Characterization of in vitro and in vivo hypomethylating effects of decitabine in acute myeloid leukemia by a rapid, specific and sensitive LC-MS/MS method

DNA hypermethylation is a common finding in malignant cells and has been explored as a therapeutic target for hypomethylating agents (e.g., decitabine). Detection of changes in DNA methylation might serve as a pharmacodynamic endpoint to establish the biological activity of these agents and predict clinical response. We developed and validated a rapid, sensitive and specific LC-MS/MS method for determination of global DNA methylation (GDM) in vitro and in vivo. Ratios of 5-methyl-2′-deoxycytidine (5mdC) to the internal standard 2-deoxyguanosine (2dG) in mass signal were used to quantify GDM levels. The assay was validated in a linear range from 40 fmol to 200 pmol 5mdC. The intra-day precision values ranged from 2.8 to 9.9% and the inter-day values from 1.1 to 15.0%. The accuracy of the assay varied between 96.7 and 109.5%. This method was initially applied for characterization of decitabine-induced GDM changes in in-vitro-treated leukemia cells. Following exposure to 2.5 μM decitabine, GDM decreased to ∼50% of the baseline value. The clinical applicability of this method was then demonstrated in bone marrow samples from patients with acute myeloid leukemia treated with decitabine. Our data support the use of our LC-MS/MS method for clinical pharmacodynamic determination of changes in GDM in vivo

Key technologies research on of soil-structure interaction base story isolated structure response in 3D seismic zone

The development of karst in Karst area leads to poor stability of stratum. If earthquake occurs, the area will produce destructive disaster. In order to improve the stability capacity of the grassroots in the region, this study investigates the seismic response of inter-story isolation structures considering soil-structure interaction (SSI) in three-dimensional earthquakes. A model of the inter-story isolation structure incorporating SSI was developed, and one-dimensional, two-dimensional, and three-dimensional ground motions were applied to compare the seismic response under different input conditions. A three-dimensional isolation system was introduced and compared with traditional horizontal isolation structures to address excessive tensile and compressive stresses on the isolation structure during three-dimensional ground motion. The results demonstrate that the seismic response to three-dimensional earthquakes surpasses one-dimensional and two-dimensional inputs. Furthermore, adding a three-dimensional isolation structure effectively isolates vertical ground motion and reduces structural seismic response. Moreover, it minimizes soil stresses on the foundation compared to traditional horizontal isolation structure, enhancing foundation stability. This study will provide theoretical value and practical guidance for the research on key technology of SSI base story isolation structure response in Karst Plateau 3D Seismic zone

Distribution of Anthocyanins Delivered from a Bioadhesive Black Raspberry Gel Following Topical Intraoral Application in Normal Healthy Volunteers

Results from our oral cavity chemoprevention trial demonstrated appreciable interpatient variations regarding chemopreventive efficacy of a freeze dried black raspberry (FBR) gel. We speculated these data reflected individual patient-related differences in absorption, target tissue uptake and local compound metabolism of key FBR compounds (anthocyanins). Accordingly, this study assessed the distribution of anthocyanins from the 10% (w/w) FBR gel in saliva, oral tissues and plasma

The positivity rates and drug resistance patterns of Mycobacterium tuberculosis using nucleotide MALDI-TOF MS assay among suspected tuberculosis patients in Shandong, China: a multi-center prospective study

ObjectiveTo investigate the positivity rates and drug resistance characteristics of Mycobacterium tuberculosis (MTB) among suspected tuberculosis (TB) patients in Shandong Province, the second-largest population province in China.MethodsA prospective, multi-center study was conducted from April 2022 to June 2023. Pathogen and drug resistance were identified using nucleotide matrix-assisted laser desorption ionization time-of-flight mass spectrometry (nucleotide MALDI-TOF MS).ResultsOf 940 suspected TB patients included in this study, 552 cases were found to be infected with MTB giving an overall positivity rate of 58.72%. Total of 346 cases were resistant to arbitrary anti-TB drug (62.68%), with Zibo (76.47%), Liaocheng and Weihai (both 69.23%) ranking top three and TB treatment history might be a related factor. Monoresistance was the most common pattern (33.53%), with isoniazid the highest at 12.43%, followed by rifampicin at 9.54%. Further analysis of gene mutations conferring resistance revealed diverse types with high heteroresistance rate found in multiple anti-TB drugs.ConclusionA relatively high rate of MTB positivity and drug resistance was found in Shandong Province during and after the COVID-19 pandemic, indicating the need for strengthening rapid identification of species and drug resistance among suspected TB patients to guide better medication and minimize the occurrence of drug resistance

