Identification and functional analysis of a deduced geraniol synthase from Camphora officinarum.

The market demand for essential oil containing citral is increasing. Our research group identified a rare chemotype of Camphora officinarum whose leaves are high in citral content by examining over 1000 wild trees across the entire native distribution area of C. officinarum in China. Because C. officinarum is suitable for large-scale cultivation, it is therefore seen as a promising source of natural citral. However, the molecular mechanism of citral biosynthesis in C. officinarum is poorly understood. In this study, transcriptomic analyses of C. officinarum with different citral contents revealed a strong positive correlation between the expression of a putative geraniol synthase gene (CoGES) and citral content. The CoGES cDNA was cloned, and the CoGES protein shared high similarity with other monoterpene synthases. Enzymatic assays of CoGES with geranyl diphosphate (GPP) as substrate yielded geraniol as the single product, which is the precursor of citral. Further transient expression of CoGES in Nicotiana benthamiana resulted in a higher relative content of geranial and the appearance of a new substance, neral. These findings indicate that CoGES is a geraniol synthase-encoding gene, and the encoded protein can catalyze the transformation of GPP into geraniol, which is further converted into geranial and neral through an unknown mechanism in vivo. These findings expand our understanding of citral biosynthesis in Lauraceae plants. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01463-4.

Straw Retention with Reduced Fertilization Enhances Soil Properties, Crop Yields, and Emergy Sustainability of Wheat-Soybean Rotation.

Cereal + legume rotation is an integrated system that facilitates soil fertility and sustainable agricultural production. However, research on the management compatibility affecting soil physico-chemical properties yields overall agro-ecosystem sustainability, but profitability is lacking, especially under straw retention and potential reductions in fertilizer application. An 11-year field experiment investigated three treatments: no straw retention + traditional mineral fertilization (TNS), straw retention + traditional mineral fertilization (TS), and straw retention + reduced mineral fertilization (DS). Compared with TNS, TS significantly improved soil physico-chemical properties, including macro-aggregates (R > 0.25 mm), porosity, field water capacity (FWC), soil organic carbon (SOC) storage, total nitrogen storage, microbial biomass carbon (MBC), and microbial biomass nitrogen (MBN) by 17.3%, 3.2%, 13.0%, 5.5%, 3.2%, 15.5%, and 13.8%, respectively. TS also significantly increased total (wheat + soybean) yields (TYs), economic profits, and emergy sustainability index (ESI) by 15.8%, 25.0%, 3.7 times that of TNS, respectively. Surprisingly, compared with TS, DS further significantly improved R > 0.25 mm, porosity, FWC, SOC storage, MBC, MBN, TY, economic profits, and ESI by 11.4%, 1.5%, 6.1%, 3.0%, 10.6%, 7.2%, 5.7%, 11.1%, and 36.5%, respectively. Overall, retaining straw with reduced fertilization enhances soil properties, yields, and emergy sustainability in wheat-soybean rotation systems.

HLTF disrupts Cas9-DNA post-cleavage complexes to allow DNA break processing.

The outcome of CRISPR-Cas-mediated genome modifications is dependent on DNA double-strand break (DSB) processing and repair pathway choice. Homology-directed repair (HDR) of protein-blocked DSBs requires DNA end resection that is initiated by the endonuclease activity of the MRE11 complex. Using reconstituted reactions, we show that Cas9 breaks are unexpectedly not directly resectable by the MRE11 complex. In contrast, breaks catalyzed by Cas12a are readily processed. Cas9, unlike Cas12a, bridges the broken ends, preventing DSB detection and processing by MRE11. We demonstrate that Cas9 must be dislocated after DNA cleavage to allow DNA end resection and repair. Using single molecule and bulk biochemical assays, we next find that the HLTF translocase directly removes Cas9 from broken ends, which allows DSB processing by DNA end resection or non-homologous end-joining machineries. Mechanistically, the activity of HLTF requires its HIRAN domain and the release of the 3'-end generated by the cleavage of the non-target DNA strand by the Cas9 RuvC domain. Consequently, HLTF removes the H840A but not the D10A Cas9 nickase. The removal of Cas9 H840A by HLTF explains the different cellular impact of the two Cas9 nickase variants in human cells, with potential implications for gene editing.

