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Glutathione transferases (GSTs) are a superfamily of dimeric proteins associated with the detoxification of various reactive electrophiles and responsive to a multitude of stressors. We individually substituted Lys64 and Glu78 with Ala using site-directed mutagenesis to understand the role of subunit interactions in the structure and enzymatic properties of a rice GST (OsGSTU17). The wild-type OsGSTU17 lost the conserved hydrogen bond between subunits in tau class GSTs due to conserved Tyr92 replaced with Phe92, but still exhibited high substrate activities, and thermal stability remained in its dimeric structure. The significant decrease in thermal stability and obvious changes in the structure of mutant K64A implied that conserved Lys64 might play an essential role in the structural stability of tau class GSTs. The mutant E78A, supposed to be deprived of hydrogen and salt bonds between subunits, appeared in the soluble form of dimers, even though its tertiary structure altered and stability declined dramatically. These results suggest that the hydrogen and ionic bonds provided by conserved residues are not as important for OsGSTU17 dimerization and enzymatic properties. These results further supplement our understanding of the relationship between the structure and function of GSTs and provide a theoretical basis for improving crop resistance through targeted modification of GSTs. [ABSTRACT FROM AUTHOR]

Heart diseases (HDs) are the leading cause of mortality worldwide, with mitochondrial dysfunction being a significant factor in their development. The recently discovered mitophagy receptor, FUNDC1, plays a critical role in regulating the homeostasis of the Mitochondrial Quality Control (MQC) system and contributing to HDs. The phosphorylation of specific regions of FUNDC1 and varying levels of its expression have been shown to have diverse effects on cardiac injury. This review presents a comprehensive consolidation and summary of the latest evidence regarding the role of FUNDC1 in the MQC system. The review elucidates the association of FUNDC1 with prevalent HDs, such as metabolic cardiomyopathy (MCM), cardiac remodeling/heart failure, and myocardial ischemia-reperfusion (IR) injury. The results indicate that the expression of FUNDC1 is elevated in MCM but reduced in instances of cardiac remodeling, heart failure, and myocardial IR injury, with divergent impacts on mitochondrial function among distinct HDs. Exercise has been identified as a powerful preventive and therapeutic approach for managing HDs. Additionally, it has been suggested that exercise-induced enhancement of cardiac function may be attributed to the AMPK/FUNDC1 pathway. [ABSTRACT FROM AUTHOR]

Although the benefits of aerobic exercise on obesity and type 2 diabetes are well-documented, the pathogenesis of type 2 diabetes and the intervention mechanism of exercise remain ambiguous. The correlation between mitochondrial quality and metabolic diseases has been identified. Disruption of the central or peripheral molecular clock can also induce chronic metabolic diseases. In addition, the interactive effects of the molecular clock and mitochondrial quality have attracted extensive attention in recent years. Exercise and a high-fat diet have been considered external factors that may change the molecular clock and metabolic state. Therefore, we utilized a DB/DB (BSK.Cg-Dock7m +/+ Leprdb/JNju) mouse model to explore the effect of chrono-aerobic exercise on the metabolic state of type 2 diabetic mice and the effect of timing exercise as an external rhythm cue on liver molecular clock-mitochondrial quality. We found that two differently timed exercises reduced the blood glucose and serum cholesterol levels in DB/DB mice, and compared with night exercise (8:00 p.m., the active period of mice), morning exercise (8:00 a.m., the sleeping period of mice) significantly improved the insulin sensitivity in DB/DB mice. In contrast, type 2 diabetes mellitus (T2DM) increased the expression of CLOCK and impaired the mitochondrial quality (mitochondrial networks, OPA1, Fis1, and mitophagy), as well as induced apoptosis. Both morning and night exercise ameliorated impaired mitochondrial quality and apoptosis induced by diabetes. However, compared with morning exercise, night exercise not only decreased the protein expression of CLOCK but also decreased excessive apoptosis. In addition, the expression of CLOCK was negatively correlated with the expression of OPA1 and Fis1. In summary, our research suggests that morning exercise is more beneficial for increasing insulin sensitivity and promoting glucose transport in T2DM, whereas night exercise may improve lipid infiltration and mitochondrial abnormalities through CLOCK–mitophagy–apoptosis in the liver, thereby downregulating glucose and lipid disorders. In addition, CLOCK-OPA1/Fis1–mitophagy might be novel targets for T2DM treatment. [ABSTRACT FROM AUTHOR]

