Identification of the first selective bioluminescent probe for real-time monitoring of carboxylesterase 2 in vitro and in vivo.

Carboxylesterase (CES), a main hydrolysis enzyme family in the human body, plays a crucial role in drug metabolism. Among them, CES1 and CES2 are the primary subtypes, and each exhibits distinct distribution and functions. However, convenient and non-invasive methods for distinguishing them and the real-time monitoring of CES2 are relatively rare, hindering the further understanding of physiological functions and underlying mechanisms. In this study, we have designed, synthesized, and evaluated the first selective bioluminescent probe (CBP 1) for CES2 with high sensitivity, high specificity and rapid reactivity. This probe offers a promising approach for the real-time detection of CES2 and its dynamic fluctuations both in vitro and in vivo.

A Novel Bifunctional µOR Agonist and σ1R Antagonist with Potent Analgesic Responses and Reduced Adverse Effects.

Bifunctional ligands possessing both µOR agonism and σ1R antagonism have shown promise in producing strong analgesic effects with reduced opioid-related side effects. However, the µOR agonism activity of most dual ligands diminishes compared with classical opioids, raising concern about their effectiveness in managing nociceptive pain. In this study, a new class of dual µOR agonist/σ1R antagonist was reported. Through structure-activity relationship analyses, we identified the optimal compound, 4x, which displayed picomolar µOR agonism activity (EC50: 0.6 ± 0.2 nM) and good σ1R inhibitory activity (Ki: 363.7 ± 5.6 nM) with excellent selectivity. Compound 4x exhibited robust analgesic effects in various pain models, with significantly reduced side effects. Importantly, compound 4x also possessed good safety profiles and no abnormalities were observed in biological parameters even under a high dosage. Our findings suggest that 4x may be a promising lead compound for developing safer opioids and warrants further in-depth studies.

Design, synthesis and biological evaluation of novel procaine derivatives for intravenous anesthesia.

A series of novel procaine derivatives for intravenous anesthesia were prepared and evaluated by physicochemical properties and pharmacodynamic experiments in vivo and in vitro. Systematic optimization of procaine led to the identification of 6f, 6g, 6h, 6o, 6p and 6q with higher TI value and moderate log D. Compared with procaine (TI = 1.65), most procaine derivatives demonstrated better security, among whichcompound 6h (TI = 2.68)was the most notable one and showed fewer adverse events in animals. The result of hNR2B-HEK293 assay indicated that compound 6h suppressed the NMDA receptor 2B subtype channel activity and it showed more than 80% inhibitory effect at the concentration of 500 µM.

Biological applications of a turn-on bioluminescent probe for monitoring sulfite oxidase deficiency in vivo.

Sulfites are widely used as preservative and antioxidant additives in food and drug. A non-invasive method for in vivo imaging of sulfite represents a powerful tool for estimating its potential effects in living organisms. Herein, we report the design, development, and application of sulfite bioluminescent probes (SBPs) for the analyte-specific detection of sulfite through sulfite-mediated intramolecular cleavage. Among them, SBP-1 exhibited the excellent responsivity, high selectivity and sensitivity. By taking advantage of this probe, the first in vivo imaging of sulfate was successfully carried out, not only to trace exogenous sulfite level in living animal, but also to investigate endogenous sulfite in a sulfite oxidase deficiency model.

Bioluminescence imaging of exogenous & endogenous cysteine in vivo with a highly selective probe.

Cysteine (Cys) is a semi-essential amino acid that exerts a vital role in numerous biological functions. A noninvasive method for in vivo imaging of cysteine could represent a valuable tool for research cysteine and its complex contributions in living organisms. Thus, we developed a turn-on bioluminescence probe (CBP) not only for detecting exogenous and endogenous cysteine in vitro and in vivo, but also for visualizing these cysteines in whole animal. The current applications may help shed light on the complex mechanisms of cysteine in miscellaneous physiological and pathological processes.

[Distribution of n-alkanes from Lake Wanghu Sediments in Relation to Environmental Changes].

