High-resolution pure shift NMR spectroscopy offers better metabolite discrimination in food quality analysis.

PSYCHE homonuclear decoupling, a prominent pure shift NMR method, is successfully applied to adulteration discrimination of honey and geographical originality identification of tea. Effects of homonuclear couplings are efficiently suppressed, producing resolution-enhanced spectra. The pair wise honey and tea samples are well separated in OPLS-DA models with high predictability. Due to the well-resolved and accurate assignment of singlet resonances after decoupling, PSYCHE is advantageous in the identification of differential components and accurate quantification of compound concentrations presented by enhanced volcano and Beeswarm plots of honey samples, while the analysis of NOESY is easily interfered by overlapped resonances, which is further proved by the STOCSY analysis, displaying the spectral stability and reproducibility. Experimental results show that PSYCHE can improve the spectral resolution of natural complex products such as honey and tea and be combined with multivariate statistical analysis and serve as a supplementary technique to the standard methods, especially for samples systems composed by a few high-content compounds

Single-Cell Systems Pharmacology Identifies Development-Driven Drug Response and Combination Therapy in B Cell Acute Lymphoblastic Leukemia

Leukemia can arise at various stages of the hematopoietic differentiation hierarchy, but the impact of developmental arrest on drug sensitivity is unclear. Applying network-based analyses to single-cell transcriptomes of human B cells, we define genome-wide signaling circuitry for each B cell differentiation stage. Using this reference, we comprehensively map the developmental states of B cell acute lymphoblastic leukemia (B-ALL), revealing its strong correlation with sensitivity to asparaginase, a commonly used chemotherapeutic agent. Single-cell multi-omics analyses of primary B-ALL blasts reveal marked intra-leukemia heterogeneity in asparaginase response: resistance is linked to pre-pro-B-like cells, with sensitivity associated with the pro-B-like population. By targeting BCL2, a driver within the pre-pro-B-like cell signaling network, we find that venetoclax significantly potentiates asparaginase efficacy in vitro and in vivo. These findings demonstrate a single-cell systems pharmacology framework to predict effective combination therapies based on intra-leukemia heterogeneity in developmental state, with potentially broad applications beyond B-ALL

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Transient prediction of annular pressure between packers in high-pressure low-permeability wells during high-rate, staged acid jobs

For high-pressure low-permeability wells, wellbore temperature drops drastically in high-rate and multistage acid fracturing process. Under the combined action of the swelling of tubing string and the contraction of annular fluid between packers, annular pressure between packers undergoes violent transient change in staged acid jobs, thereby deteriorating loading on the tubing string and packers. Based on the principle of energy conservation and wellbore heat conduction, the transient prediction of two-dimensional (2D) wellbore temperature field under pumping injection condition was established by considering the effects of heat generated by friction and convection heat exchange. Moreover, the effects of wellbore temperature/pressure changes on the annular volume between packers were analyzed. Furthermore, in combination with the transient prediction model of wellbore temperature, PVT state equation of annular fluid, the calculation model of tubing string radial deformation and the transient seepage equation of the formation, the transient prediction model of annular pressure between packers in high-pressure low-permeability wells was established. Finally, by taking a high-pressure low-permeability well as an example, annular pressure between packers was calculated and the forces on the packers and tubing string were analyzed. According to the prediction results, the tubing string, which was regarded to be safe using conventional design method, exhibited an extremely high risk of failure after taking into account the decrease in annular pressure between packers. Therefore, the decrease in annular pressure should be fully considered in the design of tubing string for high-pressure low-permeability wells in multistage acid fracturing process. In combination with sensitivity analysis results, it can be concluded that formation permeability, injection rate and formation pressure all affected the change in annular pressure between packers

Influences of Climate Change and Human Activities on NDVI Changes in China

The spatiotemporal evolution of vegetation and its influencing factors can be used to explore the relationships among vegetation, climate change, and human activities, which are of great importance for guiding scientific management of regional ecological environments. In recent years, remote sensing technology has been widely used in dynamic monitoring of vegetation. In this study, the normalized difference vegetation index (NDVI) and standardized precipitation–evapotranspiration index (SPEI) from 1998 to 2017 were used to study the spatiotemporal variation of NDVI in China. The influences of climate change and human activities on NDVI variation were investigated based on the Mann–Kendall test, correlation analysis, and other methods. The results show that the growth rate of NDVI in China was 0.003 year−1. Regions with improved and degraded vegetation accounted for 71.02% and 22.97% of the national territorial area, respectively. The SPEI decreased in 60.08% of the area and exhibited an insignificant drought trend overall. Human activities affected the vegetation cover in the directions of both destruction and restoration. As the elevation and slope increased, the correlation between NDVI and SPEI gradually increased, whereas the impact of human activities on vegetation decreased. Further studies should focus on vegetation changes in the Continental Basin, Southwest Rivers, and Liaohe River Basin