The translational landscape of bread wheat during grain development.

The dynamics of gene expression in crop grains has typically been investigated at the transcriptional level. However, this approach neglects translational regulation, a widespread mechanism that rapidly modulates gene expression to increase the plasticity of organisms. Here, we performed ribosome profiling and polysome profiling to obtain a comprehensive translatome data set of developing bread wheat (Triticum aestivum) grains. We further investigated the genome-wide translational dynamics during grain development, revealing that the translation of many functional genes is modulated in a stage-specific manner. The unbalanced translation between subgenomes is pervasive, which increases the expression flexibility of allohexaploid wheat. In addition, we uncovered widespread previously unannotated translation events, including upstream open reading frames (uORFs), downstream open reading frames (dORFs), and open reading frames (ORFs) in long noncoding RNAs, and characterized the temporal expression dynamics of small ORFs. We demonstrated that uORFs act as cis-regulatory elements that can repress or even enhance the translation of mRNAs. Gene translation may be combinatorially modulated by uORFs, dORFs, and microRNAs. In summary, our study presents a translatomic resource that provides a comprehensive and detailed overview of the translational regulation in developing bread wheat grains. This resource will facilitate future crop improvements for optimal yield and quality.

Pangenome-based trajectories of intracellular gene transfers in Poaceae unveil high cumulation in Triticeae.

Intracellular gene transfers (IGTs) between the nucleus and organelles, including plastids and mitochondria, constantly reshape the nuclear genome during evolution. Despite the substantial contribution of IGTs to genome variation, the dynamic trajectories of IGTs at the pangenomic level remain elusive. Here, we developed an approach, IGTminer, that maps the evolutionary trajectories of IGTs using collinearity and gene reannotation across multiple genome assemblies. We applied IGTminer to create a nuclear organellar gene (NOG) map across 67 genomes covering 15 Poaceae species, including important crops. The resulting NOGs were verified by experiments and sequencing data sets. Our analysis revealed that most NOGs were recently transferred and lineage specific and that Triticeae species tended to have more NOGs than other Poaceae species. Wheat (Triticum aestivum) had a higher retention rate of NOGs than maize (Zea mays) and rice (Oryza sativa), and the retained NOGs were likely involved in photosynthesis and translation pathways. Large numbers of NOG clusters were aggregated in hexaploid wheat during 2 rounds of polyploidization, contributing to the genetic diversity among modern wheat accessions. We implemented an interactive web server to facilitate the exploration of NOGs in Poaceae. In summary, this study provides resources and insights into the roles of IGTs in shaping interspecies and intraspecies genome variation and driving plant genome evolution.

Water Adsorption Isotherm and Surface Conductivity of Boroaluminosilicate Glasses.

The surface resistivity of boroaluminosilicate display glasses, which may affect the downstream display panel manufacturing, varies with the relative humidity (RH) of the environment, but the origin of this RH dependence has not been well understood. We have measured the water adsorption behavior on Corning Eagle XG (Glass-E) and Lotus NXT (Glass-L) glass panels using Brewster angle transmission infrared spectroscopy. The IR spectra of adsorbed water were analyzed to obtain the effective thickness of adsorbed water, the distribution of hydrogen-bonding interactions among the adsorbed water molecules, and the isosteric heat of water adsorption. These characteristics were compared with the electrical conductivity (inverse of resistivity) of these two glasses [Appl. Surf. Sci. 2015, 356, 1189]. This comparison revealed the correlation between the conductivity and the water layer structure, which could explain the surface resistivity difference between Glass-E and Glass-L as a function of RH. This study also disputed the previous hypothesis that the water adsorption isotherm would be governed by the areal density of the surface hydroxyl group; instead, it suggested that the network modifier ions may also play a critical role, especially in the intermediate RH regime.

Long noncoding RNA lncMREF promotes myogenic differentiation and muscle regeneration by interacting with the Smarca5/p300 complex.

