Flavor of extruded meat analogs: A review on composition, influencing factors, and analytical techniques.

Meat analogs are anticipated to alleviate environmental and animal welfare concerns as the demand for meat rises. High moisture extrusion is commonly employed to produce meat analogs, and its flavor could influence consumers' choice. To improve the development and market demand of extruded meat analogs, flavor precursors and natural spices have been used in high moisture extrusion process to directly improve the flavor profile of extruded meat analogs. Although there have been many studies on the flavor of high moisture extruded meat analogs, flavor composition and influencing factors have not been summarized. Thus, this review systematically provides the main pleasant and unpleasant flavor-active substances with 79 compounds, as well as descriptive the influence of flavor-active compounds, chemical reactions (such as lipid oxidation and the Maillard reaction), and fiber structure formation (based on extrusion process, extrusion parameters, and raw materials) on flavor of extruded meat analogs. Flavor evaluation of extruded meat analogs will toward multiple assessment methods to fully and directly characterize the flavor of extruded meat analogs, especially machine learning techniques may help to predict and regulate the flavor characteristics of extruded meat analogs.

Gas-Solid Flow Characteristics of Airflow and Dust Particles in Blasting Excavation of Underground Metal Mine Tunnels.

Effective dust removal has long been a challenge in the blasting mining of underground metal mine tunnels, and uncontrolled dust diffusion seriously endangers workers' respiratory systems and the underground space safety environment. However, the vast majority of existing numerical studies on dust diffusion are focused on coal mine fully mechanized mining, which is different from metal mine blasting excavation in terms of stope structure and dust properties. Furthermore, the mechanism by which the forced and exhaust ventilation modes affect the diffusion characteristics of inhalable particles is unclear. In this work, gas-solid flow characteristics for dust diffusion in a typical metal mine blasting tunnel were numerically investigated based on the Euler-Lagrange method, where the blasting face instantly released 6.37 × 107 particles with 100 different sizes, ranging from 0.8 to 200 µm. The interphase forces between airflow and dust particles are comprehensively modeled, and the particle diffusion effect caused by fluid turbulence is described by a discrete random walk model. Detailed information for airflow turbulence and particle migration was revealed, and dust removal efficiencies for inhalable particulate matter (PM10) by forced, exhaust, and hybrid ventilation were analyzed. Numerical results predict a complex airflow pattern in the working roadway, including the jet-flow region, return airflow core region, airflow disorder region, and secondary flow region. Dust diffusion temporal characteristics can be divided into three stages, namely, the initial stage of dust generation, the efficient ventilation and dust removal stage, and the later stage of dust diffusion. Dust diffusion spatial characteristics indicate that under the Coanda wall attachment effect, the dust concentration exhibits nonuniform distribution in both vertical and horizontal directions of the return air roadway. The dust removal efficiency of hybrid ventilation on inhalable particles above respiratory height is better than that of forced ventilation, especially in the return air roadway. The additional exhaust air duct based on forced ventilation can discharge more inhalable particles from the tunnel.

Arterial transit artifacts and carotid Plaque-RADS may predict symptoms in patients with carotid stenosis.

AIM: To analyze the correlation of carotid stenosis severity, the Plaque Reporting and Data System (RADS) score, arterial transit artifacts (ATAs), and cerebral blood flow (CBF) with clinical cerebral ischemic symptoms in patients with carotid artery stenosis (CAS). MATERIALS AND METHODS: Sixty-one patients with unilateral internal carotid artery stenosis or occlusion (≥50% stenosis) diagnosed by ultrasound, Computed Tomography(CT) angiography, or Magnetic Resonance(MR) angiography in Yichang City Central People's Hospital from January 2022 to February 2024 were retrospectively enrolled and divided into two groups according to the presence or absence of symptoms. Both groups underwent MR plaque imaging and arterial spin labeling (ASL)-based 3.0 T MRI to compare the differences in stenosis degree, Plaque-RADS score, ATA grade, and CBF between the two groups. Binary regression analysis was used to identify the parameters with statistically significant differences between the two groups and to evaluate their diagnostic efficacy using the area under the workup curve of the subjects. RESULTS: The Plaque-RADS score, ATA grade, and CBF differences in the anterior cerebral artery(ACA)blood supply region were correlated with symptoms, and the areas under the ROC curves for the CBF differences in the ACA blood supply region, Plaque-RADS score, ATA grade and a joint model that combines all three to predict symptoms in CAS patients were 0.672, 0.796, 0.788 and 0.919, respectively. CONCLUSIONS: CBF, Plaque-RADS and ATAs were identified as independent risk factors for symptoms in patients with CAS and have a certain predictive value for symptoms, and the combined predictive value is greater, potentially providing a more effective imaging modality for clinical treatment and evaluation.

