy alone, while 71 received allogeneic hematopoietic stem cell transplantation (allo-HSCT). In both treatment groups, high GOT1 expression was associated with shorter event-free survival (EFS) and overall survival (OS) (all P < 0.05). Multivariate analysis identified several independent risk factors for both EFS and OS in the chemotherapy-only group, including high GOT1 expression, age ≥60 years, white blood cell count ≥15 × 109/L, bone marrow blasts ≥70%, and DNMT3A, RUNX1 or TP53 mutations (all P < 0.05); but in the allo-HSCT group, the only independent risk factor for survival was high GOT1 expression (P < 0.05 for both EFS and OS). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the genes related to GOT1 expression were mainly concentrated in "hematopoietic cell lineage" and "leukocyte transendothelial migration" signaling pathways. Collectively, GOT1 expression may be a useful prognostic indicator in AML, especially in patients who have undergone allo-HSCT.

Association of prenatal exposure to PAHs with anti-Müllerian hormone (AMH) levels and birth outcomes of newborns.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are chemicals that cause serious concerns because of their carcinogenicity and endocrine disrupting ability. OBJECTIVE: In the current study, we studied how urinary PAH metabolites are related with the dose-effects of hormone levels and birth outcomes. METHOD: 163 pregnant women without health problems and 163 newborns were enrolled in hospitals in Guiyu (e-waste-exposed area) and Haojiang (reference area) from May 2016 to May 2017. Urine samples were collected to measure hydroxylated PAH (OH-PAH) metabolite levels. Umbilical cord blood was used for measurement of hormone levels. Anthropometric parameters of newborns, such as anogenital distance (AGD), were also measured. RESULTS: Eight of ten urinary PAH metabolites in the exposed group were significantly higher than in the reference group. Levels of umbilical cord serum estradiol (E2) and testosterone (T) in the exposed group were significantly lower than those in the reference group. Birth weight was positively correlated with 2-OHFlu (2-hydroxyfluorene). Head circumference was negatively correlated with 9-OHFlu, 3-OHPhe (3-hydroxyphenanthrene), 9-OHPhe, and Æ©OHFlu (sum of 2-OHFlu and 9-OHFlu). Serum E2 and T levels were negatively correlated with most OH-PAHs. In addition, we found that serum anti-Müllerian hormone (AMH) level was positively correlated with AGD, and serum E2 level was negatively correlated with neonatal head circumference. CONCLUSIONS: PAH exposure in pregnant women may adversely affect the birth outcomes of newborns, especially AGD; and AMH may be involved in the process. Establishing a baseline for the relationship between PAH exposure and health is important to protect the health of mothers and children living in electronic waste (e-waste) recycling areas.

Prognostic role of SCAMP family in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a malignant disease of myeloid hematopoietic stem or progenitor cells characterized by abnormal proliferation of primary and immature myeloid cells in bone marrow and peripheral blood. Gene mutation and expression profiles can be used as prognosis predictors for different prognostic subgroups. Secretory carrier-associated membrane proteins (SCAMPs) are a multigenic family with five members and act as cell surface vectors in the post-Golgi recycling pathways in mammals. Nevertheless, the prognostic and clinical influence of SCAMP family has hardly ever been illustrated in AML. In our study, expression patterns of SCAMP family (SCAMP1-5) were analyzed in 155 AML patients which were extracted from the Cancer Genome Atlas database. In chemotherapy, only subgroup, higher SCAMP1 level was significantly associated with longer EFS and OS (all P = 0.002), and SCAMP1 was confirmed to be an independent favorable factor in un-transplanted patients by Multivariate analysis (all P < 0.05). Nevertheless, in the allogeneic hematopoietic stem cell transplantation (allo-HSCT) treatment subgroup, none of the SCAMP genes had any effect on the clinical survival. Our study found that high expression level of SCAMP1 is a favorable prognostic factor in AML, but allo-HSCT may neutralize its prognostic effect.

Enhanced expression of FCER1G predicts positive prognosis in multiple myeloma.

