Napabucasin deactivates STAT3 and promotes mitoxantrone-mediated cGAS-STING activation for hepatocellular carcinoma chemo-immunotherapy.

The immune resistance of tumor microenvironment (TME) causes immune checkpoint blockade therapy inefficient to hepatocellular carcinoma (HCC). Emerging strategies of using chemotherapy regimens to reverse the immune resistance provide the promise for promoting the efficiency of immune checkpoint inhibitors. The induction of cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) in tumor cells evokes the adaptive immunity and remodels the immunosuppressive TME. In this study, we report that mitoxantrone (MIT, a chemotherapeutic drug) activates the cGAS-STING signaling pathway of HCC cells. We provide an approach to augment the efficacy of MIT using a signal transducer and activator of transcription 3 (STAT3) inhibitor called napabucasin (NAP). We prepare an aminoethyl anisamide (AEAA)-targeted polyethylene glycol (PEG)-modified poly (lactic-co-glycolic acid) (PLGA)-based nanocarrier for co-delivery of MIT and NAP. The resultant co-nanoformulation can elicit the cGAS-STING-based immune responses to reshape the immunoresistant TME in the mice orthotopically grafted with HCC. Consequently, the resultant co-nanoformulation can promote anti-PD-1 antibody for suppressing HCC development, generating long-term survival, and inhibiting tumor recurrence. This study reveals the potential of MIT to activate the cGAS-STING signaling pathway, and confirms the feasibility of nano co-delivery for MIT and NAP on achieving HCC chemo-immunotherapy.

TNFSF14+ natural killer cells prevent spontaneous abortion by restricting leucine-mediated decidual stromal cell senescence.

In preparation for a potential pregnancy, the endometrium of the uterus changes into a temporary structure called the decidua. Senescent decidual stromal cells (DSCs) are enriched in the decidua during decidualization, but the underlying mechanisms of this process remain unclear. Here, we performed single-cell RNA transcriptomics on ESCs and DSCs and found that cell senescence during decidualization is accompanied by increased levels of the branched-chain amino acid (BCAA) transporter SLC3A2. Depletion of leucine, one of the branched-chain amino acids, from cultured media decreased senescence, while high leucine diet resulted in increased senescence and high rates of embryo loss in mice. BCAAs induced senescence in DSCs via the p38 MAPK pathway. In contrast, TNFSF14+ decidual natural killer (dNK) cells were found to inhibit DSC senescence by interacting with its ligand TNFRSF14. As in mice fed high-leucine diets, both mice with NK cell depletion and Tnfrsf14-deficient mice with excessive uterine senescence experienced adverse pregnancy outcomes. Further, we found excessive uterine senescence, SLC3A2-mediated BCAA intake, and insufficient TNFRSF14 expression in the decidua of patients with recurrent spontaneous abortion. In summary, this study suggests that dNK cells maintain senescence homeostasis of DSCs via TNFSF14/TNFRSF14, providing a potential therapeutic strategy to prevent DSC senescence-associated spontaneous abortion.

Dietary vitamin K intake in relation to skeletal muscle mass and strength among adults: a cross-sectional study based on NHANES.

Background: Previous studies revealed that vitamin K might help maintain muscle homeostasis, but this association has received little attention. We aimed to explore the associations of vitamin K intake with skeletal muscle mass and strength. Methods: We included cross-sectional data from the U.S. National Health and Nutrition Examination Survey (NHANES, 2011-2018). Vitamin K intake was assessed via 24-h recall. Covariate-adjusted multiple linear regression and restricted cubic splines were used to evaluate the associations of dietary vitamin K intake with skeletal muscle mass and strength, measured by dual-energy X-ray absorptiometry and handgrip dynamometer, respectively. Results: Dietary vitamin K intake was positively associated with skeletal muscle mass in males (ß = 0.05747, p = 0.0204) but not in females. We also revealed a positive association between dietary vitamin K intake and handgrip strength within the range of 0-59.871 µg/d (P nonlinear = 0.049). However, beyond this threshold, increasing vitamin K intake did not cause additional handgrip strength improvements. Conclusion: We provided evidence for a positive relationship between dietary vitamin K intake and skeletal muscle mass in males. Moreover, our study revealed a nonlinear relationship between dietary vitamin K intake and handgrip strength, highlighting an optimal intake range.