Genome-wide association study reveals the candidate genes of humerus quality in laying duck.

Bone plays a crucial role in poultry's health and production. However, during the selection and cage farming, there has been a decline in bone quality. As the development of breeding theory, researchers find that it's possible to enhance bone quality through selective breeding.This study measure 8 humerus quality in 260 samples of the 350-day-old female duck. By descripting the basic characteristic traits, mechanical property traits we found that all the bone quality traits had a large variable coefficient, especially mechanical properties trait (20-70%), indicating that there was a large difference in bone health status among laying ducks. The phenotypic correlations showed a high correlation between weight and density, diameter and perimeter, breaking and toughness (r = 0.52-0.68). And then, we performed the Genome-wide association study (GWAS) to reveal the candidate genes of humerus quality in ducks. Seven candidate protein-coding genes were identified with perimeter trait, and 52 protein-coding genes were associated with toughness trait. We also analysed the candidate region and performed KEGG and GO analyse for 75 candidate genes. Furthermore, the expression analyse of the above candidate genes in different stage of humerus and different tissues were performed. Finally, AP2A2, SMAD3, SMNDC1, NFIA, EPHB2, PMEPA1, UNC5C, ESR1, VAV3, NFATC2 deserve further focus. The obtained results can contribute to new insight into bone quality and provide new genetic biomarkers for application in duck breeding programs.

Exosomal LRG1 promotes non-small cell lung cancer proliferation and metastasis by binding FN1 protein.

Leucine-rich α2-glycoprotein-1 (LRG1) is overexpressed in various cancers, including non-small cell lung cancer (NSCLC), but its role in NSCLC cell metastasis is not well understood. In this study, NSCLC cell exosomes were analyzed using different techniques, and the impact of exosomal LRG1 on NSCLC cell behavior was investigated through various assays both in vitro and in vivo. The study revealed that LRG1, found abundantly in NSCLC cells and exosomes, enhanced cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Exosomal LRG1 was shown to promote NSCLC cell metastasis in animal models. Additionally, the interaction between LRG1 and fibronectin 1 (FN1) in the cytoplasm was identified. It was observed that FN1 could counteract the effects of LRG1 knockdown on cell regulation induced by exosomes derived from NSCLC cells. Overall, the findings suggest that targeting exosomal LRG1 or FN1 may hold therapeutic potential for treating NSCLC.

Improvement of physicochemical properties and quercetin delivery ability of fermentation-induced soy protein isolate emulsion gel processed by ultrasound.

This study aimed to investigate the effects of ultrasonic treatment at different powers on the physicochemical properties, microstructure and quercetin delivery capacity of fermentation-induced soy protein isolate emulsion gel (FSEG). The FSEG was prepared by subjecting soy protein isolate (SPI) emulsion to ultrasonic treatment at various powers (0, 100, 200, 300, and 400 W), followed by lactic acid bacteria fermentation. Compared with the control group (0 W), the FSEG treated with ultrasound had higher hardness, water holding capacity (WHC) and rheological parameters. Particularly, at an ultrasonic power of 300 W, the FSEG had the highest hardness (101.69 ± 4.67 g) and WHC (75.20 ± 1.07%) (p < 0.05). Analysis of frequency sweep and strain scanning revealed that the storage modulus (G') and yield strains of FSEG increased after 300 W ultrasonic treatment. Additionally, the recovery rate after creep recovery test significantly increased from 18.70 ± 0.49% (0 W) to 58.05 ± 0.54% (300 W) (p < 0.05). Ultrasound treatment also resulted in an increased ß-sheet content and the formation of a more compact micro-network structure. This led to a more uniform distribution of oil droplets and reduced mobility of water within the gel. Moreover, ultrasonic treatment significantly enhanced the encapsulation efficiency of quercetin in FSEG from 81.25 ± 0.62 % (0 W) to 90.04 ± 1.54% (300 W). The bioaccessibility of quercetin also increased significantly from 28.90 ± 0.40% (0 W) to 42.58 ± 1.60% (300 W) (p < 0.05). This study enriches the induction method of soy protein emulsion gels and provides some references for the preparation of fermented emulsion gels loaded with active substances.

