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Deoxynivalenol (DON), a toxic secondary metabolite produced by Fusarium species that mainly infect cereals, causes huge economic loss to the agricultural industry. Biodegradation has emerged as a promising method owing to its high efficiency, specificity, and environment-friendly. The present study reports the procedures for obtaining a bacterial consortium YM-1 from the intestines of free-range chickens by anaerobic culture in Luria-Bertani (LB) and 96-well plates. The YM-1, mainly composed of Proteus_vulgaris, Tissierella_praeacuta, Fusobacterium_varium, uncultured_bacterium_g_Peptoniphilus, Bacteroides_uniformis, Bacteroides_vulgatus, Bacteroides_thetaiotaomicron, Clostridium_cochlearium, and Eubacterium_limosum, was able to effectively de-epoxidize 50 μg/mL DON by 99.2 % within 24 h under an anaerobic condition. The viability of the intestinal porcine epithelial cell line-J2 (IPEC-J2) was significantly damaged under 0.5 μg/mL, 1 μg/mL, or 2 μg/mL DON exposure. The products of DON degraded by YM-1, mainly consisting of de-epoxy-deoxynivalenol (DOM-1), were validated to be non-toxic to the IPEC-J2 cells. These results indicate the potential use of bacterial consortium YM-1 as a bio-agent for DON decontamination in foods and feeds.

The placenta plays a crucial role in nutrient transport and waste exchange between the dam and fetus, sustaining fetal growth. While the positive effects of 25-hydroxyvitamin D3 (25-OH-D3) on animal performance have been reported, its impact on placental function remains largely unknown. Therefore, this study aimed to investigate the effects of supplementing 25-OH-D3 in the diet of primiparous sows on reproductive performance, antioxidant capacity, placental oxidative stress, nutrient transport, and inflammatory response during mid-to-late gestation. A total of 45 healthy Landrace × Yorkshire primiparous sows on day 60 of gestation were selected and randomly allocated to three treatment groups based on body weight and backfat thickness: the control group (corn-soybean meal basal diet), the VD3 group (basal diet + 2000 IU VD3), and the 25-OH-D3 group (basal diet + 50 μg/kg 25-OH-D3). The results demonstrated that supplementation with 25-OH-D3 in the diet enhanced sows’ average litter weight and birth weight during mid-to-late gestation. Additionally, plasma malondialdehyde (MDA) concentrations in sows significantly decreased in the VD3 and 25-OH-D3 groups (p < 0.05). Furthermore, lower gene expressions of placental HO-1, GPX2, IL-8, and IL-6 were found in the VD3 or 25-OH-D3 groups (p < 0.05 or p < 0.10), while higher gene expressions of GLUT1 and SNAT2 in the placenta of sows were observed in the VD3 and 25-OH-D3 groups, respectively (p < 0.05). These findings indicate that the supplementation of VD3 and 25-OH-D3 in the diet of sows can improve their plasma oxidative stress status, enhance placental antioxidant capacity and nutrient transport, and reduce placental inflammatory responses, with more pronounced improvements in sow performance observed in sows fed diets supplemented with 25-OH-D3.

Abstract Elimination of specific enteropathogenic microorganisms is critical to gut health. However, the complexity of the gut community makes it challenging to target specific bacterial organisms. Accumulating evidence suggests that various foods can change the abundance of intestinal bacteria by modulating prophage induction. By using pathogenic Escherichia coli (E. coli) ATCC 25922 as a model in this research, we explored the potential of dietary modulation of prophage induction and subsequent bacterial survival. Among a panel of sugars tested in vitro, D-xylose was shown to efficiently induce prophages in E. coli ATCC 25922, which depends, in part, upon the production of D-lactic acid. In an enteric mouse model, prophage induction was found to be further enhanced in response to propionic acid. Dietary D-xylose increased the proportion of Clostridia which converted D-lactic acid to propionic acid. Intestinal propionic acid levels were diminished, following either oral gavage with the dehydrogenase gene (ldhA)-deficient E. coli ATCC 25922 or depletion of intestinal Clostridia by administration of streptomycin. D-Xylose metabolism and exposure to propionic acid triggered E. coli ATCC 25922 SOS response that promoted prophage induction. E. coli ATCC 25922 mutant of RecA, a key component of SOS system, exhibited decreased phage production. These findings suggest the potential of using dietary components that can induce prophages as antimicrobial alternatives for disease control and prevention by targeted elimination of harmful gut bacteria.

The gut microbiota constitutes a complex ecosystem, comprising trillions of microbes that have co-evolved with their host over hundreds of millions of years. Over the past decade, a growing body of knowledge has underscored the intricate connections among diet, gut microbiota, and human health. Bioactive polysaccharides (BPs) from natural sources like medicinal plants, seaweeds, and fungi have diverse biological functions including antioxidant, immunoregulatory, and metabolic activities. Their effects are closely tied to the gut microbiota, which metabolizes BPs into health-influencing compounds. Understanding how BPs and gut microbiota interact is critical for harnessing their potential health benefits. This review provides an overview of the human gut microbiota, focusing on its role in metabolic diseases like obesity, type II diabetes mellitus, non-alcoholic fatty liver disease, and cardiovascular diseases. It explores the basic characteristics of several BPs and their impact on gut microbiota. Given their significance for human health, we summarize the biological functions of these BPs, particularly in terms of immunoregulatory activities, blood sugar, and hypolipidemic effect, thus providing a valuable reference for understanding the potential benefits of natural BPs in treating metabolic diseases. These properties make BPs promising agents for preventing and treating metabolic diseases. The comprehensive understanding of the mechanisms by which BPs exert their effects through gut microbiota opens new avenues for developing targeted therapies to improve metabolic health.