Experiences and needs of Chinese women after a stillbirth: a qualitative phenomenological study.

OBJECTIVES: We aimed to explore the lived experiences and needs of women after a recent stillbirth event. DESIGN: Qualitative phenomenological study. SETTING: The current study was conducted in a tertiary obstetric hospital in East China between 25 January 2024 and 29 March 2024. PARTICIPANTS: 14 women having experienced a stillbirth within the last 6 months. RESULTS: Researchers agreed on four key themes including individual variations in emotional reaction and recovery, physical recovery and concerns about future pregnancies, the critical role of social support systems and variations in perceptions of stillbirth as the death of a fetus versus a human being, along with related mourning rituals. These themes collectively highlight the multifaceted nature of the stillbirth experience, underscoring the complex interplay between personal, cultural and medical factors that shape women's emotional and physical responses. CONCLUSIONS: Post-stillbirth experiences among Chinese women are deeply individualised and influenced by a complex interplay of personal emotions, cultural contexts and medical interactions. It is imperative for healthcare systems to implement tailored care strategies beyond standard protocols to proactively address their varied emotional landscapes and physical concerns with an enhanced awareness of cultural sensitivities. Specialised training for healthcare providers should be devised to recognise and respond to the unique grief processes. Comprehensive support systems should be established to significantly enhance the recovery journey by providing essential resources and community connections.

A Hypoxia-Decidual Macrophage Regulatory Axis in Normal Pregnancy and Spontaneous Miscarriage.

The significance of hypoxia at the maternal-fetal interface is proven to be self-explanatory in the context of pregnancy. During the first trimester, low oxygen conditions play a crucial role in processes such as angiogenesis, trophoblast invasion and differentiation, and immune regulation. Recently, there has been increasing research on decidual macrophages, which contribute to the maintenance of immune tolerance, placental and fetal vascular development, and spiral artery remodeling, to investigate the effects of hypoxia on their biological behaviors. On these grounds, this review describes the dynamic changes in oxygen levels at the maternal-fetal interface throughout gestation, summarizing current knowledge on how the hypoxic environment sustains a successful pregnancy by regulating retention, differentiation and efferocytosis of decidual macrophages. Additionally, we explore the relationship between spontaneous miscarriages and an abnormal hypoxia-macrophage axis, shedding light on the underlying mechanisms. However, further studies are essential to elucidate these pathways in greater detail and to develop targeted interventions that could improve pregnancy outcomes.

Boron-Doped Single-Molecule van der Waals Diode.

Single-molecule diode was the first proposed device in molecular electronics. Despite the great efforts and advances over 50 years, the reported rectification ratios, the most critical parameter of a diode, remain moderate for the single-molecule diode. Herein, we report an approach to achieve a larger rectification ratio by adopting the combined strategies of p-type boron doping, the single-layer graphene nodes, and the van der Waals layer-by-layer architecture. Measured current-voltage curves showed one of the as-fabricated single-molecule diodes hit an unprecedented large rectification ratio of 457 at ±1 V. Break junction operations and spectroscopic measurements revealed the three-atom-thick configuration of the single-molecule diodes. With the experimental and theoretical calculation results, we demonstrated the doped boron atoms induced holes to redistribute the electron density, making the asymmetric coupling at positive and negative biases, and the van der Waals interaction promoted asymmetric coupling and significantly boosted diode performance.

Bulk and single-cell RNA-seq analyses reveals canonical RNA editing associated with microglial homeostasis and its role in sepsis-associated encephalopathy.

