Serological and molecular survey of Toxoplasma gondii infection and associated risk factors in urban cats in Kunming, Southwest China.

Toxoplasma gondii (T. gondii) is a worldwide zoonotic parasite that can infect almost warm-blood animals, including humans, which seriously affect the health of host. Cats are known to be the only definitive host of T. gondii and continuously excrete highly infectious oocysts. This parasite carried by the companion animals leads to a great public health risk. However, there is little information on epidemiology of T. gondii in urban cats in Kunming, Southwest China. In the present study, a total of 231 serum and fecal samples were collected in Kunming aera, and then seroprevalence of T. gondii IgG antibodies in serum and molecular investigation in feces were analyzed to elucidate T. gondii infection in urban cats. The results revealed that 168 of 231 cats (72.7%) were positive for T. gondii antibodies, and 1 of 74 cat feces (1.4%) also showed a positive PCR for T. gondii DNA. The positive fecal sample was sequenced and then phylogenetically analyzed, and the isolate of T. gondii in the present study was closely related to T. gondii strain CN. In addition, the food, water and age of cats were identified as the risk factor for seropositivity. Overall, our findings indicate the widespread occurrence of T. gondii infection in urban cats in Kunming, Southwest China and identify food, water and age are the risk factors associated with T. gondii infection, which can provide effective information for developing strategies to prevent and control this zoonosis.

Single-nucleus transcriptomics reveal cardiac cell type-specific diversification in metabolic disease transgenic pigs.

Cardiac damage is widely present in patients with metabolic diseases, but the exact pathophysiological mechanisms involved remain unclear. The porcine heart is an ideal material for cardiovascular research due to its similarities to the human heart. This study evaluated pathological features and performed single-nucleus RNA sequencing (snRNA-seq) on myocardial samples from both wild-type and metabolic disease-susceptible transgenic pigs (previously established). We found that transgenic pigs exhibited lipid metabolism disturbances and myocardial injury after a high-fat high-sucrose diet intervention. snRNA-seq reveals the cellular landscape of healthy and metabolically disturbed pig hearts and identifies the major cardiac cell populations affected by metabolic diseases. Within metabolic disorder hearts, metabolically active cardiomyocytes exhibited impaired function and reduced abundance. Moreover, massive numbers of reparative LYVE1+ macrophages were lost. Additionally, proinflammatory endothelial cells were activated with high expression of multiple proinflammatory cytokines. Our findings provide insights into the cellular mechanisms of metabolic disease-induced myocardial injury.

Mesoscopic ring element growth and deformation induced biofilm streamer evolution in microfluidic channels.

In a fluid environment, biofilms usually form and grow into streamers attached to solid surfaces. Existing research on single streamers studied their formation and failure modes. In the experiment on biofilm growth in a microfluidic channel, we found that rings composed of bacteria and an extracellular matrix are important elements on a mesoscopic scale. In the fluid environment, the failure of these ring elements causes damage to streamers. We simulated the growth and deformation of the ring structure in the micro-channel using multi-agent simulation and fluid-structure coupling of a porous elastic body. Based on this, we simulated the biofilm evolution involving multi-ring deformation, which provides a new length scale to study the biofilm streamer dynamics in fluid environments.

The mechanism of biofilm detachment in porous medium under flow field.

Biofilms are communities formed by bacteria adhering to surfaces, widely present in porous medium, and their growth can lead to clogging. Our experiment finds that under certain flow conditions, biofilms detach in pores and form a dynamically changing flow path. We define detachment that occurs far from the boundary of the flow path (with a distance greater than 200 µm) as internal detachment and detachment that occurs at the boundary of the flow path as external detachment. To understand the mechanism of biofilm detachment, we study the detachment behaviors of the Bacillus subtilis biofilm in a porous medium in a microfluidic device, where Bacillus subtilis strain is triple fluorescent labeled, which can represent three main phenotypes during the biofilm formation: motile cells, matrix-producing cells, and spores. We find that slow small-scale internal detachment occurs in regions with very few motile cells and matrix-producing cells, and bacterial movement in these areas is disordered. The increase in the number of matrix-producing cells induces clogging, and after clogging, the rapid detachment of the bulk internal biofilm occurs due to the increased pressure difference at the inlet and outlet. When both internal and external detachments occur simultaneously, the number of matrix-producing cells in the internal detachment area is 2.5 times that in the external detachment area. The results indicate that biofilm detachment occurs in areas with fewer matrix-producing cells, as matrix-producing cells can help resist detachment by secreting extracellular polymeric substances (EPSs).