Weaning is a challenging period for piglets, characterized by stress-related growth checks, compromised immunity, and gut dysbiosis. Purslane (Portulaca oleracea L.), known for its rich content of antioxidants, has potential as a functional feed ingredient. This study investigates the effects of feeding fermented purslane (FP) on the growth performance, immune function, intestinal microbiota, and metabolic profiles of weaned piglets. Forty-eight weaned piglets were randomly divided into two groups, with eight pens in each group and three pigs in each pen: a control diet (CON group) and a diet supplemented with 0.20% FP (FP group). The experiment lasted 28 days. The results show that FP supplementation did not affect the average daily feed intake (ADFI) but significantly increased the average daily gain (ADG) during the initial 14 days post-weaning. FP supplementation decreased diarrhea occurrence, with a pronounced reduction from days 10 to 13 (p < 0.05). Immunologically, the FP group had a trend towards reduced serum IgA levels on day 14 (p < 0.10). Importantly, the serum concentrations of the pro-inflammatory cytokine IL-6 were significantly reduced on both days 14 and 28 post-weaning. The antioxidative analysis showed increased serum superoxide dismutase (SOD) and decreased catalase (CAT) activities on day 14 (p < 0.05). In addition, FP supplementation significantly decreased serum diamine oxidase (DAO) activity and D-lactate levels by day 28, indicating a potential improvement in gut integrity. Fecal microbiota assessment demonstrated a distinctive clustering of microbial communities between the FP and CON groups, with an increase in the abundance of Clostridium_sensu_stricto_1, Tyzzerella, and Prevotellaceae_NK3B31_group and a decrease in Lactobacillus, Bacillus, and Subdoligranulum in the FP group (p < 0.05). Functional predictions suggested that the relative abundance of microbial butyrate synthesis enzymes (EC 2.7.2.7 and EC 2.3.1.19) was significantly enhanced by FP treatment. This modulation was further corroborated by elevated fecal butyrate levels (p < 0.05). In summary, dietary supplementation with FP promotes early-growth performance and has beneficial effects on immune function and intestinal health in weaned piglets. The enhancements may be attributed to distinct microbiota compositional changes and targeted modulation of microbial butyrate metabolism, which are crucial for piglet post-weaning adaptation and overall health.

Summary: AGPAT2, a critical enzyme involved in the biosynthesis of phospholipids and triacylglycerol (TAG), is highly expressed in adipose tissue (AT). Whether overexpression of AGPAT2 in AT will result in increased TAG synthesis (obesity) and its metabolic complications remains unknown. We overexpressed human AGPAT2 specifically in AT using the adiponectin promoter and report increased mass of subcutaneous, gonadal, and brown AT in wild-type mice. Unexpectedly, overexpression of hAGPAT2 did not change the pattern of phospholipid or TAG concentration of the AT depots. Although there is an increase in liver weight, plasma aspartate aminotransferase, and plasma insulin at various time points of the study, it did not result in significant liver dysfunction. Despite increased adiposity in the Tg-AT-hAGPAT2;mAgpat2+/+ mice, there was no significant increase in TAG concentration of AT. Therefore, this study suggests a role of AGPAT2 in the generation of AT, but not for adipocyte TAG synthesis.

ABSTRACTThe pathogenicity of Escherichia coli (E. coli) O157:H7 is predominantly associated with Shiga toxin 2 (Stx2) that poses a huge threat to human and animal intestinal health. Production of Stx2 requires expression of stx2 gene, which is located in the genome of lambdoid Stx2 prophage. Growing evidence has implicated that many commonly consumed foods participate in the regulation of prophage induction. In this study, we aimed to explore whether specific dietary functional sugars could inhibit Stx2 prophage induction in E. coli O157:H7, thereby preventing Stx2 production and promoting intestinal health. We demonstrated that Stx2 prophage induction in E. coli O157:H7 was strongly inhibited by L-arabinose both in vitro and in a mouse model. Mechanistically, L-arabinose at doses of 9, 12, or 15 mM diminished RecA protein levels, a master mediator of the SOS response, contributing to reduced Stx2-converting phage induction. L-Arabinose inhibited quorum sensing and oxidative stress response, which are known as positive regulators of the SOS response and subsequent Stx2 phage production. Furthermore, L-arabinose impaired E. coli O157:H7 arginine transport and metabolism that were involved in producing Stx2 phage. Collectively, our results suggest that L-arabinose may be exploited as a novel Stx2 prophage induction inhibitor against E. coli O157:H7 infection.

In the weaning period, piglets often face oxidative stress, which will cause increased diarrhea and mortality. Genistein, a flavonoid, which is extracted from leguminous plants, possesses anti-inflammatory and antioxidative bioactivities. However, little is known about whether genistein could attenuate the oxidative stress that occurs in porcine intestinal epithelial cells (IPEC-J2). Herein, this experiment was carried out to investigate the protective effects of genistein in the IPEC-J2 cells oxidative stress model. Our results disclosed that H2O2 stimulation brought about a significant diminution in catalase (CAT) activity and cell viability, as well as an increase in the levels of reactive oxygen species (ROS) in IPEC-J2 cells (p < 0.05), whereas pretreating cells with genistein before H2O2 exposure helped to alleviate the reduction in CAT activity and cell viability (p < 0.05) and the raise in the levels of ROS (p = 0.061) caused by H2O2. Furthermore, H2O2 stimulation of IPEC-J2 cells remarkably suppressed gene level Nrf2 and CAT expression, in addition to protein level Nrf2 expression, but pretreating cells with genistein reversed this change (p < 0.05). Moreover, genistein pretreatment prevented the downregulation of occludin expression at the gene and protein level, and ZO-1 expression at gene level (p < 0.05). In summary, our findings indicate that genistein possesses an antioxidant capacity in IPEC-J2 cells which is effective against oxidative stress; the potential mechanism may involve the Nrf2 signaling pathway. Our findings could offer a novel nutritional intervention strategy to enhance the intestinal health of piglets during the weaning process.

