Cu(OTf)2-Phosphoric Acid-Catalyzed Tandem Oxa-Nazarov Cyclization and Dibromination of Conjugated 1,2-Diketones.

A facile tandem oxa-Nazarov cyclization and dibromination has been developed. The combination of Cu(OTf)2 and diphenyl phosphate (DPP-H) was found to synergistically promote the coupling of conjugated 1,2-diketones and N-bromosuccinimide to form 2,4-dibromo-3(2H)-furanones in good yields.

Deoxycytidine Kinase (DCK) Mutations in Human Acute Myeloid Leukemia Resistant to Cytarabine.

Resistance to cytarabine is an important cause of therapy failure in persons with acute myeloid leukemia (AML). Deoxycytidine kinase, encoded by DCK, catalyzes phosphorylation of cytarabine to cytarabine monophosphate, a necessary step for eventual incorporation of cytarabine triphosphate into DNA and for clinical efficacy. Whether DCK mutations make AML cells resistant to cytarabine is controversial. We studied DCK mutations and messenger RNA (mRNA) concentrations in leukemia cells from 10 subjects with AML who received cytarabine-based therapy and relapsed and in 2 artificially induced cytarabine-resistant AML cell lines. DCK mutations were detected in 4 subjects with AML relapsing after achieving a complete remission and receiving high-dose cytarabine postremission therapy. Most mutations were in exons 4-6 and were not present before therapy. DCK was also mutated in cytarabine-resistant but not parental AML cell lines. DCK mRNA concentrations were significantly decreased in cytarabine-resistant K562 and SHI-1 cells compared with cytarabine-sensitive parental cells. Mutation frequency of DCK and mRNA concentration did not correlate with the extent of cytarabine resistance indicating other factors operate. Overexpression of wild-type DCK restored cytarabine sensitivity to previously resistant leukemia cell lines. Our data contribute to the understanding of cytarabine resistance in persons with AML.

Comprehensive Numerical Evaluation of CO2 Huff-n-Puff in an Offshore Tight Oil Reservoir: A Case Study in Bohai Bay Area, China.

Many reports have presented that in tight formation, the flow mechanism differs from a conventional reservoir, such as molecular diffusion, Pre-Darcy flow behavior, and stress sensitivity. However, for CO2 Huff-n-Puff development, it is a challenge to synthetically research these mechanisms. Considering the above flow mechanisms and offshore engineering background, the development plan optimization becomes a key issue. In this paper, a self-developed simulator that satisfies research needs is introduced. Then, based on experimental results, the simulation is launched to analyze the effects of CO2 diffusion, Huff-n-Puff period, and permeability heterogeneity. The results indicate that molecular diffusion makes a positive contribution to the oil recovery factor. Additionally, for offshore reservoirs, limited to the development cost and CO2 facilities corrosion, when the total Huff-n-Puff time is constant, the ratio of 0.5-1.0 between the Huff period and the Puff period in every cycle performs better. Finally, the greater heterogeneity in permeability is much more favorable for the CO2 Huff-n-Puff because of more intensive transport processes in formation. These different scenarios can increase the understanding of the CO2 Huff-n-Puff in tight oil offshore reservoirs.

Numerical simulation of CO2-ECBM for deep coal reservoir with strong stress sensitivity.

CH4 production rate of coalbed methane (CBM) well decreases rapidly during primary recovery in the deeply buried coal seam, resulting in a lot of CH4 residues. CO2 pour into deep coal seam with high stress sensitivity is available for enhancing CH4 recovery by improving permeability for reservoir fracture and displacing CH4 adsorbed in matrix. A coupled adsorp-hydro-thermo-mechanical (AHTM) model for deep methane development is established by considering the coupling relationships of non-isothermal and non-constant pressure competitive adsorption between CO2 and CH4, multi-phase flow, unsteady diffusion, heat transmission and in-situ stress variety. The model is verified by historical production and then used for CO2 enhanced CBM (CO2-ECBM) of deep coal reservoir in a sedimentary basin in Northwest China. The simulation results show that: (1) For primary recovery, permeability in coal reservoir drops rapidly with the development of CBM, which seriously restricts the production of CH4. The permeability of the reservoir decreases from 7.89 × 10-16 m2 to less than 1.50 × 10-16 m2, CH4 production rate in CBM well reduces to below 2000 m3/d, and the average total CH4 content of coal reservoir is reduced by 5.49 m3/t with the decrease of only 1.12 m3/t of average adsorbed CH4 in a production duration of 2000 d (2) With 10 MPa CO2 continuous injection into coal seam after 700d of primary, the permeability for reservoir and CH4 production rate increase while the total CH4 content and adsorption CH4 content in reservoir decrease compared with the primary recovery. (3) CO2 pouring into coal reservoir increases the CH4 production time and rate, which improves CH4 recovery of coal reservoir. And it increases by 23.36 %, 23.07 % and 22.46 % with shut-in thresholds of CH4 production rate of 1000 m3/d, 800 m3/d and 600 m3/d, respectively. The investigation is of great significance for the development of deep coalbed methane.

