Coprococcus eutactus screened from healthy adolescent attenuates chronic restraint stress-induced depression-like changes in adolescent mice: Potential roles in the microbiome and neurotransmitter modulation.

The onset of depression commonly occurs in adolescence; therefore, depressive prevention and intervention are pivotal during this period. It is becoming evident that neurotransmitter imbalance and gut microbiota dysbiosis are prominent causes of depression. However, the underlying links and mechanisms remain poorly understood. In this study, with 16S ribosomal RNA gene sequencing, genus Coprococcus markedly differentiated between the healthy and unmedicated depressive adolescents. Based on this, transplantation of Coprococcus eutactus (C.e.) was found to dramatically ameliorate the chronic restraint stress (CRS) induced depression-like changes and prevent synaptic loss and glial-stimulated neuroinflammation in mice. The Ultra-high performance liquid chromatography tandem mass spectrometry analysis (UHPLC-MS/MS) further showed that neurotoxic neurotransmitters in kynurenine pathway (KP) such as 3-hydroxykynurenine (3-HK) and 3-hydroxyanthranilic acid (3-HAA) decreased in mouse brains, mechanistically deciphering the transfer of the tryptophan metabolic pathway to serotonin metabolic signaling in the brain after C.e. treatment, which was also verified in the colon. Molecularly, blockage of KP activities mediated by C.e. was ascribed to the restraint of the limit-step enzymes responsible for kynurenine, 3-HK, and quinolinic acid generation. In the colon, C.e. treatment significantly recovered goblet cells and mucus secretion in CRS mice which may ascribe to the rebalance of the disordered gut microbiota, especially Akkermansia, Roseburia, Rikenella, Blautia, and Alloprevotella. Taken together, the current study reveals for the first time the beneficial effects and potential mechanisms of C.e. in ameliorating CRS-induced depression, unraveling the direct links between C.e. treatment and neurotransmitter rebalance, which may provide efficacious therapeutic avenues for adolescent depressive intervention.

Serum N-glycomic profiling identifies candidate biomarker panels for assessing coronary artery stenosis severity.

Stenosis severity may escalate over the course of coronary artery disease (CAD), increasing the risk of death for the patient. Conventionally, the assessment of stenosis degree relies on invasive coronary angiography (ICA), an invasive examination unsuitable for patients in poor physical condition or those with contrast allergies and one that imposes a psychological burden on patients. Although abnormal serum N-glycan profiles have exhibited robust associations with various cardiovascular diseases, including CAD, their potential in diagnosing CAD stenosis remains to be determined. In this study, we performed a comprehensive analysis of serum N-glycome from 132 patients who underwent ICA and 27 healthy controls using MALDI-TOF-mass spectrometry. The patients who underwent ICA examination were categorized into four groups based on stenosis severity: no/mild/moderate/severe stenosis. Twenty-seven N-glycans were directly quantified, and 47 derived glycan traits were obtained. Notably, among these 74 glycan features, 18 exhibited variations across the study groups. Using a combination of least absolute shrinkage and selection operator and logistic regression analyses, we developed five diagnostic models for recognizing stenosis degree. Our results suggested that alterations in serum N-glycosylation modifications might be valuable for identifying stenosis degree and monitoring disease progression in individuals with CAD. It is expected to offer a noninvasive alternative for those who could not undergo ICA because of various reasons. However, the diagnostic potential of serum N-glycan panels as biomarkers requires multicenter, large cohort validation in the future.

Pt-Decorated Gold Nanoflares for High-Fidelity Phototheranostics: Reducing Side-Effects and Enhancing Cytotoxicity toward Target Cells.

