Magnetic molecularly imprinted polymers using ternary deep eutectic solvent as novel functional monomer for hydroxytyrosol separation.

In this work, magnetic molecularly imprinted polymers (MIPs) for specific recognition of Hydroxytyrosol (HT) were designed by vinyl-modified magnetic particles (Fe3O4@SiO2@VTEOs) as carrier, ternary deep eutectic solvent (DES) as functional monomer, while ethylene glycol dimethacrylate (EGDMA) as crosslinker. The optimum amount of DES was obtained by adsorption experiments (molar ratio, caffeic acid: choline chloride: formic acid = 1:6:3) which were 140 µL in total. Under the optimized amount of DES, the maximum adsorption capacity of the MIPs particles was 42.43 mg g-1, which was superior to non-imprinted polymer (4.64 mg g-1) and the imprinting factor (IF) is 9.10. Syringin and Oleuropicrin were used as two reference molecules to test the selectivity of the DES-MIPs particles. The adsorption capacity of HT was 40.11 mg g-1. Three repeated experiments show that the polymer has high stability and repeatability (RSD = 5.50).

Proteomic Analysis of Preeclampsia Amniotic Fluid Based on a Novel Solid-State Preservation Method.

Objective: Amniotic fluid (AF) plays a crucial role in diagnosing and predicting perinatal diseases, specifically preeclampsia (PE). Adequate preservation of AF samples is essential for advancing the development of PE-related biomarkers and understanding the disease's mechanisms. Materials and Methods: This study presents a method for preserving proteins in AF on a solid medium, specifically a nitrocellulose membrane, which is referred to as an AF membrane. Samples were collected from normotensive subjects and PE patients and treated with direct freezing and the AF membrane methods, respectively. Protein quality was assessed through sodium dodecyl sulfate-page and capillary electrophoresis. Liquid chromatography tandem mass spectrometry (LC-MS/MS) with data-independent acquisition was employed for proteomic analysis. Bioinformatics analysis identified differentially expressed proteins and pathways distinguishing normotensive subjects from PE patients. Results: Comparison of the AF membrane method to the direct freezing method showed no significant impact on the protein content in the AF. The preservation methods employed did not result in evident protein differences or degradation in the AF obtained from both normotensive subjects and PE patients. Analysis based on Gene Ontology and HALLMARK gene sets revealed the upregulation of pathways associated with angiotensin, reactive oxygen species, and coagulation in PE patients. Furthermore, several biomarkers previously reported to be increased in PE serum, namely ENG, ERN1, FLT1, GDF15, HSPA5, LGALS3, PAPPA, PTX3, and SERPINE1, were significantly elevated in the AF. Conclusion: The AF membrane method proved to be highly effective, reliable, and durable for preserving proteins in AF samples. Preserving AF samples in a solid state holds significant value in discovering novel protein biomarkers and investigating the underlying mechanisms of PE.

Increasing cascade dams in the upstream area reduce nutrient inputs to the Three Gorges Reservoir in China.

The upstream cascade dams play an essential role in the nutrient cycle in the Yangtze. However, there is little quantitative information on the effects of upstream damming on nutrient retention in the Three Gorges Reservoir (TGR) in China. Here, we aim to assess the impact of increasing cascade dams in the upstream area of the Yangtze on Dissolved Inorganic Nitrogen and Phosphorus (DIN and DIP) inputs to the TGR and their retention in the TGR and to draw lessons for other large reservoirs. We implemented the Model to Assess River Inputs of Nutrients to seAs (MARINA-Nutrients China-2.0 model). We ran the model with the baseline scenario in which river damming was at the level of 2009 (low) and alternative scenarios with increased damming. Our scenarios differed in nutrient management. Our results indicated that total water storage capacity increased by 98 % in the Yangtze upstream from 2009 to 2022, with 17 new large river dams (>0.5 km3) constructed upstream of the Yangtze. As a result of these new dams, the total DIN inputs to the TGR decreased by 15 % (from 768 Gg year-1 to 651 Gg year-1) and DIP inputs decreased by 25 % (from 70 Gg year-1 to 53 Gg year-1). Meanwhile, the molar DIN:DIP ratio in inputs to the TGR increased by 13 % between 2009 and 2022. In the future, DIN and DIP inputs to the TGR are projected to decrease further, while the molar DIN:DIP ratio will increase. The Upper Stem contributed 39 %-50 % of DIN inputs and 63 %-84 % of DIP inputs to the TGR in the past and future. Our results deepen our knowledge of nutrient loadings in mainstream dams caused by increasing cascade dams. More research is needed to understand better the impact of increased nutrient ratios due to dam construction.

