A small-molecule activation mechanism that directly opens the KCNQ2 channel.

Pharmacological activation of voltage-gated ion channels by ligands serves as the basis for therapy and mainly involves a classic gating mechanism that augments the native voltage-dependent open probability. Through structure-based virtual screening, we identified a new scaffold compound, Ebio1, serving as a potent and subtype-selective activator for the voltage-gated potassium channel KCNQ2 and featuring a new activation mechanism. Single-channel patch-clamp, cryogenic-electron microscopy and molecular dynamic simulations, along with chemical derivatives, reveal that Ebio1 engages the KCNQ2 activation by generating an extended channel gate with a larger conductance at the saturating voltage (+50 mV). This mechanism is different from the previously observed activation mechanism of ligands on voltage-gated ion channels. Ebio1 caused S6 helices from residues S303 and F305 to perform a twist-to-open movement, which was sufficient to open the KCNQ2 gate. Overall, our findings provide mechanistic insights into the activation of KCNQ2 channel by Ebio1 and lend support for KCNQ-related drug development.

CD11b + CD43 hi Ly6C lo splenocyte-derived macrophages exacerbate liver fibrosis via spleen-liver axis.

BACKGROUND AND AIMS: Monocyte-derived macrophages (MoMFs), a dominant population of hepatic macrophages under inflammation, play a crucial role in liver fibrosis progression. The spleen serves as an extra monocyte reservoir in inflammatory conditions; however, the precise mechanisms of involvement of the spleen in the pathogenesis of liver fibrosis remain unclear. APPROACH AND RESULTS: By splenectomy and splenocyte transfusion, it was observed that splenic CD11b + cells accumulated intrahepatically as Ly6C lo MoMFs to exacerbate CCl 4 -induced liver fibrosis. The splenocyte migration into the fibrotic liver was further directly visualized by spleen-specific photoconversion with KikGR mice and confirmed by CD45.1 + /CD45.2 + spleen transplantation. Spleen-derived CD11b + cells purified from fibrotic livers were then annotated by single-cell RNA sequencing, and a subtype of CD11b + CD43 hi Ly6C lo splenic monocytes (sM-1s) was identified, which was markedly expanded in both spleens and livers of mice with liver fibrosis. sM-1s exhibited mature feature with high expressions of F4/80, produced much ROS, and manifested preferential migration into livers. Once recruited, sM-1s underwent sequential transformation to sM-2s (highly expressed Mif , Msr1 , Clec4d , and Cstb ) and then to spleen-derived macrophages (sMφs) with macrophage features of higher expressions of CX 3 CR1, F4/80, MHC class II, and CD64 in the fibrotic hepatic milieu. Furthermore, sM-2s and sMφs were demonstrated capable of activating hepatic stellate cells and thus exacerbating liver fibrosis. CONCLUSIONS: CD11b + CD43 hi Ly6C lo splenic monocytes migrate into the liver and shift to macrophages, which account for the exacerbation of liver fibrosis. These findings reveal precise mechanisms of spleen-liver axis in hepatic pathogenesis and shed light on the potential of sM-1 as candidate target for controlling liver diseases.

Dynamic SPME-SERS Induced by Electric Field: Toward In Situ Monitoring of Pharmaceuticals and Personal Care Products.

The core of the surface-enhanced Raman spectroscopy (SERS)-based techniques for dynamic monitoring is to realize rapid and reversible adsorption. Herein, the integration technology of electro-enhanced adsorption, solid-phase microextraction, and surface-enhanced Raman spectroscopy (EE-SPME-SERS) was developed to obtain sensitive, ultrafast, and reversible SERS response toward in situ monitoring of pharmaceuticals and personal care products (PPCPs). In the EE-SPME-SERS method, a roughened Ag fiber with Au modification (r-Ag/Au fiber) was used as the SERS substrate, SPME sorbent, and working electrode. The r-Ag/Au fiber displayed good SERS sensitivity, ultrahigh photostability, and adsorption properties. The adsorption efficiency of benzidine was 76 times accelerated in EE-SPME-SERS compared to that in static adsorption. The whole process of "sampling and detection" in EE-SPME-SERS can be finished within 1 s. Reversible adsorption and desorption can be achieved in situ by switching the direction of electric field, and the regeneration process takes only a few minutes. Simulated release of benzidine from household wastewater was in situ and dynamically monitored using this strategy. EE-SPME-SERS was proved universal for ionized PPCPs and can detect multicomponents simultaneously. In addition, EE-SPME-SERS showed very good analytical properties. Great potential of EE-SPME-SERS can be expected in environmental monitoring.