Functionalized with the Au-S bond, gold nanoflares have emerged as promising candidates for theranostics. However, the presence of intracellular abundantly biothiols compromises the conventional Au-S bond, leading to the unintended release of cargoes and associated side-effects on non-target cells. Additionally, the hypoxic microenvironment in diseased regions limits treatment efficacy, especially in photodynamic therapy. To address these challenges, high-fidelity photodynamic nanoflares constructed on Pt-coated gold nanoparticles (Au@Pt PDNF) were communicated to avoid false-positive therapeutic signals and side-effects caused by biothiol perturbation. Compared with conventional photodynamic gold nanoflares (AuNP PDNF), the Au@Pt PDNF were selectively activated by cancer biomarkers and exhibited high-fidelity phototheranostics while reducing side-effects. Furthermore, the ultrathin Pt-shell catalysis was confirmed to generate oxygen which alleviated hypoxia-related photodynamic resistance and enhanced the antitumor effect. This design might open a new venue to advance theranostics performance and is adaptable to other theranostic nanomaterials by simply adding a Pt shell.

Gut lymph purification alleviates acute lung injury induced by intestinal ischemia-reperfusion in rats by removing danger-associated molecular patterns from gut lymph.

Background: The potential effect of removing danger-associated molecular patterns (DAMPs) from gut lymph on reducing acute lung injury (ALI) induced by gut ischemia-reperfusion injury (GIRI) is uncertain. This study aimed to investigate whether gut lymph purification (GLP) could improve GIRI-induced acute lung injury in rats by clearing danger-associated molecular patterns. Materials and methods: Rats were divided into four groups: Sham, GIRI, GIRI + gut lymph drainage (GLD), and GIRI + GLP. After successful modeling, lung tissue samples were collected from rats for hematoxylin-eosin (HE) staining and detection of apoptotic indexes. We detected the DAMPs levels in blood and lymph samples. We observed the microstructure of AEC Ⅱ and measured the expression levels of apoptosis indexes. Results: The GIRI group showed destruction of alveolar structure, thickened alveolar walls, and inflammatory cell infiltration. This was accompanied by significantly increased levels of high mobility group protein-1 (HMGB-1) and Interleukin-6 (IL-6), while reduced levels of heat shock protein 70 (HSP 70) and Interleukin-10 (IL-10) in both lymph and serum. In contrast, the lung tissue damage in the GIRI + GLP group was significantly improved compared to the GIRI group. This was evidenced by a reduction in the expression levels of HMGB-1 and IL-6 in both lymph and serum and an increase in HSP 70 and IL-10 levels. Additionally, organelle structure of AEC II was significantly improved in the GIRI + GLP group compared to the GIRI group. Conclusions: GLP inhibits inflammation and cell apoptosis in GIRI-induced ALI by blocking the link between DAMPs and mononuclear phagocytes, reducing the severity of ALI.

Characterizing immune variation and diagnostic indicators of preeclampsia by single-cell RNA sequencing and machine learning.

Preeclampsia is a multifactorial and heterogeneous complication of pregnancy. Here, we utilize single-cell RNA sequencing to dissect the involvement of circulating immune cells in preeclampsia. Our findings reveal downregulation of immune response in lymphocyte subsets in preeclampsia, such as reduction in natural killer cells and cytotoxic genes expression, and expansion of regulatory T cells. But the activation of naïve T cell and monocyte subsets, as well as increased MHC-II-mediated pathway in antigen-presenting cells were still observed in preeclampsia. Notably, we identified key monocyte subsets in preeclampsia, with significantly increased expression of angiogenesis pathways and pro-inflammatory S100 family genes in VCAN+ monocytes and IFN+ non-classical monocytes. Furthermore, four cell-type-specific machine-learning models have been developed to identify potential diagnostic indicators of preeclampsia. Collectively, our study demonstrates transcriptomic alternations of circulating immune cells and identifies immune components that could be involved in pathophysiology of preeclampsia.

Bisphenol F exposure induces depression-like changes: Roles of the kynurenine metabolic pathway along the "liver-brain" axis.

