Myeloid-specific Hdac10 deletion protects against LPS-induced acute lung injury via P62 acetylation at lysine 165.

BACKGROUND: Aberrant activation of macrophages is associated with pathogenesis of acute lung injury (ALI). However, the potential pathogenesis has not been explored. OBJECTIVES: We aimed to identify whether histone deacetylase (HDAC) 10 is involved in lipopolysaccharide (LPS)-exposed ALI and reveal the underlying pathogenesis by which it promotes lung inflammation in LPS-exposed ALI via modifying P62 with deacetylation. METHODS: We constructed an ALI mice model stimulated with LPS to determine the positive effect of Hdac10 deficiency. Moreover, we cultured murine alveolar macrophage cell line (MH-S cells) and primary bone marrow-derived macrophages (BMDMs) to explore the pro-inflammatory activity and mechanism of HDAC10 after LPS challenge. RESULTS: HDAC10 expression was increased both in mice lung tissues and macrophage cell lines and promoted inflammatory cytokines production exposed to LPS. Hdac10 deficiency inhibited autophagy and inflammatory response after LPS stimulation. In vivo, Hdac10fl/fl-LysMCre mice considerably attenuated lung inflammation and inflammatory cytokines release exposed to LPS. Mechanistically, HDAC10 interacts with P62 and mediates P62 deacetylation at lysine 165 (K165), by which it promotes P62 expression and increases inflammatory cytokines production. Importantly, we identified that Salvianolic acid B (SAB), an HDAC10 inhibitor, reduces lung inflammatory response in LPS-stimulated ALI. CONCLUSION: These results uncover a previously unknown role for HDAC10 in regulating P62 deacetylation and aggravating lung inflammation in LPS-induced ALI, implicating that targeting HDAC10 is an effective therapy for LPS-exposed ALI.

Ionic Pairs-Engineered Fluorinated Covalent Organic Frameworks Toward Direct Air Capture of CO2.

The covalent organic frameworks (COFs) possessing high crystallinity and capability to capture low-concentration CO2 (400 ppm) from air are still underdeveloped. The challenge lies in simultaneously incorporating high-density active sites for CO2 insertion and maintaining the ordered structure. Herein, a structure engineering approach is developed to afford an ionic pair-functionalized crystalline and stable fluorinated COF (F-COF) skeleton. The ordered structure of the F-COF is well maintained after the integration of abundant basic fluorinated alcoholate anions, as revealed by synchrotron X-ray scattering experiments. The breakthrough test demonstrates its attractive performance in capturing (400 ppm) CO2 from gas mixtures via O─C bond formation, as indicated by the in situ spectroscopy and operando nuclear magnetic resonance spectroscopy using 13C-labeled CO2 sources. Both theoretical and experimental thermodynamic studies reveal the reaction enthalpy of ≈-40 kJ mol-1 between CO2 and the COF scaffolds. This implies weaker interaction strength compared with state-of-the-art amine-derived sorbents, thus allowing complete CO2 release with less energy input. The structure evolution study from synchrotron X-ray scattering and small-angle neutron scattering confirms the well-maintained crystalline patterns after CO2 insertion. The as-developed proof-of-concept approach provides guidance on anchoring binding sites for direct air capture (DAC) of CO2 in crystalline scaffolds.

Solvation Structure of Methanol-in-Salt Electrolyte Revealed by Small-Angle X-ray Scattering and Simulations.

The solvation structure of water-in-salt electrolytes was thoroughly studied, and two competing structures─anion solvated structure and anion network─were well-defined in recent publications. To further reveal the solvation structure in those highly concentrated electrolytes, particularly the influence of solvent, methanol was chosen as the solvent for this proposed study. In this work, small-angle X-ray scattering, small-angle neutron scattering, Fourier-transform infrared spectroscopy, and Raman spectroscopy were utilized to obtain the global and local structural information. With the concentration increment, the anion network formed by TFSI- became the dominant structure. Meanwhile, the hydrogen bonds among methanol were interrupted by the TFSI- anion and formed a new connection with them. Molecular dynamic simulations with two different force fields (GAFF and OPLS-AA) are tested, and GAFF agreed with synchrotron small-angle X-ray scattering/wide-angle X-ray scattering (SAXS/WAXS) results well and provided insightful information about molecular/ion scale solvation structure. This article not only deepens the understanding of the solvation structure in highly concentrated solutions, but more importantly, it provides additional strong evidence for utilizing SAXS/WAXS to validate molecular dynamics simulations.