Preparation of Perilla frutescens L. essential oil hydrogel beads and preservation application research in strawberry.

Perilla frutescens L. essential oil (PLEO) has antibacterial and antioxidant properties, which can effectively maintain the quality of fruits and extend their shelf life. In this study, sodium alginate and chitosan were used as wall materials, and PLEO microcapsule powder was used as the core materials to prepare PLEO hydrogel beads. The best results were obtained by using 2%w/v sodium alginate and 1.5%w/v chitosan as wall materials, with a core-to-wall ratio of 2:1 and homogenized for 15 min producing PLEO hydrogel beads with encapsulation efficiency of 82.61 %. For strawberries preservation, PLEO hydrogel beads preservation group had a better effect after 5 d of storage, showing a lower decay rate (15.71 %), better maintaining the hardness of 1.75 kg/cm2, and a weight loss of 3.29 %. Furthermore, organic acids and total phenols were retained more in this group, the number of microorganisms was significantly reduced, and sensory qualities were improved, especially taste and color. This study provides important insights into the application of natural preservatives in the food industry and promotes sustainable practices in food preservation.

Contrasting carbon cycle responses of semiarid abandoned farmland to simulated warmer-drier and warmer-wetter climates.

Rewilding abandoned farmlands provides a nature-based climate solution via carbon (C) offsetting; however, the C-cycle-climate feedback in such restored ecosystems is poorly understood. Therefore, we conducted a 2-year field experiment in Loess Plateau, China, to determine the impacts of warming (∼1.4 °C) and altered precipitation (±25 %, ±50 %, and ambient), alone or in concert on soil C pools and associated C fluxes. Experimental warming significantly enhanced soil respiration without affecting the ecosystem net C uptake and soil C storage; these variables tended to increase along the manipulated precipitation gradient. Their interactions increased ecosystem net C uptake (synergism) but decreased soil respiration and soil C accumulation (antagonism) compared with a single warming or altered precipitation. Additionally, most variables related to the C cycle tended to be more responsive to increased precipitation, but the ecosystem net C uptake responded intensely to warming and decreased precipitation. Overall, ecosystem net C uptake and soil C storage increased by 94.4 % and 8.2 %, respectively, under the warmer-wetter scenario; however, phosphorus deficiency restricted soil C accumulation under these climatic conditions. By contrast, ecosystem net C uptake and soil C storage decreased by 56.6 % and 13.6 %, respectively, when exposed to the warmer-drier climate, intensifying its tendency toward a C source. Therefore, the C sink function of semiarid abandoned farmland was unsustainable. Our findings emphasize the need for management of post-abandonment regeneration to sustain ecosystem C sequestration in the context of climate change, aiding policymakers in the development of C-neutral routes in abandoned regions.

Complete telomere-to-telomere assemblies of two sorghum genomes to guide biological discovery.

The assembly of two sorghum T2T genomes corrected the assembly errors in the current reference, uncovered centromere variation, boosted functional genomics research, and accelerated sorghum improvement.

Shellac-based delivery systems for food bioactive compounds.

Shellac is a natural resin featuring some attractive properties such as amphiphilicity, pH responsiveness, biocompatibility, and biodegradability. There has been increasing interest in employing shellac for controlled delivery of food bioactive compounds. This review outlines the recent advances in different types of shellac-based delivery systems, including nanoparticles, zein-shellac particles, hydrogels, nanofibers, and nanomicelles. The preparation method, formation mechanism, structure, and delivery performance are investigated. These systems could improve the stability and shelf-life of bioactive compounds, allow for targeted release at the small intestine or colon site, and increase bioavailability. The deficiencies and challenges of each of the systems are also discussed. The promising results in this review could guide future trends in more efficient shellac-based delivery platforms for functional food applications.