Meat color traits directly influence consumer acceptability and purchasing decisions. Nevertheless, there is a paucity of comprehensive investigation into the genetic mechanisms underlying meat color traits in pigs. Utilizing genome-wide association studies (GWAS) on five meat color traits and the detection of selection signatures in pig breeds exhibiting distinct meat color characteristics, we identified a promising candidate SNP, 6_69103754, exhibiting varying allele frequencies among pigs with different meat color characteristics. This SNP has the potential to affect the redness and chroma index values of pork. Moreover, transcriptome-wide association studies (TWAS) analysis revealed the expression of candidate genes associated with meat color traits in specific tissues. Notably, the largest number of candidate genes were observed from transcripts derived from adipose, liver, lung, spleen tissues, and macrophage cell type, indicating their crucial role in meat color development. Several shared genes associated with redness, yellowness, and chroma indices traits were identified, including RINL in adipose tissue, ENSSSCG00000034844 and ITIH1 in liver tissue, TPX2 and MFAP2 in lung tissue, and ZBTB17, FAM131C, KIFC3, NTPCR, and ENGSSSCG00000045605 in spleen tissue. Furthermore, single-cell enrichment analysis revealed a significant association between the immune system and meat color. This finding underscores the significance of the immune system associated with meat color. Overall, our study provides a comprehensive analysis of the genetic mechanisms underlying meat color traits, offering valuable insights for future breeding efforts aimed at improving meat quality. [ABSTRACT FROM AUTHOR]

A well-functioning placenta is crucial for normal gestation and regulates the nutrient, gas, and waste exchanges between the maternal and fetal circulations and is an important endocrine organ producing hormones that regulate both the maternal and fetal physiologies during pregnancy. Placental insufficiency is implicated in spontaneous preterm birth (SPTB). We proposed that deficits in the capacity of the placenta to maintain bioenergetic and metabolic stability during pregnancy may ultimately result in SPTB. To explore our hypothesis, we performed a RNA-seq study in male and female placentas from women with SPTB (<36 weeks gestation) compared to normal pregnancies (≥38 weeks gestation) to assess the alterations in the gene expression profiles. We focused exclusively on Black women (cases and controls), who are at the highest risk of SPTB. Six hundred and seventy differentially expressed genes were identified in male SPTB placentas. Among them, 313 and 357 transcripts were increased and decreased, respectively. In contrast, only 61 differentially expressed genes were identified in female SPTB placenta. The ingenuity pathway analysis showed alterations in the genes and canonical pathways critical for regulating inflammation, oxidative stress, detoxification, mitochondrial function, energy metabolism, and the extracellular matrix. Many upstream regulators and master regulators important for nutrient-sensing and metabolism were also altered in SPTB placentas, including the PI3K complex, TGFB1/SMADs, SMARCA4, TP63, CDKN2A, BRCA1, and NFAT. The transcriptome was integrated with published human placental metabolome to assess the interactions of altered genes and metabolites. Collectively, significant and biologically relevant alterations in the transcriptome were identified in SPTB placentas with fetal sex disparities. Altered energy metabolism, mitochondrial function, inflammation, and detoxification may underly the mechanisms of placental dysfunction in SPTB. [ABSTRACT FROM AUTHOR]

The domestic pig (Sus scrofa) and its subfamilies have experienced long-term and extensive gene flow, particularly in Southeast Asia. Here, we analyzed 236 pigs, focusing on Yunnan indigenous, European commercial, East Asian, and Southeast Asian breeds, using the Pig Genomics Reference Panel (PGRP v1) of Pig Genotype-Tissue Expression (PigGTEx) to investigate gene flow and associated complex traits by integrating multiple database resources. In this study, we discovered evidence of admixtures from European pigs into the genome of Yunnan indigenous pigs. Additionally, we hypothesized that a potential conceptual gene flow route that may have contributed to the genetic composition of the Diannan small-ear pig is a gene exchange from the Vietnamese pig. Based on the most stringent gene introgression scan using the fd statistic, we identified three specific loci on chromosome 8, ranging from 51.65 to 52.45 Mb, which exhibited strong signatures of selection and harbored the NAF1, NPY1R, and NPY5R genes. These genes are associated with complex traits, such as fat mass, immunity, and litter weight, in pigs, as supported by multiple bio-functionalization databases. We utilized multiple databases to explore the potential dynamics of genetic exchange in Southeast Asian pig populations and elucidated specific gene functionalities. [ABSTRACT FROM AUTHOR]