Production of polyhydroxyalkanoates by engineered Halomonas bluephagenesis using starch as a carbon source.

A novel α-amylase Amy03713 was screened and cloned from the starch utilization strain Vibrio alginolyticus LHF01. When heterologously expressed in Escherichia coli, Amy03713 exhibited the highest enzyme activity at 45 °C and pH 7, maintained >50 % of the enzyme activity in the range of 25-75 °C and pH 5-9, and sustained >80 % of the enzyme activity in 25 % (w/v) of NaCl solution, thus showing a wide range of adapted temperatures, pH, and salt concentrations. Halomonas bluephagenesis harboring amy03713 gene was able to directly utilize starch. With optimized amylase expression, H. bluephagenesis could produce poly(3-hydroxybutyrate) (PHB), poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), and poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P34HB). When cultured for PHB production, recombinant H. bluephagenesis was able to grow up to a cell dry weight of 11.26 g/L, achieving a PHB titer of 6.32 g/L, which is the highest titer that has been reported for PHB production from starch in shake flasks. This study suggests that Amy03713 is an ideal amylase for PHA production using starch as the carbon source in H. bluephagenesis.

A triple increase in global river basins with water scarcity due to future pollution.

Water security is at stake today. While climate changes influence water availability, urbanization and agricultural activities have led to increasing water demand as well as pollution, limiting safe water use. We conducted a global assessment of future clean-water scarcity for 2050s by adding the water pollution aspect to the classical water quantity-induced scarcity assessments. This was done for >10,000 sub-basins focusing on nitrogen pollution in rivers by integrating land-system, hydrological and water quality models. We found that water pollution aggravates water scarcity in >2000 sub-basins worldwide. The number of sub-basins with water scarcity triples due to future nitrogen pollution worldwide. In 2010, 984 sub-basins are classified as water scarce when considering only quantity-induced scarcity, while 2517 sub-basins are affected by quantity & quality-induced scarcity. This number even increases to 3061 sub-basins in the worst case scenario in 2050. This aggravation means an extra 40 million km2 of basin area and 3 billion more people that may potentially face water scarcity in 2050. Our results stress the urgent need to address water quality in future water management policies for the Sustainable Development Goals.

Iodide manipulation using zinc additives for efficient perovskite solar minimodules.

Interstitial iodides are the most critical type of defects in perovskite solar cells that limits efficiency and stability. They can be generated during solution, film, and device processing, further accelerating degradation. Herein, we find that introducing a small amount of a zinc salt- zinc trifluoromethane sulfonate (Zn(OOSCF3)2) in the perovskite solution can control the iodide defects in resultant perovskites ink and films. CF3SOO̶ vigorously suppresses molecular iodine formation in the perovskites by reducing it to iodide. At the same time, zinc cations can precipitate excess iodide by forming a Zn-Amine complex so that the iodide interstitials in the resultant perovskite films can be suppressed. The perovskite films using these additives show improved photoluminescence quantum efficiency and reduce deep trap density, despite zinc cations reducing the perovskite grain size and iodide interstitials. The zinc additives facilitate the formation of more uniform perovskite films on large-area substrates (78-108 cm2) in the blade-coating process. Fabricated minimodules show power conversion efficiencies of 19.60% and 19.21% with aperture areas of 84 and 108 cm2, respectively, as certified by National Renewable Energy Laboratory (NREL), the highest efficiency certified for minimodules of these sizes.