The influence of the doping concentration and reverse intersystem crossing on the efficiency of tricomponent organic light-emitting diodes with the thermally activated delayed fluorescence exciplex emitter.

In this work, we fabricate a series of full-fluorescent organic light-emitting diodes (OLEDs) with the thermally activated delayed fluorescence (TADF) exciplex emitter in order to improve the efficiency through the reverse intersystem crossing (RISC) process. The TADF exciplex emitters are made up of a mixture of P-type materials (DMAC-DPS and mCBP) and n-type material (PO-T2T), among which DMAC-DPS also classes as a TADF material. The change in doping concentration will affect the intermolecular distance and the composition of TADF material and two kinds of exciplexes (DMAC-DPS:PO-T2T and mCBP:PO-T2T) in the luminescent layer (EML). Different materials and concentrations of doping not only add new RISC channels but also alter the original RISC channels, thereby affecting the performance of devices. It is beneficial for improving efficiency by increasing the proportion of independent TADF material and reducing the proportion of exciplex (DMAC-DPS:PO-T2T) in the EML, which can be controlled by doping. When the ratio of DMAC-DPS, PO-T2T and mCBP in the EML is 1 : 1 : 2, we achieve the optimal electro-optic performance in device A3, with maximum current efficiency, power efficiency, and luminance of 41.64 cd A-1, 43.42 lm W-1, and 23 080 cd m-2, respectively.

Combined Insults of a MASH Diet and Alcohol Binges Activate Intercellular Communication and Neutrophil Recruitment via the NLRP3-IL-1ß Axis in the Liver.

Binge drinking in obese patients positively correlates with accelerated liver damage and liver-related death. However, the underlying mechanism and the effect of alcohol use on the progression of metabolic-dysfunction-associated steatotic liver disease (MASLD) remain unexplored. Here, we show that short-term feeding of a metabolic-dysfunction-associated steatohepatitis (MASH) diet plus daily acute alcohol binges for three days induce liver injury and activation of the NLRP3 inflammasome. We identify that a MASH diet plus acute alcohol binges promote liver inflammation via increased infiltration of monocyte-derived macrophages, neutrophil recruitment, and NET release in the liver. Our results suggest that both monocyte-derived macrophages and neutrophils are activated via NLRP3, while the administration of MCC950, an NLRP3 inhibitor, dampens these effects.In this study, we reveal important intercellular communication between hepatocytes and neutrophils. We discover that the MASH diet plus alcohol induces IL-1ß via NLRP3 activation and that IL-1ß acts on hepatocytes and promotes the production of CXCL1 and LCN2. In turn, the increase in these neutrophils recruits chemokines and causes further infiltration and activation of neutrophils in the liver. In vivo administration of the NLRP3 inhibitor, MCC950, improves the early phase of MetALD by preventing liver damage, steatosis, inflammation, and immune cells recruitment.

Colorimetric detection of diamine using diamine oxidase and horseradish peroxidase co-incorporated hybrid microsphere as biomimetic cascade enzymes.

Dual-enzyme co-embedded materials have shown high potential for achieving efficient detection due to the convenience of two-enzyme cascade reactions. Herein, we developed a dual-enzyme hybrid microsphere (HM) based biosensor to detect diamines (histamine was included for ease of description) in aquatic products. The HM was made from diamine oxidase, horseradish peroxidase, and copper phosphate through the biomineralization method. Under optimal conditions, the system displayed linear color response to histamine of different concentrations ranging from 0 to 200 µg/mL. The detection limit of histamine was 0.15 µg/mL, showing higher sensitivity than the two-step free enzyme assay. Moreover, the detection system exhibited good specificity to diamines. The method was used to detect diamines in commercial samples, and the results were compared with those measured by the high-performance liquid chromatography method. Overall, the proposed assay exhibited high potential in diamine quantification and was readily extended to other cascade enzymatic reaction-based detection strategies.

Stable, porous, light-emitting post-modification covalent organic frameworks conjugated molecularly imprinted polymers for selective detection of pyrraline in salami products.

