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, GIPR(dn) , hIAPP and PNPLA3(I148M) . 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.Peer reviewe

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

peer reviewedSkeletal 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 mech- anisms and identifying clinical targets for metabolic diseases.National Key Research and Development Program of China3. Good health and well-bein

Potential roles of dental pulp stem cells in neural regeneration and repair

This review summarizes current advances in dental pulp stem cells (DPSCs) and their potential applications in the nervous diseases. Injured adult mammalian nervous system has a limited regenerative capacity due to an insufficient pool of precursor cells in both central and peripheral nervous systems. Nerve growth is also constrained by inhibitory factors (associated with central myelin) and barrier tissues (glial scarring). Stem cells, possessing the capacity of self-renewal and multicellular differentiation, promise new therapeutic strategies for overcoming these impediments to neural regeneration. Dental pulp stem cells (DPSCs) derive from a cranial neural crest lineage, retain a remarkable potential for neuronal differentiation, and additionally express multiple factors that are suitable for neuronal and axonal regeneration. DPSCs can also express immunomodulatory factors that stimulate formation of blood vessels and enhance regeneration and repair of injured nerve. These unique properties together with their ready accessibility make DPSCs an attractive cell source for tissue engineering in injured and diseased nervous systems. In this review, we interrogate the neuronal differentiation potential as well as the neuroprotective, neurotrophic, angiogenic, and immunomodulatory properties of DPSCs and its application in the injured nervous system. Taken together, DPSCs are an ideal stem cell resource for therapeutic approaches to neural repair and regeneration in nerve diseases

MAC-ResNet: Knowledge Distillation Based Lightweight Multiscale-Attention-Crop-ResNet for Eyelid Tumors Detection and Classification

Eyelid tumors are tumors that occur in the eye and its appendages, affecting vision and appearance, causing blindness and disability, and some having a high lethality rate. Pathological images of eyelid tumors are characterized by large pixels, multiple scales, and similar features. Solving the problem of difficult and time-consuming fine-grained classification of pathological images is important to improve the efficiency and quality of pathological diagnosis. The morphology of Basal Cell Carcinoma (BCC), Meibomian Gland Carcinoma (MGC), and Cutaneous Melanoma (CM) in eyelid tumors are very similar, and it is easy to be misdiagnosed among each category. In addition, the diseased area, which is decisive for the diagnosis of the disease, usually occupies only a relatively minor portion of the entire pathology section, and screening the area of interest is a tedious and time-consuming task. In this paper, deep learning techniques to investigate the pathological images of eyelid tumors. Inspired by the knowledge distillation process, we propose the Multiscale-Attention-Crop-ResNet (MAC-ResNet) network model to achieve the automatic classification of three malignant tumors and the automatic localization of whole slide imaging (WSI) lesion regions using U-Net. The final accuracy rates of the three classification problems of eyelid tumors on MAC-ResNet were 96.8%, 94.6%, and 90.8%, respectively

Developed and developing world responsibilities for historical climate change and CO2 mitigation

At the United Nations Framework Convention on Climate Change Conference in Cancun, in November 2010, the Heads of State reached an agreement on the aim of limiting the global temperature rise to 2 °C relative to preindustrial levels. They recognized that long-term future warming is primarily constrained by cumulative anthropogenic greenhouse gas emissions, that deep cuts in global emissions are required, and that action based on equity must be taken to meet this objective. However, negotiations on emission reduction among countries are increasingly fraught with difficulty, partly because of arguments about the responsibility for the ongoing temperature rise. Simulations with two earth-system models (NCAR/CESM and BNU-ESM) demonstrate that developed countries had contributed about 60–80%, developing countries about 20–40%, to the global temperature rise, upper ocean warming, and sea-ice reduction by 2005. Enacting pledges made at Cancun with continuation to 2100 leads to a reduction in global temperature rise relative to business as usual with a 1/3–2/3 (CESM 33–67%, BNU-ESM 35–65%) contribution from developed and developing countries, respectively. To prevent a temperature rise by 2 °C or more in 2100, it is necessary to fill the gap with more ambitious mitigation efforts