Identification of Trace Polystyrene Nanoplastics Down to 50 nm by the Hyphenated Method of Filtration and Surface-Enhanced Raman Spectroscopy Based on Silver Nanowire Membranes.

Nanoplastics are emerging pollutants that pose potential threats to the environment and organisms. However, in-depth research on nanoplastics has been hindered by the absence of feasible and reliable analytical methods, particularly for trace nanoplastics. Herein, we propose a hyphenated method involving membrane filtration and surface-enhanced Raman spectroscopy (SERS) to analyze trace nanoplastics in water. In this method, a bifunctional Ag nanowire membrane was employed to enrich nanoplastics and enhance their Raman spectra in situ, which omitted sample transfer and avoided losing smaller nanoplastics. Good retention rates (86.7% for 50 nm and approximately 95.0% for 100-1000 nm) and high sensitivity (down to 10-7 g/L for 50-1000 nm and up to 105 SERS enhancement factor) of standard polystyrene (PS) nanoplastics were achieved using the proposed method. PS nanoplastics with concentrations from 10-1 to 10-7 g/L and sizes ranging from 50 to 1000 nm were successfully detected by Raman mapping. Moreover, PS micro- and nanoplastics in environmental water samples collected from the seafood market were also detected at the µg/L level. Consequently, the proposed method provides more possibilities for analyzing low-concentration nanoplastics in aquatic environments with high enrichment efficiency, minimal sample loss, and high sensitivity.

Improvement of human platelet aggregation post-splenectomy with paraesophagogastric devascularization in chronic hepatitis B patients with cirrhotic hypersplenism.

Thrombocytopenia is a common hematological abnormality in patients with cirrhotic hypersplenism. Splenectomy with paraesophagogastric devascularization (SPD) is a conventional surgical therapy which can reverse pancytopenia in these patients. Platelets are traditionally recognized for their central role in hemostasis. However, the status of platelet aggregation in chronic hepatitis B patients with cirrhotic hypersplenism before and after SPD has not been reported yet. A total of 41 cirrhotic patients and 31 healthy controls were included in this study. Platelet aggregation was detected by AggRAM® Advanced Modular System (Helena Laboratories, USA). ELISA was used to detect the cytokines closely related to platelet aggregation. Expressions of platelet membrane glycoproteins (GPs) were evaluated by flow cytometric analysis. Platelet aggregation was found to be decreased distinctly in the cirrhotic patients, and to be restored to normal level after SPD. The cirrhotic patients showed higher plasma levels of the cytokines HMGB1, PEDF, vWF, cAMP and cGMP, which also improved partially after SPD. Moreover, the cirrhotic patients had much lower expression of GPIIb/IIIa, GPIbα and P-selectin than either the healthy controls or SPD patients at basal or activated level. Generally, SPD benefits cirrhotic patients with bleeding tendencies by improving platelet counts and aggregation. GPIIb/IIIa may be the key membrane protein responsible for the change in platelet aggregation before and after SPD.

Utilizing the moral nobility of older Chinese women in governance: The uses of humility, empathy, and an ethics of care in moral clinics in Huzhou city.

This paper examines the emergence of the role of "moral doctors" who volunteer in what are called "moral clinics" in Huzhou city. In these moral clinics, the characteristics, experiences, and attributes of older women, in particular, are highly valued and viewed as being essential to the role of the moral doctor. These moral doctors act as moral exemplars and conflict mediators in their local communities. Their moral capital and professionalism, combined with their gender, age, familial and neighborhood attributes, contribute to the accumulation of an affective feminized labor which employs the techniques of care, reason, and moral fortitude to govern the self and others. We unpack these ethical virtues exemplified by moral doctors and nurses in order to show how a female-centric "ethic of care" can become a set of techniques in governing others. In this paper, we elaborate on the role that these moral doctors perform to support the aims of the moral clinics in terms of fostering pro-social behavior and moral obligation in local communities. We argue that the performance of this type of "moral work" is both a mechanism of discipline and a process of self-actualization. We contribute to the current literature on "therapeutic governance" in China by showing how the non-expert medicalization of social ills by moral doctors is incorporated into the reproduction of social control.