Long noncoding RNAs (lncRNAs) play important roles in the spatial and temporal regulation of muscle development and regeneration. Nevertheless, the determination of their biological functions and mechanisms underlying muscle regeneration remains challenging. Here, we identified a lncRNA named lncMREF (lncRNA muscle regeneration enhancement factor) as a conserved positive regulator of muscle regeneration among mice, pigs and humans. Functional studies demonstrated that lncMREF, which is mainly expressed in differentiated muscle satellite cells, promotes myogenic differentiation and muscle regeneration. Mechanistically, lncMREF interacts with Smarca5 to promote chromatin accessibility when muscle satellite cells are activated and start to differentiate, thereby facilitating genomic binding of p300/CBP/H3K27ac to upregulate the expression of myogenic regulators, such as MyoD and cell differentiation. Our results unravel a novel temporal-specific epigenetic regulation during muscle regeneration and reveal that lncMREF/Smarca5-mediated epigenetic programming is responsible for muscle cell differentiation, which provides new insights into the regulatory mechanism of muscle regeneration.

A randomized-controlled trial of ischemia-free liver transplantation for end-stage liver disease.

BACKGROUND & AIMS: Ischemia-reperfusion injury (IRI) has thus far been considered as an inevitable component of organ transplantation, compromising outcomes, and limiting organ availability. Ischemia-free organ transplantation is a novel approach designed to avoid IRI, with the potential to improve outcomes. METHODS: In this randomized-controlled clinical trial, recipients of livers from donors after brain death were randomly assigned to receive either an ischemia-free or a 'conventional' transplant. The primary endpoint was the incidence of early allograft dysfunction. Secondary endpoints included complications related to graft IRI. RESULTS: Out of 68 randomized patients, 65 underwent transplants and were included in the analysis. 32 patients received ischemia-free liver transplantation (IFLT), and 33 received conventional liver transplantation (CLT). Early allograft dysfunction occurred in two recipients (6%) randomized to IFLT and in eight (24%) randomized to CLT (difference -18%; 95% CI -35% to -1%; p = 0.044). Post-reperfusion syndrome occurred in three recipients (9%) randomized to IFLT and in 21 (64%) randomized to CLT (difference -54%; 95% CI -74% to -35%; p <0.001). Non-anastomotic biliary strictures diagnosed with protocol magnetic resonance cholangiopancreatography at 12 months were observed in two recipients (8%) randomized to IFLT and in nine (36%) randomized to CLT (difference, -28%; 95% CI -50% to -7%; p = 0.014). The comprehensive complication index at 1 year after transplantation was 30.48 (95% CI 23.25-37.71) in the IFLT group vs. 42.14 (95% CI 35.01-49.26) in the CLT group (difference -11.66; 95% CI -21.81 to -1.51; p = 0.025). CONCLUSIONS: Among patients with end-stage liver disease, IFLT significantly reduced complications related to IRI compared to a conventional approach. CLINICAL TRIAL REGISTRATION: chictr.org. ChiCTR1900021158. IMPACT AND IMPLICATIONS: Ischemia-reperfusion injury has thus far been considered as an inevitable event in organ transplantation, compromising outcomes and limiting organ availability. Ischemia-free liver transplantation is a novel approach of transplanting donor livers without interruption of blood supply. We showed that in patients with end-stage liver disease, ischemia-free liver transplantation, compared with a conventional approach, led to reduced complications related to ischemia-reperfusion injury in this randomized trial. This new approach is expected to change the current practice in organ transplantation, improving transplant outcomes, increasing organ utilization, while providing a clinical model to delineate the impact of organ injury on alloimmunity.

Does omega-3 PUFA-enriched oral nutritional intervention benefit cancer patients receiving chemo (radio) therapy? A systematic review and meta-analysis of randomized controlled trials.