Spleen derived Monocytes Regulate Pulmonary Vascular Permeability in Hepatopulmonary Syndrome through the OSM-FGF/FGFR1 Signaling.

Hepatopulmonary syndrome (HPS) is a serious pulmonary complication in the advanced stage of liver disease. The occurrence of pulmonary edema in HPS patients is life-threatening. Increased pulmonary vascular permeability is an important mechanism leading to pulmonary edema, and endothelial glycocalyx (EG) is a barrier that maintains stable vascular permeability. However, in HPS, whether the pulmonary vascular EG changes and its regulatory mechanism are still unclear. Spleen derived monocytes are involved in the pathogenesis of HPS. However, whether they regulate the pulmonary vascular permeability in HPS patients or rats and what is the mechanism is still unclear. Healthy volunteers and HPS patients with splenectomy or not were enrolled in this study. We found that the respiration of HPS patients was significantly improved in response to splenectomy, while the endothelial glycocalyx (EG) degradation and pulmonary edema were aggravated. In addition, HPS patients expressed higher levels of oncostatin M (OSM) and fibroblast growth factor (FGF). Subsequently, the co-culture system of monocytes and human umbilical vein endothelial cells (HUVECs) was constructed. It was found that monocytes secreted OSM and activated the FGF/FGFR1 signaling pathway in HUVECs. Then, an HPS rat model was constructed by common bile duct ligation (CBDL) for in vivo verification. HPS rats were intravenously injected with OSM recombinant protein and/or TNF-α into the rats via tail vein 30 min before CBDL. The results showed that the respiration of HPS rats was improved after splenectomy, while the degradation of EG in pulmonary vessels and vascular permeability were increased, and pulmonary edema was aggravated. Moreover, the expression of OSM and FGF was upregulated in HPS rats, while both were downregulated after splenectomy. Intravenous injection of exogenous OSM eliminated the effect of splenectomy on FGF and improved EG degradation. It can be seen that during HPS, spleen-derived monocytes secrete OSM to promote pulmonary vascular EG remodeling by activating the FGF/FGFR1 pathway, thereby maintaining stable vascular permeability, and diminishing pulmonary edema. This study provides a promising therapeutic target for the treatment of HPS.

The utilization of a data fusion approach to investigate fingerprint profiles of dark tea from China's different altitudes.

Dark tea refers to a kind of post-fermented product, and its quality and price vary owing to the distinct altitudes at which it grows. In this study, a novel method based on high performance liquid chromatography with a diode-array detector (HPLC-DAD) and an evaporative light scattering detector (HPLC-ELSD) was proposed for the classification of dark teas from distinct altitudes in China. Through implementing a strategy fusing feature-level data to construct a combined dataset, the classification performance of dark teas from distinct altitudes in China was evaluated after preprocessing. The results suggested that, through the feature fusion strategy, the identification accuracy rate increased from <70% of a single detector to 76.923%. After the implementation of preprocessing, the identification accuracy rate was further improved. Typically, the model identification accuracy rate after short-time Fourier Transform (STFT) treatment reached 92.85%, and the AUROC value was higher than 0.84, exhibiting a favorable generalization ability. This study provides a new thinking for the identification technology of dark teas from different altitudes in China.

PFKFB3 controls acinar IP3R-mediated Ca2+ overload to regulate acute pancreatitis severity.