Fucoidan (FC) is known for its antioxidant properties, but it has unclear effects and mechanisms on weaned piglets. Two experiments were conducted to determine the optimal FC dosage in piglet diets and its protective effect against lipopolysaccharide (LPS)-induced oxidative stress. In experiment one, 24 low weight weaned piglets were randomly assigned to four dietary treatments: a basal diet (FC 0), or a diet supplemented with 150 (FC 150), 300 (FC 300), or 600 mg/kg FC (FC 600). In experiment two, 72 low-weaning weight piglets were randomly allocated into four treatments: a basal diet (CON), or 300 mg/kg of fucoidan added to a basal diet challenged with LPS (100 µg LPS/kg body weight) or not. The results showed that FC treatments increased the G:F ratio, and dietary FC 300 reduced the diarrhea incidence and increased the plasma IGF-1 concentrations. In addition, FC 300 and FC 600 supplementation increased the plasma SOD activity and reduced the plasma MDA concentration. LPS challenge triggered a strong systemic redox imbalance and mitochondrial dysfunction. However, dietary FC (300 mg/kg) supplementation increased the activity of antioxidant enzymes, including SOD, decreased the MDA concentration in the plasma and liver, down-regulated Keap1 gene expression, and up-regulated Nrf2, CAT, MFN2, SDHA, and UQCRB gene expression in the liver. These results indicated that dietary fucoidan (300 mg/kg) supplementation improved the growth performance and antioxidant capacity of low-weaning weight piglets, which might be attributed to the modulation of the Keap1/Nrf2 signaling pathway and the mitochondrial function in the liver.

Silybin (Si) is the main element of silymarin isolated from the seeds of Silybum marianum L. Gaernt., which has superior antioxidant properties. However, the protective role of Si in maintaining liver health under oxidative stress remains ambiguous. This study aimed to investigate the underlying mechanism of the beneficial effect of dietary Si against hepatic oxidative injury induced by paraquat (PQ) in weaned piglets. A total of 24 piglets were randomly allocated to four treatments with six replicates per treatment and 1 piglet per replicate: the control group; Si group; PQ group; and Si + PQ group. Piglets in the control group and PQ group were given a basal diet, while piglets in the Si and Si + PQ groups were given a Si-supplemented diet. On the 18th day, the pigs in the PQ treatment group received an intraperitoneal injection of PQ, and the others were intraperitoneally injected with the same volume of saline. All piglets were sacrificed on day 21 for plasma and liver sample collection. The results showed that dietary Si supplementation mitigated PQ-induced liver damage, as proven by the reduction in liver pathological changes and plasma activity of alanine transaminase and aspartate transaminase. Si also improved superoxide dismutase and glutathione peroxidase activities and total antioxidant capacity, as well as decreased malondialdehyde and hydrogen peroxide concentration in the liver, which were closely related to the activation of the nuclear factor-erythroid 2-related factor 2 signaling pathway. Meanwhile, Si reduced tumor necrosis factor-α and interleukin-8 production and their transcript levels as well as abrogated the overactivation of nuclear factor-κB induced by PQ. Importantly, Si improved mitochondrial function by maintaining mitochondrial energetics and mitochondrial dynamics, which was indicated by the elevated activity of mitochondrial complexes I and V and adenosine triphosphate content, decreased expression of dynamin 1 protein, and increased expression of mitofusin 2 protein. Moreover, Si inhibited excessive hepatic apoptosis by regulating the B-cell lymphoma-2 (Bcl-2)/Bcl-2-associated-X-protein signaling pathway. Taken together, these results indicated that Si potentially mitigated PQ-induced hepatic oxidative insults by improving antioxidant capacity and mitochondrial function and inhibiting inflammation and cell apoptosis in weaned piglets.

Summary: Genetic loss of Agpat2 in humans and mice results in congenital generalized lipodystrophy with near-total loss of adipose tissue and predisposition to develop insulin resistance, diabetes mellitus, hepatic steatosis, and hypertriglyceridemia. The mechanism by which Agpat2 deficiency results in loss of adipose tissue remains unknown. We studied this by re-expressing human AGPAT2 (hAGPAT2) in Agpat2-null mice, regulated by doxycycline. In both sexes of Agpat2-null mice, adipose-tissue-specific re-expression of hAGPAT2 resulted in partial regeneration of both white and brown adipose tissue (but only 30%–50% compared with wild-type mice), which had molecular signatures of adipocytes, including leptin secretion. Furthermore, the stromal vascular fraction cells of regenerated adipose depots differentiated ex vivo only with doxycycline, suggesting the essential role of Agpat2 in adipocyte differentiation. Turning off expression of hAGPAT2 in vivo resulted in total loss of regenerated adipose tissue, clear evidence that Agpat2 is essential for adipocyte differentiation in vivo.

Background: Many studies have demonstrated the crucial roles of 5-methylcytosine (m5C) RNA methylation in cancer pathogenesis. Methods: Two datasets, including TCGA-KIRP and ICGC, and related clinical information were downloaded, where the expression of 13 m5C regulators was examined. We applied LASSO regression to construct a multi-m5C-regulator-based signature in the TCGA cohort, which was further validated using the ICGC cohort. Univariate and multivariate Cox regressions were applied to evaluate the independent prognostic value of our model. The differences in biological functions and immune characterizations between high and low-risk groups divided based on the risk scores were also investigated via multiple approaches, such as enrichment analyses, mutation mining, and immune scoring. Finally, the sensitivities of commonly used targeted drugs were tested, and the connectivity MAP (cMAP) was utilized to screen potentially effective molecules for patients in the high-risk group. Experimental validation was done following qPCR tests in Caki-2 and HK-2 cell lines. Results: 3 m5C regulators, including ALYREF, DNMT3B and YBX1, were involved in our model. Survival analysis revealed a worse prognosis for patients in the high-risk group. Cox regression results indicated our model's superior predictive performance compared to single-factor prognostic evaluation. Functional enrichment analyses indicated a higher mutation frequency and poorer tumor microenvironment of patients in the high-risk group. qPCR-based results revealed that ALYREF, DNMT3B, and YBX1 were significantly up-regulated in Caki-2 cell lines compared with HK-2 cell lines. Molecules like BRD-K72451865, Levosimendan, and BRD-K03515135 were advised by cMAP for patients in the high-risk group. Conclusion: Our study presented a novel predictive model for KIRP prognosis. Furthermore, the results of our analysis provide new insights for investigating m5C events in KIRP pathogenesis.