Previous studies have demonstrated the roles of both microglia homeostasis and RNA editing in sepsis-associated encephalopathy (SAE), yet their relationship remains to be elucidated. In the current study, we analyzed bulk and single-cell RNA-seq (scRNA) datasets containing 107 brain tissues and microglia samples of mice with microglial depletion and repopulation to explore canonical RNA editing associated with microglia homeostasis and evaluated its role in SAE. Analysis of brain RNA-Seq of mice revealed hallmarks of microglial repopulation, including peak expressions of Apobec1 and Apobec3 at Day 5 and dramatically changed B2m RNA editing. Significant time-dependent changes in brain RNA editing during microglial depletion and microglial repopulation was primarily observed in synaptic genes, such as Tbc1d24 and Slc1a2. ScRNA-Seq revealed heterogeneous RNA editing among microglia subpopulations and their distinct changes associated with microglia homeostasis. Moreover, repopulated microglia from LPS-induced septic mice exhibited intensified up-regulation of Apobec1 and Apobec3, with distinct RNA editing responses to LPS, mainly involved in immune-related pathways. The hippocampus from septic mice induced by peritoneal contamination and infection showed upregulated Apobec1 and Apobec3 expression, and altered RNA editing in immune-related genes, such as B2m and Mier1, and nervous-related lncRNA Meg3 and Snhg11, both of which were repressed by microglial depletion. Moreover, expression of complement-related genes, such as C4b and Cd47, were substantially correlated with RNA editing activity in microglia homeostasis and SAE. Our study demonstrates canonical RNA editing associated with microglia homeostasis, and provides new insight into its potential role in SAE.

SIRT6 alleviates senescence induced by Porphyromonas gingivalis in human gingival fibroblasts.

OBJECTIVE: Bidirectional influences between senescence and inflammation are newly discovered. This study aimed to clarify the roles and mechanism of Porphyromonas gingivalis (P. gingivalis) in exacerbating senescence in human gingival fibroblasts (HGFs). DESIGN: Subgingival plaque and gingivae were collected from twenty-four periodontitis patients and eighteen periodontally healthy subjects. Quantities of P. gingivalis in subgingival plaque were explored using real-time PCR and the expressions of p53, p21 and SIRT6 in gingivae were detected by IHC. Moreover, senescence in HGFs was induced by P. gingivalis lipopolysaccharide (LPS) and the expressions of senescence-related ß-galactosidase (SA-ß-gal), p53, p21 and senescence-associated secretory phenotype (IL-6 and IL-8) with or without treatment by SIRT6 activator UBCS039 were explored by IHC, western blot and ELISA, respectively. In addition, the levels of SIRT6, Nrf2, HO-1 and reactive oxygen species (ROS) were examined by western blot and flow cytometry. RESULTS: Quantities of P. gingivalis in subgingival plaque and semi-quantitative scores of p53 and p21 in gingivae of periodontitis patients were increased compared with healthy controls (p < 0.05), while SIRT6 score in periodontitis patients was decreased (p < 0.001). Quantities of P. gingivalis were positively correlated with p53 and p21 scores (0.6 < r < 0.9, p < 0.01), and negatively correlated with SIRT6 score (-0.9 < r<-0.6, p < 0.01). Moreover, P. gingivalis LPS increased the levels of SA-ß-gal, p53, p21, IL-6, IL-8 and ROS and decreased the levels of SIRT6, Nrf2 and HO-1 in HGFs, which was rescued by UBCS039 (p < 0.05). CONCLUSIONS: P. gingivalis LPS could induce senescence of HGFs, which could be reversed by SIRT6 via Nrf2-HO-1 signaling pathway.

Dose-dependent relationship between iron metabolism and perioperative myocardial injury in cardiac surgery with cardiopulmonary bypass: A retrospective analysis.

