作者机构：
[Liu, Hongnan; Wang, Shanshan; Li, Rui; Wu, Yuliang; Xiong, Xia; Qi, Ming; Peng, Can; Yin, Yulong; Shao, Yirui; Peng, Changfeng] Chinese Acad Sci, CAS Key Lab Agroecol Proc Subtrop Reg, Hunan Prov Key Lab Anim Nutr Physiol & Metab Proc, Natl Engn Lab Pollut Control & Waste Utilizat Live, Changsha 410125, Peoples R China.;[Qi, Ming; Shao, Yirui] Univ Chinese Acad Sci, Beijing 100008, Peoples R China.;[Peng, Qingyun] Kemin China Technol Co Ltd, Zhuhai 519040, Peoples R China.;[Wu, Yuliang] Hunan Normal Univ, Coll Life Sci, Lab Anim Nutr & Human Hlth, Changsha 410081, Peoples R China.;[Peng, Changfeng] Hunan Agr Univ, Coll Anim Sci & Technol, Changsha 410000, Peoples R China.
通讯机构：
[Rui Li] C;CAS Key Laboratory of Agro-Ecological Processes in Subtropical Region, Hunan Province Key Laboratory of Animal Nutritional Physiology and Metabolic Process, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha 410125, China<&wdkj&>Author to whom correspondence should be addressed.
摘要：
Essential oils (EO) are promising feed additives for their antibacterial, antioxidant, and immune-enhancing abilities with low toxicity. Carvacrol, thymol, and cinnamaldehyde are commonly used to synthesize EO. However, few studies focus on combining these three EO in early-weaned piglets. In the present study, 24 piglets weaned at 21 d of age were randomly divided into 2 groups (6 replicate pens per group, 2 piglets per pen). The piglets were fed a basal diet (the control group) and a basal diet supplemented with 400 mg/kg EO (a blend consisting of carvacrol, thymol, and cinnamaldehyde, the EO group) for 28 days. At the end of the experiment, one piglet per pen was randomly chosen to be sacrificed. Growth performance, hematology, plasma biochemical indices, antioxidant capacity, intestinal epithelial development and immunity, colonic volatile fatty acids (VFA), and microbiota were determined. The results indicated that the diet supplemented with EO significantly improved average daily feed intake (ADFI, p < 0.01) and average daily gain (ADG, p < 0.05) in the day 0 to 28 period. EO supplementation led to a significant decrease in plasma lysozyme (p < 0.05) and cortisol levels (p < 0.01). Additionally, EO significantly promoted jejunal goblet cells in the villus, jejunal mucosa ZO-1 mRNA expression, ileal villus height, and ileal villus height/crypt depth ratio in piglets (p < 0.05). The ileal mucosal TLR4 and NFκB p-p65/p65 protein expression were significantly inhibited in the EO group (p < 0.05). Colonic digesta microbiota analysis revealed that bacteria involving the Erysipelotrichaceae family, Holdemanella genus, Phascolarctobacterium genus, and Vibrio genus were enriched in the EO group. In conclusion, these findings indicate that the EO blend improves ADG and ADFI in the day 0 to 28 period, as well as intestinal epithelial development and intestinal immunity in early-weaned piglets, which provides a theoretical basis for the combined use of EO in weaned piglets.
通讯机构：
[Shusong Wu; Jianhua He] A;Authors to whom correspondence should be addressed.<&wdkj&>Hunan Collaborative Innovation Center for Utilization of Botanical Functional Ingredients, College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China<&wdkj&>Authors to whom correspondence should be addressed.
