Nitrogen Doping-Roused Synergistic Active Sites in Perovskite Enabling Highly Selective CO2 Photoreduction into CH4.

The intricate protonation process in carbon dioxide reduction usually makes the product unpredictable. Thus, it is significant to control the reactive intermediates to manipulate the reaction steps. Here, we propose that the synergistic La-Ti active sites in the N-La2Ti2O7 nanosheets enable the highly selective carbon dioxide photoreduction into methane. In the photoreduction of CO2 over N-La2Ti2O7 nanosheets, in situ Fourier transform infrared spectra are utilized to monitor the *CH3O intermediate, pivotal for methane production, whereas such monitoring is not conducted for La2Ti2O7 nanosheets. Also, theoretical calculations testify to the increased charge densities on the Ti and La atoms and the regulated formation energy barrier of *CO and *CH3O intermediates by the constructed synergistic active sites. Accordingly, the methane formation rate of 7.97 µL h-1 exhibited by the N-La2Ti2O7 nanosheets, along with an electron selectivity of 96.6%, exceeds that of most previously reported catalysts under similar conditions.

Oral and oropharyngeal NUT carcinoma: a multicentre screening study of poorly differentiated oral cancer.

BACKGROUND AND AIMS: Nuclear protein testis (NUT) carcinoma (NC) is a rare and highly aggressive tumour characterised by chromosomal rearrangement of the nuclear protein testis family member 1 (NUTM1) gene, also known as the NUT gene. NC occurs mainly in the head and neck, mediastinum and lung. In general, primary NC in the oral cavity is extremely rare and reported sporadically. METHODS: A total of 111 formalin-fixed and paraffin-embedded specimens of poorly differentiated oral and oropharyngeal tumours were collected from 10 hospitals. NUT protein IHC staining was performed on these samples, and fluorescence in-situ hybridisation (FISH) and RNA sequencing detection were further carried out for NUT IHC-positive cases. RESULTS: The expression of NUT protein in tumour cells was detected in five cases (five of 111, 4.5%). The tumours in these cases were located in the oral floor, lip, base of the tongue, gingiva and hard palate. FISH detection results showed BRD4::NUT rearrangement in three patients and a non-BRD4::NUT rearrangement pattern in two patients. RNA sequencing results confirmed BRD4::NUT rearrangement in two cases. CONCLUSIONS: To our knowledge, this is the first and largest retrospective study of oral NC, and we found that NC is easily misdiagnosed as poorly differentiated oral squamous cell carcinoma (SCC) or poorly differentiated carcinoma. The morphology and immunophenotype of four NC cases were similar to SCC, and abrupt keratinisation was observed in three cases. Therefore, it is necessary to detect NUT protein for NC screening in oral malignant tumours with these morphologies, especially for young patients who are more likely to be misdiagnosed with other types of cancer.

Construction of ceRNA Networks at Different Stages of Somatic Embryogenesis in Garlic.