INTRODUCTION: We sought to comprehensively explore the potential linear and nonlinear relationship between preoperative iron metabolism and perioperative myocardial injury (PMI) following cardiac surgery with cardiopulmonary bypass (CPB). METHODS: Patients who underwent cardiac surgery with CPB between December 2018 and April 2021 were retrospectively collected. The measurements of iron metabolism included serum iron (SI), serum ferritin (SF), transferrin (TRF), transferrin saturation (TS), and total iron binding capacity (TIBC). Logistic regression and restricted cubic spline (RCS) models were used for linear and nonlinear analysis. The primary outcome was PMI with a 100x upper reference limit (URL). RESULTS: Of 2420 patients screened,744 eligible patients were enrolled for the final analysis. The incidence of PMI was 25.7%. No significant linear relationship was observed. In the RCS models adjusted with age (median:56), female, and history of diabetes, a statistically significant difference was detected between TRF (p for nonlinear 0.0152) or TIBC (p for nonlinear 0.0477) and PMI. The gentle U-shaped relationship observed between TRF, TIBC, and PMI suggests that when TRF and TIBC increase, the risk decreases, reaching its lowest point when TRF=2.4 and TIBC=54. Nevertheless, as TRF and TIBC continue to increase, the risk starts to rise again. Subgroup analyses yielded consistent findings, with a notable emphasis on older patients who were more susceptible to variations in iron metabolism. CONCLUSION: Iron metabolism, including TRF, and TIBC, exhibited a nonlinear relationship with PMI by the RCS model adjusted by age, gender, and history of diabetes.

Synthesis, structure, spectra, cytotoxicity and photo induced NO release of four isomeric nitrosylruthenium complexes.

Four isomeric nitrosyl ruthenium complexes [RuCl(2mqn)(Val)(NO)] (1-4) were prepared (2mqn, 2-methyl-8-hydroxyquinoline; Val, L-valine) and characterized by 1H NMR, 13C NMR, absorption spectrum, electrospray ionization mass spectrometry, and X-ray crystal diffraction. Time-resolved FT-IR and fluorescence spectroscopy were used to monitor photo-induced NO release in solution, while NO released in living cells was imaged using a selective fluorescent probe. The isomeric complexes showed different levels of cytotoxicity against HeLa cells, and slightly photo-enhanced anti-proliferative activity was observed. The isomeric complexes 1-4 inhibited the growth of HeLa cells by inducing apoptosis and promoted cell cycle arrest in the S phase. Furthermore, they showed relatively lower cytotoxicity against the human liver cell line HL-7702. The different spatial configurations of the complexes is close related with the selective binding of the isomeric complexes with serum albumin, which provide insight into the potential applications of the nitrosyl ruthenium complexes.

Apolipoprotein A-I: Potential Protection Against Intestinal Injury Induced by Dietary Lipid.

The intestinal barrier system protects the human body from harmful factors, by continuously renewing the intestinal epithelium, tight junctions and enteric microbes. However, dietary fat can harm the intestinal epithelial barrier enhancing gut permeability. In recent years, Apolipoprotein A-I has attracted much attention because of its anti-inflammatory properties. Numerous studies have demonstrated that Apolipoprotein A-I can regulate mucosal immune cells, inhibit the progression of inflammation, promote epithelial proliferation and repair, and maintain physical barrier function; it can also regulate angiogenesis, thereby improving local circulation. This article is intended to elucidate the mechanism by which Apolipoprotein A-I improves intestinal barrier damage caused by dietary fat and to review the role of Apolipoprotein A-I in maintaining intestinal homeostasis.

Quantum Confinement and End-Sealing Effects for Highly Sensitive and Stable Nitrogen Dioxide Detection: Homogeneous Integration of Ti3C2Tx-Based Flexible Gas Sensors.