关键词：
sow;oxidative stress;pregnancy;maternal metabolism;placenta;fetal development
摘要：
In the past few decades, many researchers believed that a high-fat and high-calorie diet is the most critical factor leading to metabolic diseases. However, increasing evidence shows a high-carbohydrate and low-fat diet may also be a significant risk factor. It needs a comprehensive evaluation to prove which viewpoint is more persuasive. We systematically compared the effects of high-fat and high-calorie diets and high-carbohydrate and low-fat ones on glycolipid metabolism in mice to evaluate and compare the effects of different dietary patterns on metabolic changes in mice. Sixty 8-week-old male C57BL/6 mice were divided into four groups after acclimatization and 15% (F-15), 25% (F-25), 35% (F-35), and 45% (F-45) of their dietary energy was derived from fat for 24 weeks. The body weight, body-fat percentage, fasting blood glucose, lipid content in the serum, and triglyceride content in the livers of mice showed a significantly positive correlation with dietary oil supplementation. Interestingly, the total cholesterol content in the livers of mice in the F-15 group was significantly higher than that in other groups (p < 0.05). Compared with the F-45 group, the mRNA expression of sterol synthesis and absorption-related genes (e.g., Asgr1, mTorc1, Ucp20, Srebp2, Hmgcr, and Ldlr), liver fibrosis-related genes (e.g., Col4a1 and Adamts1) and inflammation-related genes (e.g., Il-1 beta and Il-6) were significantly higher in the F-15 group. Compared with the F-45 group, the relative abundance of unclassified_f_Lachnospiraceae and Akkermansia was decreased in the F-15 group. While unclassified_f_Lachnospiraceae and Akkermansia are potentially beneficial bacteria, they have the ability to produce short-chain fatty acids and modulate cholesterol metabolism. In addition, the relative abundance of unclassified_f_Lachnospiraceae and Akkermansia was significantly positively correlated with fatty acid transporters expression and negatively correlated with that of cholesteryl acyltransferase 1 and cholesterol synthesis-related genes. In conclusion, our study delineated how a high-fat and high-calorie diet (fat supplied higher than or equal to 35%) induced obesity and hepatic lipid deposition in mice. Although the high-carbohydrate and low-fat diet did not cause weight gain in mice, it induced cholesterol deposition in the liver. The mechanism is mainly through the induction of endogenous synthesis of cholesterol in mice liver through the ASGR1-mTORC1-USP20-HMGCR signaling pathway. The appropriate oil and carbon water ratio (dietary energy supply from fat of 25%) showed the best gluco-lipid metabolic homeostasis in mice.
摘要：
A growing number of in vivo studies demonstrated that β-hydroxy-β-methyl butyrate (HMB) can serve as a lipid-lowering nutrient. Despite this interesting observation, the use of adipocytes as a model for research is yet to be explored. To ascertain the effects of HMB on the lipid metabolism of adipocytes and elucidate the underlying mechanisms, the 3T3-L1 cell line was employed. Firstly, serial doses of HMB were added to 3T3-L1 preadipocytes to evaluate the effects of HMB on cell proliferation. HMB (50 µM) significantly promoted the proliferation of preadipocytes. Next, we investigated whether HMB could attenuate fat accumulation in adipocytes. The results show that HMB treatment (50 µM) reduced the triglyceride (TG) content. Furthermore, HMB was found to inhibit lipid accumulation by suppressing the expression of lipogenic proteins (C/EBPα and PPARγ) and increasing the expression of lipolysis-related proteins (p-AMPK, p-Sirt1, HSL, and UCP3). We also determined the concentrations of several lipid metabolism-related enzymes and fatty acid composition in adipocytes. The HMB-treated cells showed reduced G6PD, LPL, and ATGL concentrations. Moreover, HMB improved the fatty acid composition in adipocytes, manifested by increases in the contents of n6 and n3 PUFAs. The enhancement of the mitochondrial respiratory function of 3T3-L1 adipocytes was confirmed via Seahorse metabolic assay, which showed that HMB treatment elevated basal mitochondrial respiration, ATP production, H(+) leak, maximal respiration, and non-mitochondrial respiration. In addition, HMB enhanced fat browning of adipocytes, and this effect might be associated with the activation of the PRDM16/PGC-1α/UCP1 pathway. Taken together, HMB-induced changes in the lipid metabolism and mitochondrial function may contribute to preventing fat deposition and improving insulin sensitivity.