Although data indicate omega-3 polyunsaturated fatty acids are beneficial nutrients in cancer therapy, the evidences for efficacy of nutritional interventions during chemo (radio) therapy are still limited. The leading goal of the present meta-analysis was to summarize randomized controlled trials involving the administration of ω-3 PUFA-enriched oral nutritional supplements during chemo (radio) therapy, and evaluate the effects on nutritional status and clinical outcomes in patients. We systematically searched PubMed, Embase, Web of Science, Cochrane databases to identify interventions assessing body weight, BMI, immune and inflammatory indicators, plasma omega-3 fatty acids and adverse events, with subgroup analyses for region, types of ω-3 fatty acids, dose, duration and dosage form. In total, 22 studies including 1155 participants met the inclusion criteria. Meta-analysis showed a significant increase in body weight (BW) (WMD = 0.59 kg, 95% CI: 0.06, 1.13, P = 0.03), body mass index (BMI) (WMD = 0.43 kg/m2, 95% CI: 0.07, 0.79, P = 0.02), and plasma total ω-3 fatty acids (SMD = 2.52, 95% CI: 1.27, 3.78, P<0.0001), and a significant reduction in plasma levels of C-reactive protein (CRP) (SMD= -0.53, 95% CI: -0.80, -0.25, P = 0.0001), tumor necrosis factor-α (TNF-α) (WMD = -0.40 pg/mL, 95% CI: -0.80, -0.01, P = 0.05), interleukin 6 (IL-6) (WMD = -1.25 pg/mL, 95% CI: -2.41, -0.10, P = 0.03) and the incidence of adverse events (RR= 0.72, 95% CI: 0.54, 0.95, P = 0.02). However, plasma albumin levels (WMD = 0.02 mg/dL, 95% CI: -0.13, 0.18, P = 0.75) was remained unaffected. Overall, our meta-analysis provides evidences that the consumption of ω-3 PUFA-enriched oral nutritional supplements exert beneficial effects on nutritional status and clinical outcomes in patients undergoing chemo (radio) therapy.

Outstanding Electrochemical Performance of Ni-Rich Concentration-Gradient Cathode Material LiNi0.9Co0.083Mn0.017O2 for Lithium-Ion Batteries.

The full-concentrationgradient LiNi0.9Co0.083Mn0.017O2 (CG-LNCM), consisting of core Ni-rich LiNi0.93Co0.07O2, transition zone LiNi1-x-yCoxMnyO2, and outmost shell LiNi1/3Co1/3Mn1/3O2 was prepared by a facile co-precipitation method and high-temperature calcination. CG-LNCM was then investigated with an X-ray diffractometer, ascanning electron microscope, a transmission electron microscope, and electrochemical measurements. The results demonstrate that CG-LNCM has a lower cation mixing of Li+ and Ni2+ and larger Li+ diffusion coefficients than concentration-constant LiNi0.9Co0.083Mn0.017O2 (CC-LNCM). CG-LNCM presents a higher capacity and a better rate of capability and cyclability than CC-LNCM. CG-LNCM and CC-LNCM show initial discharge capacities of 221.2 and 212.5 mAh g-1 at 0.2C (40 mA g-1) with corresponding residual discharge capacities of 177.3 and 156.1 mAh g-1 after 80 cycles, respectively. Even at high current rates of 2C and 5C, CG-LNCM exhibits high discharge capacities of 165.1 and 149.1 mAh g-1 after 100 cycles, respectively, while the residual discharge capacities of CC-LNCM are as low as 148.8 and 117.9 mAh g-1 at 2C and 5C after 100 cycles, respectively. The significantly improved electrochemical performance of CG-LNCM is attributed to its concentration-gradient microstructure and the composition distribution of concentration-gradient LiNi0.9Co0.083Mn0.017O2. The special concentration-gradient design and the facile synthesis are favorable for massive manufacturing of high-performance Ni-rich ternary cathode materials for lithium-ion batteries.