Our previous study found that soybean isoflavones in soybean meal play an important role in improving growth performance and antioxidant capacity in pigs. However, it is still unknown whether long-term supplementation with daidzein, an active molecule deglycosylated from daidzin, in a corn–soybean meal diet can enhance growth performance in pigs. Thus, in the present study, an animal trial was carried out to investigate the effects of dietary supplementation with daidzein on the growth performance and antioxidant capacity of pigs. A total of 80 weaned piglets (40 barrows and 40 females) were assigned to 4 treatments with 5 pens per treatment and 4 piglets per pen and fed a diet supplemented with 0, 25, 50 and 100 mg/kg daidzein for a 72-day trial. In addition, porcine intestinal epithelial cells (IPEC-J2) were used as an in vitro model to explore the underlying antioxidant mechanisms of daidzein. IPEC-J2 cells were treated with 0.6 mM hydrogen peroxide (H2O2) in the presence or absence of 40 μM daidzein. The results showed that adding 50 mg/kg of daidzein to the diet significantly improved body weight on day 72, average daily gain (ADG) during days 0 to 72 and plasma superoxide dismutase (SOD) activity on day 42, and decreased malondialdehyde (MDA) content on day 14 (P

The accurate detection of external defects in kiwifruit is an important part of postharvest quality assessment. Previous studies have not considered the problems posed by the actual grading environment. In this study, we designed a novel approach based on improved Yolov5 to achieve real-time and efficient non-destructive detection of multiple defect categories in kiwifruit. First, a kiwifruit image acquisition device based on grading lines was developed to enhance the image acquisition. Subsequently, a kiwifruit dataset was constructed based on the external defect characteristics and a new data enhancement method was proposed to augment the kiwifruit samples. Thereafter, the SPD-Conv and DW-Conv modules were combined to improve Yolov5s, with EIOU as the loss calculation function. The results demonstrated that the improved model training loss value was 0.013 lower, the convergence was accelerated, the number of parameters was reduced, and the computational effort was increased. The detection accuracies of the samples in the test set, which included healthy, leaf-rubbing damaged, healed cuts or scarred, and sunburned samples, were 98.8%, 98.7%, 97.6%, and 95.9%, respectively, with an overall detection accuracy of 97.7%. The detection time was 8.0 ms, thereby meeting real-time sorting demands. The average detection accuracy and model size of SSD, Yolov5s, Yolov7, and Yolov5-Ours were compared. When the confidence threshold was 0.5, the detection accuracy of Yolov5-Ours was 10% and 6.4% higher than that of SSD and Yolov5s, respectively. In terms of the model size, Yolov5-Ours was approximately 6.5- and 4-fold smaller than SSD and Yolov7, respectively. Thus, Yolov5-Ours achieved the highest accuracy, adaptability, and robustness for the detection of all kiwifruit categories as well as a small volume and portability. These results can provide technical support for the non-destructive detection and grading of agricultural products in the future.

The aim of this experiment is to evaluate the effects of adding porous zinc oxide, plant polyphenols, and their combination to diets without antibiotics and high-dose zinc oxide on the growth performance, diarrhea incidence, intestinal morphology, and microbial diversity of weaned piglets. A total of 150 Duroc × Landrace × Large White weaned piglets were allocated to one of five diets in a randomized complete block design with six replicates and five piglets per replicate. The experimental period was 42 d, divided into two feeding stages: pre-starter (0–14 d) and starter (14–42 d). In the pre-starter stage, the negative control group (NC) was fed a basal diet, the positive control group (PC) was fed a basal diet with 2000 mg/kg of zinc oxide, the porous zinc oxide group (PZ) was fed a basal diet with 500 mg/kg of porous zinc oxide, the plant polyphenol group (PP) was fed a basal diet with 1500 mg/kg of plant polyphenols, and the combination group (PZ + PP) was fed a basal diet with 500 mg/kg of porous zinc oxide and 1500 mg/kg of plant polyphenols. In the starter stage, the NC, PC, and PZ groups were fed a basal diet, while the PP and PZ + PP groups were fed a basal diet with 1000 mg/kg of plant polyphenols. The results showed that, (1) compared with the PZ group, adding plant polyphenols to the diet showed a trend of increasing the ADFI of weaned piglets from 14 to 28 d (p = 0.099). From days 28 to 42 and days 0 to 42, porous zinc oxide and the combination of porous zinc oxide and plant polyphenols added to the control diet improved the FCR to the level observed in pigs fed the PC diet. (2) Dietary PZ + PP tended to increase the jejunal villus height (VH) of weaned piglets (p = 0.055), and significantly increased the villus-height-to-crypt-depth ratio compared to the NC group (p < 0.05). (3) Compared with the NC group, PZ supplementation decreased the relative abundance of Firmicutes and increased the relative abundance of Bacteroidetes, and the relative abundance of Lactobacillus in the PZ and PZ + PP groups were both increased. In conclusion, porous zinc oxide and plant polyphenols may have synergistic effects in modulating intestinal health in weaned piglets and be a potential alternative to high-dose zinc oxide.

Flaxseed meal (FSM) is a byproduct of flaxseed oil extraction which has rich nutritional value and can be used as a high-quality new protein ingredient. However, the anti-nutrient factor (ANF) in FSM restricts its potential application in feed. The strategy of microbial fermentation is a highly effective approach to reducing ANF in FSM and enhancing its feeding value. However, evaluation of the nutritional value of fermented flaxseed meal (FFSM) in growing pigs has not yet been conducted. Thus, the purpose of this study was to investigate the nutritional value of FFSM in growing pigs and comparison of the effect of fermentation treatment on improving the nutritional value of FSM. Two experiments were conducted to determine the available energy value, apparent digestibility of nutrients, and standard ileal digestibility of amino acids of FSM and FFSM in growing pigs. The results showed as follows: (1) Fermentation treatment increased the levels of crude protein (CP), Ca and P in FSM by 2.86%, 9.54% and 4.56%, while decreasing the concentration of neutral detergent fiber (NDF) and acid detergent fiber (ADF) by 34.09% and 12.71%, respectively (p < 0.05); The degradation rate of CGs in FSM was 54.09% (p < 0.05); (2) The digestible energy (DE) and metabolic energy (ME) of FSM and FFSM were 14.54 MJ/kg, 16.68 MJ/kg and 12.85 MJ/kg, 15.24 MJ/kg, respectively; (3) Compared with FSM, dietary FFSM supplementation significantly increased the apparent digestibility of CP, NDF, ADF, Ca, and P of growing pigs (p < 0.05) and significantly increased the standard ileal digestibility of methionine (p < 0.05). These results indicate that fermentation treatment could effectively enhance the nutritional value of FSM and provide basic theoretical data for the application of FFSM in pig production.