通讯机构：
[Rui Li; Peng Liao] L;Laboratory of Animal Nutritional Physiology and Metabolic Process, Key Laboratory of Agro-ecological Processes in Subtropical Region, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha 410125, China
摘要：
Attapulgite is a kind of natural clay mineral. Its unique pore structure makes it an ideal adsorption material and carrier material. However, the beneficial effect of modified attapulgites (SLK) in livestock is still unknown. The study was aimed to investigate the beneficial effect of modified attapulgites on diarrhea. 135 piglets were randomly divided into 5 groups and fed with control diet, traditional antibiotic substitute (TAS) supplementation diet, 0.5 mg/kg SLK supplementation diet, 1 mg/kg SLK supplementation diet, and 1.5 mg/kg SLK supplementation diet. This experiment lased two weeks. According to our result, 1.5 mg/kg SLK supplementation diet significantly decreased diarrhea score and diarrhea frequency, and effectively increased survival rate (P < 0.05). Dietary supplementation with 1.5 mg/kg SLK significantly increased high density lipoprotein cholesterol (HDLC), and choline esterase (CHE) concentration in serum (P < 0.05). AS compared with TAS group, 1.5 mg/kg SLK supplementation diet significantly decreased villus height and increased goblet number in jejunum, and increased villus height and decreased goblet number in ileum (P < 0.05). 1.5 mg/kg SLK supplementation diet also significantly changed cecal microbial community composition, including increased Limosilactobacillus abundance (P < 0.05). 1.5 mg/kg SLK supplementation diet significantly increased colonic microbial community composition, including decreased Escherichia-shigella abundance and increased Limosilactobacillus abundance (P < 0.05). Moreover, 1.5 mg/kg SLK supplementation diet significantly increased valerate, propionate, butyrate, and total short chain fatty acid contents in colon (P < 0.05). Valerate, propionate, butyrate, and total short chain fatty acid significantly associated with Lactobacillus. Fourerenilla and Fourerenilla.unclassfied significantly associated with acetate contents in colon (P < 0.05). In conclusion, dietary supplementation with modified apptapulgites significantly regulate intestinal microbial community composition and alleviate intestinal epithelial barrier to prevent diarrhea in piglets.
作者：
Liu, Fenfen;Li, Jing;Ni, Hengjia;Azad, Md. Abul Kalam;Mo, Kaibin;...
期刊：
ANIMALS,2023年13(4):549- ISSN：2076-2615
通讯作者：
Ni, H.;Yin, Y.
作者机构：
[Liu, Fenfen; Ni, Hengjia; Li, Jing; Mo, Kaibin; Yin, Yulong; Azad, Md. Abul Kalam] Chinese Acad Sci, Inst Subtrop Agr, Hunan Res Ctr Livestock & Poultry Sci, Key Lab Agroecol Proc Subtrop Reg,Hunan Provincia, Changsha 410125, Peoples R China.;[Li, Jing] Hunan Agr Univ, Dept Anim Sci, Changsha 410125, Peoples R China.;[Mo, Kaibin] South China Agr Univ, Coll Vet Med, Guangzhou 510642, Peoples R China.