How nutrient retention and TN:TP ratios depend on ecosystem state in thousands of Chinese lakes.

Worldwide, anthropogenic activities threaten surface water quality by aggravating eutrophication and increasing total nitrogen to total phosphorus (TN:TP) ratios. In hydrologically connected systems, water quality management may benefit from in-ecosystem nutrient retention by preventing nutrient transport to downstream systems. However, nutrient retention may also alter TN:TP ratios with unforeseen consequences for downstream water quality. Here, we aim to increase understanding of how nutrient retention may influence nutrient transport to downstream systems to improve long-term water quality management. We analyzed lake ecosystem state, in-lake nutrient retention, and nutrient transport (ratios) for 3482 Chinese lakes using the lake process-based ecosystem model PCLake+. We compared a low climate change and sustainability-, and a high climate change and economy-focused scenario for 2050 against 2012. In both scenarios, the effect of nutrient input reduction outweighs that of temperature rise, resulting in more lakes with good ecological water quality (i.e., macrophyte-dominated) than in 2012. Generally, the sustainability-focused scenario shows a more promising future for water quality than the economy-focused scenario. Nevertheless, most lakes remain phytoplankton-dominated. The shift to more macrophyte-dominated lakes in 2050 is accompanied by higher nutrient retention fractions and less nutrient transport to downstream waterbodies. In-lake nutrient retention also alters the water's TN:TP ratio, depending on the inflow TN:TP ratio and the ecosystem state. In 2050 higher TN:TP ratios are expected in the outflows of lakes than in 2012, especially for the sustainability-focused scenario with strong TP loading reduction. However, the downstream impact of increased TN:TP ratios depends on actual nutrient loadings and the limiting nutrient in the receiving system. We conclude that nutrient input reductions, improved water quality, higher in-lake nutrient retention fractions, and lower nutrient transport to downstream waterbodies go hand in hand. Therefore, water quality management could benefit even more from nutrient pollution reduction than one would expect at first sight.

Polymorphism of IL-12/IL-23 axis is associated with coronary heart disease.

IL12B encodes the shared p40 subunit (IL-12p40) of IL-12 and IL-23, which have diverse immune functions and are closely related to the occurrence and development of atherosclerosis (AS). However, the exact role of IL12B in coronary heart disease (CHD) was still unknown. A case-control association analysis was performed between five single nucleotide polymorphisms (SNPs) of IL12B (rs1003199, rs3212219, rs2569254, rs2853694 and rs3212227) and CHD in Chinese Han population (1824 patients with CHD vs. 2784 controls). Logistic regression analyses were used to study the relationships between SNPs and CHD, while multiple linear regression analyses were used to test the association between the SNP and the severity of CHD. In addition, the plasma IL12B concentration of CHD patients were detected by ELISA. We detected a significant association between one of the SNPs, rs2853694-G and CHD (padj = 2.075 × 10-5 , OR, 0.773 [95% CI, 0.686-0.870]). Stratified analysis showed that rs2853694 was associated with CHD in both male and female populations and was significantly associated with both early- and late-onset CHD. In addition, rs2853694 is also related to the different types of CHD including clinical-CHD and anatomical-CHD. Moreover, there are significant differences in serum IL12B concentrations between rs2853694-TT carriers and rs2853694-GT carriers in CHD patients (p = 0.010). A common variant of IL12B was found significantly associated with CHD and its subgroups. As a shared subunit of IL-12 and IL-23, IL-12p40 may play a key role in IL-12/IL-23 axis mediated AS, which is expected to be an effective therapeutic target for CHD.