Application of small angle X-ray scattering in exploring the effect of edible oils with different unsaturation FAs on bioaccessibility of stigmasterol oleate.

BACKGROUND: Phytosterol can improve its lipid solubility, lipophilic/hydrophilic balance and bioaccessibility by esterification with fatty acids, which increases its practical application range in the food industry. In the present study, small angle X-ray scattering combined with the pH-stat in vitro digestion model was applied to continuously monitor the molecular structure evolution of mixed micelles during digestion and investigate the effect of three edible oils (olive oil with 72.41 ± 0.57% oleic, sunflower seed oil with 63.45 ± 0.78% linoleic, refined linseed oil with 51.74 ± 0.34% linolenic) on bioaccessibility of stigmasterol oleate in vitro. RESULTS: The release degree and rate of fatty acids in the three edible oil systems (kOO+ST-OA = 0.0501, kSO+ ST-OA = 0.0357, kLO+ST-OA = 0.0323) was compared. The three different edible oils had similar impact on the formation of dietary mixed micelles during the simulatedin vitro digestion of stigmasterol oleate, although there were significant differences in molecular morphology and composition of mixed micelles. The results showed that the vesicles formed by linoleic oil (SO system) or linolenic oil (LO system) were easy to dissociate. The largest average number and diameter of vesicles (5.55 × 1016 cm-3 and 2230.75 Å), the most stable vesicle structure and the fastest fatty acid release rate were observed in the OO system. CONCLUSION: Compared to linoleic (SO system) or linolenic (LO system), the oleic (OO system) could facilitate the transformation of micelles to vesicles and maintain the stability of its membrane, significantly promotin the dissolution of stigmasterol and improving bioaccessibility. © 2023 Society of Chemical Industry.

Elucidating Interfacial Chain Conformation of Superhydrophilic Polymer Brushes by Vibrational Sum Frequency Generation Spectroscopy.

Surface-tethered macromolecules (polymer brushes) are a potent means to modify surfaces with stimuli-responsive properties while avoiding delamination problems. This vibrational sum frequency generation spectroscopy study describes how the conformation of hydrophilic polymer brushes changes in response to environmental conditions, that is, changes in humidity (in air) and upon exposure to liquid water. Three hydrophilic brushes were prepared on silicon oxide surfaces by surface-initiated reversible deactivation radical polymerization of cationic (quaternary ammonium), anionic (sulfonate), and zwitterionic (containing both) monomers. The average tilt angle of methyl groups was analyzed and used to deduce the chain conformations of the polymer brushes. In air, the brush films absorb water and swell with increasing humidity. This is accompanied by the rotation of interfacial polymer chains. The degree of water uptake and chain conformation vary with the nature of the charged hydrophilic moieties. The hydrophilic polymer brush surfaces appear to remain relatively dry except in near-condensation conditions. In water, the quaternary ammonium groups of cationic and zwitterionic brushes are aligned nearly parallel to the surface. The anionic brush chains appear to assume nearly random conformations in water.

A novel lncRNA promotes myogenesis of bovine skeletal muscle satellite cells via PFN1-RhoA/Rac1.

Myogenesis, the process of skeletal muscle formation, is a highly coordinated multistep biological process. Accumulating evidence suggests that long non-coding RNAs (lncRNAs) are emerging as a gatekeeper in myogenesis. Up to now, most studies on muscle development-related lncRNAs are mainly focussed on humans and mice. In this study, a novel muscle highly expressed lncRNA, named lnc23, localized in nucleus, was found differentially expressed in different stages of embryonic development and myogenic differentiation. The knockdown and over-expression experiments showed that lnc23 positively regulated the myogenic differentiation of bovine skeletal muscle satellite cells. Then, TMT 10-plex labelling quantitative proteomics was performed to screen the potentially regulatory proteins of lnc23. Results indicated that lnc23 was involved in the key processes of myogenic differentiation such as cell fusion, further demonstrated that down-regulation of lnc23 may inhibit myogenic differentiation by reducing signal transduction and cell fusion among cells. Furthermore, RNA pulldown/LC-MS and RIP experiment illustrated that PFN1 was a binding protein of lnc23. Further, we also found that lnc23 positively regulated the protein expression of RhoA and Rac1, and PFN1 may negatively regulate myogenic differentiation and the expression of its interacting proteins RhoA and Rac1. Hence, we support that lnc23 may reduce the inhibiting effect of PFN1 on RhoA and Rac1 by binding to PFN1, thereby promoting myogenic differentiation. In short, the novel identified lnc23 promotes myogenesis of bovine skeletal muscle satellite cells via PFN1-RhoA/Rac1.