通讯机构：
[Yulong Yin; Hengjia Ni] A;Authors to whom correspondence should be addressed.<&wdkj&>Key Laboratory of Agro-Ecological Processes in Subtropical Region, Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, Hunan Research Center of Livestock and Poultry Sciences, South Central Experimental Station of Animal Nutrition and Feed Science in the Ministry of Agriculture, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha 410125, China
摘要：
Simple Summary Phytase and NSPase have been widely used to improve growth performance in swine by improving nutrient utilization. However, the effects of phytase and NSPase (beta-glucanase, xylanase, and beta-mannanase) with corn-soybean meal-based diets on the trace element deposition of pigs still remains unknown. In this study, the effects of phytase, beta-glucanase, xylanase, and beta-mannanase on the trace element deposition and intestinal health of growing-finishing pigs were compared. In conclusion, phytase and xylanase supplementation increased the zinc deposition in pigs. Additionally, the supplementation of NSPases may improve the gut health of pigs by modulating the intestinal morphology and microbiota. This study investigated the effects of supplementing phytase and non-starch polysaccharide-degrading enzymes (NSPases) to corn-soybean meal-based diet on the growth performance, trace element deposition, and intestinal health of growing-finishing pigs. Fifty pigs were randomly assigned into the control (basal diet), phytase (basal diet + 100 g/t of phytase), beta-mannanase (basal diet + 40 g/t of beta-mannanase), beta-glucanase (basal diet + 100 g/t of beta-glucanase), and xylanase (basal diet + 100 g/t of xylanase) groups. The results show that the supplementation of phytase and NSPases had no impacts (p > 0.05) on the growth performance of pigs. Compared with the control group, pigs fed with xylanase had higher (p < 0.05) Zn concentrations in the ileum and muscle and those fed with phytase had higher (p < 0.05) Zn concentrations in the ileum. Phytase and xylanase supplementation decreased (p < 0.05) fecal Zn concentrations in pigs compared with the control group (p < 0.05). In addition, phytase, beta-mannanase, beta-glucanase, and xylanase supplementation up-regulated (p < 0.05) the FPN1 expression, whereas xylanase up-regulated (p < 0.05) the Znt1 expression in the duodenum of pigs compared with the control group. Moreover, phytase, beta-glucanase, and xylanase supplementation up-regulated (p < 0.05) the jejunal Znt1 expression compared with the control group. The intestinal morphology results show that the phytase, beta-mannanase, and xylanase groups had increased villus heights (VHs), an increased villus height-crypt depth ratio (VH:CD), and decreased crypt depths (CDs) in the duodenum, whereas phytase, beta-mannanase, beta-glucanase, and xylanase groups had decreased VH and VH:CD, and increased CD in the jejunum compared with the control group (p < 0.05). Pigs fed with exogenous enzymes had decreased bacterial diversity in the cecum. The dietary supplementation of NSPases increased the relative abundance of Firmicutes and decreased spirochaetes (p < 0.05). Compared with the control group, dietary NSPase treatment decreased (p < 0.05) the opportunistic pathogens, such as Treponema_2 and Eubacterium_ruminantium. Moreover, the relative abundances of Lachnospiraceae_XPB1014 and Lachnospiraceae were enriched in the beta-glucanase and beta-mannanase groups (p < 0.05), respectively. In conclusion, phytase and xylanase supplementation may promote zinc deposition in pigs. Additionally, the supplementation of NSPases may improve the gut health of pigs by modulating the intestinal morphology and microbiota.
通讯机构：
[Qinghua Chen] C;College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China<&wdkj&>Author to whom correspondence should be addressed.