Signaling pathways involved in endoplasmic reticulum stress-induced neuronal apoptosis.

In eukaryotic cells, the endoplasmic reticulum (ER) is a very critical site for synthesis, folding, modification of protein, and calcium homeostasis. The ER responds to factors that perturb ER function such as the accumulation of unfolded proteins (ER stress) by activating unfolded protein response to relieve the stress. However, chronic or unresolved ER stress can induce neuronal apoptosis by activating c-Jun N-terminal kinase (JNK), glycogen synthase kinase 3/3ß (GSK3/3ß), CAAT/enhancer binding protein homologous protein (CHOP), and caspase-12 pathway. Research related to ER stress will provide therapeutic implications in neurological diseases.

Detection of cell-type-enriched long noncoding RNAs in atherosclerosis using single-cell techniques: A brief review.

Cardiovascular diseases are the leading causes of mortality and morbidity worldwide. Atherosclerotic plaque underlies the predominant factors and is composed of various cell types, including structure cells, such as endothelial and smooth muscle cells, and immune cells, such as macrophages and T cells. Single-cell RNA sequencing (scRNA-seq) has been extensively applied to decipher these cellular heterogeneities to expand our understanding on the mechanisms of atherosclerosis (AS) and to facilitate identifying cell-type-specific long noncoding RNAs (LncRNAs). LncRNAs have been demonstrated to deeply regulate biological activities at the transcriptional and post-transcriptional levels. A group of well-documented functional lncRNAs in AS have been studied. In our review, we selectively described several lncRNAs involved in the critical process of AS. We highlighted four novel lncRNAs (lncRNA CARMN, LINC00607, PCAT19, LINC01235) detected in scRNA-seq datasets and their functions in AS. We also reviewed open web source and bioinformatic tools, as well as the latest methods to perform an in-depth study of lncRNAs. It is fundamental to annotate functional lncRNAs in the various biological activities of AS, as lncRNAs may represent promising targets in the future for treatment and diagnosis in clinical practice.

mTOR complex 2 activation by reconstituted high-density lipoprotein prevents senescence in circulating angiogenic cells.

OBJECTIVE: Circulating angiogenic cells (CACs) participate in neovascularization and arterial repair. Although high-density lipoprotein (HDL) is known to enhance the functional activity of CACs, the mechanisms underlying this regulation are poorly understood. Here, we examined the mechanism(s) by which reconstituted HDL (rHDL) affects CAC senescence. METHODS AND RESULTS: CACs isolated from human peripheral blood and treated with rHDL displayed reduced senescence, as measured by acidic ß-galactosidase staining. This protective effect was blocked by the mammalian target of rapamycin (mTOR) inhibitor (rapamycin). According to Western blot analysis and immunoprecipitation results, rHDL promoted mTOR phosphorylation, mTOR-rictor complex formation, and mTOR-rictor-dependent Akt activation, which were accompanied by increased nuclear translocation of human telomerase reverse transcriptase and enhanced nuclear telomerase activity. Suppression of rictor gene expression with a small interfering RNA blocked mTOR-rictor complex formation and Akt activation. The suppression also abolished the rHDL-induced inhibition of CAC senescence and promotion of nuclear telomerase activity. Treatment of aged mice with rHDL attenuated spleen-derived CAC senescence. In CACs isolated from rHDL-treated aged mice, the phosphorylated mTOR and Akt levels were significantly enhanced. CONCLUSION: rHDL stimulates sustained mTOR phosphorylation and mTOR-rictor complex formation and inhibits senescence onset in CACs through mTOR complex 2 pathway activation.

Toll-like receptor 4 is up-regulated by mTOR activation during THP-1 macrophage foam cells formation.