Abstract Background Interleukin-17 (IL-17) antagonism in rats reduces the severity and progression of AKI. IL-17-producing circulating T helper-17 (TH17) cells is increased in critically ill patients with AKI indicating that this pathway is also activated in humans. We aim to compare serum IL-17A levels in critically ill patients with versus without AKI and to examine their relationship with mortality and major adverse kidney events (MAKE). Methods Multicenter, prospective study of ICU patients with AKI stage 2 or 3 and without AKI. Samples were collected at 24–48 h after AKI diagnosis or ICU admission (in those without AKI) [timepoint 1, T1] and 5–7 days later [timepoint 2, T2]. MAKE was defined as the composite of death, dependence on kidney replacement therapy or a reduction in eGFR of ≥ 30% from baseline up to 90 days following hospital discharge. Results A total of 299 patients were evaluated. Patients in the highest IL-17A tertile (versus lower tertiles) at T1 had higher acuity of illness and comorbidity scores. Patients with AKI had higher levels of IL-17A than those without AKI: T1 1918.6 fg/ml (692.0–5860.9) versus 623.1 fg/ml (331.7–1503.4), p

Oxidative stress is the major incentive for intestinal dysfunction in weaned piglets, which usually leads to growth retardation or even death. Silybin has caught extensive attention due to its antioxidant properties. Herein, we investigated the effect of dietary silybin supplementation on growth performance and determined its protective effect on paraquat (PQ)-induced intestinal oxidative damage and microflora dysbiosis in weaned piglets. In trial 1, a total of one hundred twenty healthy weaned piglets were randomly assigned into five treatments with six replicate pens per treatment and four piglets per pen, where they were fed basal diets supplemented with silybin at 0, 50, 100, 200, or 400 mg/kg for 42 days. In trial 2, a total of 24 piglets were randomly allocated to two dietary treatments with 12 replicates per treatment and 1 piglet per pen: a basal diet or adding 400 mg/kg silybin to a basal diet. One-half piglets in each treatment were given an intraperitoneal injection of paraquat (4 mg/kg of body weight) or sterile saline on day 18. All piglets were euthanized on day 21 for sample collection. The results showed that dietary supplementation with 400 mg/kg silybin resulted in a lower feed conversion ratio, diarrhea incidence, and greater antioxidant capacity in weaned piglets. Dietary silybin enhanced intestinal antioxidant capacity and mitochondrial function in oxidative stress piglets induced by PQ. Silybin inhibited mitochondria-associated endogenous apoptotic procedures and then improved the intestinal barrier function and morphology of PQ-challenged piglets. Moreover, silybin improved intestinal microbiota dysbiosis induced by the PQ challenge by enriching short-chain fatty-acid-producing bacteria, which augmented the production of acetate and propionate. Collectively, these findings indicated that dietary silybin supplementation linearly decreased feed conversion ratio and reduced diarrhea incidence in normal conditions, and effectively alleviated oxidative stress-induced mitochondrial dysfunction, intestinal damage, and microflora dysbiosis in weaned piglets.

As the first line of defence against pathogens and endotoxins crossing the intestine-blood barrier, the intestinal epithelial barrier plays a determinant role in pigs' health and growth. 4-Phenylbutyric acid (4-PBA), an aromatic fatty acid, was reported to benefit homeostasis of endoplasmic reticulum and protein synthesis. However, whether 4-PBA affects intestinal epithelial barrier function in pigs is unknown. This study aimed to explore the effects of 4-PBA on the intestinal barrier function, using in vitro models of well-differentiated intestinal porcine epithelial cell (IPEC-J2) monolayers in the transwell plates. Cell monolayers with or without 4-PBA (1.0 mmol/L) treatment were challenged with physical scratch, deoxynivalenol (DON, 2.0 μg/mL, 48 h), and lipopolysaccharide (LPS, 5.0 μg/mL, 48 h), respectively. Transepithelial electrical resistance (TEER) and fluorescein isothiocyanate-dextran (FD-4) permeability were measured to indicate barrier integrity and permeability. Real-time PCR and Western blot were conducted to determine relative gene and protein expressions of tight junction proteins. As expected, physical scratch, DON, and LPS challenges decreased TEER and increased FD-4 permeability. 4-PBA treatment accelerated cell mitigation and rehabilitation of the physical scratch-damaged intestinal epithelial barrier but did not alleviate DON or LPS induced barrier damage. However, once 48-h DON and LPS challenges were removed, rehabilitation of the epithelial barrier function of IPEC-J2 monolayer was accelerated by the 4-PBA treatment. Also, the relative gene and protein expressions of zonula occludens-1 (ZO-1), occludin, and claudin-1 were further upregulated by the 4-PBA treatment during the barrier rehabilitation. Taken together, 4-PBA accelerated the IPEC-J2 cell monolayer barrier recovering from physical scratch, DON-, and LPS-induced damage, via enhancing cell mitigation and expressions of tight junction proteins.

Background: An in silico screen was performed to identify FDA approved drugs that inhibit SARS-CoV-2 main protease (Mpro), followed by in vitro viral replication assays, and in vivo pharmacokinetic studies in mice. These studies identified atovaquone as a promising candidate for inhibiting viral replication.Methods: A 2-center, randomized, double-blind, placebo-controlled trial was performed among patients hospitalized with COVID-19 infection. Enrolled patients were randomized 2:1 to atovaquone 1500 mg BID versus matched placebo. Patients received standard of care treatment including remdesivir, dexamethasone, or convalescent plasma as deemed necessary by the treating team. Saliva was collected at baseline and twice per day for up to 10 days for RNA extraction for SARS-CoV-2 viral load measurement by quantitative reverse-transcriptase PCR. The primary outcome was the between group difference in log-transformed viral load (copies/mL) using a generalized linear mixed-effect models of repeated measures from all samples.Results: Of the 61 patients enrolled; 41 received atovaquone and 19 received placebo. Overall, the population was predominately male (63%) and Hispanic (70%), with a mean age of 51 years, enrolled a mean of 5 days from symptom onset. The log10 viral load was 5.25 copies/mL vs. 4.79 copies/mL at baseline in the atovaquone vs. placebo group. Change in viral load did not differ over time between the atovaquone plus standard of care arm versus the placebo plus standard of care arm. Pharmacokinetic (PK) studies of atovaquone plasma concentration demonstrated a wide variation in atovaquone levels, with an inverse correlation between BMI and atovaquone levels, (Rho −0.45, p = 0.02). In post hoc analysis, an inverse correlation was observed between atovaquone levels and viral load (Rho −0.54, p = 0.005).Conclusion: In this prospective, randomized, placebo-controlled trial, atovaquone did not demonstrate evidence of enhanced SARS-CoV-2 viral clearance compared with placebo. However, based on the observed inverse correlation between atovaquone levels and viral load, additional PK-guided studies may be warranted to examine the antiviral effect of atovaquone in COVID-19 patients.