Vortex fluidic regulated phospholipid equilibria involving liposomes down to sub-micelle size assemblies.

Conventional channel-based microfluidic platforms have gained prominence in controlling the bottom-up formation of phospholipid based nanostructures including liposomes. However, there are challenges in the production of liposomes from rapidly scalable processes. These have been overcome using a vortex fluidic device (VFD), which is a thin film microfluidic platform rather than channel-based, affording ∼110 nm diameter liposomes. The high yielding and high throughput continuous flow process has a 45° tilted rapidly rotating glass tube with an inner hydrophobic surface. Processing is also possible in the confined mode of operation which is effective for labelling pre-VFD-prepared liposomes with fluorophore tags for subsequent mechanistic studies on the fate of liposomes under shear stress in the VFD. In situ small-angle neutron scattering (SANS) established the co-existence of liposomes ∼110 nm with small rafts, micelles, distorted micelles, or sub-micelle size assemblies of phospholipid, for increasing rotation speeds. The equilibria between these smaller entities and ∼110 nm liposomes for a specific rotational speed of the tube is consistent with the spatial arrangement and dimensionality of topological fluid flow regimes in the VFD. The prevalence for the formation of ∼110 nm diameter liposomes establishes that this is typically the most stable structure from the bottom-up self-assembly of the phospholipid and is in accord with dimensions of exosomes.

Nanoscale Ion Transport Enhances Conductivity in Solid Polymer-Ceramic Lithium Electrolytes.

The predictive design of flexible and solvent-free polymer electrolytes for solid-state batteries requires an understanding of the fundamental principles governing the ion transport. In this work, we establish a correlation among the composite structures, polymer segmental dynamics, and lithium ion (Li+) transport in a ceramic-polymer composite. Elucidating this structure-property relationship will allow tailoring of the Li+ conductivity by optimizing the macroscopic electrochemical stability of the electrolyte. The ion dissociation from the slow polymer segmental dynamics was found to be enhanced by controlling the morphology and functionality of the polymer/ceramic interface. The chemical structure of the Li+ salt in the composite electrolyte was correlated with the size of the ionic cluster domains, the conductivity mechanism, and the electrochemical stability of the electrolyte. Polyethylene oxide (PEO) filled with lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) or lithium bis(fluorosulfonyl) imide (LiFSI) salts was used as a matrix. A garnet electrolyte, aluminum substituted lithium lanthanum zirconium oxide (Al-LLZO) with a planar geometry, was used for the ceramic nanoparticle moieties. The dynamics of the strongly bound and highly mobile Li+ were investigated using dielectric relaxation spectroscopy. The incorporation of the Al-LLZO platelets increased the number density of more mobile Li+. The structure of the nanoscale ion-agglomeration was investigated by small-angle X-ray scattering, while molecular dynamics (MD) simulation studies were conducted to obtain the fundamental mechanism of the decorrelation of the Li+ in the LiTFSI and LiFSI salts from the long PEO chain.

Revalidation of the ATTRACTION-4 study in a real-world setting: a multicenter, retrospective propensity score matching study in China.