Genome-wide identification, characterization, and expression patterns of the BZR transcription factor family in sugar beet (Beta vulgaris L.).

BACKGROUND: BRASSINAZOLE-RESISTANT (BZR) family genes encode plant-specific transcription factors (TFs) that participate in brassinosteroid signal transduction. BZR TFs have vital roles in plant growth, including cell elongation. However, little is known about BZR genes in sugar beet (Beta vulgaris L.). RESULTS: Therefore, we performed a genome-wide investigation of BvBZR genes in sugar beet. Through an analysis of the BES1_N conserved domain, six BvBZR gene family members were identified in the sugar beet genome, which clustered into three subgroups according to a phylogenetic analysis. Each clade was well defined by the conserved motifs, implying that close genetic relationships could be identified among the members of each subfamily. According to chromosomal distribution mapping, 2, 1, 1, 1, and 1 genes were located on chromosomes 1, 4, 5, 6, and 8, respectively. The cis-acting elements related to taproot growth were randomly distributed in the promoter sequences of the BvBZR genes. Tissue-specific expression analyses indicated that all BvBZR genes were expressed in all three major tissue types (roots, stems, and leaves), with significantly higher expression in leaves. Subcellular localization analysis revealed that Bv1_fxre and Bv6_nyuw are localized in the nuclei, consistent with the prediction of Wolf PSORT. CONCLUSION: These findings offer a basis to predict the functions of BZR genes in sugar beet, and lay a foundation for further research of the biological functions of BZR genes in sugar beet.

Host Protein Moloney Leukemia Virus 10 (MOV10) Acts as a Restriction Factor of Influenza A Virus by Inhibiting the Nuclear Import of the Viral Nucleoprotein.

UNLABELLED: The viral ribonucleoprotein (vRNP) complex of influenza A viruses (IAVs) contains an RNA-dependent RNA polymerase complex (RdRp) and nucleoprotein (NP) and is the functional unit for viral RNA transcription and replication. The vRNP complex is an important determinant of virus pathogenicity and host adaptation, implying that its function can be affected by host factors. In our study, we identified host protein Moloney leukemia virus 10 (MOV10) as an inhibitor of IAV replication, since depletion of MOV10 resulted in a significant increase in virus yield. MOV10 inhibited the polymerase activity in a minigenome system through RNA-mediated interaction with the NP subunit of vRNP complex. Importantly, we found that the interaction between MOV10 and NP prevented the binding of NP to importin-α, resulting in the retention of NP in the cytoplasm. Both the binding of MOV10 to NP and its inhibitory effect on polymerase activity were independent of its helicase activity. These results suggest that MOV10 acts as an anti-influenza virus factor through specifically inhibiting the nuclear transportation of NP and subsequently inhibiting the function of the vRNP complex. IMPORTANCE: The interaction between the influenza virus vRNP complex and host factors is a major determinant of viral tropism and pathogenicity. Our study identified MOV10 as a novel host restriction factor for the influenza virus life cycle since it inhibited the viral growth rate. Conversely, importin-α has been shown as a determinant for influenza tropism and a positive regulator for viral polymerase activity in mammalian cells but not in avian cells. MOV10 disrupted the interaction between NP and importin-α, suggesting that MOV10 could also be an important host factor for influenza virus transmission and pathogenicity. Importantly, as an interferon (IFN)-inducible protein, MOV10 exerted a novel mechanism for IFNs to inhibit the replication of influenza viruses. Furthermore, our study potentially provides a new drug design strategy, the use of molecules that mimic the antiviral mechanism of MOV10.

Interleukin 7 up-regulates CD95 protein on CD4+ T cells by affecting mRNA alternative splicing: priming for a synergistic effect on HIV-1 reservoir maintenance.