The objective of this study was to investigate the effects of dietary supplementation with different types of potassium and magnesium on the reproductive performance, antioxidant capacity, and immunity of sows. Forty-five Landrace × Yorkshire sows at the late gestation stage (85 d) were randomly assigned to three groups (n = 15). Sows in the control group (CON), potassium chloride and magnesium sulfate group (PM), and potassium-magnesium sulfate group (PMS) were fed with a basal diet, a basal diet supplemented with magnesium sulfate (0.20%) and potassium chloride (0.15%), or a basal diet supplemented with potassium-magnesium sulfate (0.45%), respectively. The results showed that dietary supplementation with PMS did not yield significant effects on the reproductive performance compared with the CON group (p > 0.05). However, it significantly elevated the level of insulin-like growth factor 1 (IGF-1) in plasma and immunoglobulin A (IgA) in colostrum (p < 0.05). Furthermore, PMS significantly augmented the activities of catalase (CAT) and superoxide dismutase (SOD) while reducing the levels of malondialdehyde (MDA) in comparison to the CON group (p < 0.05). Compared with the PM group, the PMS group significantly reduced the incidence rate of intrauterine growth restriction (IUGR) (p < 0.05) and significantly decreased the concentration of the proinflammatory cytokine (TNF-α) level in plasma (p < 0.05). These results indicated that dietary supplementation with PMS during late gestation could enhance sows’ antioxidant capacity and the IgA level in colostrum. These findings will provide a theoretical reference for the use of magnesium and potassium in sow production to improve sows’ health.

BackgroundThe association of near-infrared spectroscopy (NIRS) with various outcomes after pediatric cardiac surgery has been studied extensively. However, the role of NIRS in the prediction of cardiac arrest (CA) in children with heart disease has yet to be evaluated. We sought to determine if a model utilizing regional cerebral oximetry (rSO2c) and somatic oximetry (rSO2s) could predict CA in children admitted to a single-center pediatric cardiac intensive care unit (CICU).MethodsWe retrospectively reviewed 160 index CA events for patients admitted to our pediatric CICU between November 2010 and January 2019. We selected 711 control patients who did not have a cardiac arrest. Hourly data was collected from the electronic health record (EHR). We previously created a machine-learning algorithm to predict the risk of CA using EHR data. Univariable analysis was done on these variables, which we then used to create a multivariable logistic regression model. The outputs from the model were presented by odds ratio (OR) and 95% confidence interval (CI).ResultsWe created a multivariable model to evaluate the association of CA using five variables: arterial saturation (SpO2)- rSO2c difference, SpO2-rSO2s difference, heart rate, diastolic blood pressure, and vasoactive inotrope score. While the SpO2-rSO2c difference was not a significant contributor to the multivariable model, the SpO2-rSO2s difference was. The average SpO2-rSO2s difference cutoff with the best prognostic accuracy for CA was 29% [CI 26–31%]. In the multivariable model, a 10% increase in the SpO2-rSO2s difference was independently associated with increased odds of CA [OR 1.40 (1.18, 1.67), P < 0.001] at 1 h before CA. Our model predicted CA with an AUROC of 0.83 at 1 h before CA.ConclusionIn this single-center case-control study of children admitted to a pediatric CICU, we created a multivariable model utilizing hourly data from the EHR to predict CA. At 1 h before the event, for every 10% increase in the SpO2-rSO2s difference, the odds of cardiac arrest increased by 40%. These findings are important as the field explores ways to capitalize on the wealth of data at our disposal to improve patient care.

This study was conducted to investigate the effects of dietary supplementation with stimbiotics (STB) on growth performance, diarrhoea incidence, plasma antioxidant capacity, immunoglobulin concentration and hormone levels, and faecal microorganisms in weaned piglets. Compared with the control (CT) group, the addition of STB improved the body weight (BW) of piglets on days 28 and 42 (p < 0.05) and increased daily weight gain and daily feed intake from days 14–28 and throughout the trial period (p < 0.05). Correspondingly, the plasma insulin-like growth factor 1 (IGF-1) level on day 42 was significantly improved by STB (p < 0.05). VistaPros (VP) group levels of immunoglobulin (Ig) A and G were significantly higher on days 14 and 42 (p < 0.05) than the CT group levels. In addition, the activity of plasma catalase tended to be increased on day 14 (p = 0.053) in the VP group, as for superoxide dismutase, glutathione peroxidase, and malondialdehyde, STB did not significantly affect their levels (p > 0.05). Moreover, dietary STB increased the relative abundance of beneficial bacteria, including norank_f_Muribaculaceae, Rikenellaceae_RC9_gut_group, Parabacteroides, and unclassified_f__Oscillospiraceae. In summary, STB improved the immunity and IGF-1 levels in the plasma of weaned piglets and consequently promoted the growth performance of weaned piglets.