Background: Immune-checkpoint inhibitors (ICIs) combined with chemotherapy have been successfully used in clinical trials to treat advanced gastric cancer. However, the efficacy and safety of first-line immunotherapy combined with chemotherapy in Chinese patients are unknown. Methods: This multicenter retrospective study included patients with human epidermal growth factor receptor-2 (HER-2) negative advanced gastric cancer treated with first-line chemotherapy or chemotherapy with an ICI between January 2019 and December 2022. Propensity score matching was used to compare progression-free survival (PFS), overall survival, objective response rates, and adverse reactions between cohorts. Results: After propensity score matching, 138 patients, who had balanced baseline characteristics, were included in the chemotherapy and combination treatment groups. The median follow-up duration was 16.90 months, and the median PFS was 8.53 months (95% confidence interval [CI] 7.77-9.28) in the combination treatment group and 5.97 months (95% CI 4.56-7.37) in the chemotherapy group. The median survival duration was 17.05 months (95% CI 14.18-19.92) in the combination treatment group and 16.46 months (95% CI 12.99-19.93) in the chemotherapy group. The PFS subgroup analysis revealed that age ≥65 years, women, Eastern Cooperative Oncology Group performance status of 1, non-signet ring cell carcinoma, esophagogastric junction, liver metastasis, peritoneal metastasis, no massive ascites, only one metastatic organ, and combined platinum-based chemotherapy correlated with treatment benefit. The incidences of adverse events above grade 3 were comparable between groups. Conclusions: Our study confirmed the ATTRACTION-4 trial results. Compared with chemotherapy, first-line ICIs combined with chemotherapy prolonged PFS but did not improve overall survival in patients with HER-2-negative advanced gastric cancer.

Pathway complexity in fibre assembly: from liquid crystals to hyper-helical gelmorphs.

Pathway complexity results in unique materials from the same components according to the assembly conditions. Here a chiral acyl-semicarbazide gelator forms three different gels of contrasting fibre morphology (termed 'gelmorphs') as well as lyotropic liquid crystalline droplets depending on the assembly pathway. The gels have morphologies that are either hyperhelical (HH-Gel), tape-fibre (TF-Gel) or thin fibril derived from the liquid crystalline phase (LC-Gels) and exhibit very different rheological properties. The gelator exists as three slowly interconverting conformers in solution. All three gels are comprised of an unsymmetrical, intramolecular hydrogen bonded conformer. The kinetics show that formation of the remarkable HH-Gel is cooperative and is postulated to involve association of the growing fibril with a non-gelling conformer. This single molecule dynamic conformational library shows how very different materials with different morphology and hence very contrasting materials properties can arise from pathway complexity as a result of emergent interactions during the assembly process.

Chimney-Shaped Phase Diagram in a Polymer Blend Electrolyte.

The phase behavior of polymer blend electrolytes comprising poly(ethylene oxide) (PEO)/poly(methyl methacrylate) (PMMA)/lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) was determined using a combination of light and small angle neutron scattering (SANS) experiments. The results at a fixed temperature (110 °C) are presented on a PEO concentration versus salt (LiTFSI) concentration plot. The blends are miscible at all PEO concentrations in the absence of salt. With added salt, a region of immiscibility is obtained in PEO-lean polymer blend electrolytes; blends rich in PEO remain miscible at most salt concentrations. A narrow region of immiscibility juts into the miscible region, giving the phase diagram a chimney-like appearance. The data are qualitatively consistent with a simple extension of Flory-Huggins theory with a composition-dependent Flory-Huggins interaction parameter, χ, that was determined independently from SANS data from homogeneous blend electrolytes. Phase diagrams like the one we obtained were anticipated by self-consistent field theory calculations that account for correlations between ions. The relationship between these theories and measured χ remains to be established.

Grain boundary widening controls siderite (FeCO3) replacement of limestone (CaCO3).

The microstructure of minerals and rocks can significantly alter reaction rates. This study focuses on identifying transport paths in low porosity rocks based on the hypothesis that grain boundary widening accelerates reactions in which one mineral is replaced by another (replacement reaction). We conducted a time series of replacement experiments of three limestones (CaCO3) of different microstructures and solid impurity contents using FeCl2. Reacted solids were analyzed using chemical imaging, small angle X-ray and neutron scattering and Raman spectroscopy. In high porosity limestones replacement is reaction controlled and complete replacement was observed within 2 days. In low porosity limestones that contain 1-2% dolomite impurities and are dominated by grain boundaries, a reaction rim was observed whose width did not change with reaction time. Siderite (FeCO3) nucleation was observed in all parts of the rock cores indicating the percolation of the solution throughout the complete core. Dolomite impurities were identified to act as nucleation sites leading to growth of crystals that exert force on the CaCO3 grains. Widening of grain boundaries beyond what is expected based on dissolution and thermal grain expansion was observed in the low porosity marble containing dolomite impurities. This leads to a self-perpetuating cycle of grain boundary widening and reaction acceleration instead of reaction front propagation.

