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In order to find an excellent drying method for Panax notoginseng leaves (PNL), PNL were dried by using hot air drying (HAD), heat pump drying (HPD) or vacuum drying (VD). The contents of total saponins, polysaccharides, total phenols, total flavonoids, and monomer saponins, in vitro antioxidant activity and α-glucosidase inhibitory capacity of fresh and dried PNL were determined. By using gas chromatography-ion mobility spectrometry (GC-IMS) and non-targeted metabolomics, the volatile components and metabolites in fresh and dried PNL were identified and analyzed, respectively. The results showed that all three drying methods could significantly increase the contents of total saponins and polysaccharides in PNL, reduce the contents of total phenols and total flavonoids, but decrease the functional activities of PNL to varying degrees. Among the four samples, the HPD dried sample had the highest contents of total saponins and polysaccharides, the strongest 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging capacity and α-glucosidase inhibitory capacity, and moderately strong 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) cation radical scavenging capacity and ferric ion reducing antioxidant power (FRAP). High-performance liquid chromatography (HPLC) analysis showed that HPD treatment significantly reduced the contents of notoginsenosides Fc and Fe, while VD treatment showed the opposite effect. A total of 85 volatile components were detected, and the HPD dried sample showed the highest relative contents of alcohols and aldehydes, and the lowest relative content of ketones. In addition, there were significant differences between treatment groups. Furthermore, ultra-high performance liquid chromatography-quadrupole-orbitrap mass spectrometry (UPLC-Q-OT-MS) identified 659 metabolites in the fresh and HPD dried samples. In the positive and negative ion modes, 113 and 68 metabolites were significantly up-regulated, and 98 and 31 metabolites were significantly down-regulated, respectively. These differential metabolites predominately included lipids, lipid-like molecules, organic heterocyclic compounds, organic acids and their derivatives. Out of the 24 saponins in PNL, seven were significantly down-regulated and one was significantly up-regulated, which verified the HPLC results. Through the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of differential metabolites, it was found that the most likely metabolic pathways in HPD dried PNL included the biosynthesis of amino acids, 2-oxycarboxylic acid metabolism, and the biosynthesis of cofactors. In conclusion, HPD provided the best preservation of the chemical composition and functional activities of PNL, making it more suitable for drying PNL. Through multiple metabolite pathways, HPD could alter the composition of metabolites in PNL and affect its volatile components.

In this study, Panax notoginseng leaves (PNL) were separately fermented by Rhizopus oryzae, Neurospora crassa, Monascus and Mucor rouxianus, and changes in the contents of total saponins, total polysaccharides, total phenolics, and total flavonoids, as well as in vitro antioxidant activity and α-glucosidase inhibitory activity of PNL during the fermentation process were assessed. Additionally, the metabolite profiles of raw and fermented PNL were analyzed by ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS/MS). The results indicated that the contents of total saponins and total polysaccharides in PNL were significantly reduced by fermentation with each of these four fungi. Interestingly, R. oryzae, N. crassa and Monascus were found to increase the content of total phenols, while Rhizopus oryzae and Mucor rouxianus increased the total flavonoid content. Fermentation for 3–5 days significantly enhanced the antioxidant activity of PNL, and the most pronounced effect was achieved with Monascus fermentation for three days, which increased the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical cation scavenging capacity and ferric reducing capacity by 14.30%, 5.13%, and 18.40%, respectively. Moreover, the α-glucosidase inhibitory activity of PNL initially decreased and then increased during fungal fermentation, which increased by 16.03% after Monascus fermentation for six days. By untargeted metabolomics analysis, 573 metabolites were identified from PNL. After three days of Monascus fermentation, the up-regulated metabolites were significantly less than the down-regulated ones, and the predominant up-regulated metabolites were amino acids, alkaloids, carbohydrates, lipids, phenols, flavonoids, and terpenoids. Furthermore, analysis of the 21 saponins showed that only ginsenoside F2 was significantly up-regulated, while eight other saponins were significantly down-regulated. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that co-factor biosynthesis, flavonoid biosynthesis, purine metabolism, and pyrimidine metabolism were the most probable metabolic pathways during the fermentation process. In conclusion, fungal fermentation, especially Monascus fermentation, can effectively improve the functional activity of P. notoginseng by metabolic alterations through various pathways. Therefore, this study provides a scientific reference for the green processing of PNL.

In this study, by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and double-sandwich enzyme-linked immunosorbent assay (ELISA), Juglans sigillata kernels from seven different production areas in Yunnan province were screened for their Jug r 1 contents. The preparation of Jug r 1 through ammonium sulfate precipitation, gel filtration chromatography (GFC), and liquid chromatography-tandem mass spectrometry (LC-MS/MS) was optimized and the product was identified. Its structure was characterized by circular dichroism (CD) spectroscopy. Finally, Jug r 1 content in walnut protein was measured by ELISA. The results showed that walnuts from Baoshan, which had the highest contents of total protein and Jug r 1, were used for subsequent experiments. The optimal concentration of ammonium sulfate saturation was in the range from 40% to 80%, and the optimal conditions for GFC were sample concentration of 30 mg/mL, loading volume of 4 mL, and elution flow rate of 1 mL/min. Under these conditions, the recovery of Jug r 1 was 16.58%. Mass spectrometry analysis showed that this protein had the typical characterisitcs of Jug r 1. Circular dichroism spectroscopy indicated that the secondary structure of Jug r 1 was dominated by α-helix and consisted of multiple conformations. After separation and purification by a two-step process, Jug r 1 with purity more than 96% was obtained. This study can provide a scientific basis for further research on Jug r 1 and also provide a reference for the separation and purification of allergic proteins from other nuts.

