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.

Improved beluga whale optimization algorithm based cluster routing in wireless sensor networks.

Cluster routing is a critical routing approach in wireless sensor networks (WSNs). However, the uneven distribution of selected cluster head nodes and impractical data transmission paths can result in uneven depletion of network energy. For this purpose, we introduce a new routing strategy for clustered wireless sensor networks that utilizes an improved beluga whale optimization algorithm, called tCBWO-DPR. In the selection process of cluster heads, we introduce a new excitation function to evaluate and select more suitable candidate cluster heads by establishing the correlation between the energy of node and the positional relationship of nodes. In addition, the beluga whale optimization (BWO) algorithm has been improved by incorporating the cosine factor and t-distribution to enhance its local and global search capabilities, as well as to improve its convergence speed and ability. For the data transmission path, we use Prim's algorithm to construct a spanning tree and introduce DPR for determining the optimal route between cluster heads based on the correlation distances of cluster heads. This effectively shortens the data transmission path and enhances network stability. Simulation results show that the improved beluga whale optimization based algorithm can effectively improve the survival cycle and reduce the average energy consumption of the network.

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.

Oral microbiome alterations in epilepsy and after seizure control.

Background: The existing diagnostic methods of epilepsy such as history collection and electroencephalogram have great limitations in practice, so more reliable and less difficult diagnostic methods are needed. Methods: By characterizing oral microbiota in patients diagnosed with epilepsy (EPs) and patients whose seizures were under control (EPRs), we sought to discover biomarkers for different disease states. 16S rRNA gene sequencing was performed on 480 tongue swabs [157 EPs, 22 EPRs, and 301 healthy controls (HCs)]. Results: Compared with normal individuals, patients with epilepsy exhibit increased alpha diversity in their oral microbiota, and the oral microbial communities of the two groups demonstrate significant beta diversity differences. EPs exhibit a significant increase in the abundance of 26 genera, including Streptococcus, Granulicatella, and Kluyvera, while the abundance of 14 genera, including Peptostreptococcus, Neisseria, and Schaalia, is significantly reduced. The area under the receiver operating characteristic curve (AUC) of oral microbial markers in the training cohort and validation cohort was 98.85% and 97.23%, respectively. Importantly, the AUC of the biomarker set achieved 92.44% of additional independent validation sets. In addition, EPRs also have their own unique oral community. Conclusion: This study describes the characterization of the oral microbiome in EP and EPR and demonstrates the potential of the specific microbiome as a non-invasive diagnostic tool for epilepsy.

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.

Pulmonary infection and baseline mRS scores predict poor prognosis in anti-GABABR encephalitis.

Purpose: Anti-gamma-aminobutyric-acid type B receptor (anti-GABABR) encephalitis is a rare autoimmune condition caused by the presence of GABABR antibodies in the limbic system. However, its clinical features and prognostic factors are poorly understood. In this study, we aimed to explore factors that affect the response to first-line treatment in patients with anti-GABABR encephalitis. Methods: Thirty-four patients with an initial diagnosis of anti-GABABR encephalitis were retrospectively enrolled from December 2015 to June 2021. Clinical features and experimental data recorded within 24 h of admission were extracted from the patients' medical records. The modified Rankin Scale (mRS) was utilized to assess disease severity at admission and functional recovery after immunotherapy. Independent prognostic factors were determined by ordinal logistic regression analysis. Results: Of the 34 anti-GABABR encephalitis patients, 12 (35%) presented with cancer; all of these patients had lung cancer. According to multivariate regression analysis, the cancer group exhibited a decrease in the peripheral blood absolute lymphocyte count (ALC) (odds ratio [OR]: 0.063, 95% confidence interval [CI]: 0.006-0.639, P=0.019) and hyponatremia (OR: 9.268, 95% CI: 1.054-81.502, 0.045). In addition, the neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR) and platelet/lymphocyte ratio (PLR) did not significantly differ according to mRS scores in patients receiving first-line treatment. No patients with mild or moderate mRS scores (0-2) at admission developed symptoms after treatment; in contrast, only 11 patients with a severe mRS scores (≥3, 11/18) experienced symptom alleviation. Ordinal regression analysis indicated that worse prognosis was associated with pulmonary infection (OR=9.885, 95% CI: 1.106-88.323, P=0.040) and baseline mRS scores (OR= 24.047, 95% CI: 3.294-175.739, P=0.002) in the adjusted model. Conclusion: Our findings demonstrate that pulmonary infection and baseline mRS scores are independent risk factors for poor prognosis in patients with anti-GABABR encephalitis after first-line treatment. ALC and hyponatremia are potential biomarkers for anti-GABABR encephalitis cases accompanied by lung cancer.