Acute Pancreatitis (AP) is among the most common hospital gastrointestinal diagnosis; understanding the mechanisms underlying the severity of AP are critical for development of new treatment options for this disease. Here, we evaluate the biological function of phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) in AP pathogenesis in two independent genetically engineered mouse models of AP. PFKFB3 is elevated in AP and severe AP (SAP) and knockout of Pfkfb3 abrogates the severity of alcoholic SAP (FAEE-SAP). Using a combination of genetic, pharmacological, and molecular studies we define the interaction of PFKFB3 with inositol 1,4,5-trisphosphate receptor (IP3R) as a key event mediating this phenomenon. Further analysis demonstrated that the interaction between PFKFB3 and IP3R promotes FAEE-SAP severity by altering intracellular calcium homeostasis in acinar cells. Together our results support a PFKFB3-driven mechanism controlling AP pathobiology and define this enzyme as a therapeutic target to ameliorate the severity of this dismal condition.

Exosome is a Fancy Mobile Sower of Ferroptosis.

Exosomes, nano-sized small extracellular vesicles, have been shown to serve as mediators between intercellular communications by transferring bioactive molecules, such as non-coding RNA, proteins, and lipids from secretory to recipient cells, modulating a variety of physiological and pathophysiological processes. Recent studies have gradually demonstrated that altered exosome charges may represent a key mechanism driving the pathological process of ferroptosis. This review summarizes the potential mechanisms and signal pathways relevant to ferroptosis and then discusses the roles of exosome in ferroptosis. As well as transporting iron, exosomes may also indirectly convey factors related to ferroptosis. Furthermore, ferroptosis may be transmitted to adjacent cells through exosomes, resulting in cascading effects. It is expected that further research on exosomes will be conducted to explore their potential in ferroptosis and will lead to the creation of new therapeutic avenues for clinical diseases.

A Comparative Study of 2 Techniques to Avoid Bone Cement Loosening and Displacement After Percutaneous Vertebroplasty Treating Unstable Kummell Disease.

Objective: Percutaneous vertebroplasty (PVP) is currently the most common surgical procedure for unstable Kummell disease (KD), but bone cement loosening or displacement often occurs after the operation. We had been using percutaneous pediculoplasty (PPP) or a self-developed bone cement bridging screw system to avoid this severe complication. This study intends to compare the safety, advantages and disadvantages of these 2 novel surgical procedures through a 2-year follow-up evaluation. Methods: In accordance with the inclusion and exclusion criteria, from May 2017 to May 2021, 77 patients with single segmental unstable KD who had received the PVP-PPP combined therapy were included in the PPP group, and 42 patients with the same who had received the PVP-bone cement bridging screw system combined therapy were included in the screw group. All patients received the operation through unilateral approach. The changes in the vertebral body index (VBI), bisegmental Cobb angle, visual analogue scale (VAS) and Oswestry Disability Index (ODI) and the bone cement loosening rate and displacement rate at different follow-up time points were used to evaluate the clinical efficacy. Results: The average operation duration of the PPP group was 85.52±10.78 minutes (range, 70-115 minutes), and its average bone cement injection volume was 4.98±0.67 mL (range, 4-6 mL). The average operation duration of the screw group was 52.07±9.90 minutes (range, 36-65 minutes), and its average bone cement injection volume was 4.43±0.89 mL (range, 2.5-6 mL). Before operation, immediately after operation and at 6 months after operation, there was no significant difference in VBI or bisegmental Cobb angle between the screw group and the PPP group (p>0.05), while at 1-year and 2-year midterm postoperative evaluations, the screw group had higher VBI and bisegmental Cobb angle than the PPP group (p<0.05). Before operation, immediately after operation, at 6 months after operation and at 1 year after operation, there was no significant difference in VAS or ODI score between the screw group and the PPP group (p>0.05), while at 2 years after operation, the screw group still had higher VAS and ODI scores than the PPP group (p<0.05). No bone cement displacement occurred in both groups, but the rate of bone cement loosening was 14.29% in group PPP, and 0 in screw group (p<0.05). Conclusion: This 2-year follow-up study shows that the PVP-bone cement bridging screw system combined therapy had better midterm treatment efficacy than the PVP-PPP combined therapy in patients with unstable KD, and the bone cement bridging screw system is a preferred therapy with better anti cement loosening ability.