Interleukin-7 (IL-7) has been used as an immunoregulatory and latency-reversing agent in human immunodeficiency virus type 1 (HIV-1) infection. Although IL-7 can restore circulating CD4(+) T cell counts in HIV-1-infected patients, the anti-apoptotic and proliferative effects of IL-7 appear to benefit survival and expansion of HIV-1-latently infected memory CD4(+) T lymphocytes. IL-7 has been shown to elevate CD95 on CD4(+) T cells in HIV-1-infected individuals and prime CD4(+) T lymphocytes to CD95-mediated proliferative or apoptotic signals. Here we observed that through increasing microRNA-124, IL-7 down-regulates the splicing regulator polypyrimidine tract binding protein (PTB), leading to inclusion of the transmembrane domain-encoding exon 6 of CD95 mRNA and, subsequently, elevation of CD95 on memory CD4(+) T cells. Moreover, IL-7 up-regulates cellular FLICE-like inhibitory protein (c-FLIP) and stimulates c-Jun N-terminal kinase (JNK) phosphorylation, which switches CD95 signaling to survival mode in memory CD4(+) T lymphocytes. As a result, co-stimulation through IL-7/IL-7R and FasL/CD95 signal pathways augments IL-7-mediated survival and expansion of HIV-1-latently infected memory CD4(+) T lymphocytes. Collectively, we have demonstrated a novel mechanism for IL-7-mediated maintenance of HIV-1 reservoir.

Effects of carbon monoxide on quality, nutrients and antioxidant activity of post-harvest jujube.

BACKGROUND: To effectively extend the shelf life of fresh jujube, carbon monoxide (CO), as a small molecular gas, was applied to fumigate fresh jujube. The quality and antioxidant activity of jujubes fumigated with carbon monoxide at concentrations of 0 (control), 5, 10, 20 and 40 µmol L⁻¹ for 1 h under ambient temperature were investigated. RESULTS: The jujube fumigated with 10 µmol L⁻¹ CO showed the best preserving effect amongst all samples. At 30 days, the decay incidence of jujube fumigated with 10 µmol L⁻¹ CO is only two-thirds of that of control sample; its red index and weight loss rate were 22.8% and 19.4% lower, and its firmness, soluble solids content (SSC) and acidity were 18.7%, 5.4% and 12.2% higher than that of control samples, respectively. Its vitamin C and total flavonoid contents were also the highest. However, no significant difference in total polyphenol content was found. The jujubes treated with 10 µmol L⁻¹ CO exhibited the highest antioxidant activity in terms of reducing power and 2,2-diphenyl-1-(2,4,6-trinitrophenyl)hydrazyl radical scavenging activity. However, the jujubes fumigated with 40 µmol L⁻¹ CO showed inferior characteristics compared with the control sample. CONCLUSION: Fumigating jujubes with proper concentration of CO probably is a potential novel method for post-harvest jujube preservation in the future.

Characterizations of Water-Soluble Chitosan/Curdlan Edible Coatings and the Inhibitory Effect on Postharvest Pathogenic Fungi.

This study focused on developing a composite coating comprising water-soluble chitosan (CTS) and curdlan (CUR). Cherry tomatoes served as the test material for assessing the preservative efficacy of these coatings. The incorporation of CUR markedly enhanced the coating's surface properties, refined its molecular structure, and improved its tensile strength and elongation at break. Additionally, the coating demonstrated enhanced permeability to water vapor, oxygen, and carbon dioxide and improved light transmission. The storage experiment, conducted at 25 ± 1 °C with a relative humidity of approximately 92% over 10 days, revealed that the CTS/CUR composite coating at a 1:1 ratio significantly outperformed the individual CTS or CUR coating and uncoated samples in maintaining the quality of postharvest cherry tomatoes. The 1:1 CTS/CUR composite coating demonstrated superior preservative effects. This study suggested that water-soluble chitosan/curdlan composite coatings have considerable potential for use in the preservation of postharvest fruits and vegetables.

Inhibitory Effect of L-Methionine on Alternaria alternata Based on Metabolomics Analysis.