Bone Morphogenetic Protein 2 Enhances Porcine Beige Adipogenesis via AKT/mTOR and MAPK Signaling Pathways.

Bone morphogenetic protein 2 (BMP2) has been reported to regulate adipogenesis, but its role in porcine beige adipocyte formation remains unclear. Our data reveal that BMP2 is significantly induced at the early stages of porcine beige adipocyte differentiation. Additionally, supplementing rhBMP2 during the early stages, but not the late stages of differentiation, significantly enhances porcine SVF adipogenesis, thermogenesis, and proliferation. Furthermore, compared to the empty plasmid-transfected-SVFs, BMP2-overexpressed SVFs had the enhanced lipid accumulation and thermogenesis, while knockdown of BMP2 in SVFs exhibited the opposite effect. The RNA-seq of the above three types of cells revealed the enrichment of the annotation of thermogenesis, brown cell differentiation, etc. In addition, the analysis also highlights the significant enrichment of cell adhesion, the MAPK cascade, and PPARγ signaling. Mechanistically, BMP2 positively regulates the adipogenic and thermogenic capacities of porcine beige adipocytes by activating PPARγ expression through AKT/mTOR and MAPK signaling pathways.

A new method: Characterize and quantify biofilm wrinkles by UNet and Sholl Analysis.

The wrinkles on the biofilm contain a lot of information about biofilm growth, so it is essential to characterize and quantify these wrinkles from the original microscopic images to discover more rules governing the biofilm morphology evolution. However, the existing methods to extract the wrinkles are time-consuming, error-prone, and require manual calibration. We propose a new system: using a deep learning method - UNet to identify the biofilm wrinkles in the original experimental images, which can achieve fast and accurate extraction of wrinkles on biofilms. Combining the result of UNet and medical neuron analysis method - Sholl Analysis, we can easily characterize and quantity the B. subtilis biofilm wrinkles. We proposed new characterization parameters such as wrinkle density, wrinkle length, and wrinkle projection area, which can precisely partition the biofilm surface wrinkles into different regions from the biofilm center to the edge, different regions correspond to different growth stages. Our system can be applied to study biofilms growing in different kinds of environments and to study the biofilm growth mechanisms.

Glucose restriction enhances oxidative fiber formation: A multi-omic signal network involving AMPK and CaMK2.

Skeletal muscle is a highly plastic organ that adapts to different metabolic states or functional demands. This study explored the impact of permanent glucose restriction (GR) on skeletal muscle composition and metabolism. Using Glut4m mice with defective glucose transporter 4, we conducted multi-omics analyses at different ages and after low-intensity treadmill training. The oxidative fibers were significantly increased in Glut4m muscles. Mechanistically, GR activated AMPK pathway, promoting mitochondrial function and beneficial myokine expression, and facilitated slow fiber formation via CaMK2 pathway. Phosphorylation-activated Perm1 may synergize AMPK and CaMK2 signaling. Besides, MAPK and CDK kinases were also implicated in skeletal muscle protein phosphorylation during GR response. This study provides a comprehensive signaling network demonstrating how GR influences muscle fiber types and metabolic patterns. These insights offer valuable data for understanding oxidative fiber formation mechanisms and identifying clinical targets for metabolic diseases.

Unraveling the Origin of Long-Lifetime Emission in Low-Dimensional Copper Halides via a Magneto-optical Study.

The origin of the long lifetime of self-trapped exciton emission in low-dimensional copper halides is currently the subject of extensive debate. In this study, we address this issue in a prototypical zero-dimensional copper halide, Cs2(C18)2Cu2I4-DMSO, through magneto-optical studies at low temperatures down to 0.2 K. Our results exclude spin-forbidden dark states and indirect phonon-assisted recombination as the origin of the long photoluminescence lifetime. Instead, we propose that the minimal Franck-Condon factor of the radiative transition from excited states to the ground state is the decisive factor, based on the transition probability analysis. Our findings offer insights into the electronic processes in low-dimensional copper halides and have the potential to advance the application of these distinctive materials in optoelectronics.

The porous structure induced heterogeneous and localized failure of the biofilm in microfluidic channels.