Spatially confined protein assembly in hierarchical mesoporous metal-organic framework.

Immobilization of biomolecules into porous materials could lead to significantly enhanced performance in terms of stability towards harsh reaction conditions and easier separation for their reuse. Metal-Organic Frameworks (MOFs), offering unique structural features, have emerged as a promising platform for immobilizing large biomolecules. Although many indirect methods have been used to investigate the immobilized biomolecules for diverse applications, understanding their spatial arrangement in the pores of MOFs is still preliminary due to the difficulties in directly monitoring their conformations. To gain insights into the spatial arrangement of biomolecules within the nanopores. We used in situ small-angle neutron scattering (SANS) to probe deuterated green fluorescent protein (d-GFP) entrapped in a mesoporous MOF. Our work revealed that GFP molecules are spatially arranged in adjacent nanosized cavities of MOF-919 to form "assembly" through adsorbate-adsorbate interactions across pore apertures. Our findings, therefore, lay a crucial foundation for the identification of proteins structural basics under confinement environment of MOFs.

Structural insights into self-assembly of a slow-evolving and mechanically robust supramolecular gel via time-resolved small-angle neutron scattering.

The supramolecular assembly process is a widespread phenomenon found in both synthetically engineered and naturally occurring systems, such as colloids, liquid crystals and micelles. However, a basic understanding of the evolution of self-assembly processes over time remains elusive, primarily owing to the fast kinetics involved in these processes and the complex nature of the various non-covalent interactions operating simultaneously. With the help of a slow-evolving supramolecular gel derived from a urea-based gelator, we aim to capture the different stages of the self-assembly process commencing from nucleation. In particular, we are able to study the self-assembly in real time using time-resolved small-angle neutron scattering (SANS) at length scales ranging from approximately 30 Å to 250 Å. Systems with and without sonication are compared simultaneously, to follow the different kinetic paths involved in these two cases. Time-dependent NMR, morphological and rheological studies act complementarily to the SANS data at sub-micron and bulk length scales. A hollow columnar formation comprising of gelator monomers arranged radially along the long axis of the fiber and solvent in the core is detected at the very early stage of the self-assembly process. While sonication promotes uniform growth of fibers and fiber entanglement, the absence of such a stimulus helps extensive bundle formation at a later stage and at the microscopic domain, making the gel system mechanically robust. The results of the present work provide a thorough understanding of the self-assembly process and reveal a path for fine-tuning such growth processes for applications such as the cosmetics industry, 3D printing ink development and paint industry.

Manipulating Assemblies in Metallosupramolecular Gels, Driven by Isomeric Ligands, Metal Coordination, and Adaptive Binary Gelator Systems.

Metallosupramolecular gel (MSG) is a unique combination of metal-ligand coordination chemistry and supramolecular gel chemistry with extraordinary adaptivity and softness. Such materials find broad uses in industry, pharmaceutical and biomedical sectors, and in technology generation among many others. Pyridyl-appended bis(urea) gelator systems have been extensively studied as potential MSG-forming materials in the presence of various metal ions. The previous molecular engineering approaches depicted competitive intermolecular and intramolecular binding modes involving urea and pyridyl groups and further fine-tuned by the presence of various molecular spacers. In those studies, formation of intermolecular hydrogen bonding among urea moieties to form urea tape was found to be the key factor in one-dimensional assembly and gel formation. In the present study, we show how two isomeric pyridyl-appended bis(urea) ligands can be designed appropriately to essentially eliminate the interference of competitive factors, leaving the intermolecular urea assembly practically unaffected even in the presence of metal ions. We found that one of the two ligands (L2) and the mixed ligand (L1 + L2) assemblies formed gel in the presence and absence of various metal ions. A metal ion with a linear coordination geometry significantly strengthened the gels. Moreover, an inherently weak L1 + L2 assembly appears to be more adaptive in accommodating larger metal ions especially with nonlinear coordination geometry preferences. Small-angle neutron scattering and rheological, spectroscopic, and morphological characterizations, collectively, capture a detailed interplay among ligand assembly, metal-ligand coordination, and adaptivity, driven by the pure versus mixed ligand assemblies. The knowledge gathered from the present study would be highly beneficial in engineering the metallosupramolecular polymeric assemblies toward their functional applications.