[Acupoint application for Hashimoto's thyroiditis with liver-qi stagnation: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy and safety of acupoint application for Hashimoto's thyroiditis (HT) with liver-qi stagnation. METHODS: One hundred and fifty patients of HT with liver-qi stagnation were randomly divided into an acupoint application group (75 cases, 11 cases were excluded, 5 cases dropped out) and a control group (75 cases, 12 cases excluded, 3 cases dropped out). Based on the health education combined with conventional western medicine treatment, the patients in the acupoint application group were treated with acupoint application, while the patients in the control group were treated with placebo acupoint application. Shenque (CV 8), bilateral Yongquan (KI 1), Yeshi, and ashi point were selected in both groups, with Yeshi treated once a week and the remaining acupoints treated every other day, for a total of 4 weeks. The serum levels of thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb), free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH), as well as the thickness of thyroid left lobe, right lobe, and isthmus, TCM symptom score, hospital anxiety and depression scale (HADS) score, and MOS 36-item short form health survey (SF-36) score were compared between the two groups before and after treatment. Adverse reactions in both groups were observed. RESULTS: Compared with before treatment, in the acupoint application group, the serum levels of TgAb and TPOAb were reduced after treatment (P<0.05), and the scores of role physical (RP), body pain (BP), vitality (VT), role emotional (RE), and mental health (MH) in SF-36 were increased after treatment (P<0.01, P<0.001). The thickness of the thyroid isthmus after treatment was smaller than that before treatment (P<0.05), and the TCM symptom scores and HADS anxiety (HADS-A) scores after treatment were lower than those before treatment (P<0.001, P<0.01) in both groups. In the control group, the scores of physical function (PF), RP, BP, VT, and RE in SF-36 after treatment were higher than those before treatment (P<0.05, P<0.01, P<0.001). There was no statistically significant difference in serum FT3, FT4, and TSH levels within the groups (P>0.05). There was no statistically significant difference in the above indexes between the two groups (P>0.05). The incidence of adverse reactions in the acupoint application group and the control group was 20.0% (15/75) and 10.7% (8/75) respectively, with skin allergy being the main adverse reaction. CONCLUSION: Acupoint application could reduce the serum levels of TgAb and TPOAb in patients of HT with liver-qi stagnation, alleviate thyroid enlargement, improve TCM symptoms and anxiety, and improve quality of life, with safe and reliable clinical efficacy.

Exendin-4 blockade of T1R2/T1R3 activation improves Pseudomonas aeruginosa-related pneumonia in an animal model of chemically induced diabetes.

OBJECTIVE: Poorly controlled diabetes frequently exacerbates lung infection, thereby complicating treatment strategies. Recent studies have shown that exendin-4 exhibits not only hypoglycemic but also anti-inflammatory properties. This study aimed to explore the role of exendin-4 in lung infection with diabetes, as well as its association with NOD1/NF-κB and the T1R2/T1R3 sweet taste receptor. METHODS: 16HBE human bronchial epithelial cells cultured with 20 mM glucose were stimulated with lipopolysaccharide (LPS) isolated from Pseudomonas aeruginosa (PA). Furthermore, Sprague‒Dawley rats were fed a high-fat diet, followed by intraperitoneal injection of streptozotocin and intratracheal instillation of PA. The levels of TNF-α, IL-1ß and IL-6 were evaluated using ELISAs and RT‒qPCR. The expression of T1R2, T1R3, NOD1 and NF-κB p65 was assayed using western blotting and immunofluorescence staining. Pathological changes in the lungs of the rats were observed using hematoxylin and eosin (H&E) staining. RESULTS: At the same dose of LPS, the 20 mM glucose group produced more proinflammatory cytokines (TNF-α, IL-1ß and IL-6) and had higher levels of T1R2, T1R3, NOD1 and NF-κB p65 than the normal control group (with 5.6 mM glucose). However, preintervention with exendin-4 significantly reduced the levels of the aforementioned proinflammatory cytokines and signaling molecules. Similarly, diabetic rats infected with PA exhibited increased levels of proinflammatory cytokines in their lungs and increased expression of T1R2, T1R3, NOD1 and NF-κB p65, and these effects were reversed by exendin-4. CONCLUSIONS: Diabetic hyperglycemia can exacerbate inflammation during lung infection, promote the increase in NOD1/NF-κB, and promote T1R2/T1R3. Exendin-4 can ameliorate PA-related pneumonia with diabetes and overexpression of NOD1/NF-κB. Additionally, exendin-4 suppresses T1R2/T1R3, potentially through its hypoglycemic effect or through a direct mechanism. The correlation between heightened expression of T1R2/T1R3 and an intensified inflammatory response in lung infection with diabetes requires further investigation.