Understanding the mechanism of biofilm distribution and detachment is very important to effectively improve water treatment and prevent blockage in porous media. The existing research is more related to the local biofilm evolving around one or few microposts and the lack of the integral biofilm evolution in a micropost array for a longer growth period. This study combines microfluidic experiments and mathematical simulations to study the distribution and detachment of biofilm in porous media. Microfluidic chips with an array of microposts with different sizes are designed to simulate the physical pore structure of soil. The research shows that the initial formation and distribution of biofilm are influenced by bacterial transport velocity gradients within the pore space. Bacteria prefer to aggregate areas with smaller microposts, leading to the development of biofilm in those regions. Consequently, impermeable blockage structures form in this area. By analyzing experimental images of biofilm structures at the later stages, as well as coupling fluid flow and porous medium, and the finite element simulation, we find that the biofilm detachment is correlated with the morphology and permeability (kb) (from 10-15 to 10-9 m2) of the biofilm. The simulations show that there are two modes of biofilm detachment, such as internal detachment and external erosion.

Adipocyte Rnf20 ablation increases the fast-twitch fibers of skeletal muscle via lysophosphatidylcholine 16:0.

Both adipose tissue and skeletal muscle are highly dynamic tissues and interact at the metabolic and hormonal levels in response to internal and external stress, and they coordinate in maintaining whole-body metabolic homeostasis. In our previous study, we revealed that adipocyte-specific Rnf20 knockout mice (ASKO mice) exhibited lower fat mass but higher lean mass, providing a good model for investigating the adipose-muscle crosstalk and exploring the effect of the adipocyte Rnf20 gene on the physiology and metabolism of skeletal muscle. Here, we confirmed that ASKO mice exhibited the significantly increased body weight and gastrocnemius muscle weight. Fiber-type switching in the soleus muscle of ASKO mice was observed, as evidenced by the increased number of fast-twitch fibers and decreased number of slow-twitch fibers. Serum metabolites with significant alteration in abundance were identified by metabolomic analysis and the elevated lysophosphatidylcholine 16:0 [LysoPC (16:0)] was observed in ASKO mice. In addition, lipidome analysis of gonadal white adipose tissue revealed a significant increase in LysoPCs and LysoPC (16:0) in ASKO mice. Furthermore, knockdown of Rnf20 gene in 3T3-L1 cells significantly increased the secretion of LysoPC, suggesting that LysoPC might be a critical metabolite in the adipose-muscle crosstalk of ASKO mice. Furthermore, in vitro study demonstrated that LysoPC (16:0) could induce the expression of fast-twitch muscle fibers related genes in differentiated C2C12 cells, indicating its potential role in adipose-muscle crosstalk. Taken together, these findings not only expand our understanding of the biological functions of Rnf20 gene in systemic lipid metabolism, but also provide insight into adipose tissue dysfunction-induced physiological alterations in skeletal muscle.

SnRNA-Seq of Pancreas Revealed the Dysfunction of Endocrine and Exocrine Cells in Transgenic Pigs with Prediabetes.

Diabetes poses a significant threat to human health. Exocrine pancreatic dysfunction is related to diabetes, but the exact mechanism is not fully understood. This study aimed to describe the pathological phenotype and pathological mechanisms of the pancreas of transgenic pigs (PIGinH11) that was constructed in our laboratory and to compare it with humans. We established diabetes-susceptible transgenic pigs and subjected them to high-fat and high-sucrose dietary interventions. The damage to the pancreatic endocrine and exocrine was evaluated using histopathology and the involved molecular mechanisms were analyzed using single-nucleus RNA-sequencing (SnRNA-seq). Compared to wild-type (WT) pigs, PIGinH11 pigs showed similar pathological manifestations to type 2 diabetes patients, such as insulin deficiency, fatty deposition, inflammatory infiltration, fibrosis tissue necrosis, double positive cells, endoplasmic reticulum (ER) and mitochondria damage. SnRNA-seq analysis revealed 16 clusters and cell-type-specific gene expression characterization in the pig pancreas. Notably, clusters of Ainar-M and Endocrine-U were observed at the intermediate state between the exocrine and endocrine pancreas. Beta cells of the PIGinH11 group demonstrated the dysfunction with insulin produced and secret decreased and ER stress. Moreover, like clinic patients, acinar cells expressed fewer digestive enzymes and showed organelle damage. We hypothesize that TXNIP that is upregulated by high glucose might play an important role in the dysfunction of endocrine to exocrine cells in PIGinH11 pigs.

Distinct Transcriptional Responses of Skeletal Muscle to Short-Term Cold Exposure in Tibetan Pigs and Bama Pigs.