Concentrations and distribution of n-alkanes (n-C14 to n-C33) in Lake Wanghu sediment core were analyzed to investigate the environmental changes in the lake during the past~100 years. Relatively higher concentrations of mid-and long-chain n-alkanes with a strong odd-over-even carbon number predominance indicated organic matter contributions dominated by aquatic macrophytes and terrestrial plants. The lower values of 2n-C31/(n-C27+n-C29) highlighted a type of landscape dominated by woody plants. The environmental changes that have been happening over the past 100 years in Lake Wanghu can be divided into three stages, based on the organic matter sources inferred from the changes in n-alkane parameters in the sediments. Before the 1950s, higher values of terrigenous/aquatic ratio (TAR) and high-/low-molecular weight n-alkanes (H/L) indicated vascular, plant-derived sediments deposited during a low-nutrient, clear-water phase with frequent water exchange between the lake and the Yangtze River. Between the 1950s and 1980s, decrease in values of H/L and TAR, and increase in the proportion of mid-and short-chain n-alkanes indicated a shift towards mid-and shorter-chain components likely associated with the increasing contribution of macrophytes and algae. Lower 2n-C17/(n-C23+n-C25) values indicated a relatively low algal abundance. In that stage, the lake trophic state increased slightly with the decreasing influence of the Yangtze River flow. After the 1980s,H/L and TAR values increased and then decreased, total n-alkane concentrations and 2n-C17/(n-C23+n-C25) increased significantly, especially after 2000s, suggesting the main contributor to high organic matter input most likely shifted to algae because of the eutrophication caused by anthropogenic activities.

[Over One Hundred Year Sediment Record of Polycyclic Aromatic Hydrocarbons in the Lake Bosten, Xinjiang].

The vertical distributions of 16 polycyclic aromatic hydrocarbons (PAHs) were investigated from a sediment core in the Lake Bosten, Xinjiang. Meanwhile, the possible source and risk assessment of PAHs in Lake Bosten were also discussed. The total PAHs concentration in the sediment core ranged from 37.5 ng x g(-1) to 184.5 ng x g(-1), and Naphthalene and Phenanthrene were the dominant compounds throughout the core. Over the one hundred year, the vertical profile of PAHs underwent significant changes around 1950s. The vertical distributions of PAHs had little change and low molecular weight PAHs were dominant PAHs before 1950s. Since then, the high molecular weight PAHs appeared and increased with fluctuations. A sharp increase in PAHs level and individuals was observed especially after 1990s and a maximum was found in the surface sediment. The results suggested PAHs in Lake Bosten were from the local sources, which were dominated by the low temperature combustion. Besides, the abundance of PAHs from high temperature combustion processes, such as combustion of industrial coal and vehicle emission, increased significantly in recent years. However, based on the results of risk assessment, the PAHs may not induce adverse biological effects on the aquatic ecosystem in Lake Bosten.

[Effect of fertilization on the absorption, partition and accumulation of carbon and nitrogen of rice under the equal N conditions].

In this study, the assimilation, partition and accumulation of carbon (C) and nitrogen (N), as well as the relationship between C and N accumulation of rice, were studied from typical paddy ecosystems under long-term fertilizer applications with equal N inputs in subtropical China. The results showed that chemical fertilizer plus low organic manure (LOM) could promote effectively the distribution of C in the rice plant. The N content in the stem-leaf and grain of rice under organic-inorganic fertilization was 8.9-10.2 g x kg(-1) and 11.9-14.8 g x kg(-1) respectively. It was much higher than under other treatments, with about 13% - 53% and 9% - 19% higher than under the chemical fertilization (NPK), separately and 12% - 77% and 23% - 32% higher than under the control treatment (CK), respectively. The C and N storages of rice were mainly accumulated in the aboveground part. Organic-inorganic fertilization treatment possessed higher storages of C (3467.8-4 323.9 kg x hm(-2)) and N (120.3-135.2 kg x hm(-2)) in the rice grain,which was about 13% - 23% of C and 26% - 45% of N higher than under NPK treatment. It indicated that rice grain was the main sink of C and N. The organic-inorganic fertilization was in favor of C accumulation and N absorption in the rice plant and it still possesses an obvious potential in C and N sequestration and absorption in subtropical paddy field.

[Evolvement characteristics and coupling relationship of soil organic carbon and total nitrogen in subtropical paddy field ecosystem under different fertilization practices].

Soil samples were collected from long-term monitoring plots of paddy field ecosystem in Hunan Province to study the evolvement characteristics and coupling relationship of soil organic carbon and total nitrogen under different fertilization practices. The results showed that in 1986-2003, the contents of soil organic carbon and total nitrogen had a slight decrease under no fertilization (CK), basically remained stable under chemical fertilization (NPK), and increased under the combined application of organic manure and chemical fertilizers. Compared with those in CK, the contents of soil organic carbon and total nitrogen in treatments NPK, low application rate organic manure, and high application rate organic manure were increased by 13% and 18%, 54% and 45%, and 89% and 67% respectively. There was a significant positive correlation (P < 0.01) between soil organic carbon and total nitrogen. The soil C/N was around 10, with the majority ranged from 8.5 to 12.9. It was suggested that a combined application of organic manure and chemical fertilizers on paddy field could increase the sequestration and accumulation of soil carbon and nitrogen to a certain extent, and there existed a better coupling relationship between soil organic carbon and total nitrogen in paddy field ecosystem.