Systematic analysis on multiple Gene Expression Omnibus data sets reveals fierce immune response in hepatitis B virus-related acute liver failure.

Acute liver failure (ALF) caused by hepatitis B virus (HBV) is common type of liver failure in the world, with high morbidity and mortality rates. However, the prevalence, genetic background and factors determining the development of HBV-related ALF are rarely studied. In this study, we examined three Gene Expression Omnibus (GEO) data sets by bioinformatics analysis to identify differentially expressed genes (DEGs), key biological processes and pathways. Immune infiltration analysis showed high immune cells infiltration in HBV-related ALF tissue. We then confirmed natural killer cells and macrophages infiltration in clinical samples by immunohistochemistry assay, implying these cells play a significant role in HBV-ALF. We found 1277 genes were co-up-regulated and that 1082 genes were co-down-regulated in the 3 data sets. Inflammation-related pathways were enriched in the co-up-regulated genes and synthetic metabolic pathways were enriched in the co-down-regulated genes. WGCNA also revealed a key module enriching in immune inflammation response and identified 10 hub genes, differentially expressed in an independent data set. In conclusion, we identified fierce immune inflammatory response to elucidate the immune-driven mechanism of HBV-ALF and 10 hub genes based on gene expression profiles.

Dissection and validation of a QTL cluster linked to Rht-B1 locus controlling grain weight in common wheat (Triticum aestivum L.) using near-isogenic lines.

KEY MESSAGE: This study dissected and validated a QTL cluster associated with thousand grain weight on chromosome 4B using multiple near-isogenic lines in common wheat. Grain size and weight are crucial components of wheat yield. Previously, we identified a QTL cluster for thousand grain weight (TGW) on chromosome 4B using the Nongda3338 (ND3338)/Jingdong6 (JD6) doubled haploid population. Here, near-isogenic lines (NILs) in the ND3338 background were developed to dissect and validate the QTL cluster. Based on six independent BC3F3:4 heterogeneous inbred families, the 4B QTL cluster was divided into two linked QTL intervals (designated 4B.1 and 4B.2 QTL). For the 4B.1 QTL, the Rht-B1 gene, of which Rht-B1b allele reduces plant height (PH) by 21.18-29.34 cm (34.34-53.71%), was demonstrated to be the most likely candidate gene with pleiotropic effects on grain size and TGW. For the 4B.2 QTL, the NILJD6 consistently showed an increase in TGW of 3.51-7.68 g (8.84-22.77%) compared with NILND3338 across different field trials, along with a significant increase in PH of 2.26-6.71 cm (3.92-12.01%). Moreover, both QTL intervals had a larger effect on grain width than on grain length. Additionally, the first significant difference in 100-grain fresh weight and 100-grain dry weight between the NIL pairs of the 4B.1 QTL interval (Rht-B1) was observed at 6 days after pollination (DAP), while the differences were first visible at 30 DAP for the 4B.2 QTL interval. Collectively, our work provides a new example of QTL dissection for grain weight in wheat and lays a foundation for further map-based cloning of the major QTL that have potential applications in wheat molecular breeding for high yield.