Macrophage foam cells formation is the most important process in atherosclerotic plaque formation and development. Toll-like receptor 4 (TLR4) is one of the important innate immune sensors of endogenous damage signals and crucial for regulating inflammation. Growing evidence indicates that TLR4 plays a very important role in macrophage foam cells formation. However, the underlying mechanisms regulating TLR4 expression in macrophage are not fully understood. In this study, we induced THP-1 macrophage foam cells formation with oxidative modified low-density lipoprotein (ox-LDL). We observed that TLR4 mRNA and protein expression were markedly up-regulated, and the phosphorylation of mammalian target of rapamycin (mTOR) and its downstream target p70S6K were promoted during foam cells formation. The mTOR inhibitor rapamycin blocked mTOR phosphorylation and inhibited TLR4 expression induced by ox-LDL. Silencing mTOR, rictor or raptor protein expression by small interfering RNA, also inhibited the up-regulation of TLR4 expression, respectively. Inhibition of mTOR with rapamycin reversed the down-regulation of cellular lipid efflux mediator ABCA1, which resulted from the activation of TLR4 by ligands. These data suggested that TRL4 expression was up-regulated by a mechanism dependent on mTOR signal pathway activation during THP-1 macrophage foam cells formation. Inhibition of ox-LDL induced mTOR activation reduced TLR4 expression, and improved the impaired lipid efflux.

[Effects of rapamycin on cholesterol homeostasis and secretory function of 3T3-L1 cells].

OBJECTIVE: To investigate the effects of rapamycin on cholesterol homeostasis and secretory function of 3T3-L1 cells. METHODS: The in vitro cultured 3T3-L1 cells (preadipocytes) were divided into control group, rapamycin 50 nmol/L group, rapamycin 100 nmol/L group, and rapamycin 200 nmol/L group. Intracellular cholesterol level was measured by oil red O staining and high performance liquid chromatography. The secretion levels of leptin and adiponectin were assayed by enzyme-linked immunosorbent assay. The mRNA and protein expressions of peroxisome proliferator-activated receptor (PPARgamma) were assayed by quantitative real-time polymerase chain reaction and Western blot. RESULTS: Oil red O staining showed rapamycin down-regulated 3T3-L1 cells differentiation and lipid accumulation. Quantitative measurement of cholesterol with high performance liquid chromatography showed that the concentrations of free cholesterol in rapamycin treatment groups had a significant reduction. The concentrations of free cholesterol in the control group, rapamycin 50 nmol/L group, rapamycin 100 nmol/L group, and rapamycin 200 nmol/L group were (12.89 +/- 0.16), (9.84 +/- 0.45), (9.39 +/- 0.46), and (8.61 +/- 0.34) mg/ml, respectively (P < 0.05), and the concentrations of total cholesterol were (12.91 +/- 0.50), (9.94 +/- 0.96), (10.45 +/- 2.51), and (9.53 +/- 0.63) mg/ml, respectively. The leptin concentrations in the control group, rapamycin 50 nmol/L group, rapamycin 100 nmol/L group, and rapamycin 200 nmol/L group were (19.02 +/- 0.52), (16.98 +/- 0.11), (15.62 +/- 0.01), and (13.84 +/- 0.66) ng/ml, respectively. The mRNA expressions of PPARgamma in the rapamycin 50 nmol/L group, rapamycin 100 nmol/L group, and rapamycin 200 nmol/L group were significantly lower than that in control group (P < 0.05). The protein expressions of PPARgamma in the rapamycin 50 nmol/L group, rapamycin 100 nmol/L group, and rapamycin 200 nmol/L group were 80%, 74%, and 61% of that in control group (P < 0.05). After the cells were treated with rapamycin 100 nmol/L, PPARgamma blocking agent GW9662 10 micromol/L, and PPARgamma agonist troglitazone 10 micromol/L, respectively, for 96 hours, the mRNA expression of PPARgamma was (0.60 +/- 0.14), (0.67 +/- 0.03), and (1.30 +/- 0.14) of that in control group (P < 0.05). The protein expression showed a similar trend with mRNA expression (P < 0.05). After the cells were treated with rapamycin 100 nmol/L, PPARgamma blocking agent GW9662 10 micromol/L, and PPARgamma agonist troglitazone 10 micromol/L, respectively, for 96 hours, the expression of leptin in the control group, rapamycin 50 nmol/L group, rapamycin 100 nmol/L group, and rapamycin 200 nmol/L group was (19.02 +/- 0.52), (15.62 +/- 0.10), and (14.45 +/- 1.01) and (18.07 +/- 0.66) ng/ml, respectively (P < 0.05 compared with the control group). CONCLUSIONS: By downregulating the expression of PPARgamma, rapamycin can decrease cholesterol accumulation in 3T3-L1 cells and inhibit its leptin-secreting capability. This finding may provide a possible explanation for rapamycin-induced hyperlipidemia in clinical practice.