Molecular imprinting is one of the most frequently occurring post-modification in the preparation of covalent organic frameworks (COFs) to enhance selectivity and specificity. In this study, we prepared a 2D layer structure of methoxy-conjugated COFs with the modification of azide (4-azido-L-phenylalanine), named [4-ALP]0.17-COFs, which exhibited a large specific surface area of 827.6 m2/g, good stability of water, polar solvents, chemistry, and thermodynamics. Fluorescent COF nanosheets ([4-ALP]0.17-CONs) obtained by liquid-assisted ultrasonic stripping have excellent blue luminescence properties and ultra-high absolute fluorescence quantum yield of 33.34 %. The modifiable functional groups in the surface of [4-ALP]0.17-CONs interacted with the targets and functional monomers of molecularly imprinted polymers (MIPs) through hydrogen bonding interactions, to form the 3D holes with recognition sites. The quantitative detection of pyrraline (PRL) could be achieved in the concentration range of 0.05-4 µg/L with the LOD was 34.81 ng/L. The spiked recovery of PRL in meat products was 88.01-106.00 %. The [4-ALP]0.17-CONs@MIPs sensing system showed excellent stability, reliability, reusability, and practicability, promising its potential for targeted monitoring of trace molecules in real matrices.

Exogenous application of 5-NGS increased osmotic stress resistance by improving leaf photosynthetic physiology and antioxidant capacity in maize.

Background: Drought is a critical limiting factor affecting the growth and development of spring maize (Zea mays L.) seedlings in northeastern China. Sodium 5-nitroguaiacol (5-NGS) has been found to enhance plant cell metabolism and promote seedling growth, which may increase drought tolerance. Methods: In the present study, we investigated the response of maize seedlings to foliar application of a 5-NGS solution under osmotic stress induced by polyethylene glycol (PEG-6000). Four treatment groups were established: foliar application of distilled water (CK), foliar application of 5-NGS (NS), osmotic stress + foliar application of distilled water (D), and osmotic stress + foliar application of 5-NGS (DN). Plant characteristics including growth and photosynthetic and antioxidant capacities under the four treatments were evaluated. Results: The results showed that under osmotic stress, the growth of maize seedlings was inhibited, and both the photosynthetic and antioxidant capacities were weakened. Additionally, there were significant increases in the proline and soluble sugar contents and a decrease in seedling relative water content (RWC). However, applying 5-NGS alleviated the impact of osmotic stress on maize seedling growth parameters, particularly the belowground biomass, with a dry mass change of less than 5% and increased relative water content (RWC). Moreover, treatment with 5-NGS mitigated the inhibition of photosynthesis caused by osmotic stress by restoring the net photosynthetic rate (Pn) through an increase in chlorophyll content, photosynthetic electron transport, and intercellular CO2 concentration (Ci). Furthermore, the activity of antioxidant enzymes in the aboveground parts recovered, resulting in an approximately 25% decrease in both malondialdehyde (MDA) and H2O2. Remarkably, the activity of enzymes in the underground parts exhibited more significant changes, with the contents of MDA and H2O2 decreasing by more than 50%. Finally, 5-NGS stimulated the dual roles of soluble sugars as osmoprotectants and energy sources for metabolism under osmotic stress, and the proline content increased by more than 30%. We found that 5-NGS played a role in the accumulation of photosynthates and the effective distribution of resources in maize seedlings. Conclusions: Based on these results, we determined that foliar application of 5-NGS may improve osmotic stress tolerance in maize seedlings. This study serves as a valuable reference for increasing maize yield under drought conditions.

Construction and validation of a novel tumor morphology immune inflammatory nutritional score (TIIN score) for intrahepatic cholangiocarcinoma: a multicenter study.