LncRNA (long non-coding RNA) and mRNA form a competitive endogenous RNA (ceRNA) network by competitively binding to common miRNAs. This network regulates various processes of plant growth and development at the post-transcriptional level. Somatic embryogenesis is an effective means of plant virus-free rapid propagation, germplasm conservation, and genetic improvement, which is also a typical process to study the ceRNA regulatory network during cell development. Garlic is a typical asexual reproductive vegetable. Somatic cell culture is an effective means of virus-free rapid propagation in garlic. However, the ceRNA regulatory network of somatic embryogenesis remains unclear in garlic. In order to clarify the regulatory role of the ceRNA network in garlic somatic embryogenesis, we constructed lncRNA and miRNA libraries of four important stages (explant stage: EX; callus stage: AC; embryogenic callus stage: EC; globular embryo stage: GE) in the somatic embryogenesis of garlic. It was found that 44 lncRNAs could be used as precursors of 34 miRNAs, 1511 lncRNAs were predicted to be potential targets of 144 miRNAs, and 45 lncRNAs could be used as eTMs of 29 miRNAs. By constructing a ceRNA network with miRNA as the core, 144 miRNAs may bind to 1511 lncRNAs and 12,208 mRNAs. In the DE lncRNA-DE miRNA-DE mRNA network of adjacent stages of somatic embryo development (EX-VS-CA, CA-VS-EC, EC-VS-GE), by KEGG enrichment of adjacent stage DE mRNA, plant hormone signal transduction, butyric acid metabolism, and C5-branched dibasic acid metabolism were significantly enriched during somatic embryogenesis. Since plant hormones play an important role in somatic embryogenesis, further analysis of plant hormone signal transduction pathways revealed that the auxin pathway-related ceRNA network (lncRNAs-miR393s-TIR) may play a role in the whole stage of somatic embryogenesis. Further verification by RT-qPCR revealed that the lncRNA125175-miR393h-TIR2 network plays a major role in the network and may affect the occurrence of somatic embryos by regulating the auxin signaling pathway and changing the sensitivity of cells to auxin. Our results lay the foundation for studying the role of the ceRNA network in the somatic embryogenesis of garlic.

Zwitterionic Modification of Polyethyleneimine for Efficient In Vitro siRNA Delivery.

Polyethylenimine (PEI) has been widely used in gene delivery. However, its high cytotoxicity and undesired non-specific protein adsorption hinder the overall delivery efficacy and the practical applications of PEI-based gene delivery systems. In this study, we prepared hydrophobically modified PEIs (H-PEIs) via the reaction of octanal with 40% of primary amines in PEI25k and PEI10k, respectively. Two common zwitterionic molecules, 1,3-propanesultone and ß-propiolactone, were then used for the modification of the resulting H-PEIs to construct polycationic gene carriers with zwitterionic properties (H-zPEIs). The siRNA delivery efficiency and cytotoxicity of these materials were evaluated in Hela-Luc and A549-Luc cell lines. Compared with their respective parental H-PEIs, different degrees of zwitterionic modification showed different effects in reducing cytotoxicity and delivery efficiency. All zwitterion-modified PEIs showed excellent siRNA binding capacity, reduced nonspecific protein adsorption, and enhanced stability upon nuclease degradation. It is concluded that zwitterionic molecular modification is an effective method to construct efficient vectors by preventing undesired interactions between polycationic carriers and biomacromolecules. It may offer insights into the modification of other cationic carriers of nucleic acid drugs.

Effects of Wood Flour (WF) Pretreatment and the Addition of a Toughening Agent on the Properties of FDM 3D-Printed WF/Poly(lactic acid) Biocomposites.

In order to improve the properties of wood flour (WF)/poly(lactic acid) (PLA) 3D-printed composites, WF was treated with a silane coupling agent (KH550) and acetic anhydride (Ac2O), respectively. The effects of WF modification and the addition of acrylicester resin (ACR) as a toughening agent on the flowability of WF/PLA composite filament and the mechanical, thermal, dynamic mechanical thermal and water absorption properties of fused deposition modeling (FDM) 3D-printed WF/PLA specimens were investigated. The results indicated that the melt index (MI) of the specimens decreased after WF pretreatment or the addition of ACR, while the die swell ratio increased; KH550-modified WF/PLA had greater tensile strength, tensile modulus and impact strength, while Ac2O-modified WF/PLA had greater tensile modulus, flexural strength, flexural modulus and impact strength than unmodified WF/PLA; after the addition of ACR, all the strengths and moduli of WF/PLA could be improved; after WF pretreatment or the addition of ACR, the thermal decomposition temperature, storage modulus and glass transition temperature of WF/PLA were all increased, and water absorption was reduced.

Synergy between peroxisome proliferator-activated receptor γ agonist and radiotherapy in cancer.