Improved viability of probiotics by encapsulation in chickpea protein matrix during simulated gastrointestinal digestion by succinylated modification.

The potential application of succinylated chickpea protein (SCP) as a wall material for spray-dried microencapsulated probiotics was investigated. The results showed that succinylation increased the surface charge of chickpea proteins (CP) and reduced the particle size of the proteins. Meanwhile, succinylated modification decreased the solubility of protein under acidic conditions and increased the solubility in alkaline conditions. The effects of spray drying and in vitro gastrointestinal digestion on probiotics were investigated by microencapsulating chickpea protein with different degrees of N-succinylation. The results showed that all microcapsules had similar morphology, particle size and low water content. The microcapsules prepared by succinylated chickpea protein showed better stability and viability during spray drying and gastrointestinal digestion. The protective effect of probiotics was better as the degree of N-succinylation increased. In particular, the SCP-3-P sample (10 % succinic anhydride modified CP and maltodextrin) lost only 0.29 Log CFU/g throughout gastrointestinal digestion. The superior protective effect provided by succinylated CP in simulated gastric fluid (SGF) was mainly attributed to the reaction of succinic anhydride with protein to cause protein aggregation under gastric acidic conditions, reducing the infiltration of gastric acid and pepsin and maintaining the structural integrity of the microcapsules. Therefore, these findings provide a new strategy for probiotic intestinal delivery and application of chickpea protein.

Three new diterpenoids isolated from Euphorbia nematocypha Hand.-Mazz and their anti-fungal activity.

Three new diterpenoids, named nematocynine A-C (1-3), together with twelve known compounds (4-15) were isolated from the aerial part of Euphorbia nematocypha Hand.-Mazz (Hereinafter referred to E. nematocypha). Their structures were elucidated by detailed spectroscopic analysis and comparison with literature data. In addition, all the compounds were tested for their anti-candida albicans activities used alone or in combination with fluconazole against sensitive strain and resistant strain in vitro. Wherein only compound 11 shows weak activity against candida albicans resistant strain (MIC50 = 128.15 µg/mL) when used alone. Compounds 1, 4, 7, 8, 9, 10, 12, 13 and 15 in combination with fluconazole showed potent anti-fungal activities (MIC50 = 15 ± 5 µg/mL, FICI = 0.05 ± 0.04) against the Candida albicans resistant strain SC5314-FR. The synergistic effects were weaker against the Candida albicans resistant strain SC5314-FR when the compounds 2, 3, 5 and 14 were combined with fluconazole (FICI = 0.16 ± 0.06).

Matrine Mediated Immune Protection in MS by Regulating Gut Microbiota and Production of SCFAs.

There is clearly an unmet need for more effective and safer treatments for multiple sclerosis (MS). Our previous studies showed a significant therapeutic effect of matrine, a monomer of traditional herbal medicine, on experimental autoimmune encephalomyelitis (EAE) mice. To explore the mechanism of matrine action, we used 16S rRNA sequencing technology to determine the gut microbes in matrine-treated EAE mice and controls. The concentrations of short-chain fatty acids (SCFAs) were then tested by metabonomics. Finally, we established pseudo-sterile mice and transplanted into them fecal microbiota, which had been obtained from the high-dose matrine-treated EAE mice to test the effects of matrine. The results showed that matrine could restore the diversity of gut microbiota and promote the production of SCFAs in EAE mice. Transplantation of fecal microbiota from matrine-treated mice significantly alleviated EAE severity, reduced CNS inflammatory infiltration and demyelination, and decreased the level of IL-17 but increased IL-10 in sera of mice. In conclusion, matrine treatment can regulate gut microbiota and metabolites and halt the progression of MS.

Setting goals for agricultural nitrogen emission reduction to ensure safe air and groundwater quality: A case study of Quzhou, the North China Plain.