Piglets are susceptible to cold, and piglet death caused by cold stress leads to economic losses in the pig industry in cold areas. Skeletal muscle plays a key role in adaptive thermogenesis in mammals, but the related mechanism in pigs is unclear. In this study, cold-tolerant Tibetan pigs and cold-sensitive Bama pigs were subjected to either a cold environment (4 °C) or a room temperature environment (25 °C) for 3 days. The biceps femoris (BF) and longissimus dorsi muscle (LDM) were collected for phenotypic analysis, and the BF was used for genome-wide transcriptional profiling. Our results showed that Tibetan pigs had a higher body temperature than Bama pigs upon cold stimulation. RNA-seq data indicated a stronger transcriptional response in the skeletal muscle of Tibetan pigs upon cold stimulation, as more differentially expressed genes (DEGs) were identified with the same criteria (p < 0.05 and fold change > 2). In addition, distinct pathway signaling patterns in skeletal muscle upon cold exposure were found between the breeds of pigs. Mitochondrial beta-oxidation-related genes and pathways were significantly upregulated in Tibetan pigs, indicating that Tibetan pigs may use fatty acids as the primary fuel source to protect against cold. However, the significant upregulation of inflammatory response- and glycolysis-related genes and pathways in the skeletal muscle of Bama pigs suggested that these pigs may use glucose as the primary fuel source in cold environments. Together, our study revealed the distinct transcriptional responses of skeletal muscle to cold stimulation in Tibetan pigs and Bama pigs and provided novel insights for future investigation of the cold adaptation mechanism in pigs.

Indirect Bandgap Emission of the Metal Halide Perovskite FAPbI3 at Low Temperatures.

In this work, we provide a picture of the band structure of FAPbI3 by investigating low-temperature spin-related photophysics. When the temperature is lower than 120 K, two photoluminescence peaks can be observed. The lifetime of the newly emerged low-energy emission is much longer than that of the original high-energy one by two orders of magnitude. We propose that Rashba effect-caused spin-dependent band splitting is the reason for the emergence of the low-energy emission and verify this using the magneto-optical measurements.

Fecal Microbiota Was Reshaped in UCP1 Knock-In Pigs via the Adipose-Liver-Gut Axis and Contributed to Less Fat Deposition.

The relationship between the host gut microbiota and obesity has been well documented in humans and mice; however, few studies reported the association between the gut microbiota and fat deposition in pigs. In a previous study, we generated uncoupling protein 1 (UCP1) knock-in pigs (UCP1 pigs), which exhibited a lower fat deposition phenotype. Whether the gut microbiota was reshaped in these pigs and whether the reshaped gut microbiota contributes to the lower fat content remain unknown. Here, we revealed that the fecal microbiota composition and metabolites were significantly altered under both chow diet (CD) and high-fat/high-cholesterol (HFHC) diet conditions in UCP1 pigs compared to those in wild-type (WT) pigs. The abundance of Oscillospira and Coprococcus and the level of metabolite hyodeoxycholic acid (HDCA) from feces were observed to be significantly increased in UCP1 pigs. An association analysis revealed that Oscillospira and Coprococcus were significantly negatively related to backfat thickness. In addition, after fecal microbiota transplantation (FMT), the mice that were orally gavaged with feces from UCP1 pigs exhibited less fat deposition under both CD and high-fat diet (HFD) conditions, suggesting that the fecal microbes of UCP1 pigs participate in regulating host lipid metabolism. Consistently, HDCA-treated mice also exhibited reduced fat content. Mechanistically, we found that UCP1 expression in white adipose tissue alters the gut microbiota via the adipose-liver-gut axis in pigs. Our study provides new data concerning the cross talk between host genetic variations and the gut microbiota and paves the way for the potential application of microbes or their metabolites in the regulation of fat deposition in pigs. IMPORTANCE This article investigated the effect of the ectopic expression of UCP1 on the regulation of fecal microbiota composition and metabolites and which alters the fat deposition phenotype. Bacteria, including Oscillospira and Coprococcus, and the metabolite HDCA were found to be significantly increased in feces of UCP1 pigs and had a negative relationship with backfat thickness. Mice with fecal microbiota transplantation phenocopied the UCP1 pigs under both CD and HFD conditions, suggesting that the fecal microbes of UCP1 pigs participate in regulating host lipid metabolism. Our study provides new data regarding the cross talk between host genetic variations and the gut microbiota and paves the way for the potential application of microbes or their metabolic production in the regulation of fat deposition in pigs.

Nuclear-targeted EGF receptor enhances proliferation and migration of human anaplastic thyroid cancer cells.

