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To understand that 18β-Glycyrrhetic acid 3-O-mono-β-D-glucuronide (GAMG) showed better pharmacological activity and drug-like properties than 18β-Glycyrrhizin (GL); a rapid and sensitive HPLC-MS/MS method was established for the simultaneous determination of GAMG and its metabolite 18β-Glycyrrhetinic acid (GA) in rat plasma and tissues after oral administration of GAMG or GL. This analytical method was validated by linearity, LLOQ, specificity, recovery rate, matrix effect, etc. After oral administration, GAMG exhibited excellent Cmax (2377.57 ng/mL), Tmax (5 min) and AUC0-T (6625.54 mg/L*h), which was much higher than the Cmax (346.03 ng/mL), Tmax (2.00 h) and AUC0-T (459.32 mg/L*h) of GL. Moreover, GAMG had wider and higher tissue distribution in the kidney, spleen, live, lung, brain, etc. These results indicated that oral GAMG can be rapidly and efficiently absorbed and be widely distributed in tissues to exert stronger and multiple pharmacological activities. This provided a physiological basis for guiding the pharmacodynamic study and clinical applications of GAMG.

The structure–tissue exposure/selectivity relationship (STR) aids in lead optimization to improve drug candidate selection and balance clinical dose, efficacy, and toxicity. In this work, butyrocholinesterase (BuChE)-targeted cannabidiol (CBD) carbamates were used to study the STR in correlation with observed efficacy/toxicity. CBD carbamates with similar structures and same molecular target showed similar/different pharmacokinetics. L2 and L4 had almost same plasma exposure, which was not correlated with their exposure in the brain, while tissue exposure/selectivity was correlated with efficacy/safety. Structural modifications of CBD carbamates not only changed drug plasma exposure, but also altered drug tissue exposure/selectivity. The secondary amine of carbamate can be metabolized into CBD, while the tertiary amine is more stable. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters can be used to predict STR. Therefore, STR can alter drug tissue exposure/selectivity in normal tissues, impacting efficacy/toxicity. The drug optimization process should balance the structure–activity relationship (SAR) and STR of drug candidates for improving clinical trials.

To address the high energy consumption and carbon emissions associated with cold storage operations, a novel refrigeration system is proposed, which utilizes the natural refrigerant CO2 and integrates an innovative control strategy. Experimental validations were conducted in Changsha (a subtropical monsoon climate) and Changchun (a continental monsoon climate), which are two regions representing typical climatic zones in China, to assess the system’s energy-saving potential, temperature stability, and environmental impacts with the total equivalent warming impact and life cycle carbon performance methods. For Changchun, the total equivalent warming impact reached 78.3 kg CO2e/kg, reflecting reductions of 99.5% in direct emissions and 58.6% in indirect emissions compared with R410A systems, as mentioned in the reference. The life cycle carbon performance was reduced by 85.1% and 72.2% compared with the two experiment cases, with indirect emissions from energy consumption comprising the largest share. The system maintained exceptional temperature stability, with vertical-layer variations remaining under 1 °C. These findings demonstrate this system’s adaptability to achieve energy and emission reductions across diverse climates, providing a sustainable framework for future cold storage design aligned with global carbon neutrality goals.

Novel scaffolds are expected to treat Alzheimer’s disease, pyrazole-5-fluorosulfates were found as selective BuChE inhibitors. Compounds K1–K26 were assayed for ChE inhibitory activity, amongst them, compound K3 showed potent BuChE and hBuChE inhibition (IC50 = 0.79 μM and 6.59 μM). SAR analysis showed that 1-, 3-, 4-subtituent and 5-fluorosulfate of pyrazole ring affected BuChE inhibitory activity. Molecular docking showed that the fluorosulfate increased the binding affinity of hBuChE through π-sulphur interaction. Compound K3 was a reversible, mixed and non-competitive BuChE inhibitor (Ki = 0.77 μM) and showed remarkable neuroprotection, safe toxicological profile and BBB penetration. In vivo behavioural study showed that K3 treatment improved the Aβ1 − 42-induced cognitive impairment, and significantly prevented the effects of Aβ1 − 42 toxicity. Therefore, selective BuChE inhibitor K3 has potential to be further developed as AD therapeutics.

Sulphur fluoride exchange (SuFEx) is a category of click chemistry that enables covalent linking of modular units through sulphur connective hubs. Here, we reported an efficient synthesis and in situ screening method for building a library of sulphonamides on the picomolar scale by SuFEx reaction between a sulphonyl fluoride (RSO 2 F) core and primary or secondary amines. This biocompatible SuFEx reaction would allow us to rapidly synthesise sulphonamide molecules, and evaluate their ChE inhibitory activity. Compound T14-A24 was identified as a reversible, competitive, and selective AChE inhibitor (K i = 22 nM). The drug-like evaluation showed that T14-A24 had benign BBB penetration, remarkable neuroprotective effect, and safe toxicological profile. In vivo behavioural study showed that T14-A24 treatment improved the Aβ 1 − 42 -induced cognitive impairment, significantly prevented the effects of Aβ 1 − 42 toxicity. Therefore, this SuFEx click reaction can accelerate the discovery of lead compounds.