Liraglutide Improves Endothelial Function via the mTOR Signaling Pathway.

BACKGROUND: Mammalian target of rapamycin (mTOR) is crucial for endothelial function. This study is aimed at assessing whether the glucagon-like peptide-1 (GLP-1) analogue liraglutide has a protective effect on endothelial function via the mTOR signaling pathway. METHODS: Human umbilical vein endothelial cells (HUVECs) were administered liraglutide (100 nM) for 0, 10, 30, 60, 720, and 1440 minutes, respectively. Then, the expression and phosphorylation levels of mTOR, mTOR-Raptor complex (mTORC1), and mTOR-Rictor complex (mTORC2) were determined by Western blot and immunoprecipitation, while mTORC1 and mTORC2 expression was blocked by siRNA-Raptor and siRNA-Rictor, respectively. Akt phosphorylation was detected by Western blot. HUVECs were then incubated with liraglutide in the absence or presence of Akt inhibitor IV. Nitric oxide (NO) release was assessed by the nitrate reductase method. Phosphorylated endothelial nitric oxide synthase (eNOS), human telomerase reverse transcriptase (hTERT), and apoptosis-related effectors were assessed for protein levels by Western blot. Telomerase activity was evaluated by ELISA. RESULTS: Sustained mTOR phosphorylation, mTORC2 formation, and mTORC2-dependent Akt phosphorylation were induced by liraglutide. In addition, eNOS phosphorylation, NO production, nuclear hTERT accumulation, and nuclear telomerase activity were enhanced by mTORC2-mediated Akt activation. Liraglutide also showed an antiapoptotic effect by upregulating antiapoptotic proteins and downregulating proapoptotic proteins in an mTORC2-Akt activation-dependent manner. CONCLUSION: Liraglutide significantly improves endothelial function, at least partially via the mTORC2/Akt signaling pathway.

Assessment of the Redox Characteristics of Iron Ore by Introducing Biomass Ash in the Chemical Looping Combustion Process: Biomass Ash Type, Constituent, and Operating Parameters.

Chemical looping combustion (CLC) is a potential CO2 capture and sequestration (CCS) technology that can easily separate CO2 and H2O without energy loss and greatly improve the efficiency of carbon capture. Due to the inherent defects of natural iron ore, such as low reactivity and poor oxygen carrying capacity, four kinds of biomass ashes (rape stalk ash, rice stalk ash, platane wood ash, and U. lactuca ash) that have different constituents of K, Na, Ca, and Si were applied to modify the redox performance of natural iron ore. The effects of biomass ash type, constituent, reaction temperature, H2O vapor flow rate, and redox cycle on the CLC process were assessed experimentally in a batch fluidized bed reactor system. Oxygen carrier physicochemical characteristics were determined by several analytical techniques. The results showed that rape stalk ash, platane wood ash, and U. lactuca ash with a high K content and high K/Si ratio significantly improved the reactivity and cycle stability of iron ore, even after 10 redox cycles, while rice straw ash with a low K/Si ratio showed an inhibitory effect due to the formation of bridge eutectics, which enhanced agglomeration. In a range from 800 to 950 °C, higher temperatures led to a much better ability to promote the CLC process than lower temperatures. A higher flow rate of H2O had little effect on the further promotion of the CLC process due to hydrogen inhibition. It is believed that the application of BA-modified iron ore oxygen carriers is an effective strategy to improve the CLC process.

Overexpression of P-selectin glycoprotein ligand-1 enhances adhesive properties of endothelial progenitor cells through Syk activation.