Setting nitrogen (N) emission targets for agricultural systems is crucial to prevent to air and groundwater pollution, yet such targets are rarely defined at the county level. In this study, we employed a forecasting-and-back casting approach to establish human health-based nitrogen targets for air and groundwater quality in Quzhou county, located in the North China Plain. By adopting the World Health Organization (WHO) phase I standard for PM2.5 concentration (35 µg m-3) and a standard of 11.3 mg NO3--N L-1 for nitrate in drinking water, we found that ammonia (NH3) emissions from the entire county must be reduced by at least 3.2 kilotons year-1 in 2050 to meet the WHO's PM2.5 phase I standard. Additionally, controlling other pollutants such as sulfur dioxide (SO2) and nitrogen oxides (NOx) is necessary, with required reductions ranging from 16% to 64% during 2017-2050. Furthermore, to meet the groundwater quality standard, nitrate nitrogen (NO3--N) leaching to groundwater should not exceed 0.8 kilotons year-1 by 2050. Achieving this target would require a 50% reduction in NH3 emissions and a 21% reduction in NO3--N leaching from agriculture in Quzhou in 2050 compared to their respective levels in 2017 (5.0 and 2.1 kilotons, respectively). Our developed method and the resulting N emission targets can support the development of environmentally-friendly agriculture by facilitating the design of control strategies to minimize agricultural N losses.

Molecular and proteomic response of Pseudomonas fluorescens biofilm cultured on lettuce (Lactuca sativa L.) after ultrasound treatment at different intensity levels.

Ultrasonic treatment is widely used for surface cleaning of vegetables in the processing of agricultural products. In the present study, the molecular and proteomic response of Pseudomonas fluorescens biofilm cultured on lettuce was investigated after ultrasound treatment at different intensity levels. The results show that the biofilm was efficiently removed after ultrasound treatment with intensity higher than 21.06 W/cm2. However, at an intensity of less than 18.42 W/cm2, P. fluorescens was stimulated by ultrasound leading to promoted bacterial growth, extracellular protease activity, extracellular polysaccharide secretion (EPS), and synthesis of acyl-homoserine lactones (AHLs) as quorum-sensing signaling molecules. The expression of biofilm-related genes, stress response, and dual quorum sensing system was upregulated during post-treatment ultrasound. Proteomic analysis showed that ultrasound activated proteins in the flagellar system, which led to changes in bacterial tendency; meanwhile, a large number of proteins in the dual-component system began to be regulated. ABC transporters accelerated the membrane transport of substances inside and outside the cell membrane and equalized the permeability conditions of the cell membrane. In addition, the expression of proteins related to DNA repair was upregulated, suggesting that bacteria repair damaged DNA after ultrasound exposure.

Identification, characterization and expression analysis of wheat RSH family genes under abiotic stress.

Guanosine pentaphosphate and guanosine tetraphosphate are collectively called (p)ppGpp (Guanosine tetraphosphate and pentaphosphate). (p)ppGpp content in plants is affected by conditions such as light, salt, pH, UV light, and environmental phytohormones. The synthesis and hydrolysis of (p)ppGpp in plants is accomplished by a class of proteins called RSH (RelA/SpoT homologs). To date, a systematic and comprehensive genome-wide analysis of the RSH gene family in wheat and its closely related species has not been conducted. In this study, 15, 14, 12, and 8 members of RSH were identified in wheat (Triticum aestivum), Triticum dicoccoides, Triticum urartu and Aegilops tauschii respectively. Based on the conserved structural domains of the RSH genes, the TaRSHs have been categorized into TaRSH and TaCRSH. The gene duplications in the TaRSH gene family were all identified as segmental duplications indicating that the TaRSH family plays a significant role in expansion and that segmental duplications maintain a degree of genetic stability. Through the analysis of transcriptome data and RT-qPCR experiments, it was observed that the expression levels of TaRSHs were upregulated in response to abiotic stress. This upregulation suggests that TaRSHs play a crucial role in enhancing the resilience of wheat to adverse environmental conditions during its growth and development. Their increased expression likely contributes to the acquisition of stress tolerance mechanisms in wheat. Especially under NaCl stress, the expression levels increased most significantly. The more detailed systematic analysis provided in this article will help us understand the role of TaRSHs and provide a reference for further research on its molecular biological functions in wheat.

