Regulation of carboxylesterases and its impact on pharmacokinetics and pharmacodynamics: an up-to-date review

Carboxylesterase 1 (CES1) and carboxylesterase 2 (CES2) are among the most abundant hydrolases in humans, catalyzing the metabolism of numerous clinically important medications, such as methylphenidate and clopidogrel. The large interindividual variability in the expression and activity of CES1 and CES2 affects the pharmacokinetics (PK) and pharmacodynamics (PD) of substrate drugs. This review provides an up-to-date overview of CES expression and activity regulations and examines their impact on the PK and PD of CES substrate drugs. The literature search was conducted on PubMed from inception to January 2024. Current research revealed modest associations of CES genetic polymorphisms with drug exposure and response. Beyond genomic polymorphisms, transcriptional and posttranslational regulations can also significantly affect CES expression and activity and consequently alter PK and PD. Recent advances in plasma biomarkers of drug-metabolizing enzymes encourage the research of plasma protein and metabolite biomarkers for CES1 and CES2, which could lead to the establishment of precision pharmacotherapy regimens for drugs metabolized by CESs. Moreover, our understanding of tissue-specific expression and substrate selectivity of CES1 and CES2 has shed light on improving the design of CES1- and CES2-activated prodrugs.</p

Plant growth promoting bacteria and citric acid promote growth and cadmium phytoremediation in ryegrass

Based on the growth-promoting effect of plant growth promoting bacteria on plants and the mobilization of Cd by citric acid, an experiment was designed in which the combined treatment of Bacillus megaterium and citric acid promoted ryegrass to repair Cd-contaminated soil. This study aimed to evaluate the effects of different treatments on the antioxidant enzyme activity, photosynthesis intensity, Cd accumulation, and rhizosphere cadmium migration under cadmium contamination conditions. And the soil morphology and structure changes were studied by infrared spectroscopy FourierTransformInfrared(FT-IR) and scanning electron microscope Energy Dispersive Spectrometer(SEM-EDS) before and after different treatments. The results show that the combined treatment of Bacillus megaterium and citric acid significantly improved the oxidative stress defense and plant photosynthesis and increased of rye biomass. rye biomass 1.28 times higher than CK treatment. Joint treatment significantly increased the amount of shoot accumulation of Cd, 2.31 times higher than CK treatment, increased the migration and accumulation of cadmium. FTIR and SEM-EDS also showed that the organic constituents such as O-H, C-O and C-N in soils as a major mechanism for mobilization of the heavy metal Cd. Thus, the combined treatment of Bacillus megaterium and citric acid can promote plant growth, improve the damage to ryegrass caused by single organic acid addition, and improve the plant extraction efficiency, which is a feasible way to repair Cd-contaminated soil through activated extraction system. The novelty of this study is the combined application of bacteria and chelating agents to ryegrass to improve phytoremediation efficiency. Bacillus giganosus has a good role in promoting the growth of ryegrass. As citrate, a small molecule chelate, can activate heavy metal cadmium and detoxify heavy metals, so it was selected. This study revealed in detail the response of ryegrass to the heavy metal Cd after exogenous addition of Bacillus gigansus and citrate, which is important for the application of cadmium removal by phytoremediation. Exogenous Bacillus megaterium has a pro-growth effect on ryegrass. The combined treatment of Bacillus megaterium and citric acid significantly improved oxidative defense mechanisms in ryegrass to alleviate Cd stress in plants. FTIR and SEM-EDS showed that the joint treatment significantly improved the soil nutrient content. Combined application of citric acid and Bacillus megaterium showed the highest removal rate of cadmium.</p

Cell-Dependent Activation of ProTide Prodrugs and Its Implications in Antiviral Studies

The ProTide prodrug design is a powerful tool to improve cell permeability and enhance the intracellular activation of nucleotide antiviral analogues. Previous in vitro studies showed that the activation of ProTide prodrugs varied in different cell lines. In the present study, we investigated the activation profiles of two antiviral prodrugs tenofovir alafenamide (TAF) and sofosbuvir (SOF) in five cell lines commonly used in antiviral research, namely, Vero E6, Huh-7, Calu-3, A549, and Caco-2. We found that TAF and SOF were activated in a cell-dependent manner with Vero E6 being the least efficient and Huh-7 being the most efficient cell line for activating the prodrugs. We also demonstrated that TAF was activated at a significantly higher rate than SOF. We further analyzed the protein expressions of the activating enzymes carboxylesterase 1, cathepsin A, histidine triad nucleotide-binding protein 1, and the relevant drug transporters P-glycoprotein and organic anion-transporting polypeptides 1B1 and 1B3 in the cell lines using the proteomics data extracted from the literature and proteome database. The results revealed significant differences in the expression patterns of the enzymes and transporters among the cell lines, which might partially contribute to the observed cell-dependent activation of TAF and SOF. These findings highlight the variability of the abundance of activating enzymes and transporters between cell lines and emphasize the importance of selecting appropriate cell lines for assessing the antiviral efficacy of nucleoside/nucleotide prodrugs