Bisphenol F (BPF), one of the major alternatives of Bisphenol A (BPA), is becoming extensively used in industrial production with great harm to human beings and environment. Recent studies have revealed that environmental exposure is crucial to the initiation and development of depression. Thereby, the aim the present study is to ascertain the correlationship between the BPF exposure and depression occurrence. In the current study, BPF strikingly triggered depression-like changes in mice through the sucrose preference test (SPT), tail suspension test (TST) and forced swim test (FST), accompanied by the perturbation of the kynurenine (KYN) metabolic pathway along the "liver-brain" axis. Mechanistically, the neurotransmitters from the tryptophan metabolic pathway were converted to the toxic KYN pathway after BPF treatment. With the ELISA assay, it revealed that the toxic KYN metabolites, including KYN and 3-hydroxykynurenine (3-HK), were strikingly increased in the mouse brains which was ascribed to the enhanced expression of the rate-limiting enzymes Indoleamine 2,3-dioxygenase (IDO1) and Kynurenine 3-monooxygenase (KMO) respectively. Interestingly, the increased brain KYN induced by BPF was also validated partially from the periphery, since the ELISA and western blotting results indicated the significantly increased KYN in the serum and L-type amino acid transporter 1 (LAT1) in the brain, the key transporter responsible for KYN and 3-HK crossing the blood-brain barrier. Intriguingly, the liver-derived KYN metabolic pathway was the important source of the peripheral KYN and 3-HK, as BPF substantially enhanced hepatic IDO1, Tryptophan, 2, 3-dioxygenase (TDO2), and KMO levels indicated by western blotting. This study is the first to delineate previously unrecognized BPF-induced depression by regulating the KYN metabolic pathway along the "liver-brain" axis; therefore, targeting LAT1 or hepatic KYN signaling may provide a potentially unique therapeutic intervention in BPF-induced depression.

An optimization strategy for charged aerosol detection to linearize the detector response in the multicomponent quantitative analysis of Qishen Yiqi dripping pills.

Charged aerosol detection, increasingly recognized for quantifying pharmaceutical compounds with weak ultraviolet absorption, is a universal detection technique for high-performance liquid chromatography (HPLC). Charged aerosol detection shows a non-linear response with increasing analyte concentration over a wide range, limiting its versatility in various analytical applications. In this work, a co-optimization strategy for power function value (PFV) and power laws was proposed and applied to broaden the linear range of the standard curve of saccharides in Qishen Yiqi dripping pills using the HPLC-charged aerosol detection (HPLC-CAD) method. Power function values for all analytes were optimized based on empirical models. Subsequently, the optimum power laws were investigated based on a preferred PFV. Additionally, various regression equations were evaluated to ensure the accuracy and precision of the results. With the optimized PFV and power law, the ordinary least squares model demonstrated a satisfactory fit. The optimal PFVs and power laws expanded the standard curve's linear range by 2.7 times compared to default settings, reducing model uncertainty. This paper presents a vital method for developing a multi-component quantitative HPLC-CAD approach without external data transformation outside the provided software, especially suitable for analytical applications of traditional Chinese medicine with significant quality differences.

Pre-gelatinized high-amylose starch enables easy preparation of flexible and antimicrobial composite films for fresh fruit preservation.

While high-amylose starch (HAS) possesses advantageous properties such as high resistant starch content and favorable mechanical attributes, its gelatinization constraints have limited its applicability. This study enhances its versatility by focusing on pre-gelatinized (PG) HAS with exceptional rehydratability, achieved by disorganizing native HAS granules (with amylose contents of 55 % and 68 %, respectively) using a 33 % CaCl2 solution, followed by water-ethanol precipitation and freeze-drying. The resulting PG-HAS exhibited elevated amylose content (61 % and 75 %) with minimal changes in amylose molecular weight. PG-HAS displayed superior water-absorption index (WAI) and water-soluble index (WSI) compared to native HAS, further improved by 2 % CaCl2 solution incorporation. Furthermore, composite films were prepared by mixing PG-HAS with PVA at a 6:4 (w/w) ratio. The PG-G50 (61 % amylose content)/PVA composite film exhibited remarkable elongation (131.1 ± 5.4 %), nearly three times that of a normal corn starch (NCS, with 27 % amylose)/PVA film, attributed to improved starch dispersity and higher amylose content. Nonetheless, the PG-G70 (75 % amylose content)/PVA film at the same ratio showed lower elongation (54.7 ± 8.0 %), potentially due to strong cohesive forces between amylose chains that impede starch-PVA interactions. Moreover, the PG-HAS/PVA composite films, enriched with antibacterial agents, demonstrated effective antibacterial properties with a gradual and sustained release of active compounds. Notably, the PG-G50/PVA/tannic acid (TA) film effectively preserved fresh apple slices by inhibiting bacteria growth and preventing browning. These findings underscore the excellent rehydration of PG-HAS and its potential as an inner packaging material for irregularly shaped foods, such as sliced fruits or meats, due to its nontoxic nature, softness and flexibility, which allows the film to maintain close contact with food surfaces.