The Influence of Personal Evaluation and Social Support on Career Expectations of College Students.

This study aimed to investigate the factors influencing career expectations, determine the influence of college students' personal ability on personal evaluation in the process of gaining employment, and further explore the impact of personal evaluation and social support on career expectations. This study used a random sampling method to administer questionnaires to final-year undergraduates majoring in the liberal arts, science, art, and sports at two Chinese universities. Career expectations were positively correlated with satisfaction. The preferred employer for graduates is a school. In selecting a career, college students believed that exerting their talents was most important. Personal evaluations had a significant effect on self-development in career expectations. The level of social support had a significant effect on prestige and welfare stability in career expectations.

Two New Prostaglandin-Like Compounds from Callicarpa arborea Roxb and Their NLRP3 Inflammasome Activation Inhibitory Activity.

Two new prostaglandin-like compounds callicarboric acids A-B (1-2), along with six known compounds (3-8) were isolated from the stems of Callicarpa arborea Roxb. Their structures were determined with the help of modern spectroscopic techniques such as NMR, UV, IR, HR-ESI-MS, ECD, and ORD with the assistance of quantum chemical calculations. Compound 1 exhibited remarkable anti-NLRP3 inflammasome activation potential, demonstrating an IC50 value of 0.74 µM. Additionally, by reducing GSDMD-NT production, inhibiting caspase-1 activation, and suppressing IL-1ß secretion, it effectively mitigated NLRP3 inflammasome-induced pyroptosis in J774A.1 cells. These findings indicate that compound 1 possesses the capability to be a valuable candidate for further research and development as an NLRP3 inflammasome inhibitor.

Three New Clerodane Diterpenoids and Their NLRP3 Inflammasome Activation Inhibitory Activity from Callicarpa arborea Roxb.

Three new compounds callicarpenoids A-C (1-3), were isolated from the stems of Callicarpa arborea Roxb together with fifteen known compounds (4-18). The structures of these compounds were elucidated using advanced spectroscopic techniques, including 1D and 2D NMR, UV, IR, HR-ESI-MS, ECD, ORD, and quantum chemical calculations. Compound 3, a rare rearranged diterpenoid with a fused 5/6-ring system demonstrated strong potential as an inhibitor of the NLRP3 inflammasome activation with an IC50 value of 3.153 µM. It effectively reduced GSDMD-NT production, inhibited caspase-1 activation, and suppressed IL-1ß secretion, thereby mitigating NLRP3 inflammasome-induced pyroptosis in J774A.1 cells. These findings suggest that compound 3 warrants further research and development as a promising NLRP3 inflammasome inhibitor.

Coupling dynamics of respiration, gas exchange, and Pseudomonas fluorescens growth on fresh-cut cucumber (Cucumis sativus L.) in passive modified atmosphere packing.

This study established microbial growth models for fresh-cut cucumber packaged with different O2 transmission rate (OTR) films. Biaxially oriented polyamide/low-density polyethylene (BOPA/LDPE) film (Ⅰ: OTR5, Ⅳ: OTR48) and polyethylene (PE) film (Ⅱ: OTR2058, Ⅲ: OTR3875) were used to construct a passive modified atmosphere packaging (MAP). Mathematic models have been established to account for dynamic variations in the O2/CO2 concentration and their impacts on Pseudomonas fluorescens growth. The coupling models included: 1) respiration models of cucumber and P. fluorescens based on Michaëlis-Menten equation, 2) coupling gas exchange models based on Fick's law that contained models of P. fluorescens growth and respiration, 3) coupling microbial growth models contained respiration and gas exchange models. Coupling model with Baranyi function successfully fitted variations of O2/CO2 concentration and P. fluorescens growth in the two packaging. In addition, quality properties of packed fresh-cut cucumber were determined. The film Ⅳ (OTR48) as a high barrier film showed the highest inhibition of P. fluorescens growth, adequately retained its colour, firmness and total soluble solid (TSS) concentration in contrast to the PE films packaging. The constructed coupling models can be utilized for assessing the shelf life and microbial growth of fresh-cut vegetables with spoilage dominated by pseudomonads.

