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

Remote sensing and environmental assessment of wetland ecological degradation in the Small Sanjiang Plain, Northeast China

IntroductionThe plain marsh wetland ecosystems are sensitive to changes in the natural environment and the intensity of human activities. The Sanjiang Plain is China’s largest area of concentrated marsh wetland, the Small Sanjiang Plain is the most important component of the Sanjiang Plain. However, with the acceleration of the urbanization and development of large-scale agricultural reclamation activities in the Small Sanjiang Plain in Northeast China, the wetland has been seriously damaged. In light of this degradation this study examines the Small Sanjiang Plain.MethodsFrom the four aspects of area, structure, function, and human activities, we try to construct a wetland degradation comprehensive index (WDCI) in cold region with expert scoring methods and analytic hierarchy process (AHP), coupled with network and administrative unit. The objective was to reveal the degradation of wetlands in Northeast China over three decades at a regional scale.ResultsThe results showed that (1) the overall wetland area decreased between 1990 and 2020 by 39.26×103 hm2. Within this period a significant decrease of 336.56×103 hm2 occurred between 1990 and 200 and a significant increase of 214.62×103 hm2 occurred between 2010 and 2020. (2) In terms of structural changes, the fractal dimension (FRAC) has the same trend as the Landscape Fragmentation Index (LFI) with little change. (3) In terms of functional changes, the average above-ground biomass (AGB) increased from 1029.73 kg/hm2 to 1405.38 kg/hm2 between 1990 and 2020 in the study area. (4) In terms of human activities, the average human disturbance was 0.52, 0.46, 0.57 and 0.53 in 1990, 2000, 2010 and 2020, with the highest in 2010. (5) The composite wetland degradation index shows that the most severe wetland degradation was 49.61% in 2010 occurred between 1990 and 2020. (6) Among the severely deteriorated trajectory types in 2010–2020, mild degradation → serious degradation accounted for the largest area of 240.23×103 hm2, and the significant improvement trajectory type in 1990–2000 accounted for the largest area of 238.50×103 hm2.DiscussionIn brief, we conclude that the degradation of the Small Sanjiang Plain wetland was caused mainly by construction, overgrazing, deforestation, and farmland reclamation. This study can also provide new views for monitoring and managing wetland degradation by remote sensing in cold regions

Advances in Molecular Quantum Chemistry Contained in the Q-Chem 4 Program Package

A summary of the technical advances that are incorporated in the fourth major release of the Q-Chem quantum chemistry program is provided, covering approximately the last seven years. These include developments in density functional theory methods and algorithms, nuclear magnetic resonance (NMR) property evaluation, coupled cluster and perturbation theories, methods for electronically excited and open-shell species, tools for treating extended environments, algorithms for walking on potential surfaces, analysis tools, energy and electron transfer modelling, parallel computing capabilities, and graphical user interfaces. In addition, a selection of example case studies that illustrate these capabilities is given. These include extensive benchmarks of the comparative accuracy of modern density functionals for bonded and non-bonded interactions, tests of attenuated second order Møller–Plesset (MP2) methods for intermolecular interactions, a variety of parallel performance benchmarks, and tests of the accuracy of implicit solvation models. Some specific chemical examples include calculations on the strongly correlated Cr2 dimer, exploring zeolite-catalysed ethane dehydrogenation, energy decomposition analysis of a charged ter-molecular complex arising from glycerol photoionisation, and natural transition orbitals for a Frenkel exciton state in a nine-unit model of a self-assembling nanotube

Interpreting the Molecular Mechanisms of Yinchenhao Decoction on Hepatocellular Carcinoma through Absorbed Components Based on Network Pharmacology

To investigate the mechanisms through which Yinchenhao decoction (YCHD) inhibits hepatocellular carcinoma (HCC), we analyzed YCHD ingredients absorbed into the bloodstream by using network pharmacology. We conducted a weighted gene coexpression network analysis on gene expression data collected from the Gene Expression Omnibus and The Cancer Genome Atlas databases to derive an HCC gene set; moreover, we used four online prediction system databases to predict the potential targets of YCHD ingredients absorbed into the bloodstream. We discovered that YCHD directly interfered with 17 HCC-related disease targets. Subsequent gene ontology enrichment analyses of these 17 disease targets revealed that YCHD exhibited effects through 17 biological processes, 7 molecular functions, and 9 cellular components. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated 14 pathways through which YCHD inhibits HCC. We observed similar trends in how the 17 small molecules interfered with the key target set. We surmised that YCHD inhibits HCC by regulating inflammatory and metabolic pathways. Network pharmacological analysis of YCHD ingredients absorbed into the bloodstream may provide new insights and serve as a new method for discovering the molecular mechanisms through which YCHD inhibits HCC