Omega-3 polyunsaturated fatty acids promote SNAREs mediated GLUT4 vesicle docking and fusion.

Glucose homeostasis imbalance and insulin resistance (IR) are major contributors to the incidence of type 2 diabetes. Omega-3 polyunsaturated fatty acids (PUFAs) are key ingredients for maintaining cellular functions and improving insulin sensitivity. However, how omega-3 PUFAs modulate the dynamic process of glucose transport at the cellular level remains unclear. Here we unraveled eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may regulate the glucose transporter 4 (GLUT4) vesicle trafficking in both normal and IR adipocytes. Both omega-3 PUFAs significantly increase glucose consumption within a range of 10-32% in the basal state. Furthermore, both EPA (200 µM) and DHA (100 µM) may significantly promote the serine/threonine protein kinase (Akt) phosphorylation by 70% and 40% in the physiological state of adipocytes, respectively. Both omega-3 PUFAs significantly advanced the Akt phosphorylation in a dose-dependent way and showed a ∼2-fold increase at the dose of 200 µM in the IR pathological state. However, they could not up-regulate the expression of GLUT4 and insulin-regulated aminopeptidase protein. We further revealed that both omega-3 PUFAs dynamically promote insulin-stimulated GLUT4 vesicle translocation and soluble N-ethylmaleimide-sensitive factor attachment protein receptor mediated vesicle docking and fusion to the plasma membrane via specifically modulating the expression of vesicle-associated membrane protein 2. Understanding the mechanisms by which omega-3 PUFAs modulate cellular metabolism and IR in peripheral tissues may provide novel insights into the potential impact of omega-3 PUFAs on the metabolic function and the management of IR.

Degradation of Adsorbed Bisphenol A by Soluble Mn(III).

Bisphenol A (BPA), a high production volume chemical and potential endocrine disruptor, is found to be associated with sediments and soils due to its hydrophobicity (log KOW of 3.42). We used superfine powdered activated carbon (SPAC) with a particle size of 1.38 ± 0.03 µm as a BPA sorbent and assessed degradation of BPA by oxidized manganese (Mn) species. SPAC strongly sorbed BPA, and desorption required organic solvents. No degradation of adsorbed BPA (278.7 ± 0.6 mg BPA g-1 SPAC) was observed with synthetic, solid α-MnO2 with a particle size of 15.41 ± 1.35 µm; however, 89% mass reduction occurred following the addition of 0.5 mM soluble Mn(III). Small-angle neutron scattering data suggested that both adsorption and degradation of BPA occurred in SPAC pores. The findings demonstrate that Mn(III) mediates oxidative transformation of dissolved and adsorbed BPA, the latter observation challenging the paradigm that contaminant desorption and diffusion out of pore structures are required steps for degradation. Soluble Mn(III) is abundant near oxic-anoxic interfaces, and the observation that adsorbed BPA is susceptible to degradation has implications for predicting, and possibly managing, the fate and longevity of BPA in environmental systems.

Eicosapentaenoic and docosahexaenoic acids attenuate hyperglycemia through the microbiome-gut-organs axis in db/db mice.