Effect of Kangfuxiaomi suppository on pelvic inflammatory disease in rats.

Pelvic inflammatory disease (PID) is commonly encountered in gynecological practice. Kangfuxiaomi suppository, made from the compound extract of Periplaneta Americana, is a Traditional Chinese Medicine remedy widely used for the treatment of gynecological disorders. This study aimed to preliminarily explore the therapeutic effect of Kangfuxiaomi suppository in a rat model of PID established by chemical injury and pathogen infection. The key parameters assessed were vulvar inflammation score, vaginal + uterine organ index, and serum levels of interleukin (IL)- 8; tumor necrosis factor (TNF)-α; C-reactive protein (CRP); superoxide dismutase (SOD); and malondialdehyde (MDA). In addition, levels of IL-6, cyclooxygenase (COX)- 2, and IL-2 in cervical tissues as well as that of IL-1ß and prostaglandin E-2 (PGE2) in uterine tissues were measured. The expression levels of nuclear factor-kappa B (NF-κB) p65 and Toll-like receptor 4 (TLR4) in uterine tissues were detected by immunohistochemical method. After Kangfuxiaomi suppository treatment, the vulva inflammation score and histopathological score of PID rats showed a tendency to decrease. Serum IL-8, TNF-α, CRP, and MDA levels were reduced, while SOD levels were significantly increased. Levels of IL-6, IL-2, and COX-2 in cervical tissues were somewhat decreased, and PGE2 and IL-1ß levels in uterine tissue were significantly decreased. Moreover, the levels of NF-κB p65 and TLR4 protein expression were also decreased. These findings demonstrated the therapeutic effect of Kangfuxiaomi suppository in PID rats. The underlying mechanism may involve enhanced antioxidant capacity and decreased secretion of proinflammatory factors via the NF-κB/TLR4 signaling pathway.

Layer-by-layer reinforced-mediated sustained-release nanoantioxidants for long-lasting prevention against drug-induced liver injury.

Drug-induced liver injury (DILI) is a commonly encountered and diagnostically complex etiology of acute liver failure, characterized by early indications of hepatic oxidative stress. The most economical approach for DILI treatment is effective and durable oxidative stress prevention. Herein, we propose a long-lasting nanoantioxidant called PDA-Zn-BAI NPs characterized by sustained-release of baicalein (a natural antioxidant) for the long-lasting prevention of DILI. It is constructed using dopamine as an intermediate and layer-by-layer reinforcement strategy based on Zn2+-mediated coordination bonding, π-π stacking, and steric hindrance made of polydopamine network. Optimized PDA-Zn-BAI NPs performed a satisfactory sustained-release effect (36.67% ± 6.67 in normal condition and 60.32% ± 3.19 in acid condition of cumulative release within 5 days). Furthermore, it's been found that PDA-Zn-BAI NPs could continuously be accumulated in the liver with negligible hepatotoxicity and were activated to effectively scavenge reactive oxygen species to break off the damage of acetaminophen to the liver within 5 days (ALT as an indicator, > 70% prevention effect lasts for 5 days), which was vital for the long-lasting prevention of DILI. The long-lasting detoxification by PDA-Zn-BAI NPs in patients with DILI suggested a potential clinical application, especially for those patients who need prolonged administration of hepatotoxic drugs.