Alternaria alternata is the main pathogenic fungus of postharvest black spots in fruits and vegetables. This study aimed to explore the antifungal activity of methionine on A. alternata in vitro and to reveal related antifungal mechanisms through a metabolomics analysis. The results showed that the inhibitory effects of L-methionine (Met) treatment on mycelium growth, spore germination, and the germ tube elongation of A. alternata were enhanced with an increase in the Met concentration, but the inhibitory effects decreased when the Met concentration was higher than 50 mmolL-1. The results of propidium iodide staining and scanning electron microscopy showed that the Met treatment damaged the plasma membrane integrity of the A. alternata spores and caused an irreversible deformation of mycelium. In addition, after the Met treatment, the leakage of electrolytes, nucleic acid, and proteins in the A. alternata cells was significantly higher than that in the control group, indicating that the Met treatment increased the permeability of the cell membranes. Eighty-one different metabolites, divided into seven categories, were identified through the metabolomics analysis, including forty-three downregulated metabolites and thirty-eight upregulated metabolites. Among them, these differential metabolites were mainly involved in amino acid synthesis and metabolism, the pentose phosphate pathway, and the TCA cycle. Therefore, the antifungal effect of the Met treatment on A. alternata was mainly to damage the integrity of the cell membranes, make nucleic acid and protein contents leak, and affect the TCA cycle, carbohydrate metabolism, amino acid synthesis metabolism, and the metabolic pathways associated with cell membrane biosynthesis. Thus, the growth and development of A. alternata were inhibited. The research enriched the investigation of the effect of the antifungal mechanism of Met treatment on A. alternata and provided a theoretical basis for the application of Met to prevent and treat postharvest black spots in fruits and vegetables.

Genome-wide characterization of the xyloglucan endotransglucosylase/hydrolase family genes and their response to plant hormone in sugar beet.

Xyloglucan endotransglucosylase/hydrolases (XTHs) play a crucial role in plant growth and development. However, their functional response to phytohormone in sugar beet still remains obscure. In this study, we identified 30 putative BvXTH genes in the sugar beet genome. Phylogenetic and evolutionary relationship analysis revealed that they were clustered into three groups and have gone through eight tandem duplication events under purifying selection. Gene structure and motif composition analysis demonstrated that they were highly conserved and all contained one conserved glycoside hydrolase family 16 domain (Glyco_hydro_16) and one xyloglucan endotransglycosylase C-terminus (XET_C) domain. Transcriptional expression analysis exhibited that all BvXTHs were ubiquitously expressed in leaves, root hairs and tuberous roots, and most of them were up-regulated by brassinolide (BR), jasmonic acid (JA), abscisic acid (ABA) and gibberellic acid (GA3). Further mutant complementary experiment demonstrated that expression of BvXTH17 rescued the retarded growth phenotype of xth22, an Arabidopsis knock out mutant of AtXTH22. The findings in our work provide fundamental information on the structure and evolutionary relationship of the XTH family genes in sugar beet, and reveal the potential function of BvXTH17 in plant growth and hormone response.

Antifungal Activities of L-Methionine and L-Arginine Treatment In Vitro and In Vivo against Botrytis cinerea.

Gray mold caused by Botrytis cinerea is a common postharvest fungal disease in fruit and vegetables. The prevention and treatment of postharvest gray mold has been one of the hot research issues addressed by researchers. This study aimed to investigate the effect of L-methionine and L-arginine on Botrytis cinerea in vitro and on cherry tomato fruit. The results of the in vitro experiment showed that L-methionine and L-arginine had significant inhibitory effects on the mycelial growth and spore germination of Botrytis cinerea, and the inhibitory effects were enhanced with increasing L-methionine or L-arginine concentration. In addition, L-methionine and L-arginine treatment increased the leakage of Botrytis cinerea electrolytes, proteins and nucleic acids. The experiment involving propidium iodide staining and malondialdehyde content assay also confirmed that L-methionine and L-arginine treatment could lead to cell membrane rupture and lipid peroxidation. The results of scanning electron microscopy further verified that the morphology of hyphae was damaged, deformed, dented and wrinkled after treatment with L-methionine or L-arginine. Fruit inoculation experiments displayed that L-methionine and L-arginine treatments significantly inhibited the occurrence and development of gray mold in postharvest cherry tomato. Therefore, treatment with L-methionine or L-arginine might be an effective means to control postharvest gray mold in fruit and vegetables.

Inhibition Mechanism of Water-Soluble Chitosan-Curdlan Composite Coating on the Postharvest Pathogens of Serratia marcescens and Pseudomonas syringae in Cherry Tomatoes.