Pnpla5-knockout rats exhibit reduced expression levels of proteins involved in steroid metabolism and wound healing compared to wild-type rats.

BACKGROUND: Patatin-like phospholipase domain containing 5 (PNPLA5) is a newly-discovered lipase. Although the PNPLA family plays critical roles in diverse biological processes, the biological functions of PNPLA5 mostly unknown. We previously found that the deletion of Pnpla5 in rats causes a variety of phenotypic abnormalities. In this study, we further explored the effects of Pnpla5 knockout (KO) on male rats. RESULTS: The body weight and testicular or epididymal tissue weight of three to six 3-month-old Pnpla5 KO or wild-type (WT) male Sprague-Dawley rats were measured. The protein expression levels were also measured via western blotting and iTRAQ (isobaric tags for relative and absolute quantitation) analyses. No significant difference between Pnpla5 KO and WT rats, regarding body weight, testicular or epididymal tissue weight, or hormone levels, were found. However, the relative testicular tissue weight of the KO (Pnpla5-/-) rats was higher (P < 0.05) than that of WT rats. Significant increases in apoptotic cells numbers (P < 0.001) and BAX and Caspase-9 expression levels were observed in the testicular tissue of Pnpla5-/- rats. Moreover, iTRAQ analysis revealed that the levels of proteins involved in steroid metabolism and wound healing were significantly decreased in Pnpla5-/- rats. CONCLUSION: This study revealed that Pnpla5 knockout induced apoptosis in rat testes. We also ascertained that Pnpla5 plays an important role in lipid metabolism, wound healing, and affects reproductive organs negatively, providing new target genes and pathways that can be analyzed to unravel the biological function of Pnpla5.

Enhancing Animal Disease Resistance, Production Efficiency, and Welfare through Precise Genome Editing.

The major goal of animal breeding is the genetic enhancement of economic traits. The CRISPR/Cas system, which includes nuclease-mediated and base editor mediated genome editing tools, provides an unprecedented approach to modify the mammalian genome. Thus, farm animal genetic engineering and genetic manipulation have been fundamentally revolutionized. Agricultural animals with traits of interest can be obtained in just one generation (and without long time selection). Here, we reviewed the advancements of the CRISPR (Clustered regularly interspaced short palindromic repeats)/Cas (CRISPR associated proteins) genome editing tools and their applications in animal breeding, especially in improving disease resistance, production performance, and animal welfare. Additionally, we covered the regulations on genome-edited animals (GEAs) and ways to accelerate their use. Recommendations for how to produce GEAs were also discussed. Despite the current challenges, we believe that genome editing breeding and GEAs will be available in the near future.

Changes in the Mucosa-Associated Microbiome and Transcriptome across Gut Segments Are Associated with Obesity in a Metabolic Syndrome Porcine Model.

Several studies have suggested a role for gut mucosa-associated microbiota in the development of obesity, but the mechanisms involved are poorly defined. Here, the impact of the gut mucosa-associated microbiota on obesity and related metabolic disorders was evaluated in a metabolic syndrome (MetS) porcine model. Body composition was determined among male Wuzhishan minipigs consuming a high-energy diet (HED) and compared to that of those consuming a normal diet (ND), and gut segments (duodenum, jejunum, ileum, cecum, colon, and rectum) were sampled for paired analysis of mucosa-associated microbiota and transcriptome signatures with 16S rRNA gene and RNA sequencing, respectively. Our data indicated that long-term HED feeding significantly increased body weight and visceral fat deposition and aggravated metabolic disorders. Specially, HED feeding induced mucosa-associated microbiota dysbiosis and selectively increased the abundance of the families Enterobacteriaceae, Moraxellaceae, and Lachnospiraceae in the upper intestine. The association analysis indicated that specific bacteria play key roles in adiposity, e.g., Lactobacillus johnsonii in the duodenum, Actinobacillus indolicus in the jejunum, Acinetobacter johnsonii in the ileum, Clostridium butyricum in the cecum, Haemophilus parasuis in the colon, and bacterium NLAEzlP808, Halomonas taeheungii, and Shewanella sp. JNUH029 in the rectum. Transcriptome data further revealed intestinal lipid metabolism and immune dysfunction in the MetS individuals, which may be associated with obesity and related metabolic disorders. Our results indicated that gut mucosa-associated microbiota dysbiosis has the potential to exacerbate obesity, partially through modulating systemic inflammatory responses. IMPORTANCE Obesity is a major risk factor for metabolic syndrome, which is the most common cause of death worldwide, especially in developed countries. The link between obesity and gut mucosa-associated microbiota is unclear due to challenges associated with the collection of intestinal samples from humans. The current report provides the first insight into obesity-microbiome-gut immunity connections in a metabolic syndrome (MetS) porcine model. The present results show that dysbiosis of mucosal microbiota along the entire digestive tract play a critical role in the proinflammatory response in the host-microbial metabolism axis, resulting in obesity and related metabolic disorders in the MetS model.