The communication between mitochondria and the endoplasmic reticulum (ER) is facilitated by a dynamic membrane structure formed by protein complexes known as mitochondria-associated membranes (MAMs). The structural and functional integrity of MAMs is crucial for insulin signal transduction, relying heavily on their regulation of intracellular calcium homeostasis, lipid homeostasis, mitochondrial quality control, and endoplasmic reticulum stress (ERS). This article reviews recent research findings, suggesting that exercise may promote the remodeling of MAMs structure and function by modulating the expression of molecules associated with their structure and function. This, in turn, restores cellular homeostasis and ultimately contributes to the amelioration of insulin resistance (IR). These insights provide additional possibilities for the study and treatment of insulin resistance-related metabolic disorders such as obesity, diabetes, fatty liver, and atherosclerosis. [ABSTRACT FROM AUTHOR]

The teat number is a pivotal reproductive trait that significantly influences the survival rate of piglets. A meta-analysis is a robust instrument, enhancing the universality of research findings and improving statistical power by increasing the sample size. This study aimed to identify universal candidate genes associated with teat number traits using a genome-wide association study (GWAS) meta-analysis with three breeds. We identified 21 chromosome threshold significant single-nucleotide polymorphisms (SNPs) associated with five teat number traits in single-breed and cross-breed meta-GWAS analyses. Using a co-localization analysis of expression quantitative trait loci and GWAS loci, we detected four unique genes that were co-localized with cross-breed GWAS loci associated with teat number traits. Through a meta-analysis and integrative analysis, we identified more reliable candidate genes associated with multiple-breed teat number traits. Our research provides new information for exploring the genetic mechanism affecting pig teat number for breeding selection and improvement. [ABSTRACT FROM AUTHOR]

Pear black spot disease, caused by Alternaria alternata, is a devastating disease in pears and leads to enormous economic losses worldwide. In this investigation, we isolated a Streptomyces odonnellii SZF-179 from the rhizosphere soil of pear plants in China. Indoor confrontation experiments results showed that both SZF-179 and its aseptic filtrate had excellent inhibitory effects against A. alternata. Afterwards, the main antifungal compound of SZF-179 was identified as polyene, with thermal and pH stability in the environment. A microscopic examination of A. alternata mycelium showed severe morphological abnormalities caused by SZF-179. Protective studies showed that SZF-179 fermentation broth could significantly reduce the diameter of the necrotic lesions on pear leaves by 42.25%. Furthermore, the potential of fermentation broth as a foliar treatment to control black leaf spot was also evaluated. Disease indexes of 'Hosui' and 'Wonwhang' pear plants treated with SZF-179 fermentation broth were lower than that of control plants. Overall, SZF-179 is expected to be developed into a safe and broad-spectrum biocontrol agent. No studies to date have evaluated the utility of S. odonnellii for the control of pear black spot disease; our study fills this research gap. Collectively, our findings provide new insights that will aid the control of pear black spot disease, as well as future studies of S. odonnellii strains. [ABSTRACT FROM AUTHOR]

Metabolic diseases are growing in prevalence worldwide. Although the pathogenesis of metabolic diseases remains ambiguous, the correlation between cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) and metabolic diseases has been identified recently. Exercise is an effective intervention protecting against metabolic diseases, however, the role of the cGAS-STING signaling pathway in this process is unclear, and the effect and mechanism of different exercise intensities on metabolic disorders are still unknown. Thus, we explored the association between exercise to ameliorate HFD-induced metabolic disorders and the cGAS-STING signaling pathway and compared the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT). Male C57BL/6 mice (6–8 weeks old) were fed HFD for 8 weeks to establish a metabolic disease model and were subjected to 8-week MICT or HIIT training. Glucose tolerance tests (GTT) and insulin tolerance tests (ITT) were used to assess glucose metabolism. Serum triglyceride (TG) and total cholesterol (TC) were measured to evaluate lipid metabolism. Oil red staining was used to observe the lipid droplets in the gastrocnemius muscle. An enzyme-linked immunosorbent assay was used to detect the serum inflammatory factors IL-6 and IFN-β. The protein expression of the cGAS-STING signaling pathway was detected by the WesTM automatic protein expression analysis system. We reported that HFD induced metabolic disorders with obesity, abnormal glucolipid metabolism, and significant inflammatory responses. Both HIIT and MICT ameliorated the above adverse reactions, but MICT was superior to HIIT in improving glucolipid disorders. Additionally, HIIT significantly increased the expression of STING protein, as well as the phosphorylation of TBKI and the ratio of p-IRF3/IRF3. MICT only increased the expression of STING protein. Our findings suggest that HIIT may alleviate HFD-induced metabolic disorder phenotype through the cGAS-STING signaling pathway. However, the improvement of MICT on metabolic disorder phenotype is less associated with the cGAS-STING pathway, which needs to be further explored. [ABSTRACT FROM AUTHOR]