P-selectin glycoprotein ligand-1 (PSGL-1) not only functions as an anchor molecule to capture monocytes and other leukocytes to endothelial cells in ischemic tissue by its interaction with P-selectin, but also transduces signals to initiate firm adhesion. Endothelial progenitor cells are derived from monocytes and play a very important role in neovascularization. Transplantation of endothelial progenitor cells is a promising therapeutic strategy to improve treatment of ischemic disease such as myocardial and cerebral infarction; however, its efficacy is now limited by the fact that few of the transplanted cells adhere to and accumulate in the ischemic tissue. In this study we aimed to investigate whether the overexpression of PSGL-1 gene promotes endothelial progenitor cells adhesion activity and explore the underlying mechanisms. We found that after transfection with human PSGL-1 gene, endothelial progenitor cells exhibited higher affinity to activated human umbilical vein endothelial cells or recombined P-selectin/ICAM-1 monolayer. The overexpression of PSGL-1-enhanced beta2-integrin expression on endothelial progenitor cells surface, and this effect was Syk dependent. The specific Syk inhibitor abolished the elevating effect of overexpression of PSGL-1 on surface beta2-integrin expression and the adhesive affinity of endothelial progenitor cells. These results suggested that Syk plays a key role in signal transduction downstream of PSGL-1 in endothelial progenitor cells, and the overexpression of PSGL-1 improves endothelial progenitor cells adhesive properties through enhanced activation of Syk and following integrin activation.

[Improved angiogenesis by P-selectin glycoprotein ligand-1 overexpression in endothelial progenitor cells].

OBJECTIVE: To explore whether overexpression of P-selectin glycoprotein ligand-1 (PSGL-1) promotes the adhesive ability of endothelial progenitor cells and functionally facilitates neovascularization in mouse model of hindlimb ischemia. METHODS: Rat endothelial progenitor cells were transfected with recombinant adenovirus vector encoding human PSGL-1. The mRNA and protein expression levels of PSGL-1 were measured by RT-PCR and Western blot, respectively. The effect of overexpression of PSGL-1 in endothelial progenitor cells was analyzed by adherence assay. Histological examination of skeletal muscle sections retrieved from the mouse ischemic hindlimbs was performed, and the hindlimb blood flow was measured by laser Doppler flow meter. RESULTS: Adenovirus vector expressing of PSGL-1 gene was successfully constructed with high titer of 3.1 × 10¹¹ pfu/ml. After transfection, PSGL-1 gene was highly expressed in the transfected endothelial progenitor cells. In vitro assay showed that overexpression of PSGL-1 enhanced the adhesive properties of endothelial progenitor cells. When the transfected endothelial progenitor cells were transplanted into the ischemic hindlimb of nude mice, the number of new capillary vessels was (41.0 ± 2.2)/HPF compared to that of (21.0 ± 2.5)/HPF in the negative control group and (10.0 ± 1.6)/HPF in the blank control group (P < 0.01). Furthermore, the blood flow was increased in the experimental group (119.1% ± 7.0%), whereas in the negative control group, it was (93.3% ± 3.0%) and in the blank control group it was (76.3% ± 12.0%), P < 0.01. CONCLUSIONS: Overexpression of PSGL-1 enhances the adhesive and angiogenic properties of endothelial progenitor cells. The approach may provide an effective therapeutic strategy to improve the efficiency of cell-based proangiogenic therapy.

[Prevention of rupture of atherosclerotic plaque by Candesartan in rabbit model].

OBJECTIVE: To evaluate Candesartan therapeutic effect against atherosclerotic plaque rupture and to explore the related mechanisms. METHODS: Thirty-four New Zealand White male rabbits were randomly divided into three groups: the control group, the model control group and the Candesartan intervention group. The control group rabbits were fed with a normal diet. Rabbits of the latter two groups were fed with a 1% high-cholesterol diet and received a balloon catheter injury respectively one week after the cholesterol feeding. Candesartan (0.5 mgⁱkg⁻¹â±d⁻¹) was given to the Candesartan group rabbits 2 days before the performance of the balloon catheter injury. By the end of 12(th) week of the experiment, Russell's viper venom was used for rabbits of both the model control and the Candesartan groups in order to induce rupture of the plaques developed and followed by sacrifice of all the rabbits of the 3 groups. The aortas were removed and fixed for histological evaluation. Immunohistochemistry of MMP-9, macrophage markers and collagen were performed. The protein expression of MMP-9 was determined using Western blot analysis. RESULTS: In the model control group, 7 of 9 rabbits with a total of 12 plaques developed rupture and thrombosis of the plaques after the induction. In contrast, only 2 of 10 rabbits with a total of 3 plaques demonstrated rupture and thrombosis in the Candesartan group (P < 0.05). The control group rabbits did not have plaque rupture and thrombosis. Compared with the model group, both the percentage area of MMP-9 and macrophages in the plaques were significantly decreased in the Candesartan group (12.35% ± 4.28% vs 32.58% ± 9.16%, P < 0.05; 13.87% ± 4.91% vs 23.8% ± 7.45%, P < 0.05). There was an increased percentage of collagen content in total plaques of the Candesartan group (30.27% ± 11.36% vs 4.18% ± 1.28%, P < 0.01). Compared with the model group, the protein expression of MMP-9 was significantly decreased in the Candesartan group (P < 0.01). CONCLUSION: Candesartan has a preventive value against atherosclerotic plaque rupture in hypercholesterolemic rabbits, likely through its reduction of MMP-9 expression, inhibition of macrophage accumulation and increase of collagen content within the plaques.