BACKGROUND: Tumor morphology, immune function, inflammatory levels, and nutritional status play critical roles in the progression of intrahepatic cholangiocarcinoma (ICC). This multicenter study aimed to investigate the association between markers related to tumor morphology, immune function, inflammatory levels, and nutritional status with the prognosis of ICC patients. Additionally, a novel tumor morphology immune inflammatory nutritional score (TIIN score), integrating these factors was constructed. METHODS: A retrospective analysis was performed on 418 patients who underwent radical surgical resection and had postoperative pathological confirmation of ICC between January 2016 and January 2020 at three medical centers. The cohort was divided into a training set (n = 272) and a validation set (n = 146). The prognostic significance of 16 relevant markers was assessed, and the TIIN score was derived using LASSO regression. Subsequently, the TIIN-nomogram models for OS and RFS were developed based on the TIIN score and the results of multivariate analysis. The predictive performance of the TIIN-nomogram models was evaluated using ROC survival curves, calibration curves, and clinical decision curve analysis (DCA). RESULTS: The TIIN score, derived from albumin-to-alkaline phosphatase ratio (AAPR), albumin-globulin ratio (AGR), monocyte-to-lymphocyte ratio (MLR), and tumor burden score (TBS), effectively categorized patients into high-risk and low-risk groups using the optimal cutoff value. Compared to individual metrics, the TIIN score demonstrated superior predictive value for both OS and RFS. Furthermore, the TIIN score exhibited strong associations with clinical indicators including obstructive jaundice, CEA, CA19-9, Child-pugh grade, perineural invasion, and 8th edition AJCC N stage. Univariate and multivariate analysis confirmed the TIIN score as an independent risk factor for postoperative OS and RFS in ICC patients (p < 0.05). Notably, the TIIN-nomogram models for OS and RFS, constructed based on the multivariate analysis and incorporating the TIIN score, demonstrated excellent predictive ability for postoperative survival in ICC patients. CONCLUSION: The development and validation of the TIIN score, a comprehensive composite index incorporating tumor morphology, immune function, inflammatory level, and nutritional status, significantly contribute to the prognostic assessment of ICC patients. Furthermore, the successful application of the TIIN-nomogram prediction model underscores its potential as a valuable tool in guiding individualized treatment strategies for ICC patients. These findings emphasize the importance of personalized approaches in improving the clinical management and outcomes of ICC.

The burden of knee osteoarthritis worldwide, regionally, and nationally from 1990 to 2019, along with an analysis of cross-national inequalities.

OBJECTIVE: To describe the disease burden of knee osteoarthritis (KOA) globally, regionally, and in 204 countries by age, sex, and sociodemographic index (SDI) from 1990 to 2019, and to explore cross-national inequalities across SDI. METHODS: The Global Burden of Disease (GBD) 2019 database collected data on KOA worldwide from 1990 to 2019, including prevalence, incidence, years lived with disability (YLDs). The average annual percentage change (AAPC) was used to measure temporal trends. In addition, the inequality slope index and the health concentration index were calculated to quantify the unequal distribution of the burden of KOA across 204 countries worldwide. RESULTS: In 2019, the global age-standardized prevalence rate increased by 7.5% compared with 1990, and the age-standardized incidence rate increased by about 6.2%; The age-standardized YLDs rate increased by about 7.8%. In addition to the Republic of Korea and the United States of America, the disease burden of KOA has increased year by year in other countries around the world. The incidence of KOA was highest at ages 50-59, while the prevalence and rates of YLDs were highest at ages 75-84. The burden of KOA was higher in women than in men. Cross-country inequality suggests that the inequality in the burden of KOA between high SDI and low SDI countries becomes greater, and that countries with high SDI bear a disproportionately high burden. CONCLUSION: The global KOA burden has risen steadily between 1990 and 2019, and cross-national inequality gaps remain large. Targeted measures must therefore be taken to address this inequality and the increasing global KOA disease burden.

Identification of key genes controlling monoterpene biosynthesis of Citral-type Cinnamomum bodinieri Levl. Based on transcriptome and metabolite profiling.