Background: Multiple myeloma (MM) is the second most common hematologic malignancy worldwide and does not have sufficient prognostic indicators. FCER1G (Fc fragment Of IgE receptor Ig) is located on chromosome 1q23.3 and is involved in the innate immunity. Early studies have shown that FCER1G participates in many immune-related pathways encompassing multiple cell types. Meanwhile, it is associated with many malignancies. However, the relationship between MM and FCER1G has not been studied. Methods: In this study, we integrated nine independent gene expression omnibus (GEO) datasets and analyzed the associations of FCER1G expression and myeloma progression, ISS stage, 1q21 amplification and survival in 2296 myeloma patients and 48 healthy donors. Results: The expression of FCER1G showed a decreasing trend with the advance of myeloma. As ISS stage and 1q21 amplification level increased, the expression of FCER1G decreased (P = 0.0012 and 0.0036, respectively). MM patients with high FCER1G expression consistently had longer EFS and OS across three large sample datasets (EFS: P = 0.0057, 0.0049, OS: P = 0.0014, 0.00065, 0.0019 and 0.0029, respectively). Meanwhile, univariate and multivariate analysis indicated that high FCER1G expression was an independent favorable prognostic factor for EFS and OS in MM patients (EFS: P = 0.006, 0.027, OS: P =0.002,0.025, respectively). Conclusions: The expression level of FCER1G negatively correlated with myeloma progression, and high FCER1G expression may be applied as a favorable biomarker in MM patients.

High expression of chaperonin-containing TCP1 subunit 3 may induce dismal prognosis in multiple myeloma.

The prognosis role of CCT3 in MM and the possible pathways it involved were studied in our research. By analyzing ten independent datasets (including 48 healthy donors, 2220 MM, 73 MGUS, and 6 PCL), CCT3 was found to express higher in MM than healthy donors, and the expression level was gradually increased from MGUS, SMM, MM to PCL (all P < 0.01). By analyzing three independent datasets (GSE24080, GSE2658, and GSE4204), we found that CCT3 was a significant indicator of poor prognosis (all P < 0.01). KEGG and GSEA analysis showed that CCT3 expression was associated with JAK-STAT3 pathway, Hippo signaling pathway, and WNT signaling pathway. In addition, different expressed genes analysis revealed MYC, which was one of the downstream genes regulated by JAK-STAT3 pathway, was upregulated in MM. This confirms that JAK-STAT3 signaling pathway may promote the progress of disease which was regulated by CCT3 expression. Our study revealed that CCT3 may play a supporting role at the diagnosis of myeloid, and high expression of CCT3 suggested poor prognosis in MM. CCT3 expression may promote the progression of MM mainly by regulating MYC through JAK-STAT3 signaling pathway.

Prognostic Value of MicroRNA-20b in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a highly heterogeneous disease that requires fine-grained risk stratification for the best prognosis of patients. As a class of small non-coding RNAs with important biological functions, microRNAs play a crucial role in the pathogenesis of AML. To assess the prognostic impact of miR-20b on AML in the presence of other clinical and molecular factors, we screened 90 AML patients receiving chemotherapy only and 74 also undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) from the Cancer Genome Atlas (TCGA) database. In the chemotherapy-only group, high miR-20b expression subgroup had shorter event-free survival (EFS) and overall survival (OS, both P < 0.001); whereas, there were no significant differences in EFS and OS between high and low expression subgroups in the allo-HSCT group. Then we divided all patients into high and low expression groups based on median miR-20b expression level. In the high expression group, patients treated with allo-HSCT had longer EFS and OS than those with chemotherapy alone (both P < 0.01); however, there were no significant differences in EFS and OS between different treatment subgroups in the low expression group. Further analysis showed that miR-20b was negatively correlated with genes in "ribosome," "myeloid leukocyte mediated immunity," and "DNA replication" signaling pathways. ORAI2, the gene with the strongest correlation with miR-20b, also had significant prognostic value in patients undergoing chemotherapy but not in the allo-HSCT group. In conclusion, our findings suggest that high miR-20b expression is a poor prognostic indicator for AML, but allo-HSCT may override its prognostic impact.

High IFITM3 expression predicts adverse prognosis in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a malignancy caused by the uncontrolled and dysregulated clonal expansion of abnormal myeloid primordial cells. In general, the prognosis of AML remains poor despite new discoveries in its pathogenesis and treatment. It is crucial to find early and sensitive biomarkers and continue to explore active targeted treatments. Interferon-induced transmembrane protein (IFITM) family is an important part of the interferon signaling pathway and participate in the regulation of immune cell signaling, adhesion, cancer, and liver cell migration. However, the clinical and prognostic value of the IFITM family in AML has rarely been studied. We screened The Cancer Genome Atlas database and found 155 AML patients with IFITM family (IFITM1-5) expression data. In patients who only received chemotherapy, those with high IFITM3 expression had significantly shorter event-free survival (EFS) and overall survival (OS) than patients with low expression (all P < 0.05). Multivariate analysis demonstrated that high IFITM3 expression was an independent risk factor for EFS and OS in patients only received chemotherapy (all P < 0.05). In patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), however, all IFITM members had no impact on either EFS or OS. In conclusion, our study elucidated that high IFITM3 expression could be an adverse prognostic factor for AML, whose effect might be overcome by allo-HSCT.