The real-time and room-temperature detection of nitrogen dioxide (NO2) holds significant importance for environmental monitoring. However, the performance of NO2 sensors has been hampered by the trade-off between the high sensitivity and stability of conventional sensitive materials. Here, we present a novel fully flexible paper-based gas sensing structure by combining a homogeneous screen-printed titanium carbide (Ti3C2Tx) MXene-based nonmetallic electrode with a MoS2 quantum dots/Ti3C2Tx (MoS2 QDs/Ti3C2Tx) gas-sensing film. These precisely designed gas sensors demonstrate an improved response value (16.3% at 5 ppm) and a low theoretical detection limit of 12.1 ppb toward NO2, which exhibit a remarkable 3.5-fold increase in sensitivity compared to conventional Au interdigital electrodes. The outstanding performance can be attributed to the integration of the quantum confinement effect of MoS2 QDs and the conductivity of Ti3C2Tx, establishing the main active adsorption sites and enhanced charge transport pathways. Furthermore, an end-sealing effect strategy was applied to decorate the defect sites with naturally oxygen-rich tannic acid and conductive polymer, and the formed hydrogen bonding network at the interface effectively mitigated the oxidative degradation of the Ti3C2Tx-based gas sensors. The exceptional stability has been achieved with only a 1.8% decrease in response over 4 weeks. This work highlights the innovative design of high-performance gas sensing materials and homogeneous gas sensor techniques.

The plant extract PNS mitigates atherosclerosis via promoting Nrf2-mediated inhibition of ferroptosis through reducing USP2-mediated Keap1 deubiquitination.

BACKGROUND AND PURPOSE: Atherosclerosis is the basis of cardiovascular disease. Ferroptosis is a form of programmed cell death characterized by lipid peroxidation, which contributes to atherogenesis. The plant extract PNS (Panax notoginseng saponins), containing the main active ingredients of Panax notoginseng, exhibits anti-atherogenic properties. Herein, we determined whether PNS and its major components could attenuate atherosclerosis by suppressing ferroptosis and revealed the underlying mechanism(s). EXPERIMENTAL APPROACH: The anti-atherogenic effects of PNS and their association with inhibition of ferroptosis was determined in apoE-/- mice. In vitro, the anti-ferroptotic effect and mechanism(s) of PNS components were demonstrated in the presence of ferroptosis inducers. Expression of ferroptosis markers and the ubiquitination of Keap1 were evaluated in USP2-/- macrophages. Finally, the anti-atherogenic effect of USP2 knockout was determined by using USP2-/- mice treated with high-fat diet (HFD) and AAV-PCSK9. KEY RESULTS: PNS inhibited ferroptosis and atherosclerosis in vivo. PNS suppressed ferroptosis and ferroptosis-aggravated foam cell formation and inflammation in vitro. Mechanistically, PNS and its components activated Nrf2 by antagonizing Keap1, which was attributed to the inhibition of USP2 expression. USP2 knockout antagonized ferroptosis and ferroptosis-aggravated foam cell formation and inflammation, thus mitigating atherosclerosis. USP2 knockout abolished inhibitory effects of PNS on foam cell formation and inflammation in vitro. CONCLUSION AND IMPLICATIONS: PNS reduced USP2-mediated Keap1 de-ubiquitination and promoted Keap1 degradation, thereby activating Nrf2, improving iron metabolism and reducing lipid peroxidation, thus contributing to an anti-atherosclerotic outcome. Our study revealed the mechanism(s) underlying inhibition of ferroptosis and atherosclerosis by PNS.

Ultrasound-Based Deep Learning Radiomics Nomogram for Tumor and Axillary Lymph Node Status Prediction After Neoadjuvant Chemotherapy.