Characterization of the complete chloroplast genome of Malus spectabilis ‘Guanghui’

Malus spectabilis ‘Guanghui’ is an important ornamental plant, which complete chloroplast genome (Accession: MT501657) was sequenced, assembled and annotated. The genome size is 1601,230 bp and the overall GC content is 36.50%, with large single-copy (LSC, 89,310bp) regions, small single-copy (SSC, 19,196 bp) regions, and two inverted repeat regions (IRs, 23,632bp each). A total of 129 genes are successfully annotated, including 84 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The phylogenetic relationships showed that Malus spectabilis ‘Guanghui’ is closely related to the species of Malus sieversii

Hsa_circ_0037897 may be a risk factor for essential hypertension via hsa-miR-145-5p

Objectives: This study aims to investigate the association between hsa_circ_0037897 and essential hypertension (EH) and to evaluate the diagnostic value of biomarker hsa_circ_0037897 in EH. Methods: This study included 92 EH patients and 92 sex- and age- (±3 years) matched subjects as control. qRT-PCR was performed to measure the expression level of circRNA and miRNA. Logistic regression analysis model was used to assess independent association between hsa_circ_0037897 and EH. Results: The expression level of hsa_circ_0037897 in EH patients was significantly higher (p < .001) compared to the control group, while hsa-miR-145-5p had significantly lower expression(p = .002) than the control group. The area under the ROC curve (AUC) of hsa_circ_0037897 was 0.656. Furthermore, the AUC increased to 0.714 when hsa_circ_0037897 was combined with hsa-miR-145-5p, BMI and smoking. Conclusion: The present results suggested that the high expression of hsa_circ_0037897 may be a risk factor for EH, and hsa_circ_0037897 has certain diagnostic value for EH

Characterization of the complete chloroplast genome of Punica granatum ‘Luqing1’

Punica granatum ‘Luqing1’ is an important d fruit tree with high quality and strong cold-resistance. The complete chloroplast genome (Accession: MN630638) was sequenced, assembled, and annotated. The size of chloroplast genome was 158,638 bp with large single-copy (LSC, 89,021 bp) regions, small single-copy (SSC, 18,685 bp) regions, and two inverted repeat regions (IRs, 25,466 bp each). A total of 130 genes were successfully annotated, including 85 protein-coding genes, 37 tRNA genes, and eight rRNA genes. The phylogenetic relationships showed that P. granatum ‘Luqing1’ was closely related with different pomegranate cultivars

The first complete chloroplast genome of Hovenia acerba Lindl.

Hovenia acerba Lindl. is an important medicinal plant, for which complete chloroplast genome (Accession: MN782301) was sequenced, assembled and annotated. The genome size is 161,668 bp and the overall GC content is 36.69%, with large single-copy (LSC, 89,451bp) regions, small single-copy (SSC, 18,979 bp) regions, and two inverted repeat regions (IRs, 26,619 bp each). A total of 130 genes are successfully annotated, including 85 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The phylogenetic relationships showed that H. acerba is closely related to the species of Ziziphus genus

Characterization and phylogenetic analysis of the complete chloroplast genome of Cercis canadensis ‘Forest Pansy’

Cercis canadensis ‘Forest Pansy’ is a tree species with high ornamental value, which complete chloroplast (cp) genome was sequenced, assembled, and annotated. The genome size is 158,960 bp with a total GC content of 36.17%. The cp genome is made up of a large single-copy region (88,114 bp), a small single-copy region (19,590 bp), and two inverted repeat regions (25,628 bp each). It contains 128 genes, including 84 protein-coding genes, 36 tRNA genes, and 8 rRNA genes. Eighteen genes were duplicated in IRs. The maximum-likelihood (ML) phylogenetic analysis indicated that the Leguminosae species are grouped together, and C. canadensis ‘Forest Pansy’ is closely related to C. canadensis. The result would provide valuable information for genetic studies on Cercis genus