Ultra-Tough and Highly Stretchable Dual-Crosslinked Eutectogel Based on Coordinated and Non-Coordinated Two Types Deep Eutectic Solvent Mixture.

Eutectogels are gaining attention in flexible device applications for their superior ionic conductivity, stability, biocompatibility, and cost-effectiveness. However, most existing eutectogels suffer from low strength and toughness. Herein, ultra-tough and highly stretchable polyacrylamide (PAM) eutectogels featuring a dual-crosslinked network comprising chemical cross-linking and physical cross-linking facilitated by metal coordination bonds and hydrogen bonds are developed. This is achieved through a controlled strategy involving polymerization of acrylamide in a coordinated metal salt-type deep eutectic solvent (DES) combined with a non-coordinated choline chloride (ChCl)-type DES mixture. By varying the molar ratio of these two types of DES, exceptional and adjustable mechanical properties of the resulting eutectogel are achieved, including a high tensile strength ranging from 2.9 to 8.2 MPa and elongation at break ranging from 1725 to 747%, at a 70 wt% DES content. Furthermore, the reversible non-covalent crosslinking in these eutectogels enables self-recovery and self-healing capabilities of eutectogels. The prepared eutectogels also exhibit outstanding ionic conductivity (3.56 mS cm-1 ), making them well-suited for use as strain sensors in human motion detection. The toughening strategy is universally effective for creating tough eutectogels using coordinated metal salt-type DES with various metal ions, as well as a diverse range of coordinatable polymers.

One-step, reagent-free construction of nano-enzyme as visual and reusable biosensor for oxidase substrates.

The substrates of oxidase are biologically essential substances that are closely associated with human physiological health. However, current biosensing methods suffer from tough recyclability and undesired denaturation of enzyme due to impurity interference. Herein, we have developed a visual and reusable biosensor for detecting substrate using glucose oxidase (GOx) as a model oxidase. GOx was immobilized onto gold nanoparticles (AuNPs) at -20 °C in one step without additional reagents. The resulting nano-enzyme generated coloimetric signals by coupling with horseradish peroxidase (HRP) using TMB as the substrate. Our results demonstrated that the immobilized GOx exhibited satisfactory sensitivity (0.68 µM) for glucose detection and higher inherent stability than free GOx under harsh conditions, enabling reliable detection of glucose in complex fluids (colored beverages and saliva). Furthermore, the nano-enzyme retained 80 % activity even after four cycles of catalytic oxidation. This strategy constructs a universal biosensor for substrates with nano-enzyme which rely only on intrinsic cysteine within the oxidase while avoiding functional handle modification.

Perfluoroalkyl-Decorated Noble-Metal-Free MOFs for the Highly Efficient One-Pot Four-Component Coupling between Aldehydes, Amines, Alkynes, and Flue Gas CO2.