BACKGROUND: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been suggested to prevent the development of metabolic disorders. However, their individual role in treating hyperglycemia and the mechanism of action regarding gut microbiome and metabolome in the context of diabetes remain unclear. RESULTS: Supplementation of DHA and EPA attenuated hyperglycemia and insulin resistance without changing body weight in db/db mice while the ameliorative effect appeared to be more pronounced for EPA. DHA/EPA supplementation reduced the abundance of the lipopolysaccharide-containing Enterobacteriaceae whereas elevated the family Coriobacteriaceae negatively correlated with glutamate level, genera Barnesiella and Clostridium XlVa associated with bile acids production, beneficial Bifidobacterium and Lactobacillus, and SCFA-producing species. The gut microbiome alterations co-occurred with the shifts in the metabolome, including glutamate, bile acids, propionic/butyric acid, and lipopolysaccharide, which subsequently relieved ß cell apoptosis, suppressed hepatic gluconeogenesis, and promoted GLP-1 secretion, white adipose beiging, and insulin signaling. All these changes appeared to be more evident for EPA. Furthermore, transplantation with DHA/EPA-mediated gut microbiota mimicked the ameliorative effect of DHA/EPA on glucose homeostasis in db/db mice, together with similar changes in gut metabolites. In vitro, DHA/EPA treatment directly inhibited the growth of Escherichia coli (Family Enterobacteriaceae) while promoted Coriobacterium glomerans (Family Coriobacteriaceae), demonstrating a causal effect of DHA/EPA on featured gut microbiota. CONCLUSIONS: DHA and EPA dramatically attenuated hyperglycemia and insulin resistance in db/db mice, which was mediated by alterations in gut microbiome and metabolites linking gut to adipose, liver and pancreas. These findings shed light into the gut-organs axis as a promising target for restoring glucose homeostasis and also suggest a better therapeutic effect of EPA for treating diabetes. Video abstract.

A single center retrospective study of paraneoplastic neurological syndromes with positive onconeural antibodies.

Paraneoplastic neurological syndromes (PNS) are rare immune-mediated disorders, and the detection of onconeural antibodies is helpful for PNS diagnosis. The aim of this study was to investigate the clinical characteristics of patients with PNS with positive onconeural antibodies in a single center in Hubei, China. We retrospectively analyzed the clinical characteristics of 54 patients with positive onconeural antibodies from January 2016 to September 2020. Among 780 patients with suspected PNS, 54 (6.9%) had positive onconeural antibodies. Of those 54 patients, 28 (51.8%) were diagnosed with definite PNS and 13 (24.1%) with possible PNS. Eighteen (33.3%) patients were confirmed with cancer. Ten PNS syndromes were detected among the 28 patients with definite PNS, and they had either classical (12/28, 42.8%) or non-classical syndromes (17/28, 60.7%). Peripheral neuropathy (9/28, 32.1%), subacute cerebellar degeneration (4/28, 14.3%), and limbic encephalitis (4/28, 14.3%) were the most common PNS syndromes. The anti-CV2/CRMP5-antibody was observed most frequently. Lung cancer was the most common tumor type. For patients with possible PNS, peripheral neuropathy was the most common PNS syndrome, and the anti-Tr-antibody was the most frequent onconeural antibody. Immunotherapy was effective in treating PNS. The anti-CV2/CRMP5-antibody was the most subsequently observed antibody. The manifestations of PNS are diverse and include peripheral neuropathy, subacute cerebellar degeneration, and limbic encephalitis. In patients with PNS, lung cancer was the most common tumor.

Mixed conjugated linoleic acid sex-dependently reverses high-fat diet-induced insulin resistance via the gut-adipose axis.

Conjugated linoleic acid (CLA) may prevent the development of obesity and metabolic disorders. However, the effects of CLA on inflammation and glucose metabolism are controversial. The underlying mechanisms governing the gut microbiota and sexual dimorphisms have also not been elucidated. The present study assessed the effect of CLA on glucose and lipid metabolism in established obesity and examined the mechanism of action based on gut microbiota. Four-week-old C57BL/6J mice were fed a high-fat diet (HFD) for 10 weeks to induce obesity. The diet-induced obese (DIO) mice were fed an HFD supplemented with mixed CLA (50% cis-9, trans-11 isomer and 50% trans-10, cis-12 isomers, 0.2% wt/wt) for 15 weeks. CLA supplementation remarkably reversed body weight in both sexes. CLA favored anti-inflammatory microbiota in male mice, mediating increased short-chain fatty acids and decreased lipopolysaccharide (LPS) production, which alleviated global inflammation and improved insulin sensitivity via inhibition of the TLR4-NF-κB pathway in adipose tissue. CLA promoted the growth of hydrogen sulfide-producing Desulfovibrio and the release of LPS in female mice, which aggravated adipose inflammation and insulin resistance. Although CLA impaired glucose metabolism in females, brown adipose tissue was significantly activated with browning of white adipose tissue in both sexes, which led to enhanced energy expenditure. Fecal transplantation from CLA-treated mice to DIO mice mimicked the sex-dependent phenotype. In conclusion, CLA decreased body weight and increased energy expenditure but sex-dependently modulated insulin resistance via the gut-adipose axis.