Major and Trace Element Geochemistry of Pyrite and Pyrrhotite from Stratiform and Lamellar Orebodies: Implications for the Ore Genesis of the Dongguashan Copper (Gold) Deposit, Eastern China

The Dongguashan copper (gold) deposit in Anhui Province is one of the largest copper (gold) deposits in the Tongling ore district, which is the most important region in the Middle–Lower Yangtze River Metallogenic Belt, Eastern China. Stratiform and lamellar orebodies are the major deposit types. Pyrite and pyrrhotite from the stratiform deposit type (Py I, Po I) and lamellar deposit type (Py II, Po II) are investigated using Electron-probe Microanalyses (EPMA) and Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS). Py I, Py II, Po I and Po II have high contents of Cu, Co, Au and Se, low contents of As, Pb and Zn, with Co/Ni ratios of 0.50−48.00, 4.00−45.00, 1.55−14.45 and 1.02−1.36, respectively, most of which are greater than 1 and vary widely; these characteristics are consistent with those of pyrite with a magmatic–hydrothermal origin. The higher Au/Ag and Fe/(S + As) ratios of pyrite and crystallization temperatures (286–387 °C) of hexagonal pyrrhotite indicate that the mineralization occurrs in environments with medium- to high-temperatures, high sulfur fugacity and medium-shallow depths. Therefore, we suggest that the Dongguashan copper (gold) deposit is a stratabound skarn-type ore deposit associated with magma intrusion activity during the Yanshanian Period

Indium Mineralization in the Xianghualing Sn-Polymetallic Orefield in Southern Hunan, Southern China

Although numerous W–Sn–Pb–Zn polymetallic deposits are located in southern Hunan, and In-bearing deposits are related to W–Sn–Pb–Zn polymetallic deposits, Indium mineralization in southern Hunan is poorly studied. In order to investigate the In mineralization of the Xianghualing orefield, which is a typical orefield in southern Hunan, ore bulk chemistry, microscopic observation, and electron-probe microanalysis of vein-type (type-I) and porphyry-type (type-II) Sn–Pb–Zn orebodies were studied. The In contents of the type-I orebodies varies from 0.79 to 1680 ppm (avg. 217 ppm, n = 29), and that of the type-II orebodies varies from 10 to 150 ppm (avg. 64 ppm, n = 10). Although chalcopyrite and stannite contain trace amounts of In, sphalerite is the most important In-rich mineral in the orefield. Sphalerite in type-I orebodies contains from <0.02 to 21.96 wt % In, and in type-II orebodies contains from <0.02 to 0.39 wt % In. Indium-rich chemical-zoned sphalerite contains 7 to 8 wt % In in its core and up to 21.96 wt % In in its rim. This sphalerite may be the highest In-bearing variety in Southern China. The Cd contents of the In-rich sphalerite ranges from 0.35 to 0.45 wt %, which places it in the the “Indium window” of the Cu–In–S phases. The geological and structural features of the Xianghualing orefield indicate that the In mineralization of the two types of In-bearing Sn–Pb–Zn orebodies is related to the volatile-rich, In-rich, A-type granites, and is controlled by the normal faults of magmatic-diapiric activity extensional features

Geology and Geochemistry of the Shizitou Molybdenum Deposit, Jiangxi Province: Implications for Geodynamic Setting and Metallogenesis

The Shizitou molybdenum (Mo) deposit in Yongping, Jiangxi, is an important, recently discovered deposit in the eastern section of the Qin-Hang metallogenic belt. The Mo deposit is located in the outer contact zone between the porphyritic biotite granite and the Neoproterozoic migmatite, and present in the deep central part of the intrusion. Re-Os dating and S and Pb isotopic analysis have been conducted to assess the metallogenesis of the Shizitou Mo deposit. S, Pb and Re isotopes show that the ore-forming materials were derived from the porphyritic biotite granitic magma, which originated from the mixing of mantle and crust. Re-Os dating of molybdenite from the ores gives a model age from 156.9 +/- 2.2 to 158.5 +/- 2.4 Ma, with a weighted mean age of 158 +/- 1 Ma and an isochron age of 158.0 +/- 2.5 Ma. Geological and geochemical characteristics of the ore deposit and the related granitoids indicate that the Shizitou deposit is a Climax-type Mo deposit. Based on previous studies of the Qin-Hang metallogenic belt, two metallogenic events are believed to have occurred during 172-145 Ma and 137-132 Ma. These two metallogenic periods are consistent with the timing of two metallogenic peaks during the middle to late Jurassic and the Cretaceous in South China. These events represent responses to the partial backarc extension associated with the subduction of the Izanagi plate beneath the Eurasian continent and the rapid northeastward movement of the subducting Izanagi plate