Chinese and Europeans with acute myeloid leukemia have discordant mutation topographies.

Although the topography of mutations in persons of predominately European-descent with acute myeloid leukemia (AML) is well-described this is less so in Asians. We studied AML-related mutations in 289 consecutive Chinese (mostly Han) with newly-diagnosed de novo AML. Full-length coding sequence of NPM1 and CEBPA, IDH1 and IDH2 hotspot mutations and WT1 mutations in exons 7 and 9 were analyzed by PCR as were correlations with clinical and laboratory variables. CEBPA mutations were detected in 20% of subjects (95% confidence interval [CI] 15, 25%), NPM1 mutations in 20% (15, 25%), IDH1 mutations in 4% (1, 6%), IDH2 mutations in 11% (7, 15%) and WT1 mutations in 6% (3, 9%). A comparison of these data with mutation frequencies in persons of predominately European-descent with AML indicates a higher frequency of CEBPA mutations, a similar frequency of IDH2 mutations and lower frequencies of NPM1, IDH1 and WT1 mutations. Our data indicate different topographies of AML-associated mutations in Chinese compared with persons of predominately European descent suggesting genetic background, life-style, environment and perhaps other variables may influence these differences.

[Urokinase receptor expression in atherosclerotic plaques of human femoral arteries].

OBJECTIVE: To observe the urokinase receptor (uPAR) expression in atherosclerotic plaques of human femoral arteries. METHODS: Human femoral artery samples were collected from patients underwent femoral endarterectomy. Normal internal mammary artery samples were taken from bypass surgery served as control. uPAR protein distribution at shoulders, lipid pool and rupture sites of a plaque and the association with macrophages and smooth muscle cells (SMCs) were detected by immunohistochemistry methods. RESULTS: There was no uPAR expression in intima or tunica media of normal internal mammary arteries. In atherosclerotic lesions of femoral artery, the mean optical density (A) of uPAR was 92 +/- 37 in intima and 46 +/- 28 in tunica media (P < 0.05). The intimal uPAR was coexisted with macrophages and SMCs. uPAR expression was observed at plaque shoulders and lipid pool, while the maximal expression was found at rupture sites. CONCLUSION: The increased expression of uPAR in atherosclerotic lesion and uPAR distribution at shoulders, lipid pool, as well as rupture sites of plaques suggest a role of uPAR in plaque rupture process.

[The effect of serum high-density lipoprotein on the growth rate of human endothelial progenitor cells].

OBJECTIVE: To study the effect of high-density lipoprotein (HDL) on the proliferation of endothelial progenitor cells (EPC) isolated from human umbilical cord blood; to further explore its effect on prevention and development of atherogenesis. METHODS: EPC isolated by density gradient centrifugation were cultured in a M200 medium. Immunofluorescence staining for CD133, CD34, KDR and Factor VIII were adopted respectively as the specific markers for identification. The effect of HDL on EPC proliferation was estimated on the 7th day of cell cultivation using MTT assay, confocal microscopy and fluorescence activated cell sorting. RESULTS: HDL, when incubated with EPC, was able to promote remarkably the proliferation rate of EPC, dose- and time-dependent. HDL participated in the transcriptional regulation of cell cycle by affecting the regulatory proteins such as cyclin D1. CONCLUSIONS: A subtype of progenitor cells was isolated from human cord blood with a potential of differentiating into mature endothelial cells (known as endothelial progenitor cells). HDL plays an important role on EPC fluorescence activated cell sorting differentiation and proliferation. Further studies are required to identify the signal pathway and the molecular mechanism of HDL effect on EPC proliferation.

Evaluation of co-pyrolysis petrochemical wastewater sludge with lignite in a thermogravimetric analyzer and a packed-bed reactor: Pyrolysis characteristics, kinetics, and products analysis.