Evaluation of Two Major Rhodiola Species and the Systemic Changing Characteristics of Metabolites of Rhodiola crenulata in Different Altitudes by Chemical Methods Combined with UPLC-QqQ-MS-Based Metabolomics.

Rhodiola species have a long history of use in traditional medicine in Asian and European countries and have been considered to possess resistance to the challenges presented by extreme altitudes. However, the influence of different Rhodiola species on quality is unclear, as well as the influence of altitude on phytochemicals. In this study, the phenolic components and antioxidant abilities of two major Rhodiola species are compared, namely Rhodiolacrenulata and Rhodiola rosea, and the metabolomes of Rhodiolacrenulata from two representative elevations of 2907 and 5116 m are analyzed using a UPLC-QqQ-MS-based metabolomics approach. The results show that the phenolic components and antioxidant activities of Rhodiolacrenulata are higher than those of Rhodiola rosea, and that these effects in the two species are positively correlated with elevation. Here, 408 metabolites are identified, of which 178 differential metabolites (128 upregulated versus 50 downregulated) and 19 biomarkers are determined in Rhodiola crenulata. Further analysis of these differential metabolites showed a significant upregulation of flavonoids, featuring glucosides, the enhancement of the phenylpropanoid pathway, and the downregulation of hydrolyzed tannins in Rhodiola crenulata as elevation increased. Besides, the amino acids of differential metabolites were all upregulated as the altitude increased. Our results contribute to further exploring the Rhodiola species and providing new insights into the Rhodiola crenulata phytochemical response to elevation.

A Theoretical View of Linear Backpropagation and its Convergence.

Backpropagation (BP) is widely used for calculating gradients in deep neural networks (DNNs). Applied often along with stochastic gradient descent (SGD) or its variants, BP is considered as a de-facto choice in a variety of machine learning tasks including DNN training and adversarial attack/defense. Recently, a linear variant of BP named LinBP was introduced for generating more transferable adversarial examples for performing black-box attacks, by (Guo et al. 2020). Although it has been shown empirically effective in black-box attacks, theoretical studies and convergence analyses of such a method is lacking. This paper serves as a complement and somewhat an extension to Guo et al. (2020) paper, by providing theoretical analyses on LinBP in neural-network-involved learning tasks, including adversarial attack and model training. We demonstrate that, somewhat surprisingly, LinBP can lead to faster convergence in these tasks in the same hyper-parameter settings, compared to BP. We confirm our theoretical results with extensive experiments.

Antioxidant interaction between α-tocopherol and γ-oryzanol in HepG2 cells.

Minor constituents exhibit certain antioxidant interactions in vitro, and the effects in different media are different. However, it is not clear whether there are antioxidant interactions in cells after digestion and absorption. We utilized the cellular antioxidant evaluation model in HepG2 cells to study the antioxidant interaction between α-tocopherol and γ-oryzanol, and the interaction mechanism of a binary mixture was also illustrated. A cellular antioxidant assay (CAA) model and a combined index (CI) method were firstly used to explore the antioxidant activity and interaction of the binary mixture in HepG2 cells. The CAA value was positively correlated with the single addition concentration, while the results displayed a biphasic tendency with increasing concentrations of the binary mixture. The combination of TO11 (1 µg mL-1 α-tocopherol and 10 µg mL-1 γ-oryzanol) showed the greatest antioxidant activity and synergistic effect, and the maximum CAA value reached up to 94.84 ± 4.2. Then the mechanism of the synergistic antioxidant effect of the binary mixture was explained from three aspects including cellular uptake, intracellular reactive oxygen species (ROS) level and endogenous enzyme activity. The results demonstrated that the antioxidant interaction of the binary mixture in cells was related to cellular uptake of minor constituents, and the combination of TO11 exerted a synergistic effect by scavenging ROS and up-regulating glutathione peroxidase (GSH-Px) activity, resulting in the strongest cellular antioxidant activity. This study throws light on the nature of antioxidant interaction between minor constituents, which may contribute to the development of related functional foods and rational dietary collocation.

