Lactate Decreases Bortezomib Sensitivity and Predicts Poor Clinical Outcomes of Multiple Myeloma

Objective:Metabolic disorders are regarded as hallmarks of multiple myeloma(MM)and are responsible for rapid cancer cell proliferation and tumor growth.However,the exact biological roles of metabolites in MM cells have not been fully explored.This study aimed to explore the feasibility and clinical significance of lactate for MM and investigate the molecular mechanism of lactic acid(Lac)in the proliferation of myeloma cells and cell sensitivity to bortezomib(BTZ).Methods:Metabolomic analysis of the serum was carried out to obtain metabolites expression and clinical characteristics in MM patients.The CCK8 assay and flow cytometry were used to detect cell proliferation,apoptosis,and cell cycle changes.Western blotting was used to detect the potential mechanism and apoptosis-and cycle-related protein changes.Results:Lactate was highly expressed in both the peripheral blood and bone marrow of MM patients.It was significantly correlated with Durie-Salmon Staging(DS Staging)and the International Staging System(ISS Staging)and the serum and urinary involved/uninvolved free light chain ratios.Patients with relatively high lactate levels had a poor treatment response.Moreover,in vitro experiments showed that Lac could promote the proliferation of tumor cells and decrease the proportion of G0/G1-phase cells,which was accompanied by an increased proportion of S-phase cells.In addition,Lac could decrease tumor sensitivity to BTZ by disrupting the expression of nuclear factor kappa B subunit 2(NFκB2)and Re1B.Conclusion:Metabolic changes are important in MM cell proliferation and treatment response;lactate could be used as a biomarker in MM and as a therapeutic target to overcome cell resistance to BTZ.

Sources of rare earth elements REE+Y(REY)in Bayili Coal Mine from Wensu County of Xinjiang,China

By analyses on the trace elements of coals,host-rocks and wall-rocks,this study aims to trace the sources and evaluate the utilization prospects of REE+Y(REY)in coals from Bayili Coal Mine(Wensu,Xinjiang,China).The distribution patterns of REY in the coals are divided into two groups,flat-type and heavy REE-enrichment type(H-type).The REY of the former was mainly from the gneisses of the basement of the coal-bearing basin,and that of the later was partly from hydrothermal solution.The host-rocks show two types of REY patterns,middle REE-enrichment type(M-type)and H-type,which are due to the injection of REY from acid terrestrial water and hydrothermal solution,respectively.Almost all the coal samples are plotted into the promising area on the diagram of percentage of critical elements(REY_(def,rel))vs ratio of sum of critical elements to the sum of excessive elements(C_(outl))and half of the coal samples have high contents of Ga closing to the cut-off grade of Ga deposit as by-product,which indicate that the REY and Ga in Bayili Coal Mine are of utilization prospects as by-product.

Trigger and noise filtering algorithms for the LHAASO water Cherenkov detector array

Introduction The Large High Altitude Air Shower Observatory(LHAASO)will be constructed at Mt.Haizishan,Sichuan Province,China.Among several detector components of the LHAASO,the Water Cherenkov Detector Array(WCDA)is of great importance for gamma-ray astronomy from 100 GeV to 30 TeV.The single-channel counting rate of a photo-multiplier tube can reach as high as 30-35 kHz,most of them are background noise hits from the low energy cosmic ray showers,bringing a big challenge on data transferring,data storage and event reconstruction.Methods In this paper,a dedicated trigger scheme and a fast noise filtering method aiming to deal with these high rate background noise hits are introduced.These methods are tested with some Monte Carlo simulation data,showing a fair efficiency in filtering background noise hits,while most of the real shower signals are kept.Conclusion This method is proposed to be applied in a stage of the online processing just after the data are acquired in LHAASO-WCDA.