Glioblastoma is one of the most aggressive and treatment‐resistant forms of primary brain cancer, posing significant challenges in effective therapy. This study aimed to enhance the effectiveness of glioblastoma therapy by developing a unique nanomedicine composed of Pluronic F127‐complexed PEGylated poly(glutamic acid)‐cisplatin (PLG‐PEG/PF127‐CDDP). PLG‐PEG/PF127‐CDDP demonstrated an optimal size of 133.97 ± 12.60 nm, facilitating efficient cell uptake by GL261 glioma cells. In vitro studies showed significant cytotoxicity against glioma cells with a half‐maximal (50%) inhibitory concentration (IC50) of 12.61 µg mL−1 at 48 h and a 72.53% ± 1.89% reduction in cell invasion. Furthermore, PLG‐PEG/PF127‐CDDP prolonged the circulation half‐life of cisplatin to 9.75 h in vivo, leading to a more than 50% reduction in tumor size on day 16 post‐treatment initiation in a murine model of glioma. The treatment significantly elevated lactate levels in GL261 cells, indicating enhanced metabolic disruption. Therefore, PLG‐PEG/PF127‐CDDP offers a promising approach for glioblastoma therapy due to its effects on improving drug delivery efficiency, therapeutic outcomes, and safety while minimizing systemic side effects. This work underscores the potential of polymer‐based nanomedicines in overcoming the challenges of treating brain tumors, paving the way for future clinical applications. [ABSTRACT FROM AUTHOR]

Background: Kinase D‐interacting substrate of 220 kDa (KIDINS220) is a multifunctional scaffolding protein essential for neuronal development. It has been implicated in neurological diseases with either autosomal dominant (AD) or autosomal recessive (AR) inheritance patterns. The molecular mechanisms underlying the AR/AD dual nature of KIDINS220 remain elusive, posing challenges to genetic interpretation and clinical interventions. Moreover, increased KIDINS220 exhibited neurotoxicity, but its role in neurodevelopment remains unclear. Objective: The aim was to investigate the genotype–phenotype correlations of KIDINS220 and elucidate its pathophysiological role in neuronal development. Methods: Whole‐exome sequencing was performed in a four‐generation family with cerebral palsy. CRISPR/Cas9 was used to generate KIDINS220 mutant cell lines. In utero electroporation was employed to investigate the effect of KIDINS220 variants on neurogenesis in vivo. Results: We identified in KIDINS220 a pathogenic nonsense variant (c.4177C > T, p.Q1393*) that associated with AD cerebral palsy. We demonstrated that the nonsense variants located in the terminal exon of KIDINS220 are gain‐of‐function (GoF) variants, which enable the mRNA to escape nonsense‐mediated decay and produce a truncated yet functional KIDINS220 protein. The truncated protein exhibited significant resistance to calpain and consequently accumulated within cells, resulting in the hyperactivation of Rac1 and defects in neuronal development. Conclusions: Our findings demonstrate that the location of variants within KIDINS220 plays a crucial role in determining inheritance patterns and corresponding clinical outcomes. The proposed interaction between Rac1 and KIDINS220 provides new insights into the pathogenesis of cerebral palsy, implying potential therapeutic perspectives. © 2023 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Introduction: In obesity-related type 2 diabetes mellitus (T2DM), M1 macrophages aggravate chronic inflammation and insulin resistance. ISG15-conjugation enzyme E2L6 (Ube2L6) has been demonstrated as a promoter of obesity and insulin resistance. This study investigated the function and mechanism of Ube2L6 in M1 macrophage polarization in obesity. Methods: Obesity was induced in Ube2L6AKO mice and age-matched Ube2L6flox/flox control mice by high-fat diet (HFD). Stromal vascular cells were isolated from the epididymal white adipose tissue of mice. Polarization induction was performed in mouse bone marrow-derived macrophages (BMDMs) by exposure to IFN-γ, lipopolysaccharide, or IL-4. F4/80 expression was assessed by immunohistochemistry staining. Expressions of M1/M2 macrophage markers and target molecules were determined by flow cytometry, RT-qPCR, and Western blotting, respectively. Protein interaction was validated by co-immunoprecipitation (Co-IP) assay. The release of TNF-α and IL-10 was detected by ELISA. Results: The polarization of pro-inflammatory M1 macrophages together with an increase in macrophage infiltration was observed in HFD-fed mice, which could be restrained by Ube2L6 knockdown. Additionally, Ube2L6 deficiency triggered the repolarization of BMDMs from M1 to M2 phenotypes. Mechanistically, Ube2L6 promoted the expression and activation of signal transducer and activator of transcription 1 (STAT1) through interferon-stimulated gene 15 (ISG15)-mediated ISGlylation, resulting in M1 macrophage polarization. Conclusion: Ube2L6 exerts as an activator of STAT1 via post-translational modification of STAT1 by ISG15, thereby triggering M1 macrophage polarization in HFD-fed obese mice. Overall, targeting Ube2L6 may represent an effective therapeutic strategy for ameliorating obesity-related T2DM. [ABSTRACT FROM AUTHOR]

This paper presents a collaborative planning method of an electricity-gas-storage regional integrated energy system based on LSTM neural network and demand response. First, the LSTM Neural network is used for load forecasting, and the energy hub structure of the electric gas storage system is established. Then, the mathematical models of power storage, gas storage, electric network topology, gas network topology, and P2G are established to minimize the expansion cost of the electricity-gas-storage system, and the collaborative planning of energy storage, power lines, and natural gas pipelines is proposed based on the existing electric gas coupling integrated energy system. The original model which is difficult to solve is transformed into a mixed-integer linear programming model by introducing auxiliary variables, and the CPLEX solver is called to solve it. Finally, the economic advantages of collaborative planning of electricity-gas-storage system are verified by an example, and the connection of power storage and gas storage can reduce system pressure and optimize equipment selection.