Insects, as the most diverse and numerous group in the animal kingdom, are at least partly dependent on the reproduction process, which is strictly regulated by the ‘classic’ insect hormones: juvenile hormone (JH), and 20-hydroxyecdysone (20E). However, the regulatory mechanism governing the reproduction of JH and 20E in Spodoptera frugiperda remains unclear. In this study, ovarian development and ovulation in female S. frugiperda were assessed through dissection of the ovaries following treatment with JH analog (JHA) and 20E. Moreover, the expression patterns of the JH-signal and 20E-signal-related genes were determined by quantitative PCR (qPCR), and RNA interference (RNAi) was used to investigate the role of JH and 20E-induced genes. Ovarian development was observed by microdissection, and JH and 20E titers were determined by ELISA. Kr-h1, Vg, and USP expression were determined by qPCR. Dissection and qPCR results showed that JHA and 20E promoted ovarian development, egg maturation, and egg laying by upregulating Methoprene-Tolerant (Met) and Ecdysone Receptor (EcR)expression. Additionally, the RNAi results showed that the injection of dsMet and dsEcR markedly delayed ovarian development, inhibited egg maturation, and halted egg production. Knockdown of Met and EcR significantly reduced JH and 20E content and inhibited the transcription of Kr-h1 and USP. These results indicate that JH and 20E facilitate adult reproduction through the methoprene-tolerant gene and ecdysone receptor gene in female S. frugiperda.

The whitefly Bemisia tabaci is a phloem-feeding pest that lives predominantly on herbaceous species and causes serious damage to hosts. Whitefly saliva is thought to contain proteins that modulate plant defences and facilitate feeding. A predicted secreted protein, laccase 1 (LAC1), was found in the salivary gland transcriptome of B. tabaci and might be existed in the watery saliva of B. tabaci . As LAC1 has a potential role in detoxification of secondary plant compounds in insects, we speculated that it may participate in the insect’s response to plant defences. Here, we cloned the complete cDNA of LAC1 and found that (1) LAC1 was highly expressed in the salivary gland (SG) and midgut; (2) LAC1 transcript level in head (containing SG) was 2.1 times higher in plant-fed than in diet-fed whiteflies and 1.6 times higher in the head and 23.8 times higher in the midgut of whiteflies that fed on jasmonic acid (JA)-sprayed plants than on control plants; and (3) silencing LAC1 decreased the survival rate of plant-fed whiteflies but had a marginal effect on whiteflies raised on an artificial diet. These results indicate that LAC1 enables whiteflies to overcome the chemical defences of host plants and might act as an effector in saliva.

ABSTRACT The agromyzid leafminer Liriomyza trifolii (Burgess) is an important polyphagous pest of vegetable crops and ornamental plants. It is native to the Americas but has spread throughout the world over the past 50 years. Previous molecular research has indicated that this species contains highly distinct mitochondrial lineages suggestive of cryptic species. To better interpret the mitochondrial divergence, we used anchored hybrid enrichment datasets in order to conduct genome‐wide phylogenetic analyses. We found that individuals of L. trifolii from pepper and tomatillo populations form a monophyletic group (“PT group”) distinct from the remaining L. trifolii (“non‐PT group”). These results corroborate previous mitochondrial and nuclear datasets and indicate an absence of gene flow between the PT and non‐PT groups. This is consistent with previous work on reproductive isolation and oviposition preferences, and provides substantial evidence that the PT group represents a distinct and previously unrecognized species. The presence of two species within a nominally single pest species has important implications for management. Although there was only weak genetic differentiation between geographically disparate groups of non‐PT L. trifolii, a monophyletic group of Chinese specimens was found in a coalescent‐based analysis that is concordant with the history of invasions in Asia. Our study provides important new insight into geographic and host‐associated structure in L. trifolii.

The thermodynamic and kinetic mechanisms of Taixi anthracite during its graphitization process were explored. To understand the variation trends of carbon arrangement order, microcrystal size, and graphitization degree against temperature during the graphitization process, a series of experiments were performed using Raman spectroscopy and X-ray diffraction (XRD). Subsequently, the influencing factors of the dominant reaction at different temperatures were analyzed using thermodynamics and kinetics. The results showed that the graphitization process of Taixi anthracite can be divided into three stages from the perspective of reaction thermodynamics and kinetics. Temperature played a crucial role in the formation and growth of a graphitic structure. Meanwhile, multivariate mechanisms coexisted in the graphitization process. At ultrahigh temperatures, the defects of synthetic graphite could not be completely eliminated and perfect graphite crystals could not be produced. At low temperatures, the reaction is mainly controlled by dynamics, while at high temperatures, thermodynamics dominates the direction of the reaction.

The ecosystem of extra-high mountain areas is very fragile. Understanding local vegetation changes is crucial for projecting ecosystem dynamics. In this paper, we make a case for Himalayan mountain areas to explore vegetation dynamics and their influencing factors. Firstly, the interannual trends of the normalized difference vegetation index (NDVI) were extracted by the Ensemble Empirical Mode Decomposition (EEMD) algorithm and linear regression method. Moreover, the influence of environmental factors on interannual NDVI trends was assessed using the Random Forests algorithm and partial dependence plots. Subsequently, the time-lag effects of seasonal NDVI on different climatic factors were discussed and the effects of these factors on seasonal NDVI changes were determined by partial correlation analysis. The results show that (1) an overall weak upward trend was observed in NDVI variations from 1982 to 2015, and 1989 is considered to be the breakpoint of the NDVI time series; (2) interannual temperature trends and the shortest distance to large lakes were the most important factors in explaining interannual NDVI trends. Temperature trends were positively correlated with NDVI trends. The relationship between the shortest distance to large lakes and the NDVI trend is an inverted U-shaped; (3) the time-lags of NDVI responses to four climatic factors were shorter in Autumn than that in Summer. The NDVI responds quickly to precipitation and downward long-wave radiation; (4) downward long-wave radiation was the main climate factor that influenced NDVI changes in Autumn and the growing season because of the warming effect at night. This study is important to improve the understanding of vegetation changes in mountainous regions.