关键词：
piglets;weaning stress;fermented chinese herbal medicine;nutrients digestibility;intestinal health
摘要：
Simple Summary Fermented Chinese herbs can be used as a natural additive in the diet of weaned pigs, and they can play an important role in regulating microbial flora and intestinal health. This study aimed to investigate fermented Chinese herb supplementation in newly weaned piglets' diets and its effects on intestinal microbial composition and growth performance. Studies have found that dietary supplementation of fermented Chinese herbs can promote intestinal health and improve growth performance of weaned piglets by regulating intestinal flora. To investigate the effects of fermented Chinese herbal medicine on growth performance, diarrhea rate, nutrient digestibility, and intestinal health of weaned piglets, and to provide the theoretical basis for applying fermented Chinese herbal medicines to weaned piglet production, a total of 162 weaned and castrated piglets at 25 days of age (Duroc x Landrace x Yorkshire, half male and half female) with an initial body weight of 7.77 +/- 0.03 kg were randomly divided into the following three groups according to the principle of similar body weight: basal diet (CON) group, basal diet + 3 kg/t fermented Chinese herbal medicine (LFHM) group, and basal diet + 5 g/kg fermented Chinese herbal medicine (HFHM) group. Each group underwent six replicates and there were nine piglets in each replicate. The experiment lasted 24 days, i.e., 3 days for preliminary feeding, and 21 days for the experiment. From Day 1 of the experiment, the piglets were observed and recorded for diarrhea each day. As compared with the CON group, the results indicated: Following the addition of fermented Chinese herbal medicine, the piglets in the LFHM and HFHM groups increased final weight (FW); average daily feed intake (ADFI); average daily gain (ADG) (p < 0.01); apparent digestibility of crude protein (CP) (p < 0.05); as well as chymotrypsin, alpha-amylase, and lipase activities (p < 0.01). In addition, alpha-amylase activity in the LFHM group was higher than that in the HFHM group (p < 0.05); chymotrypsin activity in the LFHM group was lower than that in the HFHM group (p < 0.05); as compared with the CON group, the LFHM and the HFHM increased villus height (VH) and crypt depth (CD) in piglet jejunum; isovaleric acid concentration with the HFHM was higher than those with the CON and the LFHM (p < 0.05), but butyrate concentration with the HFFM was lower than those with the CON and the LFHM (p < 0.05). The high-throughput 16S rRNA sequencing of intestinal microbiota results showed that the LFHM and the HFHM affected the microbial alpha diversity index in weaned piglet colon (p < 0.01). In conclusion, fermented Chinese herbs can improve the growth performance of weaned piglets by promoting the secretion of intestinal digestive enzymes, changing intestinal microbial diversity, regulating the contents of intestinal short chain fatty acids (SCFAs), promoting intestinal health, and improving nutrients digestibility.
通讯机构：
[Kang Yao; Qian Jiang] A;Authors to whom correspondence should be addressed.<&wdkj&>National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Laboratory of Animal Nutritional Physiology and Metabolic Process, Key Laboratory of Agro-Ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha 410125, China<&wdkj&>College of Animal Science and Technology, Hunan Agricultural University, Changsha 410000, China<&wdkj&>Authors to whom correspondence should be addressed.<&wdkj&>National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Laboratory of Animal Nutritional Physiology and Metabolic Process, Key Laboratory of Agro-Ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha 410125, China<&wdkj&>Institute of Subtropical Agriculture, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Beijing 100008, China
关键词：
alpha-ketoglutarate;bone growth;apparent digestibility of phosphorus;piglets
摘要：
Simple Summary Intensive farming in the modern pig industry has resulted in an increase in phosphorus pollution, which is a major environmental concern. The dietary intake of phosphorus is primarily employed for the growth and metabolism of pig bones. Dietary strategies to improve bone growth can be utilized to optimize the utilization of dietary phosphorus and reduce its release into the environment. Interestingly, recent studies have shown that alpha-ketoglutarate, an intermediate metabolite in the tricarboxylic acid cycle, improves osteogenesis in vitro. Therefore, we hypothesized that dietary alpha-ketoglutarate supplementation would have a positive effect on bone growth, and thereby improve the utilization of dietary phosphorus and calcium in piglets. In the present study, we found that dietary alpha-ketoglutarate supplementation improves bone growth, such as bone density, length, and weight in piglets. Of note, our study further demonstrated that alpha-ketoglutarate supplementation improves the apparent ileal and total tract digestibility of phosphorus and calcium in piglets' diets. Our findings may provide a nutritional strategy for diminishing phosphorus pollution originating from the pig industry. Phosphorus (P) pollution from modern swine production is a major environmental problem. Dietary interventions to promote bone growth can improve the utilization of dietary P, and thereby reduce its emission. Recent in vitro studies have shown that alpha-ketoglutarate (AKG) exerts a pro-osteogenic effect on osteoblast cells. This study aimed to evaluate the effects of AKG supplementation on bone growth, P and Ca digestion, and the gut microbial profile in piglets. Thirty-two piglets were randomly assigned into two dietary groups. The piglets were fed a basic diet containing 10 g/kg AKG or 10 g/kg maize starch (control) for 28 days. On days 21-28, titanium dioxide was used as an indicator to determine the apparent digestibility of P. AKG supplementation improved the bone mineral density, length, weight, and geometrical and strength properties of the femur and tibia. Furthermore, AKG supplementation increased apparent ileal and total tract digestibility of P. Colonic microbiota analysis results showed that AKG supplementation increased alpha-diversity and beneficial bacteria, including Lactobacillus and Clostridium butyricum, and decreased nitrogen fixation and chemoheterotrophy. Together, AKG supplementation improves bone growth, the utilization of dietary P, and the colonic microbial profile, which may provide a nutritional strategy for diminishing P pollution originating from the pig industry.