Cherry tomatoes, a very popular fruit, are highly susceptible to microbial infestation, which cause significant economic losses. In order to preserve cherry tomatoes better, we treat them with a Chitosan (CTS) and Curdlan (CUR) composite coating. The lowest inhibitory concentration of CTS/CUR composite coating on Serratia marcescens and Pseudomonas syringae, the growth curves, and the changes of the cell lysis rate were determined to explore the inhibitory mechanism of CTS/CUR composite coating on Serratia marcescens and Pseudomonas syringae and the microscopic morphology of Serratia marcescens and Pseudomonas syringae was observed using scanning electron microscopy at the same time. The results showed that the CTS/CUR composite coating could effectively inhibit the growth of Serratia marcescens and Pseudomonas, and the inhibitory effect reflected the concentration-dependent characteristics. The electron microscopy results indicated that the inhibition of Serratia marcescens and Pseudomonas syringae by the CTS/CUR composite coating might originate from its disruptive effect on the cell wall and cell membrane of the bacterium.

Development and Characterization of Modified Gelatin-Based Cling Films with Antimicrobial and Antioxidant Activities and Their Application in the Preservation of Cherry Tomatoes.

The utilization of functional cling films presents a promising approach to alleviate post-harvest spoilage caused by microbial activity, oxidative metabolism, and moisture loss in agricultural products. To overcome the environmental problems of conventional packaging materials, in this study, we developed functional fruit and vegetable cling films based on glycidyltrimethylammonium chloride and rosemarinic acid cross-linked gelatin (RQ-GEL). The results indicate that the prepared RQ-GEL film possesses excellent UV light barrier properties and mechanical performance. RQ-GEL inhibited S. aureus and E. coli by 93.79% and 92.04%, respectively. DPPH and ABTS free radical scavenging activities were as high as 87.69% and 84.6%. In the cherry tomato preservation experiment, when compared to uncovered samples, the RQ-GEL group had a 29.77% reduction in weight loss and a significant 26.92% reduction in hardness. Meanwhile, the RQ-GEL group delays the decline of fruit total soluble solids and titratable acidity content, and prolongs the preservation period of cherry tomatoes. Hence, RQ-GEL cling film is poised to emerge as a promising packaging material for the post-harvest preservation of agricultural products.

Characterization and Antioxidant and Antibacterial Activities of Carboxymethylated Tamarind Seed Polysaccharide Composite Films Incorporated with ε-Polylysine and Their Application in Fresh-Cut Green Bell Pepper Preservation.

Traditional petroleum-based food-packaging materials have poor permeability, limited active packaging properties, and difficulty in biodegradation, limiting their application. We developed a carboxymethylated tamarind seed polysaccharide composite film incorporated with ε-polylysine (CTPε) for better application in fresh-cut agricultural products. The CTPε films exhibit excellent water vapor barrier properties, but the mechanical properties are slightly reduced. Fourier transform infrared spectroscopy and X-ray diffraction spectra indicate the formation of hydrogen bonds between ε-PL and CTP, leading to their internal reorganization and dense network structure. With the increase of ε-PL concentration, composite films showed notable inhibition of postharvest pathogenic fungi and bacteria, a significant enhancement of 2,2'- azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radical-scavenging activity, and gradual improvement of wettability performance. Cytotoxicity experiments confirmed the favorable biocompatibility when ε-PL was added at 0.3% (CTPε2). In fresh-cut bell pepper preservation experiments, the CTPε2 coating effectively delayed weight loss and malondialdehyde increase preserved the hardness, color, and nutrients of fresh-cut peppers and prolonged the shelf life of the fresh-cut peppers, as compared with the control group. Therefore, CTPε composite films are expected to be a valuable packaging material for extending the shelf life of freshly cut agricultural products.

Fenugreek extract improves diabetes-induced endothelial dysfunction via the arginase 1 pathway.