Revealing the mechanism and function underlying pairwise temporal coupling in collective motion.

Coordinated motion in animal groups has predominantly been studied with a focus on spatial interactions, such as how individuals position and orient themselves relative to one another. Temporal aspects have, by contrast, received much less attention. Here, by studying pairwise interactions in juvenile zebrafish (Danio rerio)-including using immersive volumetric virtual reality (VR) with which we can directly test models of social interactions in situ-we reveal that there exists a rhythmic out-of-phase (i.e., an alternating) temporal coordination dynamic. We find that reciprocal (bi-directional) feedback is both necessary and sufficient to explain this emergent coupling. Beyond a mechanistic understanding, we find, both from VR experiments and analysis of freely swimming pairs, that temporal coordination considerably improves spatial responsiveness, such as to changes in the direction of motion of a partner. Our findings highlight the synergistic role of spatial and temporal coupling in facilitating effective communication between individuals on the move.

Harmonizing three-dimensional MRI using pseudo-warping field guided GAN.

In pursuit of cultivating automated models for magnetic resonance imaging (MRI) to aid in diagnostics, an escalating demand for extensive, multisite, and heterogeneous brain imaging datasets has emerged. This potentially introduces biased outcomes when directly applied for subsequent analysis. Researchers have endeavored to address this issue by pursuing the harmonization of MRIs. However, most existing image-based harmonization methods for MRI are tailored for 2D slices, which may introduce inter-slice variations when they are combined into a 3D volume. In this study, we aim to resolve inconsistencies between slices by introducing a pseudo-warping field. This field is created randomly and utilized to transform a slice into an artificially warped subsequent slice. The objective of this pseudo-warping field is to ensure that generators can consistently harmonize adjacent slices to another domain, without being affected by the varying content present in different slices. Furthermore, we construct unsupervised spatial and recycle loss to enhance the spatial accuracy and slice-wise consistency across the 3D images. The results demonstrate that our model effectively mitigates inter-slice variations and successfully preserves the anatomical details of the images during the harmonization process. Compared to generative harmonization models that employ 3D operators, our model exhibits greater computational efficiency and flexibility.

Nonuniform and pathway-specific laminar processing of spatial frequencies in the primary visual cortex of primates.

The neocortex comprises six cortical layers that play a crucial role in information processing; however, it remains unclear whether laminar processing is consistent across all regions within a single cortex. In this study, we demonstrate diverse laminar response patterns in the primary visual cortex (V1) of three male macaque monkeys when exposed to visual stimuli at different spatial frequencies (SFs). These response patterns can be categorized into two groups. One group exhibit suppressed responses in the output layers for all SFs, while the other type shows amplified responses specifically at high SFs. Further analysis suggests that both magnocellular (M) and parvocellular (P) pathways contribute to the suppressive effect through feedforward mechanisms, whereas amplification is specific to local recurrent mechanisms within the parvocellular pathway. These findings highlight the non-uniform distribution of neural mechanisms involved in laminar processing and emphasize how pathway-specific amplification selectively enhances representations of high-SF information in primate V1.

Targeting OXCT1-mediated ketone metabolism reprograms macrophages to promote antitumor immunity via CD8+ T cells in hepatocellular carcinoma.