The non-noble-metal catalysed-multicomponent reactions between flue gas CO2 and cheap industrial raw stocks into high value-added fine chemicals is a promising manner for the ideal CO2 utilization route. To achieve this, the key fundamental challenge is the rational development of highly efficient and facile reaction pathway while establishing compatible catalytic system. Herein, through the stepwise solvent-assisted linker installation, post-synthetic fluorination and metalation, we report the construction of a series of perfluoroalkyl-decorated noble-metal-free metal-organic frameworks (MOFs) PCN-(BPY-CuI)-(TPDC-Fx ) [BPY=2,2'-bipyridine-5,5'-dicarboxylate, TPDC-NH2 =2'-amino-[1,1':4',1''-terphenyl]-4,4''-dicarboxylic acid] that can catalyze the one-pot four-component reaction between alkyne, aldehyde, amine and flue gas CO2 for the preparation of 2-oxazolidinones. Such assembly endows the MOFs with superhydrophobic microenvironment, superior water resistance and highly stable catalytic site, leading to 21 times higher turnover numbers than that of homogeneous counterparts. Mechanism investigation implied that the substrates can be efficiently enriched by the MOF wall and then the adsorbed amine species act as an extrinsic binding site towards dilute CO2 through their strong preferential formation to carbamate acid. Moreover, density functional theory calculations suggest the tetrahedral geometry of Cu in MOF offers special resistance towards amine poisoning, thus maintaining its high efficiency during the catalytic process.

Comprehensive Overview the Role of Glycosylation of Extracellular Vesicles in Cancers.

Extracellular vesicles (EVs) are membranous structures secreted by various cells carrying diverse biomolecules. Recent advancements in EV glycosylation research have underscored their crucial role in cancer. This review provides a global overview of EV glycosylation research, covering aspects such as specialized techniques for isolating and characterizing EV glycosylation, advances on how glycosylation affects the biogenesis and uptake of EVs, and the involvement of EV glycosylation in intracellular protein expression, cellular metastasis, intercellular interactions, and potential applications in immunotherapy. Furthermore, through an extensive literature review, we explore recent advances in EV glycosylation research in the context of cancer, with a focus on lung, colorectal, liver, pancreatic, breast, ovarian, prostate, and melanoma cancers. The primary objective of this review is to provide a comprehensive update for researchers, whether they are seasoned experts in the field of EVs or newcomers, aiding them in exploring new avenues and gaining a deeper understanding of EV glycosylation mechanisms. This heightened comprehension not only enhances researchers' knowledge of the pathogenic mechanisms of EV glycosylation but also paves the way for innovative cancer diagnostic and therapeutic strategies.

Homocysteine and Lp-PLA2 levels: Diagnostic value in coronary heart disease.

Coronary heart disease (CHD) is the leading cause of mortality worldwide. Identifying effective diagnostic markers and understanding risk factors is crucial for prevention and management. This study aimed to investigate the levels of homocysteine (Hcy) and lipoprotein-associated phospholipase A2 (Lp-PLA2) in human plasma and their roles in the diagnosis and prognosis of CHD. A retrospective study was conducted on 232 patients with CHD, divided into Acute Myocardial Infarction, unstable angina pectoris, and stable angina pectoris groups, and a control group of 75 healthy adults. Blood samples were analyzed for serum Hcy and Lp-PLA2 levels using the cycling enzyme method and ELISA method, respectively. Statistical analyses were performed to evaluate the risk factors, and diagnostic efficacy was assessed using receiver operating characteristic (ROC) curves. No significant differences in age and sex were observed between the study and control groups, whereas marked disparities in risk factors such as obesity, hypertension, diabetes, and hyperlipidemia were noted. Significant differences in serum Hcy and Lp-PLA2 levels were identified among the CHD subgroups. Univariate and multivariate logistic regression analyses revealed that Hcy, Lp-PLA2, hypertension, and hyperlipidemia were significant risk factors for CHD. The combined diagnostic Area Under the Curve (AUC) for Hcy and Lp-PLA2 was found to be higher than that when using them individually. This study identified the elevation of Hcy and Lp-PLA2 levels as independent risk factors for CHD, and their conjoint analysis significantly enhanced clinical diagnostic efficacy. These findings provide valuable insights for CHD diagnosis, treatment, and prevention, highlighting the importance of these markers in CHD management.