Long-term, multidomain analyses to identify the breed and allelic effects in MSTN-edited pigs to overcome lameness and sustainably improve nutritional meat production.

Beef and mutton production has been aided by breeding to integrate allelic diversity for myostatin (MSTN), but a lack of diversity in the MSTN germplasm has limited similar advances in pig farming. Moreover, insurmountable challenges with congenital lameness and a dearth of data about the impacts of feed conversion, reproduction, and meat quality in MSTN-edited pigs have also currently blocked progress. Here, in a largest-to-date evaluation of multiple MSTN-edited pig populations, we demonstrated a practical alternative edit-site-based solution that overcomes the major production obstacle of hindlimb weakness. We also provide long-term and multidomain datasets for multiple breeds that illustrate how MSTN-editing can sustainably increase the yields of breed-specific lean meat and the levels of desirable lipids without deleteriously affecting feed-conversion rates or litter size. Apart from establishing a new benchmark for the data scale and quality of genome-edited animal production, our study specifically illustrates how gene-editing site selection profoundly impacts the phenotypic outcomes in diverse genetic backgrounds.

Integrated analysis of DNA methylome and transcriptome reveals the differences in biological characteristics of porcine mesenchymal stem cells.

BACKGROUND: Bone marrow (BM) and umbilical cord (UC) are the main sources of mesenchymal stem cells (MSCs). These two MSCs display significant differences in many biological characteristics, yet the underlying regulation mechanisms of these cells remain largely unknown. RESULTS: BMMSCs and UCMSCs were isolated from inbred Wuzhishan miniature pigs and the first global DNA methylation and gene expression profiles of porcine MSCs were generated. The osteogenic and adipogenic differentiation ability of porcine BMMSCs is greater than that of UCMSCs. A total of 1979 genes were differentially expressed and 587 genes were differentially methylated at promoter regions in these cells. Integrative analysis revealed that 102 genes displayed differences in both gene expression and promoter methylation. Gene ontology enrichment analysis showed that these genes were associated with cell differentiation, migration, and immunogenicity. Remarkably, skeletal system development-related genes were significantly hypomethylated and upregulated, whereas cell cycle genes were opposite in UCMSCs, implying that these cells have higher cell proliferative activity and lower differentiation potential than BMMSCs. CONCLUSIONS: Our results indicate that DNA methylation plays an important role in regulating the differences in biological characteristics of BMMSCs and UCMSCs. Results of this study provide a molecular theoretical basis for the application of porcine MSCs in human medicine.

Rapid visual genotyping method for germline mutants with small genomic fragment deletion by allele-specific PCR and lateral flow nucleic acid biosensor.

BACKGROUND: Genome-editing techniques incorporating artificial nucleases develop rapidly and enable efficient and precise modification of genomic DNA of numerous organisms. The present research aimed to establish a rapid, sensitive and visual method for genotyping of germline genome-edited mutants with small genomic fragment deletion. METHODS AND RESULTS: The genome-edited pigs with 2-bp deletion and 11-bp deletion of Myostatin (MSTN) gene generated by TALENs system were used as test materials to check the proposed allele-specific PCR (AS-PCR) and lateral flow nucleic acid biosensor (LFNAB) cascade method. AS-PCR can produce products with different tags to distinguish genome-edited alleles and wild-type alleles. A LFNAB was applied to do visual detection of AS-PCR products without using additional instruments. Furthermore, we demonstrated that AS-PCR and LFNAB cascade could accurately and visually distinguish genome-edited pigs with small genomic fragment deletion of Myostatin (MSTN) gene and wild-type pigs with limit of detection (LOD) of 0.1 ng. CONCLUSION: The proposed AS-PCR and LFNAB cascade can do rapid and visual genotyping of genome-edited mutants with small genomic fragment deletion, serving as a platform for genome-edited animal genotyping.

Single-cell-type transcriptomic analysis reveals distinct gene expression profiles in wheat guard cells in response to abscisic acid.