摘要：
Simple Summary Nowadays, iron complexation of polysaccharides has recently become a popular topic in glycobiology research. A macromolecular polysaccharide known as polysaccharide-iron complex can affect blood pressure, blood sugar levels, immunity, blood circulation, and has the potential to improve and regulate active substances that exist in animal blood. In this study, an organic iron complex generated from tapioca starch and ferric chloride was utilized. This product is a self-developed, plant-derived, natural compound that has a wide variety of sources and is cost-effective. The results of this study demonstrate that maternal supplementary tapioca polysaccharide iron can improve their feed intake and reproductive performance, adjust the nutritional composition of colostrum, enhance the antioxidant and immunological performance of piglets, and stimulate hormone release in blood, leading to enhanced piglet production performance. Furthermore, this study reveals the correlation between the components of colostrum, cord blood, and piglet performance when sows are fed supplements with tapioca polysaccharide iron. The purpose of this study was to investigate the effect of maternal supplementation with TpFe (tapioca polysaccharide iron) on reproductive performance, colostrum composition, cord blood active components of sows, and growth performance of their nursing piglets. Sixty healthy Duroc x Landrace x Yorkshire sows were randomly assigned to three groups at day 85 of gestation. The experimental diets included a basal diet supplemented with 100 mg/kg FeSO4 & BULL;H2O (CON group), the basal diet supplemented with 50 mg/kg TpFe (TpFe50 group), and the basal diet supplemented with 100 mg/kg TpFe (TpFe100 group), as calculated by Fe content. The experiment lasted from day 85 of gestation to the end of weaning (day 21 of lactation). Results showed that maternal supplementation with 100 mg/kg TpFe improved (p < 0.05) feed intake during lactation, live births, and birth weight of the litter (alive) and increased (p < 0.05) colostrum IgM (immunoglobulin m), IgA (immunoglobulin A), as well as the IgG levels, while it decreased (p < 0.05) the urea nitrogen and somatic cell count of sows. Moreover, sows in the TpFe100 group had higher (p < 0.05) serum iron levels and IgG. Additionally, maternal supplementation with 100 mg/kg TpFe increased (p < 0.05) iron level, total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-px), catalase (CAT), IgG, red blood cells (RBC), and hemoglobin (Hb) of cord blood, similar with the iron content, T-AOC, GSH-px, IgG, RBC, Hb, hematocrit (HCT), and mean corpuscular volume (MCV) of weaned piglet blood. The diarrhea and mortality rates among the nursing piglets were decreased (p < 0.05), while the average weight at day 21 of age was increased (p < 0.05) in the TpFe100 group. Serum PRL (prolactin) levels of sows exhibited a positive correlation (p < 0.05) with live births. Suckling piglet diarrhea was positively correlated with colostrum urea nitrogen level but negatively correlated with colostrum IgM, IgG, and cord blood Hb content (p < 0.05). The mortality of suckling piglets was negatively correlated with serum iron content and IgM in colostrum, GSH-px, and IgG in cord serum of sows (p < 0.05). The average weight of weaning piglets was positively (p < 0.05) related to colostrum IgM and IgG levels, as well as cord serum RBC counts of sows on day 21. In conclusion, maternal supplementation with TpFe can improve the active components of colostrum and umbilical cord blood and improve the growth performance of suckling piglets.