INTRODUCTION: Epidermal growth factor (EGF) has various important physiological functions, which it exerts by binding to the epidermal growth factor receptor (EGFR). Reports show that EGF expression is strongly correlated with the occurrence and development of many types of tumour. To date, however, the relationship between EGF/EGFR and the occurrence and development of thyroid carcinoma remains unclear. MATERIAL AND METHODS: In the current study, we investigated this phenomenon using human anaplastic thyroid carcinoma cell lines (SUN-80). RESULTS: The results indicated that EGF triggered the EGFR-mediated intracellular signalling pathway, including signal transducers and activators of transcription 1/3/5 (STAT1/3/5) and protein kinase B (AKT) in a time- and dose-dependent manner. In addition, results from EGF-induced EGFR internalization and co-localization analyses showed that clathrin, Rab5/7, and EEA1 play critical roles in the intracellular trafficking of EGF/EGFR. Interestingly, EGF triggered EGFR translocation into the nucleus, while nuclear-localized EGFR affected cell cycle distribution, thereby significantly promoting the ration of S phase. Overall, these findings indicated that nuclear EGFR exerts biological activity and physiological functions, including changing cell cycle, which in turn promotes proliferation and migration of SUN-80 cells. CONCLUSION: These findings lay a foundation for further explorations seeking to understand the biological effects of the EGF/EGFR system on the occurrence and development of thyroid cancer.

Functional and Genetic Characterization of Porcine Beige Adipocytes.

Beige adipocytes are a distinct type of fat cells with a thermogenic activity that have gained substantial attention as an alternative cellular anti-obesity target in humans. These cells may provide an alternative strategy for the genetic selection of pigs with reduced fat deposition. Despite the presence of beige adipocytes in piglets, the molecular signatures of porcine beige adipocytes remain unclear. Here, white and beige adipocytes from Tibetan piglets were primarily cultured and differentiated. Compared to the white adipocytes, the beige adipocytes exhibited a stronger thermogenic capacity. RNA-sequencing-based genome-wide comparative analyses revealed distinct gene expression profiles for white and beige adipocytes. In addition, two genes, integrin alpha-2 (ITGA2) and calponin 1 (CNN1), which were specifically differentially expressed in porcine beige adipocytes, were further functionally characterized using a loss-of-function approach. Our data showed that both genes were involved in differentiation and thermogenesis of porcine beige adipocytes. Collectively, these data furthered our understanding of gene expression in porcine white and beige adipocytes. Elucidating the genetic basis of beige adipogenesis in pigs will pave the way for molecular design breeding in both pigs and large animal models of human diseases.

Effects of dexmedetomidine on nuclear factor-KB inhibitor protein kinase/ nuclear factor-KB inhibitor protein a/nuclear factor-KB pathway and cognitive dysfunction in rats with post-traumatic stress disorder / 解剖学报

Objective To investigate the effects of dexmedetomidine (DEX) on the nuclear factor-KB inhibitor protein kinase (IKK)/nuclear factor-KB inhibitor protein a (IKB(X)/nuclear factor-KB (N F - K B) pathway and cognitive dysfunction in rats with post-traumatic stress disorder (PTSD) . Methods Rats were randomly divided into control group, model group, positive group and DEX group. Except for the control group, the PTSD model was constructed by single prolonged stress method (SPS), and the corresponding drugs were given after the completion the model. Open field test and Morris water maze method were used to detect the autonomous activity, learning and memory ability of rats; HE staining was used to observe the morphological characteristics of cerebral cortex and hippocampus; ELISA and Western blotting were used to detect the contents of interleukin (IL)-1(3, IL-6, tumor necrosis factor a (TNF-a) and the expression levels of IKK, IKB(X, purinergic ligand-gated ion channel 7 receptor (P2X7R), leucine-rich repeat domain protein 3(NALP3) in hippocampus; the NF-KB activity was assessed by electrophoretic mobility shift assay (EMSA). Results Compared with the control group, the cerebral cortex and hippocampal CA1 region of model group were in structural disorders, nuclear pyysis and other pathological changes happend, learning and memory ability of rats decreased (P < 0. 05), contents of IL-lp, IL-6 and TNF-a, expression levels of IKK, IKB(X, P2X7R and NALP3, NF-KB activity in hippocampus increased (P<0. 05); Compared with the model group, the pathological phenomena in cerebral cortex and hippocampal CA1 area of rats in positive group and DEX group were in alleviated, and the changes of the above indexes were opposite to those of model group (P<0. 05) . Conclusion DEX can significantly improve the autonomous activity ability and learning and memory ability in PTSD rats, reduce inflammatory reaction in hippocampus and improve cognitive dysfunction, which may be related to the down-regulation of IKK/TKBQ!/NF-KB pathway.