Stomatal closure, driven by shrinking guard cells in response to the accumulation of abscisic acid (ABA) under drought stress, has a great impact on plant growth and environmental acclimation. However, the molecular regulatory mechanism underlying the turgor alteration of guard cells remains elusive, especially in cereal grasses. Here, we develop a modified enzyme digestion-based approach for the isolation of wheat (Triticum aestivum L.) guard cells. With this approach, we can remove mesophyll, pavement cells and subsidiary cells successively from the epidermis of the trichomeless coleoptile in wheat and preserve guard cells on the cuticle layers in an intact and physiologically active conditions. Using a robust single-cell-type RNA sequencing analysis, we discovered 9829 differentially expressed genes (DEGs) as significantly up- or down-regulated in guard cells in response to ABA treatment. Transcriptome analysis revealed a large percent of DEGs encoding multiple phytohormone signalling pathways, transporters, calcium signalling components, protein kinases and other ABA signalling-related proteins, which are primarily involved in key signalling pathways in ABA-regulated stomatal control and stress response. Our findings provide valuable resource for investigating the transcriptional regulatory mechanism underlying wheat guard cells in response to ABA.

Si doped Fe-N/C catalyst for oxygen reduction reaction directed by ordered mesoporous silica nanospheres template strategy.

Template-assisted synthesis strategy is an effective approach to prepare high performance oxygen reduction catalyst. The Fe-N/C catalysts were prepared via high temperature pyrolysis of the composites containing Fe-loaded mesoporous silica nanospheres and polypyrrole wrapped on it (Fe/mSiO2@PPY). Fe loading ways combined with polymerization means of pyrrole greatly influence the structure and morphology of the final catalysts. By controlling the type of templates (mesoporous, microporous and nonporous templates) and synthesis conditions, Si doped Fe-N/C (Si-Fe-N/C) catalyst with hollow shell structures was obtained. The multiple heteroatom co-doping of Si, Fe and N in carbon framework are confirmed by EDS, XPS and Raman. The co-doping of Fe and N increases the oxygen reduction reaction (ORR) catalytic activities, while the doping of Si facilitates graphitization degree of carbon framework. The electrochemical performance of the Si-Fe-N/C catalyst was evaluated by the linear sweep voltammograms (LSV). It exhibits higher current density (5.4 mA cm-2) and more positive half-wave potential (0.83 V vs. RHE), which is comparable to commercial Pt/C catalyst. Stability tests show that the Si-Fe-N/C catalyst possesses excellent durability and more than 90% of its original activity can be retained after 50,000 s running at 0.68 V (vs. RHE).

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.

Gut Microbiome Distinguishes Patients With Epilepsy From Healthy Individuals.

Objective: The gut microecosystem is the largest microecosystem in the human body and has been proven to be linked to neurological diseases. The main objective of this study was to characterize the fecal microbiome, investigate the differences between epilepsy patients and healthy controls, and evaluate the potential efficacy of the fecal microbiome as a diagnostic tool for epilepsy. Design: We collected 74 fecal samples from epilepsy patients (Eps, n = 24) and healthy controls (HCs, n = 50) in the First Affiliated Hospital of Zhengzhou University and subjected the samples to 16S rRNA MiSeq sequencing and analysis. We set up a train set and a test set, identified the optimal microbial markers for epilepsy after characterizing the gut microbiome in the former and built a diagnostic model, then validated it in the validation group. Results: There were significant differences in microbial communities between the two groups. The α-diversity of the HCs was higher than that of the epilepsy group, but the Venn diagram showed that there were more unique operational taxonomic unit (OTU) in the epilepsy group. At the phylum level, Proteobacteria and Actinobacteriota increased significantly in Eps, while the relative abundance of Bacteroidota increased in HCs. Compared with HCs, Eps were enriched in 23 genera, including Faecalibacterium, Escherichia-Shigella, Subdoligranulum and Enterobacteriaceae-unclassified. In contrast, 59 genera including Bacteroides, Megamonas, Prevotella, Lachnospiraceae-unclassified and Blautia increased in the HCs. In Spearman correlation analysis, age, WBC, RBC, PLT, ALB, CREA, TBIL, Hb and Urea were positively correlated with most of the different OTUs. Seizure-type, course and frequency are negatively correlated with most of the different OTUs. In addition, twenty-two optimal microbial markers were identified by a fivefold cross-validation of the random forest model. In the established train set and test set, the area under the curve was 0.9771 and 0.993, respectively. Conclusion: Our study was the first to characterize the gut microbiome of Eps and HCs in central China and demonstrate the potential efficacy of microbial markers as a noninvasive biological diagnostic tool for epilepsy.