Angiogenesis and inflammation are crucial processes through which the tumor microenvironment (TME) influences tumor progression. In this study, we showed that peroxisome proliferator-activated receptor γ (PPARγ) is not only expressed in CT26 and 4T1 tumor cell lines but also in cells of TME, including endothelial cells and tumor-associated macrophages (TAM). In addition, we showed that rosiglitazone may induce tumor vessel normalization and reduce TAM infiltration. Additionally, 4T1 and CT26 tumor-bearing mice treated with rosiglitazone in combination with radiotherapy showed a significant reduction in lesion size and lung metastasis. We reported that a single dose of 12 Gy irradiation strongly inhibits local tumor angiogenesis. Secretion of C-C motif chemokine ligand 2 (CCL2) in response to local irradiation facilitates the recruitment of migrating CD11b+ myeloid monocytes and TAM to irradiated sites that initiate vasculogenesis and enable tumor recurrence after radiotherapy. We found that rosiglitazone partially decreases CCL2 secretion by tumor cells and reduces the infiltration of CD11b+ myeloid monocytes and TAM to irradiated tumors, thereby delaying tumor regrowth after radiotherapy. Therefore, combination of the PPARγ agonist rosiglitazone with radiotherapy enhances the effectiveness of radiotherapy to improve local tumor control, decrease distant metastasis risks and delay tumor recurrence.

Prevention of acute liver injury by suppressing plasma kallikrein-dependent activation of latent TGF-ß.

Acute liver injury (ALI) is highly lethal acute liver failure caused by different etiologies. Transforming growth factor ß (TGF-ß) is a multifunctional cytokine and a well-recognized inducer of apoptotic and necrotic cell death in hepatocytes. Latent TGF-ß is activated partly through proteolytic cleavage by a serine protease plasma kallikrein (PLK) between the R58 and L59 residues of its propeptide region. Recently, we developed a specific monoclonal antibody to detect the N-terminal side LAP degradation products ending at residue R58 (R58 LAP-DPs) that reflect PLK-dependent TGF-ß activation. This study aimed to explore the potential roles of PLK-dependent TGF-ß activation in the pathogenesis of ALI. We established a mouse ALI model via the injection of anti-Fas antibodies (Jo2) and observed increases in the TGF-ß1 mRNA level, Smad3 phosphorylation, TUNEL-positive apoptotic hepatocytes and R58-positive cells in the liver tissues of Jo2-treated mice. The R58 LAP-DPs were observed in/around F4/80-positive macrophages, while macrophage depletion with clodronate liposomes partly alleviated the Jo2-induced liver injury. Blocking PLK-dependent TGF-ß activation using either the serine proteinase inhibitor FOY305 or the selective PLK inhibitor PKSI-527 or blocking the TGF-ß receptor-mediated signaling pathway using SB431542 significantly prevented Jo2-induced hepatic apoptosis and mortality. Furthermore, similar phenomena were observed in the mouse model of ALI with the administration of acetaminophen (APAP). In summary, R58 LAP-DPs reflecting PLK-dependent TGF-ß activation may serve as a biomarker for ALI, and targeting PLK-dependent TGF-ß activation has potential as a therapeutic strategy for ALI.

Quality of life changes in patients undergoing treatment for hepatocellular carcinoma.