Distribution characteristics, source attribution, and health risk assessment of organophosphate esters in indoor and outdoor dust from various microenvironments in Beijing.

The occurrence and profiles of organophosphate esters (OPEs) were studied in indoor and outdoor dusts from various microenvironments, including forty-seven outdoor dusts from green belts, roads, parks and residence areas, seventy-seven indoor dusts from private cars, print shops, taxis, furniture shops, offices, dormitories, shopping malls and residences house in different districts in Beijing. The total concentrations (Σ12OPEs) were eighteen times higher in indoor dusts (7.14 ×102 to 2.24 ×104 ng/g) than in outdoor dusts (36.0-1.56 ×103 ng/g). OPEs concentrations in samples from taxi and private cars were obviously higher than other indoor microenvironments. Both indoor and outdoor microenvironments also showed different compositional profiles of OPEs, indicating that polyurethane foam/building materials and hydraulic fluids/plastics were the greatest contributions in different microenvironments, with chlorinated alkyl phosphates (Cl-OPEs) being the predominant compound in both indoor dust (52.1-86.5%) and outdoor dust samples (42.6-81.3%). The uncertainty was reduced by Monte Carlo simulation, and the pollution levels of 50th and 95th percentiles were employed to calculate the average daily dosage, which was then used to calculate hazard quotient (HQ) for assessing the health risks to adults and children. Results showed that OPEs were safe even at extremely consumed concentration percentile (95th) in all groups.

A lipidomic approach to bisphenol F-induced non-alcoholic fatty liver disease-like changes: altered lipid components in a murine model.

Bisphenol A (BPA), a typical environmental endocrine disruptor, is an "obesogen" that can induce lipid accumulation in the liver. Highly similar in structure to BPA, bisphenol F (BPF) is becoming the dominant BPA substitute on the market, which attracts more and more attention due to its potential adverse effects. Recently, BPF exposure is found to cause non-alcoholic fatty liver disease (NAFLD)-like changes; however, the underlying toxic effects remain poorly understood. Therefore, in the current study, we focused on BPF-mediated lipid homeostasis, especially the alterations of lipid components and metabolism. In human serum, the BPF levels in healthy controls and NAFLD patients were assessed by ELISA, and BPF-induced disturbance of lipid metabolism was evaluated in mouse model via non-targeted lipomic methods with ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry. It suggested that BPF exposure was positively correlated with NAFLD severity and triglyceride level in patients. Based on the relationships, lipid metabolites were assessed in mouse livers between control and BPF-treated group, and it revealed that twenty-six lipid metabolites (including phospholipids, sphingolipids, and glycerides) were significantly changed in mouse livers. Phosphatidylcholine, phosphatidylethanolamine, and diglyceryl ester levels were lower than those in the control mice; hexose ceramide content in sphingolipids markedly increased in BPF-treated mouse livers. Noteworthily, the glycerophospholipid metabolic pathway was found to be the most pronounced in BPF-induced disturbance of lipid metabolism. Therefore, the current study, for the first time, is deciphering the BPF-induced lipid metabolic disturbance, which may provide novel intervention strategies for BPF-induced NAFLD-like changes.

Discovery of age-related early-stage glycated proteins based on deep quantitative serum glycated proteome analysis.