BACKGROUND & AIMS: The liver is the main organ of ketogenesis, while ketones are mainly metabolized in peripheral tissues via the critical enzyme OXCT1. We previously found that ketolysis is reactivated in hepatocellular carcinoma (HCC) cells through OXCT1 expression to promote tumor progression; however, whether OXCT1 regulates antitumor immunity remains unclear. METHODS: To investigate the expression pattern of OXCT1 in hepatocellular carcinoma in vivo, we conducted multiplex immunohistochemistry (mIHC) experiments on human HCC specimens. To explore the role of OXCT1 in mouse hepatocellular carcinoma tumor-associated macrophages (TAMs), we generated LysMcreOXCT1f/f (OXCT1 conditional knockout in macrophages) mice. RESULTS: Here, we found that inhibiting OXCT1 expression in tumor-associated macrophages reduced CD8+ T-cell exhaustion through the succinate-H3K4me3-Arg1 axis. Initially, we found that OXCT1 was highly expressed in liver macrophages under steady state and that OXCT expression was further increased in TAMs. OXCT1 deficiency in macrophages suppressed tumor growth by reprogramming TAMs toward an antitumor phenotype, reducing CD8+ T-cell exhaustion and increasing CD8+ T-cell cytotoxicity. Mechanistically, high OXCT1 expression induced the accumulation of succinate, a byproduct of ketolysis, in TAMs, which promoted Arg1 transcription by increasing the H3K4 trimethylation (H3K4me3) level in the Arg1 promoter. In addition, Pimozide, an inhibitor of OXCT1, suppressed Arg1 expression as well as TAM polarization toward the protumor phenotype, leading to decreasing CD8+ T-cell exhaustion and deceleration of tumor growth. Finally, high expression of OXCT1 in macrophages was positively associated with poor survival in HCC patients. CONCLUSIONS: In conclusion, our results demonstrate that OXCT1 epigenetically suppresses antitumor immunity, suggesting that suppressing OXCT1 activity in TAMs is an effective approach for treating liver cancer. IMPACT AND IMPLICATIONS: The intricate metabolism of liver macrophages plays a critical role in shaping HCC progression and immune modulation. Targeting macrophage metabolism to counteract immune suppression presents a promising avenue for HCC. Here, we found that ketogenesis gene OXCT1 was highly expressed in tumor-associated macrophages and promoted tumor growth by reprogramming TAMs toward a protumor phenotype. And the strategic pharmacological intervention or genetic downregulation of OXCT1 in TAMs enhances the antitumor immunity and decelerated tumor growth. Our results suggest that suppressing OXCT1 activity in TAMs is an effective approach for treating liver cancer.

Genome-wide association analysis explores the genetic loci of amino acid content in duck's breast muscle.

BACKGROUND: Amino acids are the basic components of protein and an important index to evaluate meat quality. With the rapid development of genomics, candidate regions and genes affecting amino acid content in livestock and poultry have been gradually revealed. Hence, genome-wide association study (GWAS) can be used to screen candidate loci associated with amino acid content in duck meat. RESULT: In the current study, the content of 16 amino acids was detected in 358 duck breast muscles. The proportion of Glu to the total amino acid content was relatively high, and the proportion was 0.14. However, the proportion of Met content was relatively low, at just 0.03. By comparative analysis, significant differences were found between males and females in 3 amino acids, including Ser, Met, and Phe. In addition, 12 SNPs were significantly correlated with Pro content by GWAS analysis, and these SNPs were annotated by 7 protein-coding genes; 8 significant SNPs were associated with Tyr content, and these SNPs were annotated by 6 protein-coding genes. At the same time, linkage disequilibrium (LD) analysis was performed on these regions with significant signals. The results showed that three SNPs in the 55-56 Mbp region of chromosome 3 were highly correlated with the leader SNP (chr3:55526954) that affected Pro content (r2 > 0.6). Similarly, LD analysis showed that there were three SNPs in the 21.2-21.6 Mbp region of chromosome 13, which were highly correlated with leader SNP (chr13:21421661) (r2 > 0.6). Moreover, Through functional enrichment analysis of all candidate genes. The results of GO enrichment analysis showed that several significant GO items were associated with amino acid transport function, including amino acid transmembrane transport and glutamine transport. The results further indicate that these candidate genes are closely associated with amino acid transport. Among them, key candidate genes include SLC38A1. For KEGG enrichment analysis, CACNA2D3 and CACNA1D genes were covered by significant pathways. CONCLUSION: In this study, GWAS analysis found a total of 28 significant SNPs affecting amino acid content. Through gene annotation, a total of 20 candidate genes were screened. In addition, Through LD analysis and enrichment analysis, we considered that SERAC1, CACNA2D3 and SLC38A1 genes are important candidate genes affecting amino acid content in duck breast muscle.