Meat quality is an important economic trait that influences the development of the pig industry. Skeletal muscle development and glycolytic potential (GP) are two crucial aspects that significantly impact meat quality. It has been reported that abnormal skeletal muscle development and high glycogen content results in low meat quality. However, the genetic mechanisms underlying these factors are still unclear. Compared with intensive pig breeds, Chinese indigenous pig breeds, such as the Jinhua pig, express superior meat quality characteristics. The differences in the meat quality traits between Jinhua and intensive pig breeds make them suitable for uncovering the genetic mechanisms that regulate meat quality traits. In this study, the Jinhua pig breed and five intensive pig breeds, including Duroc, Landrace, Yorkshire, Berkshire, and Pietrain pig breeds, were selected as experimental materials. First, the FST and XP-EHH methods were used to screen the selective signatures on the genome in the Jinhua population. Then, combined with RNA-Seq data, the study further confirmed that SOCS3 could be a key candidate gene that influences meat quality by mediating myoblast proliferation and glycometabolism because of the down-regulated expression of SOCS3 in Jinhua pigs compared with Landrace pigs. Finally, through SOCS3 knockout (KO) and overexpression (OE) experiments in mouse C2C12 cells, the results showed that SOCS3 regulated the cell proliferation of myoblasts. Moreover, SOCS3 is involved in regulating glucose uptake by the IRS1/PI3K/AKT signaling pathway. Overall, these findings provide a basis for the genetic improvement of meat quality traits in the pig industry. [ABSTRACT FROM AUTHOR]

Modern sugarcane cultivars were generated through interspecific crossing of the stress resistance Saccharum spontaneum and the high sugar content Saccharum officinarum which was domesticated from Saccharum robustum. Magnesium deficiency (MGD) is particularly prominent in tropical and subtropical regions where sugarcane is grown, but the response mechanism to MGD in sugarcane remains unknown. Physiological and transcriptomic analysis of the three founding Saccharum species under different magnesium (Mg) levels was performed. Our result showed that MGD decreased chlorophyll content and photosynthetic efficiency of three Saccharum species but led to increased starch in leaves and lignin content in roots of Saccharum robustum and Saccharum spontaneum. We identified 12,129, 11,306 and 12,178 differentially expressed genes (DEGs) of Saccharum officinarum, Saccharum robustum and Saccharum spontaneum, respectively. In Saccharum officinarum, MGD affected signal transduction by up-regulating the expression of xylan biosynthesis process-related genes. Saccharum robustum, responded to the MGD by regulating the expression of transcription and detoxification process-related genes. Saccharum spontaneum, avoids damage from MGD by regulating the expression of the signing transduction process and the transformation from growth and development to reproductive development. This novel repertoire of candidate genes related to MGD response in sugarcane will be helpful for engineering MGD tolerant varieties. [ABSTRACT FROM AUTHOR]

Alisol B 23-acetate (AB23A), a natural triterpenoid, has been reported to exert hepatoprotective and antitumor activities. Aiming to investigate the anti-inflammatory activity, this study examined the effect of AB23A on mast cells and allergic reaction. AB23A inhibited the degranulation of mast cells stimulated by immunoglobulin E/antigen (IgE/Ag), and also decreased the synthesis of leukotriene C4 (LTC4), production of interlukin-6 (IL-6), and expression of cyclooxygenase-2 (COX-2) in a concentration-dependent manner with no significant cytotoxicity in bone marrow-derived mast cells (BMMCs). AB23A inhibited spleen tyrosine kinase (Syk) and the downstream signaling molecules including phospholipase Cγ (PLCγ), serine-threonine protein kinase/inhibitor of nuclear factor kappa-B kinase/nuclear factor kappa-B (Akt/IKK/NF-κB), and mitogen-activated protein kinases/cytosolic phospholipase A2 (MAPK/cPLA2). Furthermore, AB23A blocked mobilization of Ca2+. Similar results were obtained in other mast cell lines Rat basophilic leukemia (RBL)-2H3 cells and a human mast cell line (HMC-1). In addition, AB23A attenuated allergic responses in an acute allergy animal model, passive cutaneous anaphylaxis (PCA). Taken together, this study suggests that AB23A inhibits the activation of mast cells and ameliorates allergic reaction, and may become a lead compound for the treatment of mast cell-mediated allergic diseases. [ABSTRACT FROM AUTHOR]