Gut barrier disruption is the initial pathogenesis of various diseases. We previously reported that dietary allicin improves tight junction proteins in the endoplasmic reticulum stressed jejunum. However, whether the allicin benefits the gut barrier within mycotoxin or endotoxin exposure is unknown. In the present study, IPEC-J2 cell monolayers within or without deoxynivalenol (DON) or lipopolysaccharide (LPS) challenges were employed to investigate the effects of allicin on intestinal barrier function and explore the potential mechanisms. Results clarified that allicin at 2 μg/mL increased the viability, whereas the allicin higher than 10 μg/mL lowered the viability of IPEC-J2 cells via inhibiting cell proliferation. Besides, allicin increased trans-epithelial electric resistance (TEER), decreased paracellular permeability, and enhanced ZO-1 integrity of the IPEC-J2 cell monolayers. Finally, allicin supplementation prevented the LPS-induced barrier damages via activating Nrf2/HO-1 pathway-dependent antioxidant system. In conclusion, the present study strongly confirmed allicin as an effective nutrient to improve intestinal barrier function and prevent bacterial endotoxin-induced barrier damages.

Bacillus licheniformis (B. Licheniformis) has been considered to be an effective probiotic to maintain gut health and boost productivity in the pig industry, but there is no complete understanding of its mechanisms. We determined whether weaned piglets exposed to BL−S6 (probiotic) had altered intestinal barrier function or microbiota composition. In our study, 108 weaned piglets (54 barrows and 54 gilts) were divided equally into three groups, each with six pens and six piglets/pen, and fed a basal diet supplemented without or with antibiotic (40 g/t of Virginiamycin and 500 g/t of Chlortetracycline) or probiotic (1000 g/t of B. Licheniformis) for a 14-day trial. On day 14, one piglet was chosen from each pen to collect blood and intestinal samples. Compared with the control group, dietary supplementation with a probiotic promoted body weight (BW) gain and average daily gains (ADG) while reducing diarrhea incidence (p < 0.05). Probiotics enhanced superoxidase dismutase (SOD) activity and decreased malondialdehyde (MDA) levels in serum (p < 0.05), and increased the level of mRNA expression of SOD1, Nrf2, and HO-1 (p < 0.05) in the jejunum mucosa. Moreover, supplementation with probiotics improved intestinal mucosal integrity as evidenced by higher villus heights and a higher ratio of villus heights to crypt depths (duodenum and jejunum) and higher mRNA and protein levels of occludin and ZO-1 in jejunum mucosa (p < 0.05). The intestinal sIgA levels (p < 0.05) were elevated in the probiotic group, and that of serum immunoglobulin A (IgA) tended to be higher (p = 0.09). Furthermore, weaning piglets who were given probiotics had a better balance of the cecum microbiota, with lactobacillus abundance increased and clostridium_sensu_stricto_1 abundance decreased. In conclusion, dietary supplementation with the probiotic BL−S6 promoted intestinal integrity, which was associated, in part, with modulating intestinal barrier function and microbial diversity in weaned piglets; it may offer a promising alternative to antibiotics to prevent diarrhea.

Flaxseed meal (FSM) is rich in protein, α-linolenic acid, dietary fiber, flaxseed gum, and other bioactive substances. The total protein content of these components is up to 30%. Thus, FSM can be used as a high-quality protein feed resource. However, due to the presence of anti-nutritional factors, such as cyanogenic glycosides (CGs), phytic acid, anti-vitamin B6 factor, and other anti-nutritional factors, the application of FSM is restricted in animal diets. Recently, the interest in decreasing anti-nutritional factors and improving the nutritional value of FSM has been increasing in the field of animal nutrition. Therefore, this paper reviews the nutritional components, anti-nutritional factors, and the CG detoxification methods of FSM as well as its application in livestock and poultry, in order to provide a theoretical reference for the application of FSM in animal husbandry.

Chenodeoxycholic acid (CDCA), a primary bile acid (BA), has been demonstrated to play an important role as a signaling molecule in various physiological functions. However, the role of CDCA in regulating intestinal epithelial cell (IEC) function remains largely unknown. Herein, porcine intestinal epithelial cells (IPEC-J2) were used as an in vitro model to investigate the effects of CDCA on IEC proliferation and explore the underlying mechanisms. IPEC-J2 cells were treated with CDCA, and flow cytometry and transcriptome analysis were adopted to investigate the effects and potential molecular mechanisms of CDCA on the proliferation of IECs. Our results indicated that adding 50 μmol/L of CDCA in the media significantly increased the proliferation of IPEC-J2 cells. In addition, CDCA treatment also hindered cell apoptosis, increased the proportion of G0/G1 phase cells in the cell cycle progression, reduced intracellular ROS, and MDA levels, and increased mitochondrial membrane potential, antioxidation enzyme activity (T-AOC and CAT), and intracellular ATP level (p < 0.05). RNA-seq results showed that CDCA significantly upregulated the expression of genes related to cell cycle progression (Cyclin-dependent kinase 1 (CDK1), cyclin G2 (CCNG2), cell-cycle progression gene 1 (CCPG1), Bcl-2 interacting protein 5 (BNIP5), etc.) and downregulated the expression of genes related to mitochondrial biogenesis (ND1, ND2, COX3, ATP6, etc.). Further KEGG pathway enrichment analysis showed that CDCA significantly enriched the signaling pathways of DNA replication, cell cycle, and p53. Collectively, this study demonstrated that CDCA could promote IPEC-J2 proliferation by regulating cell cycle progression and mitochondrial function. These findings provide a new strategy for promoting the intestinal health of pigs by regulating intestinal BA metabolism.

The present study determined the effects of live yeast (LY) supplementation during middle–late gestation and the lactation period in primiparous sows on reproductive parameters, lactation performance, and immunity, and also explores the carryover effects in their offspring. On day (d) 60 of gestation, 16 crossbred primiparous sows were randomly assigned to two dietary treatments (with or without supplementation of 425 mg/kg of live yeast; LYT and CT, respectively) homogeneous for body weight (BW) and backfat thickness. Experimental diets were applied from day 60 of gestation to the end of lactation. At weaning, 60 piglets with an average BW of each treatment were selected based on their source litter and assigned to two groups corresponding to the original treatments received by their mothers. Each group had five replicates of six piglets each and was fed a basal diet for 42 days. The results showed that LY supplementation significantly increased the serum IgA and IgG concentrations of sows at farrowing and weaning stages, and of piglets on day 14 and 28 post weaning. No significant differences were found in reproductive and lactation performance, while minor effects were observed on antioxidant capacity. In conclusion, live yeast addition during middle–late gestation and the whole lactation period resulted in enhanced immunity of primiparous sows and their offspring, therefore, improving maternal and progeny health.