Human body networks mechanisms of melatonin and its clinical applications / 中国临床药理学与治疗学

Melatonin is mainly an endogenous indoleamine hormone with many physiological functions. Melatonin not only plays an important role in the treatment of sleep disorders, but also plays an important role in the treatment of nervous system diseases, cancer, cardiovascular diseases, and bone diseases. In this paper, the human Melatonin is mainly an endogenous indoleamine hormone with many physiological functions. Melatonin not only plays an important role in the treatment of sleep disorders, but also plays an important role in the treatment of nervous system diseases, cancer, cardiovascular diseases, and bone diseases. In this paper, the human body networks mechanisms and the clinical applications of melatonin were summarized to provide reference for exploring the focus and direction of further clinical application research.

RNF20 affects porcine adipocyte differentiation via regulation of mitotic clonal expansion.

OBJECTIVES: RNF20 is recognized as a main E3 ligase for monoubiquitination of histone H2B at lysine 120 (H2Bub). The critical role of RNF20 and H2Bub in various molecular events, such as DNA replication, RNA transcription, and DNA damage response, has been widely investigated and documented. However, its role in porcine adipogenesis remains unknown. In this study, we aimed to clarify the effect of RNF20 on porcine preadipocyte differentiation. MATERIALS AND METHODS: Backfat tissues from fat-type pigs (Bama and Meishan) and lean-type pigs (Yorkshire and Landrace) were collected to detect the expression level of RNF20. Preadipocytes were isolated from Bama piglets and induced to differentiation. Small interfering RNAs were applied to deplete RNF20. Oil Red O staining, quantitative real-time PCR, RNA-seq, Western blot analysis, and EdU assays were performed to study the regulatory mechanism of RNF20 during adipogenesis. RESULTS: We found that the expression levels of RNF20 and H2Bub were significantly higher in backfat tissues from fat-type pigs than in those from lean-type pigs. Consistently, the significantly induced expression of RNF20 and H2Bub was also observed in porcine differentiated adipocytes. In addition, knockdown of RNF20 greatly inhibited porcine adipogenesis, as evidenced by dramatically decreased lipid droplet formation and lower expression levels of adipogenic transcription masters in RNF20 knockdown cells. Mechanistically, the depletion of RNF20 decreases the cell proliferation and the level of p-C/EBPß via the Ras-Raf-MEK1/2-ERK1/2 cascade pathway at the mitotic clonal expansion phase and therefore suppresses cell differentiation. CONCLUSIONS: Our results demonstrate that RNF20 is required for porcine preadipocyte differentiation.

CD8+ T Cells Involved in Metabolic Inflammation in Visceral Adipose Tissue and Liver of Transgenic Pigs.

Anti-inflammatory therapies have the potential to become an effective treatment for obesity-related diseases. However, the huge gap of immune system between human and rodent leads to limitations of drug discovery. This work aims at constructing a transgenic pig model with higher risk of metabolic diseases and outlining the immune responses at the early stage of metaflammation by transcriptomic strategy. We used CRISPR/Cas9 techniques to targeted knock-in three humanized disease risk genes, GIPRdn , hIAPP and PNPLA3I148M . Transgenic effect increased the risk of metabolic disorders. Triple-transgenic pigs with short-term diet intervention showed early symptoms of type 2 diabetes, including glucose intolerance, pancreatic lipid infiltration, islet hypertrophy, hepatic lobular inflammation and adipose tissue inflammation. Molecular pathways related to CD8+ T cell function were significantly activated in the liver and visceral adipose samples from triple-transgenic pigs, including antigen processing and presentation, T-cell receptor signaling, co-stimulation, cytotoxicity, and cytokine and chemokine secretion. The similar pro-inflammatory signaling in liver and visceral adipose tissue indicated that there might be a potential immune crosstalk between the two tissues. Moreover, genes that functionally related to liver antioxidant activity, mitochondrial function and extracellular matrix showed distinct expression between the two groups, indicating metabolic stress in transgenic pigs' liver samples. We confirmed that triple-transgenic pigs had high coincidence with human metabolic diseases, especially in the scope of inflammatory signaling at early stage metaflammation. Taken together, this study provides a valuable large animal model for the clinical study of metaflammation and metabolic diseases.