Eicosapentaenoic and Docosahexaenoic Acids Differentially Alter Gut Microbiome and Reverse High-Fat Diet-Induced Insulin Resistance.

SCOPE: To assess the individual effects of dietary eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on insulin resistance (IR), gut microbiome, and gut metabolites in high-fat-diet-induced obese (DIO) mice. METHODS AND RESULTS: DIO mice are fed an either high-fat diet (HFD), EPA (1% w/w) enriched HFD, or DHA (1% wt/wt) enriched HFD for 15 weeks. Both EPA and DHA supplements reverse hyperglycemia and IR but do not affect body weight in DIO mice while DHA exhibits a more pronounced ameliorative effect in male mice. Both EPA- and DHA-enriched Lactobacillus and short-chain fatty acids (SCFAs)-producing species from Lachnospiraceae while reduced lipopolysaccharide (LPS)-producing Bilophila and Escherichia/Shigella. Compared with EPA, DHA-supplemented mice have more abundant propionic/butyric acid-producing bacteria, including Coprococcus, Butyricimonas synergistica, Bacteroides acidifaciens, and Intestinimonas, and less-abundant LPS-correlated species Streptococcus and p-75-a5. The shifts in gut microbiome co-occurred with the changes in levels of propionic/butyric acid, circulating LPS, and serotonin. Additionally, EPA/DHA supplementation attenuates adipose inflammation with upregulated glucose transporter 4 and Akt phosphorylation, indicating the improvement of insulin signaling. CONCLUSION: EPA and DHA differentially reverse IR and relieve adipose inflammation while modulating gut microbiome and SCFAs/LPS production, underscoring the gut-adipose axis as a primary target of EPA/DHA.

Adsorption of Fatty Acid Molecules on Amine-Functionalized Silica Nanoparticles: Surface Organization and Foam Stability.

The crucial roles of the ionization state and counterion presence on the phase behavior of fatty acid in aqueous solutions are well-established. However, the effects of counterions on the adsorption and morphological state of fatty acid on nanoparticle surfaces are largely unknown. This knowledge gap exists due to the high complexity of the interactions between nanoparticles, counterions, and fatty acid molecules in aqueous solution. In this study, we use adsorption isotherms, small angle neutron scattering, and all-atom molecular dynamic simulations to investigate the effect of addition of ethanolamine as a counterion on the adsorption and self-assembly of decanoic acid onto aminopropyl-modified silica nanoparticles. We show that the morphology of the fatty acid assemblies on silica nanoparticles changes from discrete surface patches to a continuous bilayer by increasing concentration of the counterion. This morphological behavior of fatty acid on the oppositely charged nanoparticle surface alters the interfacial activity of the fatty acid-nanoparticle complex and thus governs the stability of the foam formed by the mixture. Our study provides new insights into the structure-property relationship of fatty acid-nanoparticle complexes and outlines a framework to program the stability of foams formed by mixtures of nanoparticles and amphiphiles.

Observation of Ion Electrosorption in Metal-Organic Framework Micropores with In Operando Small-Angle Neutron Scattering.

A molecular-level understanding of transport and adsorption mechanisms of electrolyte ions in nanoporous electrodes under applied potentials is essential to control the performance of double-layer capacitors. Here, in operando small-angle neutron scattering (SANS) is used to directly detect ion movements into the nanopores of a conductive metal-organic framework (MOF) electrode under operating conditions. Neutron-scattering data reveals that most of the void space within the MOF is accessible to the solvent. Upon the addition of the electrolyte sodium triflate (NaOTf), the ions are adsorbed on the outer surface of the protrusions to form a 30 Šlayer instead of entering the ionophobic pores in the absence of an applied charging potential. The changes in scattering intensity when potentials are applied suggests the ion rearrangement in the micropores following different mechanisms depending on the electrode polarization. These observations shed insights on ion electrosorption in electrode materials.