PURPOSE: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. One of the primary treatment goals for incurable advanced cases is to prolong quality of life (QoL). Thus, to determine which HCC therapies may be linked to a more favorable QoL, we assessed the association between QoL changes and different treatments in HCC patients. METHODS: We analyzed a non-randomized multicenter longitudinal study, which included 171 patients treated with surgery (n = 53), ablation (n = 53) or embolization (n = 65) from seven centers: four Asian and three European sites. All participants completed the EORTC QLQ-C30 and QLQ-HCC18 questionnaires before and after treatment. Propensity scores were calculated and used in addition to race for adjustment in the logistic regression model to account for the confounding effects of patient characteristics including age, gender, race, employment, living with family, at least one comorbid condition, years since diagnosis, prior treatment history, BCLC stage, Child-Pugh grade, cirrhosis, bilirubin levels and QoL score before treatment. RESULTS: After adjustment for confounders, patients tended to have higher odds of QoL deterioration when treated with ablation versus embolization (dyspnea: p = 0.019; appetite loss: p = 0.018; body image: p = 0.035) or ablation versus surgery (dyspnea: p = 0.099; appetite loss: p = 0.100; body image: p = 0.038). CONCLUSIONS: There were significant differences in QoL deterioration across different treatment groups. This information may assist patients and providers when selecting patient-centered treatment approaches for HCC.

Corrigendum: Neurovascular crosstalk and cerebrovascular alterations: an underestimated therapeutic target in autism spectrum disorders.

[This corrects the article DOI: 10.3389/fncel.2023.1226580.].

Affect and stress detection based on feature fusion of LSTM and 1DCNN.

The impact of emotions on health, especially stress, is receiving increasing attention. It is important to provide a non-invasive affect detection system that can be continuously monitored for a long period of time. Multi-sensor fusion strategies can better improve the performance of affect detection models, but there are also problems such as insufficient feature extraction and poor spatiotemporal feature fusion. Therefore, this study proposes a feature-level fusion method based on long short-term memory and one-dimensional convolutional neural network to extract temporal and spatial features of electrocardiogram, electromyogram, electrical activity, temperature, accelerator and response data, respectively, and then fuse them in a summation fashion for affect and stress detection. In particular, we added the tanh activation function before feature fusion, which can improve the model's performance. We used the wearable affect and stress detection dataset to train the model, which includes three different emotion states (neutral, stress, and amusement) for three-class emotion classification with accuracy and F1-scores of 87.82% and 86.68%, respectively. Due to the importance of stress, we also studied binary classification for stress detection, where neutral and amusement were combined as non-stress, with accuracy and F1-scores of 94.9% and 94.98%, respectively. The performance of the proposed model outperforms other control models and can effectively improve the performance of affect and stress detection, and promote medical care, health care and elderly care.

Mutational analysis of pulmonary large cell neuroendocrine carcinoma: APC gene mutations identify a good prognostic factor.

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a highly aggressive neoplasm with biological heterogeneity. Mutations in multiple genes have been identified in LCNEC. However, associations between gene alterations, histopathological characteristics, and prognosis remain ambiguous. Here, we investigated the clinicopathologic, immunohistochemical, and genomic characteristics of 19 patients with LCNEC and 9 patients with atypical carcinoid (AC). We revealed high mutation frequencies of TP53 (89.5 %), RB1 (42.1 %), APC (31.6 %), and MCL1 (31.6 %) in LCNEC, while genetic alterations were rarely found in AC. APC alterations mainly occurred to the exon 16 and were only identified in LCNEC with wild-type RB1. The 19 LCNEC were further subgrouped into APC wild-type (LCNEC-APCMT, 6/19) and APC-mutated (LCNEC-APCWT, 13/19) subgroups. In comparison with LCNEC-APCWT, LCNEC-APCMT displayed lower TMB (median: 12.64 vs 4.20, P = 0.045), and relatively mild cytologic atypia. In addition, LCNEC-APCMT distinguished itself from AC and LCNEC-APCWT by obviously downregulated expression of neuroendocrine markers (CD56 and Syn, P < 0.01) and significantly altered expression of genes downstream of APC (ß-catenin migrating into the cytoplasm and nucleus, P < 0.001; c-Myc upregulating, P = 0.005). The OS of LCNEC-APCMT was numerically intermediate between AC and LCNEC-APCWT. We first proposed that APC alterations were common in LCNEC with wild-type RB1 and that LCNEC-APCMT was associated with lower TMB and better OS in comparison with LCNEC-APCWT.

