A Chromatographic Approach for High-Precision Eu Isotope Analysis.

Eu isotopes are promising tracers across various scientific domains such as planetary, earth, and marine science, yet their high-precision analysis has been challenging due to the similar geochemical properties of rare earth elements (REEs). In this study, a novel two-column chromatographic approach was developed utilizing AG50W-X12 and TODGA resins to separate Eu effectively from matrix and interfering elements like Ba, Nd, Sm, and Gd, while ensuring high Eu yields (99.4 ± 0.4%, n = 19) and low blanks (<20 pg). The robustness of this method is evidenced by various rock types and different Eu loading masses. The efficient purification of Eu facilitated the establishment of a high-precision calibration technique with standard-sample bracketing (SSB) and internal normalization (Nd). When a Nu Plasma 1700 multicollector-inductively coupled plasma-mass spectrometry (MC-ICP-MS) instrument was employed, repeated purification and analysis of various Geological Reference Materials (GRMs) confirmed that the long-term external precision of δ153/151Eu is better than 0.04‰ (2 standard deviation (2SD)), which represents a 2-5-fold increase in precision compared to previously reported methods. Additionally, the high-precision Eu isotopic compositions of five GRMs, including basalts, andesite, syenite, and marine sediment, were measured. The high-precision Eu isotope techniques presented herein open up new avenues for Eu isotope geochemistry.

Reshaping tumor microenvironment by regulating local cytokines expression with a portable smart blue-light controlled device.

Cytokines have attracted sustained attention due to their multi-functional cellular response in immunotherapy. However, their application was limited to their short half-time, narrow therapeutic window, and undesired side effects. To address this issue, we developed a portable smart blue-light controlled (PSLC) device based on optogenetic technology. By combining this PSLC device with blue-light controlled gene modules, we successfully achieved the targeted regulation of cytokine expression within the tumor microenvironment. To alter the tumor microenvironment of solid tumors, pro-inflammatory cytokines were selected as blue-light controlled molecules. The results show that blue-light effectively regulates the expression of pro-inflammatory cytokines both in vitro and in vivo. This strategy leads to enhanced and activated tumor-infiltrating immune cells, which facilitated to overcome the immunosuppressive microenvironment, resulting in significant tumor shrinkage in tumor-bearing mice. Hence, our study offers a unique strategy for cytokine therapy and a convenient device for animal studies in optogenetic immunotherapy.

Characterization of the cHS4 insulator in mouse embryonic stem cells.

Synthetic biology circuits are often constructed with multiple gene expression units assembled in close proximity, and they can be used to perform complex functions in embryonic stem cells (ESCs). However, mutual interference between transcriptional units has not been well studied in mouse ESCs. To assess the efficiency of insulators at suppressing promoter interference in mouse ESCs, we used an evaluation scheme in which a tunable tetracycline response element promoter is connected to a constant Nanog promoter. The chicken hypersensitive site 4 (cHS4) insulator, widely used both for enhancer blocking and for barrier insulation in vitro and in vivo, was positioned between the two expression units for assessment. By inserting the cassette into various loci of the mouse ESC genome with PiggyBac transposon, we were able to quantitatively examine the protective effect of cHS4 by gradually increasing the transcriptional activity of the tetracycline response element promoter with doxycycline and then measuring the transcriptional activity of the Nanog promoter. Our results indicate that the cHS4 insulator has minimal insulating effects on promoter interference in mouse ESCs. Further studies show that the cHS4 insulation effect may be promoter specific and related to interaction with CCCTC-binding factor-mediated loop formation. In addition, we also compared DNA transposition and transgene expression with or without the cHS4 insulator using well-established ESC reporters. The results indicate that cHS4 has no apparent effects on DNA transposition and transgene expression levels, but exerts modest protective effects on long-term transgene silencing.