The citral-type is the most common chemotype in Cinnamomum bodinieri Levl (C. bodinieri), which has been widely used in the daily necessities, cosmetics, biomedicine, and aromatic areas due to their high citral content. Despite of this economic prospect, the possible gene-regulatory roles of citral biosynthesis in the same geographic environment remains unknown. In this study, the essential oils (EOs) of three citral type (B1, B2, B3) and one non-citral type (B0) varieties of C. bodinieri were identified by GC-MS after hydrodistillation extraction in July. 43 components more than 0.10% were identified in the EOs, mainly composed of monoterpenes (75.8-91.84%), and high content citral (80.63-86.33%) were identified in citral-type. Combined transcriptome and metabolite profiling analysis, plant-pathogen interaction(ko04626), MAPK signaling pathway-plant(ko04016), starch and sucrose metabolism(ko00500), plant hormone signal transduction(ko04075), terpenoid backbone biosynthesis (ko00900) and monoterpenoid biosynthesis (ko00902) pathways were enriched significantly. The gene expression of differential genes were linked to the monoterpene content, and the geraniol synthase (CbGES), alcohol dehydrogenase (CbADH), geraniol 8-hydroxylase-like (CbCYP76B6-like) and 8-hydroxygeraniol dehydrogenase (Cb10HGO) were upregulated in the citral-type, indicating that they were associated with high content of geraniol and citral. The activities of CbGES and CbADH in citral type were higher than in non-citral type, which was corroborated by enzyme-linked immunosorbent assay (ELISA). This study on the accumulation mechanism of citral provides a theoretical basis for the development of essential oil of C. bodinieri.

Regulating Protons to Tailor the Enol Conversion of Quinone for High-Performance Aqueous Zinc Batteries.

Quinone-based electrodes using carbonyl redox reactions are promising candidates for aqueous energy storage due to their high theoretical specific capacity and high-rate performance. However, the proton storage manners and their influences on the electrochemical performance of quinone are still not clear. Herein, we reveal that proton storage could determine the products of the enol conversion and the electrochemical stability of the organic electrode. Specifically, the protons preferentially coordinated with the prototypical pyrene-4,5,9,10-tetraone (PTO) cathode, and increasing the proton concentration in the electrolyte can improve its working potentials and cycling stability by tailoring the enol conversion reaction. We also found that exploiting Al2(SO4)3 as a pH buffer can increase the energy density of the Zn||PTO batteries from 242.8 to 284.6 Wh kg-1. Our research has a guiding significance for emphasizing proton storage of organic electrodes based on enol conversion reactions and improving their electrochemical performance.

Phase Engineering of High-Entropy Alloy for Enhanced Electrocatalytic Nitrate Reduction to Ammonia.

Directly electrochemical conversion of nitrate (NO3 -) is an efficient and environmentally friendly technology for ammonia (NH3) production but is challenged by highly selective electrocatalysts. High-entropy alloys (HEAs) with unique properties are attractive materials in catalysis, particularly for multi-step reactions. Herein, we first reported the application of HEA (FeCoNiAlTi) for electrocatalytic NO3 - reduction to NH3 (NRA). The bulk HEA is active for NRA but limited by the unsatisfied NH3 yield of 0.36 mg h-1 cm-2 and Faradaic efficiency (FE) of 82.66 %. Through an effective phase engineering strategy, uniform intermetallic nanoparticles are introduced on the bulk HEA to increase electrochemical active surface area and charge transfer efficiency. The resulting nanostructured HEA (n-HEA) delivers enhanced electrochemical NRA performance in terms of NH3 yield (0.52 mg h-1 cm-2) and FE (95.23 %). Further experimental and theoretical investigations reveal that the multi-active sites (Fe, Co, and Ni) dominated electrocatalysis for NRA over the n-HEA. Notably, the typical Co sites exhibit the lowest energy barrier for NRA with *NH2 to *NH3as the rate-determining step.

Fast detection of tryptamine in meat products with azide-functionalized covalent organic frameworks confined in molecularly imprinted polymers.

