化学最新文献

Cell viability assessments are a critical step in numerous research, clinical and drug development processes. Electrokinetic techniques, such as electrorotation and dielectrophoresis, have shown promise as viability assessment methods, but often under specific and limited conditions. This study explores insulator-based electrokinetic (iEK) systems as a promising analytical alternative, leveraging differences in electromigration to rapidly separate viable and nonviable cells in a microfluidic system. To demonstrate broad efficacy and domain-agnostic discrimination, two prokaryotic bacterial lines (Escherichia coli and Salmonella Typhimurium) and two eukaryotic yeast strains (Saccharomyces cerevisiae ATCC 4098 and ATCC 9080) were studied. This work expands upon previous studies by performing separations in the weak and moderate electric field regimes, thus utilizing the linear and nonlinear regimes of electrophoresis as an adaptive separation mechanism for discriminating viable from nonviable cells. The results confirm that iEK systems can effectively and quantitatively separate viable and nonviable populations across distinct cellular domains (prokaryotic and eukaryotic), achieving high resolution (all Rs > 1.2) and good reproducibility across all conditions tested. This validation establishes iEK electrophoresis as a novel and robust analytical platform for rapid, quantitative cell viability assessment across a variety of disciplines.

The introduction of chemical fragment spaces as a way to model large chemical spaces led to readily available compound libraries several orders of magnitude larger than seen before. The possibility of efficient similarity search based on molecular fingerprint comparison in such chemical fragment spaces was introduced by the SpaceLight algorithm for the first time. In this work, we introduce weighted SpaceLight, an enhancement that allows the algorithm to focus the search on important areas of a query molecule, increasing the local similarity while increasing variability in other areas, ultimately providing more structural control over the results. Due to the size of chemical fragment spaces, such customization methodologies become crucial to avoid millions of hits which have to be postfiltered. We demonstrate how weighted SpaceLight produces more molecules that preserve selected substructures during similarity search and how it can be adapted for different search scenarios. Combining global fingerprint similarity with a focus on specific substructures bridges the gap between existing search methods like SpaceLight and SpaceMACS and offers a new level of control for chemical space exploration in drug discovery.

As a core medication for the prevention and treatment of cerebral vasospasm, especially after aneurysmal subarachnoid hemorrhage, real-time monitoring of nimodipine (NMD) concentration helps evaluate the adequacy of drug therapy and holds great significance for ensuring patient life and health. Herein, based on dual functional monomers, a molecularly imprinted electrochemical sensor (MIECS) for the detection of NMD with nitrogen-doped multi-walled carbon nanotubes (N-CNTs) and Fe-MOFs was developed. Fe-MOFs provided a large specific surface area, offering more space for generating imprinting sites, while N-CNTs enhanced the conductivity of the electrode. 2-Amino-5-mercapto-1,3,4-thiadiazole (AMT) and o-phenylenediamine (o-PD) served as dual functional monomers and NMD as the template molecule. A molecularly imprinted polymer (MIP) membrane was prepared on the electrode surface by electropolymerization. Compared to single functional monomers, the dual functional monomers exhibited better selectivity and specificity in NMD recognition. Under optimal experimental conditions, the response of the MIECS to NMD showed a linear relationship ranging from 10^-14 M to 10^-8 M, with a detection limit of 2.97 × 10^-15 M. Satisfactory recovery rates were obtained in the detection of human serum and tablets. This multi-parametric enhancement establishes a new paradigm for therapeutic drug monitoring in clinical neurology and pharmaceutical quality control.

Using a coupling between capillary electrophoresis and ICP-MS (CE-ICP-MS), the gluconate (GLU) complexation of plutonium in the major oxidation states (III)-(VI) as well as Am(III), Th(IV), Np(V), and U(VI) was investigated at pH ≤ 4. CE-ICP-MS enabled the determination of the Pu oxidation state by comparing its electrophoretic mobility to that of a redox-analogous actinide (An). For the Am(III)/Pu(III) pair, the complex formation constants of three successive binary [An(GLU)_x]^3-x (x = 1-3) complexes could be determined. For Np(V)/Pu(V), the complex formation constants of the first binary [AnO₂(GLU)]_(aq) complex were determined in accordance with previous literature for Np(V), and those of the second [AnO₂(GLU)₂]^- complex were estimated. For U(VI)/Pu(VI), the constants of the [AnO₂(GLU)]⁺, [AnO₂(GLU_-H)]_(aq), and [AnO₂(GLU_-H)(GLU)]^- complexes were also determined in accordance with previous literature for U(VI). Plutonium in the oxidation states (III), (V), and (VI) behaved very similarly to the redox analogues. This was not the case for Th(IV)/Pu(IV). Here, the first five binary [Th(GLU)_x]^4-x (x = 1-5) complexes were determined for Th(IV), whereas mixed Pu-OH-GLU complexes were proposed for Pu(IV). The comparison of the first complex formation constants of the binary An-GLU complexes suggests a different bonding motif between An^3+/4+ and AnO₂^+/2+, with AnO₂^+/2+ forming the weaker complexes.

Visualization of lysosomes in living cells is essential for understanding their physiological functions; yet, most probes that target the lysosomal interior often disrupt luminal chemistry, exhibit signal leakage, and fail to support long-term imaging. To address these challenges, we developed RELAY (Relocation of Endocytic Leaflet tAg to modifY organelles), a topology-preserving labeling strategy to transfer the inner-leaflet tags on the plasma membrane to the cytosol-facing outer leaflet of lysosomes. RELAY employs liposome-cell membrane fusion to anchor fluorescent DNA probes with phosphorothioate (PS) backbones on the cytoplasmic inner leaflet of the plasma membrane, followed by endocytic trafficking that preserves the membrane topology and relocates the probes onto the lysosomal outer surface. Because this labeling occurs on the lysosomal exterior that is protected from luminal degradation and the PS backbone resists nuclease degradation, RELAY enables highly stable asymmetric labeling that sustains week-long lysosome imaging in living cells. Using this approach, we visualized lysosomal dynamics during cellular senescence and discovered random, unidirectional, intercellular lysosomal transfer in cell-cell communications via tunnelling nanotubes. Holding the capability for prolonged, high-fidelity visualization of lysosomes, RELAY facilitates the exploration of their biological functions.

Bioinspired micropatterned surfaces have been studied as a way to enhance or control interfacial mechanical properties. Here, we study friction for the relative sliding of two interdigitated pillar surfaces. The overall frictional force originates from individual pillar-pillar interactions across the interface as well as the interpillar coupling within each substrate. In this study, we develop a layer-based physical model to simulate the contact and sliding behavior of these pillar arrays. The system is modeled as comprising four layers of nodes, with uniform shear displacement applied to the top layer, while the bottom one is held fixed. Nodes in the inner two layers represent the joints between the pillars and the substrate. The model predicts shear friction force and reveals underlying deformation mechanisms at various misorientations and height overlaps, in good agreement with measured friction in sliding experiments.