Application of Roasting Flotation Technology to Enrich Valuable Metals from Spent LiFePO₄ Batteries

The application of lithium-ion batteries (LIBs) in electric vehicles has attracted wide attention in recent years, especially LiFePO4 batteries that have been extensively used in large electric buses and cars. The increased demand for LIBs has greatly stimulated lithium-ion battery production, which subsequently has led to greatly increased quantities of spent LIBs. From the perspective of environmental protection and resource recovery, the recycling of spent LIBs is of great significance. In this study, the roasting flotation technology was applied to enrich valuable metals from the mixed electrode powder of spent LiFePO4 batteries. Roasting could thoroughly remove the organic outer layer coated on the surface of electrode-active materials, which improved the flotation enrichment efficiency of valuable metals in the mixed electrode powder of spent LiFePO4 batteries. Under the optimum conditions of roasting at 500 °C for 1 h, the enrichment efficiency of Li and Fe reached the best. The recovery and the enrichment ratio of Li were 95.87% and 1.37, respectively, while the recovery and the enrichment ratio of Fe were 95.25% and 1.36, respectively. Roasting flotation was an efficient process to enrich valuable metals from spent LiFePO4 batteries without wasting graphite resources

Additional file 1 of Disrupted topological organization of functional brain networks in Alzheimer’s disease patients with depressive symptoms

Additional file 1

Efficient synthesis of 3-hydroxy chromones via oxidative cyclization mediated by lipase

In this work, an efficient synthesis of 3-hydroxy chromones was accomplished through oxidative cyclization mediated by lipase. This enzymatic process has salient features of environmental friendliness, mild reaction condition, satisfactory yield, green reusable biocatalyst, and short reaction time. The proposed method expands the application of lipase in organic synthesis.</p

Dinitrogen Functionalization Affording Chromium Hydrazido Complex

A series of trinuclear and dinuclear Cr­(I)–N2 complexes bearing cyclopentadienyl-phosphine ligands were synthesized and characterized. Further reduction of the Cr­(I)–N2 complexes generated anionic Cr(0)–N2 complexes, which could react with Me3SiCl to afford the first chromium hydrazido complex from N2 functionalization. These complexes were found to be effective catalysts for the transformation of N2 into N­(SiMe3)3

Study on the Resistance Distribution at the Contact between Molybdenum Disulfide and Metals

Contact resistance hinders the high performance of electrical devices, especially devices based on two-dimensional (2D) materials, such as graphene and transition metal dichalcogenide. To engineer contact resistance, understanding the resistance distribution and carrier transport behavior at the contact area is essential. Here, we developed a method that can be used to obtain some key parameters of contact, such as transfer length (<i>L</i>_t), sheet resistance of the 2D materials beneath the contacting metal (<i>R</i>_sh), and contact resistivity between the 2D materials and the metal electrode (ρ_c). Using our method, we studied the contacts between molybdenum disulfide (MoS₂) and metals, such as titanium and gold, in bilayer and few-layered MoS₂ devices. Especially, we found that <i>R</i>_sh is obviously larger than the sheet resistance of the same 2D materials in the channel (<i>R</i>_ch) in all the devices we studied. With the increasing of the back-gate voltage, <i>L</i>_t increases and <i>R</i>_sh, ρ_c, <i>R</i>_ch, and the contact resistance <i>R</i>_c decrease in all the devices we studied. Our results are helpful for understanding the metal–MoS₂ contact and improving the performances of MoS₂ devices

Fingerprint of the Interbond Electron Hopping in Second-Order Harmonic Generation

We experimentally explore the fingerprint of the microscopic electron dynamics in second-order harmonic generation (SHG). It is shown that the interbond electron hopping induces a novel source of nonlinear polarization and plays an important role even when the driving laser intensity is 2 orders of magnitude lower than the characteristic atomic field. Our model predicts anomalous anisotropic structures of the SHG yield contributed by the interbond electron hopping, which is identified in our experiments with ZnO crystals. Moreover, a generalized second-order susceptibility with an explicit form is proposed, which provides a unified description in both the weak and strong field regimes. Our work reveals the nonlinear responses of materials at the electron scale and extends the nonlinear optics to a previously unexplored regime, where the nonlinearity related to the interbond electron hopping becomes dominant. It paves the way for realizing controllable nonlinearity on an ultrafast time scale