RATIONALE AND OBJECTIVES: This study aims to explore the feasibility of the deep learning radiomics nomogram (DLRN) for predicting tumor status and axillary lymph node metastasis (ALNM) after neoadjuvant chemotherapy (NAC) in patients with breast cancer. Additionally, we employ a Cox regression model for survival analysis to validate the effectiveness of the fusion algorithm. MATERIALS AND METHODS: A total of 243 patients who underwent NAC were retrospectively included between October 2014 and July 2022. The DLRN integrated clinical characteristics as well as radiomics and deep transfer learning features extracted from ultrasound (US) images. The diagnostic performance of DLRN was evaluated by constructing ROC curves, and the clinical usefulness of models was assessed using decision curve analysis (DCA). A survival model was developed to validate the effectiveness of the fusion algorithm. RESULTS: In the training cohort, the DLRN yielded area under the receiver operating characteristic curve values of 0.984 and 0.985 for the tumor and LNM, while 0.892 and 0.870, respectively, in the test cohort. The consistency indices (C-index) of the nomogram were 0.761 and 0.731, respectively, in the training and test cohorts. The Kaplan-Meier survival curves showed that patients in the high-risk group had significantly poorer overall survival than patients in the low-risk group (P < 0.05). CONCLUSION: The US-based DLRN model could hold promise as clinical guidance for predicting the status of tumors and LNM after NAC in patients with breast cancer. This fusion model can also predict the prognosis of patients, which could help clinicians make better clinical decisions.

Massive acceleration of SN2 reaction using the oriented external electric field.

Nucleophilic substitution is one of the most fundamental chemical reactions, and the pursuit of high reaction rates of the reaction is one of the ultimate goals in catalytic and organic chemistry. The reaction barrier of the nucleophilic substitution originates from the highly polar nature of the transition state that can be stabilized under the electric field created by the solvent environment. However, the intensity of the induced solvent-electric field is relatively small due to the random orientation of solvent molecules, which hinders the catalytic effects and restricts the reaction rates. This work shows that oriented external electric fields applied within a confined nanogap between two nanoscopic tips could accelerate the Menshutkin reaction by more than four orders of magnitude (over 39 000 times). The theoretical calculations reveal that the electric field inside the nanogap reduces the energy barrier to increase the reaction rate. Our work suggests the great potential of electrostatic catalysis for green synthesis in the future.

Wide-range and high-accuracy wireless sensor with self-humidity compensation for real-time ammonia monitoring.

Real-time and accurate biomarker detection is highly desired in point-of-care diagnosis, food freshness monitoring, and hazardous leakage warning. However, achieving such an objective with existing technologies is still challenging. Herein, we demonstrate a wireless inductor-capacitor (LC) chemical sensor based on platinum-doped partially deprotonated-polypyrrole (Pt-PPy+ and PPy0) for real-time and accurate ammonia (NH3) detection. With the chemically wide-range tunability of PPy in conductivity to modulate the impedance, the LC sensor exhibits an up-to-180% improvement in return loss (S11). The Pt-PPy+ and PPy0 shows the p-type semiconductor nature with greatly-manifested adsorption-charge transfer dynamics toward NH3, leading to an unprecedented NH3 sensing range. The S11 and frequency of the Pt-PPy+ and PPy0-based sensor exhibit discriminative response behaviors to humidity and NH3, enabling the without-external-calibration compensation and accurate NH3 detection. A portable system combining the proposed wireless chemical sensor and a handheld instrument is validated, which aids in rationalizing strategies for individuals toward various scenarios.

Highly Sensitive Ammonia Gas Sensors at Room Temperature Based on the Catalytic Mechanism of N, C Coordinated Ni Single-Atom Active Center.