Ginsenoside Rb1 ameliorates cisplatin-induced learning and memory impairments.

BACKGROUND: Ginsenoside Rb1 (Rb1), a dominant component from the extract of Panax ginseng root, exhibits neuroprotective functions in many neurological diseases. This study was intended to investigate whether Rb1 can attenuate cisplatin-induced memory impairments and explore the potential mechanisms. METHODS: Cisplatin was injected intraperitoneally with a dose of 5 mg/kg/wk, and Rb1 was administered in drinking water at the dose of 2 mg/kg/d to rats for 5 consecutive wk. The novel objects recognition task and Morris water maze were used to detect the memory of rats. Nissl staining was used to examine the neuron numbers in the hippocampus. The activities of superoxide dismutase, glutathione peroxidase, cholineacetyltransferase, acetylcholinesterase, and the levels of malondialdehyde, reactive oxygen species, acetylcholine, tumor necrosis factor-α, interleukin-1ß, and interleukin-10 were measured by ELISA to assay the oxidative stress, cholinergic function, and neuroinflammation in the hippocampus. RESULTS: Rb1 administration effectively ameliorates the memory impairments caused by cisplatin in both novel objects recognition task and Morris water maze task. Rb1 also attenuates the neuronal loss induced by cisplatin in the different regions (CA1, CA3, and dentate gyrus) of the hippocampus. Meanwhile, Rb1 is able to rescue the cholinergic neuron function, inhibit the oxidative stress and neuroinflammation in cisplatin-induced rat brain. CONCLUSION: Rb1 rescues the cisplatin-induced memory impairment via restoring the neuronal loss by reducing oxidative stress and neuroinflammation and recovering the cholinergic neuron functions.

Genomic Analysis Reveals Specific Patterns of Homozygosity and Heterozygosity in Inbred Pigs.

The inbred strain of miniature pig is an ideal model for biomedical research due to its high level of homozygosity. In this study, we investigated genetic diversity, relatedness, homozygosity, and heterozygosity using the Porcine SNP60K BeadChip in both inbred and non-inbred Wuzhishan pigs (WZSPs). Our results from multidimensional scaling, admixture, and phylogenetic analyses indicated that the inbred WZSP, with its unique genetic properties, can be utilized as a novel genetic resource for pig genome studies. Inbreeding depression and run of homozygosity (ROH) analyses revealed an average of 61 and 12 ROH regions in the inbred and non-inbred genomes of WZSPs, respectively. By investigating ROH number, length, and distribution across generations, we further briefly studied the impacts of recombination and demography on ROH in these WZSPs. Finally, we explored the SNPs with higher heterozygosity across generations and their potential functional implications in the inbred WZSP. We detected 56 SNPs showing constant heterozygosity with He = 1 across six generations in inbred pigs, while only one was found in the non-inbred population. Among these SNPs, we observed nine SNPs located in swine RefSeq genes, which were found to be involved in signaling and immune processes. Together, our findings indicate that the inbred-specific pattern of homozygosity and heterozygosity in inbred pigs can offer valuable insights for elucidating the mechanisms of inbreeding in farm animals.

Treadmill Exercise Ameliorates Depression-Like Behavior in the Rats With Prenatal Dexamethasone Exposure: The Role of Hippocampal Mitochondria.

Prenatal exposure to synthetic glucocorticoids (sGCs) can increase the risk of affective disorders, such as depression, in adulthood. Given that exercise training can ameliorate depression and improve mitochondrial function, we sought to investigate whether exercise can ameliorate depression-like behavior induced by prenatal sGC exposure and mitochondria function contributes to that behavior. At first, we confirmed that prenatal dexamethasone (Dex) administration in late pregnancy resulted in depression-like behavior and elevated level of circulatory corticosterone in adult offspring. We then found that mRNA and protein expression of a number of mitochondrial genes was changed in the hippocampus of Dex offspring. Mitochondria in the hippocampus showed abnormal morphology, oxidative stress and dysfunction in Dex offspring. Intracerebroventricular (ICV) injection of the mitochondrial superoxide scavenger mitoTEMPO significantly alleviated depression-like behavior but did not significantly affect circulatory corticosterone level in Dex offspring. The adult Dex offspring treated with treadmill exercise starting at four-weeks of age showed ameliorated depressive-like behavior, improved mitochondrial morphology and function and reduced circulatory corticosterone level. Our data suggest mitochondria dysfunction contributes to depression-like behavior caused by prenatal sGC exposure. Intervention with exercise training in early life can reverse depression caused by prenatal Dex exposure, which is associated with improvement of mitochondrial function in the hippocampus.