Functional Covalent Organic Frameworks' Microspheres Synthesized by Self-Limited Dynamic Linker Exchange for Stationary Phases.

Synthesizing uniform functional covalent organic framework (COF) microspheres is the prerequisite of applying COFs as novel stationary phases for liquid chromatography. However, the synthesis of functionalized COF microspheres is challenging due to the difficulty in maintaining microspheric morphology when conferring functions. Here, a facile and universal "self-limited dynamic linker exchange" strategy is developed to achieve surface functionalization of uniform COF microspheres. Six different types of COF microspheres are constructed, showing the universality and superiority of the strategy. The library of COF microspheres' stationary phases can be further enriched on demand by varying different functional building blocks. The "self-limited dynamic linker exchange" is attributed to the result of a delicate balance of reaction thermodynamics and molecular diffusion energy barrier. As a demonstration, the chiral functional COF microspheres are used as stationary phases of chiral chromatography and realized effective enantioseparation.

Confined CO in a sandwich structure promotes C-C coupling in electrocatalytic CO2 reduction.

Microenvironment regulation near the catalyst surface plays a critical role in heterogeneous electrocatalytic reactions. The local concentration of reactants and intermediates significantly affects the reaction kinetics and product selectivity. Herein, we propose an innovative strategy of utilizing the spatial confinement effect in a sandwich-structured C/Cu/C assembly to regulate kinetic mass transport during the electrocatalytic CO2 reduction reaction. The sandwich C/Cu/C assembly catalyst was successfully prepared using a simple bidirectional freezing and freeze-drying method. The sandwich structure changes the free diffusion pathway of the CO intermediate within the sandwich interlayer and helps confine CO with locally increased CO concentration near the catalyst surface, which in turn promotes C-C coupling and thus improves the reaction activity and doubles the C2 product selectivity compared to its disordered mixture counterpart. This kinetics regulation in the sandwich structure may provide a new insight into the catalyst design and inspire the understanding of the structure-performance relationship in electrocatalysis.

Transcriptome sequencing of garlic reveals key genes related to the heat stress response.

With global warming, heat stress has become an important factor that seriously affects crop yield and quality. Therefore, understanding plant responses to heat stress is important for agricultural practice, but the molecular mechanism of high-temperature tolerance in garlic remains unclear. In this study, 'Xusuan No. 6' was used as the experimental material. After heat stress for 0 (CK), 2 and 24 h, transcriptome sequencing was used to screen metabolic pathways and differentially expressed genes (DEGs) closely related to heat stress and was further verified by quantitative real-time polymerase chain reaction (qRT-PCR). A total of 86,110 unigenes obtained from the raw transcriptome sequencing data were spliced. After 2 h of heat treatment, the expression levels of 8898 genes increased, and 3829 genes were decreased in leaves. After 24 h, the expression levels of 7167 genes were upregulated, and 3176 genes were downregulated. Gene Ontology enrichment analysis showed that DEGs were mainly enriched in seven categories: cellular processes, metabolic processes, binging, catalytic activity, cellular anatomical entity and protein-containing complex response to stimulus. Kyoto Encyclopedia of Genes and Genomes pathway enrichment showed that DEGs are involved in protein processing in the endoplasmic reticulum, plant hormone signal transduction, phenylpropanoid biosynthesis, and photosynthetic antenna proteins. Six genes were selected and further verified by qRT-PCR. In this study, the full-length transcriptome of garlic was constructed, and the regulatory genes related to the heat resistance of garlic were studied. Taken together, these findings can provide a theoretical basis for the cloning of heat resistance genes in garlic and for the analysis of heat resistance mechanisms.

Neurovascular crosstalk and cerebrovascular alterations: an underestimated therapeutic target in autism spectrum disorders.