Aging is a pressing global health issue that is linked to various diseases, such as diabetes and Alzheimer's disease. It is well known that glycation plays a pathological role in the aging process and age-related diseases. Thus, it is of great significance to discover protein glycation at an early stage for monitoring and intervention in the aging process. However, the endogenous age-related early-stage glycated proteome remains insufficiently profiled. To address this research gap, our study focuses on assessing glycated proteomics profiles in the serum of mice. We employ a robust and quantitative strategy previously developed by our team, to analyze endogenous glycated proteome in serum samples of 4 age groups of mice (10 weeks, 16 weeks, 48 weeks and 80 weeks). In total, 2959 endogenous glycated peptides corresponding to 296 serum proteins are identified from 48 runs of serum samples from 16 mice across the four age groups. By comparing these glycated peptides between adjacent age groups, we discover 49 glycated peptides from 35 proteins that show significant upregulation between the 48-week and 80-week age groups. Furthermore, we identify 10 glycated proteins (or protein groups) that are significantly upregulated only between the 48-week and 80-week age groups, including lecithin-cholesterol acyltransferase (LCAT) and apolipoprotein A-II (Apo A-II). These novel findings provide unique signatures for understanding the aging process and age-related diseases. By shedding light on the early-stage glycated proteome, our study contributes valuable insights that may have implications for future interventions and therapeutic approaches.

Schisandra lignans ameliorate nonalcoholic steatohepatitis by regulating aberrant metabolism of phosphatidylethanolamines.

Nonalcoholic steatohepatitis (NASH) is a spectrum of chronic liver disease characterized by hepatic lipid metabolism disorder. Recent reports emphasized the contribution of triglyceride and diglyceride accumulation to NASH, while the other lipids associated with the NASH pathogenesis remained unexplored. The specific purpose of our study was to explore a novel pathogenesis and treatment strategy of NASH via profiling the metabolic characteristics of lipids. Herein, multi-omics techniques based on LC-Q-TOF/MS, LC-MS/MS and MS imaging were developed and used to screen the action targets related to NASH progress and treatment. A methionine and choline deficient (MCD) diet-induced mouse model of NASH was then constructed, and Schisandra lignans extract (SLE) was applied to alleviate hepatic damage by regulating the lipid metabolism-related enzymes CES2A and CYP4A14. Hepatic lipidomics indicated that MCD-diet led to aberrant accumulation of phosphatidylethanolamines (PEs), and SLE could significantly reduce the accumulation of intrahepatic PEs. Notably, exogenous PE (18:0/18:1) was proved to significantly aggravate the mitochondrial damage and hepatocyte apoptosis. Supplementing PE (18:0/18:1) also deteriorated the NASH progress by up regulating intrahepatic proinflammatory and fibrotic factors, while PE synthase inhibitor exerted a prominent hepatoprotective role. The current work provides new insights into the relationship between PE metabolism and the pathogenesis of NASH.

Insight into the mechanisms of neuroendocrine toxicity induced by 6:2FTCA via thyroid hormone disruption.

6:2 fluorotonic carboxylic acid (6:2 FTCA), a novel substitute for perfluorooctanoic acid (PFOA), is being used gradually in industrial production such as coatings or processing aids, and its detection rate in the aqueous environment is increasing year by year, posing a potential safety risk to aquatic systems and public health. However, limited information is available on the effects and mechanism of 6:2 FTCA. Therefore, this study was conducted to understand better the neuroendocrine effects of early exposure to 6:2 FTCA and the underlying mechanisms on zebrafish. In this study, zebrafish embryos were treated to varied doses of 6:2 FTCA (0, 0.08 µg/mL, 0.8 µg/mL and 8 µg/mL) at 4 h post-fertilization (hpf) for a duration of six days, which exhibited a pronounced inhibition of early growth and induced a disorganized swim pattern characterized by reduced total swim distance and average swim speed. Simultaneously, the thyroid development of zebrafish larvae was partially hindered, accompanied by decreased T3 levels, altered genes associated with the expression of thyroid hormone synthesis, transformation and transportation and neurotransmitters associated with tryptophan and tyrosine metabolic pathways. Molecular docking results showed that 6:2 FTCA has a robust binding energy with the thyroid hormone receptor (TRß). Moreover, exogenous T3 supplementation can partially restore the adverse outcomes. Our findings indicated that 6:2 FTCA acts as a thyroid endocrine disruptor and can induce neuroendocrine toxic effects. Furthermore, our results show that targeting TRß may be a potentially therapeutic strategy for 6:2 FTCA-induced neuroendocrine disrupting effects.