Tryptamine is a biogenic amine that affects organoleptic quality through the generation of off-odours in foods. Herein, imine-based covalent organic frameworks (COFs) were synthesized via Schiff base reactions and postmodified with click chemistry to generate azide-functionalized COFs with tunable azide units on the walls. The combination of molecular imprinting with COFs enabled the specific recognition of the targets. The resulting optosensing system (azide-functionalized COFs@MIPs) was used as a sample-to-answer analyser for detecting tryptamine (detection time within 10 min). A linear relationship was observed for the fluorescence response to tryptamine concentrations in the range of 3-120 µg L-1, with a limit of detection of 1.74 µg L-1. The recoveries for spiked samples were satisfactory, with relative standard deviations <9.90%. The optosensing system is a potential tool for the quantitative detection of tryptamine in meat products because of its lower cost, shorter processing time, and simpler processing steps compared to conventional chromatographic techniques.

Comparison of anti-allergic activities of different types of lotus seed resistant starch in OVA-induced mouse model.

Currently, evidence from observational studies suggests dietary fiber intake may be associated with decreased risk of food allergy. As a type of dietary fiber, resistant starch was also widely reported to possess anti-allergic properties. However, there is a relative paucity of studies assessing the influence of resistant starch types on their anti-allergic activity and its possible underlying mechanisms. In the current study, the anti-allergic effects of RS3-type (retrograded starch), RS4-type (chemically modified starch, cross-bonded), and RS5-type (starch-palmitic acid complex) of lotus seed resistant starch were evaluated in the OVA (100 mg/kg)-induced food allergic mice model. The results showed that oral administration of RS3 or RS4 lotus seed resistant starch (0.3 g/100 g b.w.) for 25 days significantly improved adverse symptoms of food allergy such as weight loss, increases in allergy symptom score and diarrhea rate; with significant reduction of serum specific antibody IgE, TNF-α, IL-4 levels and improved Th1/Th2 balance being observed. The mechanism may involve the regulation of lotus seed resistant starch on intestinal flora and the metabolites short-chain fatty acids and bile acids. Taken together, the findings may enhance understanding towards ameliorative effects of resistant starch on food allergy, and offer valuable insights for the exploration of novel anti-allergic bioactive compounds.

Neutrophil extracellular traps activate hepatic stellate cells and monocytes via NLRP3 sensing in alcohol-induced acceleration of MASH fibrosis.

OBJECTIVE: Alcohol use in metabolic dysfunction-associated steatohepatitis (MASH) is associated with an increased risk of fibrosis and liver-related death. Here, we aimed to identify a mechanism through which repeated alcohol binges exacerbate liver injury in a high fat-cholesterol-sugar diet (MASH diet)-induced model of MASH. DESIGN: C57BL/6 mice received either chow or the MASH diet for 3 months with or without weekly alcohol binges. Neutrophil infiltration, neutrophil extracellular traps (NETs) and fibrosis were evaluated. RESULTS: We found that alcohol binges in MASH increase liver injury and fibrosis. Liver transcriptomic profiling revealed differential expression of genes involved in extracellular matrix reorganisation, neutrophil activation and inflammation compared with alcohol or the MASH diet alone. Alcohol binges specifically increased NET formation in MASH livers in mice, and NETs were also increased in human livers with MASH plus alcohol use. We discovered that cell-free NETs are sensed via Nod-like receptor protein 3 (NLRP3). Furthermore, we show that cell-free NETs in vitro induce a profibrotic phenotype in hepatic stellate cells (HSCs) and proinflammatory monocytes. In vivo, neutrophil depletion using anti-Ly6G antibody or NET disruption with deoxyribonuclease treatment abrogated monocyte and HSC activation and ameliorated liver damage and fibrosis. In vivo, inhibition of NLRP3 using MCC950 or NLRP3 deficiency attenuated NET formation, liver injury and fibrosis in MASH plus alcohol diet-fed mice (graphical abstract). CONCLUSION: Alcohol binges promote liver fibrosis via NET-induced activation of HSCs and monocytes in MASH. Our study highlights the potential of inhibition of NETs and/or NLRP3, as novel therapeutic strategies to combat the profibrotic effects of alcohol in MASH.