摘要：
RNA N6-methyladenosine (m(6)A ) modification is one of the principal post-transcriptional modifications and plays a dynamic role in testicular development and spermatogenesis. However, the role of m(6)A in porcine testis is understudied. Here, we performed a comprehensive analysis of the m(6)A transcriptome-wide profile in Shaziling pig testes at birth, puberty, and maturity. We analyzed the total transcriptome m(6)A profile and found that the m(6)A patterns were highly distinct in terms of the modification of the transcriptomes during porcine testis development. We found that key m(6)A methylated genes (AURKC, OVOL, SOX8, ACVR2A, and SPATA46) were highly enriched during spermatogenesis and identified in spermatogenesis-related KEGG pathways, including Wnt, cAMP, mTOR, AMPK, PI3K-Akt, and spliceosome. Our findings indicated that m(6)A methylations are involved in the complex yet well-organized post-transcriptional regulation of porcine testicular development and spermatogenesis. We found that the m(6)A eraser ALKBH5 negatively regulated the proliferation of immature porcine Sertoli cells. Furthermore, we proposed a novel mechanism of m(6)A modification during testicular development: ALKBH5 regulated the RNA methylation level and gene expression of SOX9 mRNA. In addition to serving as a potential target for improving boar reproduction, our findings contributed to the further understanding of the regulation of m(6)A modifications in male reproduction.
摘要：
Innate immunity is the first line of defense against viral pathogens. Retinoic Acid-Inducible Gene 1 (RIG-I) is a pattern recognition receptor that recognizes virus-associated double-stranded RNA and initiates the interferon responses. Besides signal transduction, RIG-I exerts direct antiviral functions to displace viral proteins on dsRNA via its Helicase activity. Nevertheless, this effector-like activity of RIG-I against herpesviruses remains largely unexplored. It has been previously reported that herpesviruses deamidate RIG-I, resulting in the abolishment of its Helicase activity and signal transduction. In this study, we discovered that RIG-I possessed signaling-independent antiviral activities against murine gamma herpesviruses 68 (γHV68, murid herpesvirus 4). Importantly, a Helicase-dead mutant of RIG-I (K270A) demonstrated comparable inhibition on herpesviruses lytic replication, indicating that this antiviral activity is Helicase-independent. Mechanistically, RIG-I bound the Replication and Transcription Activator (RTA) and diminished its nuclear localization to repress viral transcription. We further demonstrated that RIG-I blocked the nuclear translocation of ORF21 (Thymidine Kinase), ORF75c (vGAT), both of which form a nuclear complex with RTA and RNA polymerase II (Pol II) to facilitate viral transcription. Moreover, RIG-I retained ORF59 (DNA processivity factor) in the cytoplasm to repress viral DNA replication. Altogether, we illuminated a previously unidentified, Helicase-independent effector-like function of RIG-I against γHV68, representing an exquisite host strategy to counteract viral manipulations on innate immune signaling. IMPORTANCE: Retinoic acid-inducible gene I (RIG-I), a member of DExD/H box RNA helicase family, functions as a key pattern recognition receptor (PRR) responsible for the detection of intracellular double-stranded RNA (dsRNA) from virus-infected cells and induction of type I interferon (IFN) responses. Nevertheless, our understanding of the helicase-independent effector-like activity of RIG-I against virus infection, especially herpesvirus infection, remains largely unknown. Herein, by deploying murine gamma herpesviruses 68 (γHV68) as a model system, we demonstrated that RIG-I possessed an interferon and helicase-independent antiviral activity against γHV68 via blocking the nuclear trafficking of viral proteins, which concomitantly repressed the viral early transcription and genome replication thereof. Our work illuminates a previously unidentified antiviral strategy of RIG-I against herpesvirus infection.