Mystery of bisphenol F-induced nonalcoholic fatty liver disease-like changes: Roles of Drp1-mediated abnormal mitochondrial fission in lipid droplet deposition.

As one of the major substitutes for bisphenol A (BPA), bisphenol F (BPF) has been widely used. Our previous study demonstrated that BPF exposure facilitates lipid droplet deposition in hepatic cells, contributing to nonalcoholic fatty liver disease (NAFLD)-like changes. However, the underlying mechanisms remain poorly understood. Here, with a metabolic cage system, we observed the perturbation of energy metabolism in mice treated with BPF. BPF obviously suppressed metabolic capacity, which manifested as decreased energy expenditure, low O2 consumption and CO2 levels in mice. Consistent with the in vivo results, a Seahorse XF Cell Mito Stress Test showed significant reductions in mitochondrial ATP production capacity, maximum respiratory capacity, and residual respiratory capacity after BPF treatment in an in vitro study. Electron microscopy revealed a striking increase in mitochondrial fission that was synchronous with excessive expression and activation of dynamin-related protein 1 (Drp1). Intriguingly, chemical inhibition of Drp1 by Mdivi-1 and/or silencing of Drp1 dramatically hampered mitochondrial fission and ameliorated BPF-induced lipid droplet deposition both in mouse liver and human hepatic cells. Mechanistically, mitochondrial dynamics imbalance played prominent roles in these processes, since suppression of Drp1 by chemical inhibition or knockdown substantially reversed BPF-induced mitochondrial fission and ameliorated the suppression of mitochondrial metabolism as well as excessive mitochondrial ROS, which was verified to be key to lipid droplet deposition. Collectively, the findings of the current study reveal previously unrecognized effects involving Drp1-mediated mitochondrial injury in BPF-induced lipid droplet deposition. Therefore, targeted intervention against mitochondrial dysfunction may be a promising therapeutic strategy for BPF-induced NAFLD-like changes.

Stepwise assembly of thiacalix[4]arene-protected Ag/Ti bimetallic nanoclusters: accurate identification of catalytic Ag sites in CO2 electroreduction.

The accurate identification of catalytic sites in heterogeneous catalysts poses a significant challenge due to the intricate nature of controlling interfacial chemistry at the molecular level. In this study, we introduce a novel strategy to address this issue by utilizing a thiacalix[4]arene (TC4A)-protected Ti-oxo core as a template for loading Ag1+ ions, leading to the successful synthesis of a unique Ag/Ti bimetallic nanocluster denoted as Ti8Ag8. This nanocluster exhibits multiple surface-exposed Ag sites and possesses a distinctive "core-shell" structure, consisting of a {Ti4@Ag8(TC4A)4} core housing a {Ti2O2@Ag4(TC4A)2} motif and two {Ti@Ag2(TC4A)} motifs. To enable a comprehensive analysis, we also prepared a Ti2Ag4 cluster with the same {Ti2O2@Ag4(TC4A)2} structure found within Ti8Ag8. The structural disparities between Ti8Ag8 and Ti2Ag4 provide an excellent platform for a comparison of catalytic activity at different Ag sites. Remarkably, Ti8Ag8 exhibits exceptional performance in the electroreduction of CO2 (eCO2RR), showcasing a CO faradaic efficiency (FECO) of 92.33% at -0.9 V vs. RHE, surpassing the FECO of Ti2Ag4 (69.87% at -0.9 V vs. RHE) by a significant margin. Through density functional theory (DFT) calculations, we unveil the catalytic mechanism and further discover that Ag active sites located at {Ti@Ag2(TC4A)} possess a higher εd value compared to those at {Ti2O2@Ag4(TC4A)2}, enhancing the stabilization of the *COOH intermediate during the eCO2RR. This study provides valuable insights into the accurate identification of catalytic sites in bimetallic nanoclusters and opens up promising avenues for efficient CO2 reduction catalyst design.