Inhibitory effect and molecular mechanism on tyrosinase and browning of fresh-cut apple by longan shell tannins.

Tyrosinase is a biological macromolecule closely related to browning of fruit and vegetables, melanin production, and tyrosinase inhibitors are usually used to prevent browning and pigmentation. In this study, longan shell tannins (LSTs) were screened as tyrosinase inhibitors and their structures were proved to be mixtures of procyanidins (condensed tannins) and ellagitannins (hydrolyzed tannins). Enzymatic experiments verified that LSTs were efficient inhibitors, and the IC50 values for monophenolase and bisphenolase were 176.04 ± 10 and 59.94 ± 5 µg mL-1, respectively. Fluorescence detections and molecular docking revealed that the combination of LSTs to tyrosinase was mainly driven by hydrogen bonding, hydrophobic interaction, as well as van der Waals force, which changed the microenvironment of tyrosine and tryptophan residues as well as enzyme conformation. Circular dichroism and molecular dynamics simulation showed that LSTs affected secondary structures of tyrosinase, resulting in structural stretching and conformational modification of the enzyme. In addition, preservation studies demonstrated that LSTs owned the ability to delay the browning of fresh-cut apples by inhibiting phenolic metabolism, strengthening the antioxidant system, and reducing lipid peroxidation. This paper testified that LSTs are exteaordinary tyrosinase inhibitors, and offered a scientific foundation for the application of LSTs in food industry and medicine.

Acer truncatum Bunge seed oil ameliorated oxaliplatin-induced demyelination by improving mitochondrial dysfunction via the Pink1/Parkin mitophagy pathway.

Dietary nutritional support for special populations is an effective and feasible method to improve the quality of life of patients and reduce medical pressure. Acer truncatum Bunge seed oil (ATSO) is widely recognized for its ability to promote nerve myelin regeneration. To evaluate the ameliorative effects of ATSO on chemotherapy-induced demyelination, a zebrafish model of chemotherapy-induced demyelination was established. The results showed that 100 µg mL-1 of ATSO reversed tail morphology damage, axon degeneration, touch response delay, ROS level upregulation and the expression of myelin basic protein decrease in chemotherapy-induced zebrafish. In addition, the expression of myelin markers (including sox10, krox20, and pmp22) in oxaliplatin-induced cells was markedly reversed by ATSO and its active components (gondoic acid, erucic acid, and nervonic acid). ATSO and its active components could reverse demyelination by ameliorating mitochondrial dysfunction. Conversely, linoleic acid and linolenic acid promoted demyelination by exacerbating mitochondrial dysfunction. Moreover, the Pink1/Parkin pathway was recognized as the main reason for ATSO and its active components improving mitochondrial function by activating mitophagy and restoring autophagic flow. Taken together, this study demonstrated that ATSO and its active components could be further developed as novel functional food ingredients to antagonize demyelination.

Long-term exposure to fine particulate matter constituents and cognitive impairment among older adults: An 18-year Chinese nationwide cohort study.