Endothelial dysfunction (ED) is an initiating trigger and key factor in vascular complications, leading to disability and mortality in individuals with diabetes. The research concerning therapeutic interventions for ED has gained considerable interest. Fenugreek, a commonly used edible plant in dietary consumption, has attracted significant attention due to its management of diabetes and its associated complications. The research presented in this study examines the potential therapeutic benefits of fenugreek in treating ED and investigates the underlying mechanism associated with its effects. The analysis on fenugreek was performed using 70% ethanol extract, and its chemical composition was analyzed using ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). In total, we identified 49 compounds present in the fenugreek extract. These compounds encompass flavonoids, saponins, and phospholipids. Then, the models of ED in streptozotocin-induced diabetic mice and high glucose-induced isolated rat aortas were established for research. Through vascular function testing, it was observed that fenugreek extract effectively improved ED induced by diabetes or high glucose. By analyzing the protein expression of arginase 1 (Arg1), Arg activity, Arg1 immunohistochemistry, nitric oxide (NO) level, and the protein expression of endothelial nitric oxide synthase (eNOS), p38 mitogen-activated protein kinase (p38 MAPK), and p-p38 MAPK in aortas, this study revealed that the potential mechanism of fenugreek extract in anti-ED involves the downregulation of Arg1, leading to enhanced NO production. Furthermore, analysis of serum exosomes carrying Arg activity indicates that fenugreek may decrease the activity of Arg transported by serum exosomes, potentially preventing the increase in Arg levels triggered by the uptake of serum exosomes by vascular endothelial cells. In general, this investigation offers valuable observations regarding the curative impact of fenugreek extract on anti-ED in diabetes, revealing the involvement of the Arg1 pathway in its mechanism.

Gallic Acid Alleviates Cognitive Impairment by Promoting Neurogenesis via the GSK3ß-Nrf2 Signaling Pathway in an APP/PS1 Mouse Model.

Background: Neuronal loss occurs early and is recognized as a hallmark of Alzheimer's disease (AD). Promoting neurogenesis is an effective treatment strategy for neurodegenerative diseases. Traditional Chinese herbal medicines serve as a rich pharmaceutical source for modulating hippocampal neurogenesis. Objective: Gallic acid (GA), a phenolic acid extracted from herbs, possesses anti-inflammatory and antioxidant properties. Therefore, we aimed to explore whether GA can promote neurogenesis and alleviate AD symptoms. Methods: Memory in mice was assessed using the Morris water maze, and protein levels were examined via western blotting and immunohistochemistry. GA's binding site in the promoter region of transcription regulator nuclear factor erythroid 2-related factor 2 (Nrf2) was calculated using AutoDock Vina and confirmed by a dual luciferase reporter assay. Results: We found that GA improved spatial memory by promoting neurogenesis in the hippocampal dentate gyrus zone. It also improved synaptic plasticity, reduced tau phosphorylation and amyloid-ß concentration, and increased levels of synaptic proteins in APP/PS1 mice. Furthermore, GA inhibited the activity of glycogen synthase kinase-3ß (GSK-3ß). Bioinformatics tools revealed that GA interacts with several amino acid sites on GSK-3ß. Overexpression of GSK-3ß was observed to block the protective effects of GA against AD-like symptoms, while GA promoted neurogenesis via the GSK-3ß-Nrf2 signaling pathway in APP/PS1 mice. Conclusions: Based on our collective findings, we hypothesize that GA is a potential pharmaceutical agent for alleviating the pathological symptoms of AD.

Preparation of Fresh-Keeping Paper Using Clove Essential Oil through Pickering Emulsion and Maintaining the Quality of Postharvest Cherry Tomatoes.

This study focused on developing a Pickering emulsion fresh-keeping paper that contained clove essential oil (CEO). Cherry tomatoes served as the test material for assessing the preservative efficacy of fresh-keeping paper. The results showed that Pickering emulsion had strong stability. Additionally, the fresh-keeping paper had a good antioxidant activity and sustained-release effect on CEO. In terms of the preservation effect, 0.75 wt% CEO Pickering emulsion paper reduced the decay incidence and weight loss of cherry tomatoes during 12-day storage. Fresh-keeping paper could also play a positive role in protecting the sensory index and color difference of tomatoes. It slowed the decline rate of soluble solid concentration (SSC) and titrable acid (TA). The vitamin C (Vc) and hardness of preserved tomatoes using fresh-keeping paper were maintained at a high level. The paper also inhibited the growth of microorganisms significantly. Therefore, 0.75 wt% CEO Pickering emulsion fresh-keeping paper displayed considerable potential for application in the preservation of postharvest fruits and vegetables. It is a novel fruit and vegetable preservation material worthy of development.