Normal brain development, function, and aging critically depend on unique characteristics of the cerebrovascular system. Growing evidence indicated that cerebrovascular defects can have irreversible effects on the brain, and these defects have been implicated in various neurological disorders, including autism spectrum disorder (ASD). ASD is a neurodevelopmental disorder with heterogeneous clinical manifestations and anatomical changes. While extensive research has focused on the neural abnormalities underlying ASD, the role of brain vasculature in this disorder remains poorly understood. Indeed, the significance of cerebrovascular contributions to ASD has been consistently underestimated. In this work, we discuss the neurovascular crosstalk during embryonic development and highlight recent findings on cerebrovascular alterations in individuals with ASD. We also discuss the potential of vascular-based therapy for ASD. Collectively, these investigations demonstrate that ASD can be considered a neurovascular disease.

HLA-DRB1*14:54 Is Associated with Pulmonary Alveolar Proteinosis: A Retrospective Real-World Audit.

BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disease characterized by abnormal accumulation of pulmonary surfactant lipids in alveoli or terminal bronchioles, leading to increased infection risk and progressive respiratory failure. Approximately more than 90% of all cases are autoimmune PAP (aPAP). Since one of the predisposing factors has been identified as genes located within the major-histocompatibility-complex region, an investigation of human leukocyte antigen (HLA) alleles associated with the risk of aPAP is warranted. METHODS: We retrospectively studied 60 patients pathologically diagnosed with PAP from 2019 to 2022. Patients were divided into the aPAP group or secondary PAP (sPAP) group according to their clinical information. Qualified DNA was extracted from the paraffin-embedded tissue of 28 patients, and the PCR-sequence-based typing method was used for HLA-DRB1 genotyping. RESULTS: A similar HLA-DRB1 allele profile (including the HLA-DRB1*08:03) between the aPAP group and sPAP group was revealed, except that HLA-DRB1*14:54, which has never been reported in aPAP patients, was only detected in the aPAP group rather than the sPAP group (19.4% vs. 0.0%, p = 0.030). Under inhaled granulocyte-macrophage colony-stimulating factor therapy, more clinical remission was observed in HLA-DRB1*14:54 carriers rather than in HLA-DRB1*08:03 carriers (80.0% vs. 57.1%). CONCLUSIONS: Our real-world study revealed for the first time that a population with HLA-DRB1*14:54 was subject to aPAP, and HLA-DRB1*14:54 might imply a response in aPAP patients to inhaled granulocyte-macrophage colony-stimulating factor in aPAP patients.

Technical Issues of Vim-PSA Double-Target DBS for Essential Tremor.

BACKGROUND: Deep brain stimulation (DBS) is an effective surgical treatment for essential tremor (ET), with the ventral intermediate nucleus (Vim) and posterior subthalamic area (PSA) as the most common targets. The stimulation efficacy of ET with Vim-PSA double-target DBS has been reported. Herein, we aim to propose surgical techniques for Vim-PSA double-target DBS surgery. METHODS: This study enrolled six patients with ET who underwent Vim-PSA double-target electrode implantation from October 2019 to May 2022. The targets were located and adjusted using coordinates and multimodality MRI images. A burr hole was accurately drilled in line with the electrode trajectory under the guidance of a stereotactic frame. Novel approaches were adopted during the electrode implantation process for pneumocephalus reduction, including "arachnoid piamater welding" and "water sealing". Electrophysiological recording was used to identify the implantation sites of the electrodes. A 3D reconstruction model of electrodes and nuclei was established to facilitate programming. RESULTS: The combination of coordinates and multimodality MRI images for target location and adjustment enabled the alignment of Vim and PSA. Postoperative CT scanning showed that the electrode was precisely implanted. Stereotactic guidance facilitated accurate burr hole drilling. "Arachnoid piamater welding" and "water sealing" were efficient in reducing pneumocephalus. Intraoperative electrophysiological verified the efficacy of Vim-PSA double-target DBS surgery. CONCLUSIONS: The methods for target location and adjustment, accurate drilling of the burr hole, reduction in pneumocephalus, and intraoperative electrophysiological verification are key issues in DBS surgery targeting both the Vim and PSA. This study may provide technical support for Vim-PSA DBS, especially for surgeons with less experience in functional neurosurgery.