BACKGROUND: Although growing evidence has shown independent links of long-term exposure to fine particulate matter (PM2.5) with cognitive impairment, the effects of its constituents remain unclear. This study aims to explore the associations of long-term exposure to ambient PM2.5 constituents' mixture with cognitive impairment in Chinese older adults, and to further identify the main contributor. METHODS: 15,274 adults ≥ 65 years old were recruited by the Chinese Longitudinal Healthy Longevity Study (CLHLS) and followed up through 7 waves during 2000-2018. Concentrations of ambient PM2.5 and its constituents (i.e., black carbon [BC], organic matter [OM], ammonium [NH4+], sulfate [SO42-], and nitrate [NO3-]) were estimated by satellite retrievals and machine learning models. Quantile-based g-computation model was employed to assess the joint effects of a mixture of 5 PM2.5 constituents and their relative contributions to cognitive impairment. Analyses stratified by age group, sex, residence (urban vs. rural), and region (north vs. south) were performed to identify vulnerable populations. RESULTS: During the average 3.03 follow-up visits (89,296.9 person-years), 4294 (28.1%) participants had developed cognitive impairment. The adjusted hazard ratio [HR] (95% confidence interval [CI]) for cognitive impairment for every quartile increase in mixture exposure to 5 PM2.5 constituents was 1.08 (1.05-1.11). BC held the largest index weight (0.69) in the positive direction in the qg-computation model, followed by OM (0.31). Subgroup analyses suggested stronger associations in younger old adults and rural residents. CONCLUSION: Long-term exposure to ambient PM2.5, particularly its constituents BC and OM, is associated with an elevated risk of cognitive impairment onset among Chinese older adults.

4,4-Dimethylsterols Reduces Fat Accumulation via Inhibiting Fatty Acid Amide Hydrolase In Vitro and In Vivo.

4,4-Dimethylsterols constitute a unique class of phytosterols responsible for regulating endogenous cannabinoid system (ECS) functions. However, precise mechanism through which 4,4-dimethylsterols affect fat metabolism and the linkage to the ECS remain unresolved. In this study, we identified that 4,4-dimethylsterols, distinct from 4-demethseterols, act as inhibitors of fatty acid amide hydrolases (FAAHs) both in vivo and in vitro. Genetic ablation of FAAHs (faah-1) abolishes the effects of 4,4-dimethylsterols on fat accumulation and locomotion behavior in a Caenorhabditis elegans model. We confirmed that dietary intervention with 4,4-dimethylsterols in a high-fat diet (HFD) mouse model leads to a significant reduction in body weight (>11.28%) with improved lipid profiles in the liver and adipose tissues and increased fecal triacylglycerol excretion. Untargeted and targeted metabolomics further verified that 4,4-dimethylsterols influence unsaturated fatty acid biosynthesis and elevate oleoyl ethanolamine levels in the intestine. We propose a potential molecular mechanism in which 4,4-dimethylsterols engage in binding interactions with the catalytic pocket (Ser241) of FAAH-1 protein due to the shielded polarity, arising from the presence of 2 additional methyl groups (CH3). Consequently, 4,4-dimethylsterols represent an unexplored class of beneficial phytosterols that coordinate with FAAH-1 activity to reduce fat accumulation, which offers new insight into intervention strategies for treating diet-induced obesity.

Impact of dietary n-6/n-3 fatty acid ratio of atherosclerosis risk: A review.

Atherosclerosis is a causative factor associated with cardiovascular disease (CVD). Over the past few decades, extensive research has been carried out on the relationship between the n-6/n-3 fatty acid ratio of ingested lipids and the progression of atherosclerosis. However, there are still many uncertainties regarding the precise nature of this relationship, which has led to challenges in providing sound dietary advice to the general public. There is therefore a pressing need to review our current understanding of the relationship between the dietary n-6/n-3 fatty acid ratio and atherosclerosis, and to summarize the underlying factors contributing to the current uncertainties. Initially, this article reviews the association between the n-6/n-3 fatty acid ratio and CVDs in different countries. A summary of the current understanding of the molecular mechanisms of n-6/n-3 fatty acid ratio on atherosclerosis is then given, including inflammatory responses, lipid metabolism, low-density lipoprotein cholesterol oxidation, and vascular function. Possible reasons behind the current controversies on the relationship between the n-6/n-3 fatty acid ratio and atherosclerosis are then provided, including the precise molecular structures of the fatty acids, diet-gene interactions, the role of fat-soluble phytochemicals, and the impact of other nutritional factors. An important objective of this article is to highlight areas where further research is needed to clarify the role of n-6/n-3 fatty acid ratio on atherosclerosis.