Co-pyrolysis characteristics of petrochemical wastewater sludge and Huolinhe lignite were investigated using thermogravimetric analyzer and packed-bed reactor coupled with Fourier transform infrared spectrometer and gas chromatography. The pyrolysis characteristics of the blends at various sludge blending ratios were compared with those of the individual materials. Thermogravimetric experiments showed that the interactions between the blends were beneficial to generate more residues. In packed-bed reactor, synergetic effects promoted the release of gas products and left less liquid and solid products than those calculated by additive manner. Fourier transform infrared spectrometer analysis showed that main functional groups in chars gradually disappeared with pyrolysis temperatures increasing, and H2O, CH4, CO, and CO2 appeared in volatiles during pyrolysis. Gas compositions analysis indicated that, the yields of H2 and CO clearly increased as the pyrolysis temperature and sludge blending ratio increasing, while the changes of CH4 and CO2 yields were relatively complex.

BCL11A expression in acute myeloid leukemia.

BACKGROUND: BCL11A encodes a C2H2 type zinc-finger protein. During normal haematopoietic cell differentiation BCL11A expression is down-regulated. Data in mice suggest up-regulation of BCL11A is involved in the pathogenesis of myeloid leukaemias. BCL11A expression in persons with acute myeloid leukaemia (AML) is not systematically studied. OBJECTIVE: Interrogate associations between BCL11A expression at diagnosis and clinical and laboratory valuables and outcomes in newly-diagnosed persons with AML. METHODS: We determined BCL11A mRNA levels in bone marrow and blood mononuclear cells in 292 consecutive newly-diagnosed subjects with AML by reverse transcript and real-time polymerase chain reaction. Data were compared to mRNA levels in bone marrow cells of normals. RESULTS: Subjects with BCL11A transcript levels at diagnosis exceeding the median value of 2.434 (±3.423 SD; 25th-75th inter-quartile range, 1.33-4.29) had higher WBC levels, a greater proportion of bone marrow myeloblasts, were more likely to be FAB M0 subtype, less likely to be FAB M3 subtype, more likely to be in the intermediate cytogenetic risk cohort, less likely to have a complex karyotype and more likely to have DNMT3A(R882) and FLT3-ITD mutations than subjects with transcript levels below the median value. In 89 subjects receiving conventional induction chemotherapy the complete remission rate was 54% (95% confidence interval [CI]; 33, 75%) in the lower BCL11A cohort and 65% (45, 85%; P=0.26) in the higher BCL11A cohort. 3 year survival was 33% (2, 65%) in the lower BCL11A cohort and 15% (0, 39%; P=0.35) in the high BCL11A cohort. CONCLUSION: BCL11A transcript levels at diagnosis was significantly associated with several clinical and laboratory variables. There were also non-significant associations with complete remission rate and survival. These data suggest a possible role for BCL11A expression in AML biology.

Effect of oxidized-LDL on NF-kappaB nuclear translocation in aortic smooth muscle cells originated from rats of different ages.

OBJECTIVE: To investigate the molecular mechanism of atherosclerosis that related to age. METHODS: Immunohistochemistry staining and Western blot were adopted to determine the nuclear translocation of nuclear factor-kappa B (NF-kappaB) and expression of platelet-derived growth factor B (PDGF-B) in smooth muscle cells (SMCs) co-cultured with low density lipoprotein (LDL), oxidized LDL (ox-LDL), and ox-LDL+high density lipoprotein (HDL) originated from rats of 2 and 10 months old respectively. Fat stain was used to identify the lipid intake in SMCs. RESULTS: The optimal stimulation time of ox-LDL to SMCs was 12 hours. NF-kappaB intensity increased in most nuclei of SMCs that originated from rats of either 2 or 10 months old co-cultured with ox-LDL. The intensity of NF-KB and the amount of intracellular lipid taken in SMCs were more obvious in cells from 10-month-old rats than from the younger ones. Change of PDGF-B expression in SMCs was not remarkable in each group of rats. CONCLUSIONS: The 10-month-old rats are more susceptive to ox-LDL than 2-month-old rats in activating nuclear translocation of NF-kappaB. Maybe this is one of the important reasons contributing to the difference between the older and younger rats on the initiation and development of atherosclerosis lesion. Expression of PDGF-B is not associated with the activity of nuclear translocation of NF-kappaB.