Significant challenges are posed by the limitations of gas sensing mechanisms for trace-level detection of ammonia (NH3). In this study, we propose to exploit single-atom catalytic activation and targeted adsorption properties to achieve highly sensitive and selective NH3 gas detection. Specifically, Ni single-atom active sites based on N, C coordination (Ni-N-C) were interfacially confined on the surface of two-dimensional (2D) MXene nanosheets (Ni-N-C/Ti3C2Tx), and a fully flexible gas sensor (MNPE-Ni-N-C/Ti3C2Tx) was integrated. The sensor demonstrates a remarkable response value to 5 ppm NH3 (27.3%), excellent selectivity for NH3, and a low theoretical detection limit of 12.1 ppb. Simulation analysis by density functional calculation reveals that the Ni single-atom center with N, C coordination exhibits specific targeted adsorption properties for NH3. Additionally, its catalytic activation effect effectively reduces the Gibbs free energy of the sensing elemental reaction, while its electronic structure promotes the spill-over effect of reactive oxygen species at the gas-solid interface. The sensor has a dual-channel sensing mechanism of both chemical and electronic sensitization, which facilitates efficient electron transfer to the 2D MXene conductive network, resulting in the formation of the NH3 gas molecule sensing signal. Furthermore, the passivation of MXene edge defects by a conjugated hydrogen bond network enhances the long-term stability of MXene-based electrodes under high humidity conditions. This work achieves highly sensitive room-temperature NH3 gas detection based on the catalytic mechanism of Ni single-atom active center with N, C coordination, which provides a novel gas sensing mechanism for room-temperature trace gas detection research.

Effects of 6-methoxybenzoxazolinone (6-MBOA) on animals: state of knowledge and open questions.

6-methoxybenzoxazolinone (6-MBOA) is a secondary plant metabolite predominantly found in monocotyledonous plants, especially Gramineae. In damaged tissue, 2-ß-D-glucopyranosyloxy-4-hydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA-Glc) is hydrolyzed to DIMBOA, which spontaneously decomposes into 6-MBOA. It is commonly detected in plants consumed by voles and livestock and can also be present in cereal-based products. Discovered in 1955, this compound is renowned for its ability to trigger animal reproduction. However, there is a lack of research on its functional and mechanistic properties, leaving much of their potential unexplored. This review aimed to comprehensively summarize the effects of 6-MBOA on animal reproduction and human health, as well as its defensive role against herbivores. Studies have shown that 6-MBOA effectively inhibits the digestion, development, growth, and reproduction of insects. 6-MBOA may act as a partial agonist of melatonin and exert a regulatory role in mammalian reproduction, resulting in either promoting or inhibiting effects. 6-MBOA has been theorized to possess anti-tumor, anti-AIDS, anti-anxiety, and weight-loss effects in humans. However, insufficient attention has been paid to its defense properties against mammalian herbivores, and the mechanisms underlying its effects on mammalian reproduction remain unclear. In addition, research on its impact on human health is still in its preliminary stages. The review emphasizes the need for further systematic and comprehensive research on 6-MBOA to fully understand its diverse functions. Elucidating the effects of 6-MBOA on animal reproduction, adaptation, and human health would advance our understanding of plant-herbivore coevolution and the influence of environmental factors on animal population dynamics. Furthermore, this knowledge could potentially promote its application in human health and animal husbandry.

Fabrication and characterization of novel TGase-mediated glycosylated whey protein isolate nanoparticles for curcumin delivery.

The aim of this study was to fabricate novel transglutaminase (TGase)-mediated glycosylated whey protein isolate (WPI) nanoparticles for the encapsulation and delivery of curcumin. The influences of glycosylation on the physiochemical properties, stability, bioavailability, and antioxidant properties of WPI nanoparticles loaded with curcumin were investigated. Composite nanoparticles exhibited uniform distribution and small particle sizes. The main driving forces for the formation of curcumin nanoparticles were electrostatic interactions, hydrogen bonding, and hydrophobic interactions. The encapsulation and loading efficiency of curcumin after TGase-type glycosylation were significantly increased in comparison to WPI-curcumin nanoparticles. Glycosylated WPI-curcumin nanoparticles had stronger antioxidant properties and stability to resist external environmental changes than WPI-curcumin nanoparticles. In addition, glycosylated WPI-curcumin nanoparticles showed a controlled release and enhanced curcumin bioavailability in vitro gastrointestinal digestion. This study provides novel insights for self-assembled glycosylated protein nanoparticles as delivery systems for protecting hydrophobic nutrients.