Trends in online searching toward suicide pre-, during, and post the first wave of COVID-19 outbreak in China.

COVID-19 may increase the risk of suicide, but the conclusion is still unclear. This study was designed to assess the impact of COVID-19 on suicide pre-, during, and post the first wave of COVID-19 in China. It was reported that online public searching was associated with their offline thoughts and behaviors. Therefore, this study was designed to explore the online search for suicide pre-, during, and post-COVID-19 in China. The keywords on suicide, COVID-19, unemployment, and depression were collected in 2019 and 2020 using the Baidu Search Index (BSI). A time-series analysis examined the dynamic correlations between BSI-COVID-19 and BSI-suicide. A generalized estimating equation model was used to calculate the coefficients of variables associated with the BSI-suicide. The BSI-suicide showed a significant increase (15.6%, p = 0.006) from the 5th to 9th week, which was also the point of the first wave of the COVID-19 outbreak. A time-series analysis between BSI-suicide and BSI-COVID-19 showed that the strongest correlation occurred at lag 1+ and lag 2+ week. In the pre-COVID-19 model, only BSI-depression was highly associated with BSI-suicide (ß = 1.38, p = 0.008). During the COVID-19 model, BSI-depression (ß = 1.77, p = 0.040) and BSI-COVID-19 (ß = 0.03, p < 0.001) were significantly associated with BSI-suicide. In the post-COVID-19 model, BSI depression (ß = 1.55, p = 0.010) was still highly associated with BSI-suicide. Meanwhile, BSI-unemployment (ß = 1.67, p = 0.007) appeared to be linked to BSI-suicide for the first time. There was a surge in suicide-related online searching during the early stage of the first wave of the COVID-19 outbreak. Online suicide search volume peaked 1-2 weeks after the COVID-19 peak. The BSI of factors associated with suicide varied at different stages of the COVID-19 pandemic. The findings in this study are preliminary and further research is needed to arrive at evidence of causality.

Ferulic Acid Prevents Nonalcoholic Fatty Liver Disease by Promoting Fatty Acid Oxidation and Energy Expenditure in C57BL/6 Mice Fed a High-Fat Diet.

There is a consensus that ferulic acid (FA), the most prominent phenolic acid in whole grains, displays a protective effect in non-alcoholic fatty liver disease (NAFLD), though its underlying mechanism not fully elucidated. This study aimed to investigate the protective effect of FA on high-fat diet (HFD)-induced NAFLD in mice and its potential mechanism. C57BL/6 mice were divided into the control diet (CON) group, the HFD group, and the treatment (HFD+FA) group, fed with an HFD and FA (100 mg/kg/day) by oral gavage for 12 weeks. Hematoxylin and eosin (H&E) staining and Oil Red O staining were used to evaluate liver tissue pathological changes and lipid accumulation respectively. It was demonstrated that FA supplementation prevented HFD-induced NAFLD, which was evidenced by the decreased accumulation of lipid and hepatic steatosis in the HFD+FA group. Specifically, FA supplementation decreased hepatic triacylglycerol (TG) content by 33.5% (p < 0.01). Metabolic cage studies reveal that FA-treated mice have elevated energy expenditure by 11.5% during dark phases. Mechanistically, FA treatment increases the expression of rate-limiting enzymes of fatty acid oxidation and ketone body biosynthesis CPT1A, ACOX1 and HMGCS2, which are the peroxisome proliferator-activated receptors α (PPARα) targets in liver. In conclusion, FA could effectively prevent HFD-induced NAFLD possibly by activating PPARα to increase energy expenditure and decrease the accumulation of triacylglycerol in the liver.