Our objective was to evaluate the effects of dietary supplementation with glycerol monolaurate (GML) or the combination (Solider, SOL) of GML and tributyrin (TB) on the growth performance and rumen microbiome of weaned lambs. Thirty-six male Hu lambs (11.46 ± 0.88 kg BW and 40 ± 5 days of age) were divided into three treatment groups: (1) CON: basal diet, (2) GML: basal diet supplemented with GML at 1.84 g/kg DM, and (3) SOL: basal diet supplemented with SOL at 3 g/kg DM. GML increased the final BW (p = 0.04) and ADG (p = 0.02) compared with CON. There were no significant differences in the DMI (p > 0.10) among the three treatment groups. GML and SOL tended to decrease the dry matter intake/average daily gain (p = 0.07) compared with CON. GML tended to increase the apparent digestibility of CP (p = 0.08) compared with CON. SOL increased the apparent digestibility of NDF (p = 0.04) compared with CON. The Chao1 and Shannon indexes of SOL were both significantly higher than those of the other groups (p = 0.01). LefSE analysis showed that Bifidobacteriaceae of the Bifidobacteriales was enriched in the GML group. In addition, compared with GML, SOL reduced the relative abundance of Actinobacteria (p < 0.01) and increased the relative abundance of Verrucomicrobia (p = 0.05), and GML reduced the relative abundance of Ruminococcus (p = 0.03). Our results indicated that dietary supplementation with GML or SOL improved growth performance and feed conversion, and changed the rumen microbiome of weaned lambs.

Background: Fetal-placental development depends on a continuous and efficient supply of nutrients from maternal blood that are acquired by exchange through the placenta. However, the placenta is a low permeability barrier, and effective transport of substances depends on specific transport mechanisms. Active transport requires that ions or nutrients be moved against an electrical and/or concentration gradient. In pigs, active transport of ions occurs across the chorioallantois placenta to produce an electrochemical gradient that changes throughout gestation. The aim of this study was to utilize Ussing chambers to detect regulation of ion transport across the porcine chorioallantois by a factor(s) within the uterine-placental environment of pigs. Methods: For the measurement of transchorioallantoic voltage potential as an index of ion transport across the placenta, pieces of chorioallantoic tissue from Day 60 of gestation were mounted into the cassettes of Ussing chambers, and treatments were added to the mucasal side of the tissue. Treatments included: (1) media incubated with Day 60 chorioallantois (placenta-conditioned media); (2) osteopontin/secreted phosphoprotein 1 (OPN/SPP1) purified from cow’s milk; (3) placenta-conditioned media from which OPN/SPP1 was removed; and (4) recombinant rat OPN with an intact RGD integrin binding sequence or a mutated RAD sequence. Ouabain was added to both sides of the chamber. Immunofluorescence was utilized to localize beta 3 integrin, aquaporin 8 and OPN/SPP1 in porcine placental tissues, and OPN/SPP1 within porcine lung, kidney and small intestine. Results: Day 60 chorioallantoic membranes had greater transepithelial voltage in the presence of porcine placenta-conditioned media, indicating that a molecule(s) released from the placenta increased ion transport across the placenta. OPN/SPP1 purified from cow’s milk increased ion transport across the placenta. When OPN/SPP1 was removed from placenta-conditioned media, ion transport across the placenta did not increase. Recombinant rat OPN/SPP1 with a mutated RGD sequence that does not bind integrins (RAD) did not increase ion transport across the placenta. Ouabain, an inhibiter of the sodium-potassium ion pump, ablated ion transport across the placenta. Conclusions: The present study documents a novel pericellular matrix role for OPN/SPP1 to bind integrins and increase ion transport across the porcine chorioallantoic placenta.

Background: Increasing the dietary provision of L-arginine to pregnant swine beginning at Day 14 of gestation enhances embryonic survival, but the underlying mechanisms are largely unknown. Objective: This study determined the effects of dietary supplementation with 0.8% L-arginine to gilts between Days 14 and 25 of gestation on the global expression of genes in their placentae. Methods: Between Days 14 and 24 of gestation, gilts were fed 2 kg of a corn- and soybean meal-based diet (containing 12.0% crude protein and 0.70% Arg) supplemented with 0.8% L-arginine or without L-arginine (0.0%; with 1.64% L-alanine as the isonitrogenous control). On Day 25 of gestation, 30 min after the consumption of their top dressing containing 8 g L-arginine or 16.4 g L-alanine, gilts underwent hysterectomy to obtain placentae, which were snap-frozen in liquid nitrogen. Total RNAs were extracted from the frozen tissues and used for microarray analysis based on the 44-K Agilent porcine gene platform. Results: L-Arginine supplementation affected placental expression of 575 genes, with 146 genes being up-regulated and 429 genes being down-regulated. These differentially expressed genes play important roles in nutrient metabolism, polyamine production, protein synthesis, proteolysis, angiogenesis, immune development, anti-oxidative responses, and adhesion force between the chorioallantoic membrane and the endometrial epithelium, as well as functions of insulin, transforming growth factor beta, and Notch signaling pathways. Conclusion: Dietary supplementation with L-arginine plays an important role in regulating placental gene expression in gilts. Our findings help to elucidate mechanisms responsible for the beneficial effect of L-arginine in improving placental growth and embryonic/fetal survival in swine.

This study evaluated the effects of dietary gallic acid (GA) on growth performance, diarrhea incidence and plasma antioxidant status of weaned piglets regardless of whether weaning weight was high or low. A total of 120 weaned piglets were randomly allocated to four treatments in a 42-day experiment with a 2 × 2 factorial treatment arrangement comparing different weaning weights (high weight (HW) or low weight (LW), 8.49 ± 0.18 kg vs. 5.45 ± 0.13 kg) and dietary treatment (without supplementation (CT) or with supplementation of 400 mg/kg of GA). The results showed that HW piglets exhibited better growth performance and plasma antioxidant capacity. Piglets supplemented with GA had higher body weight (BW) on day 42 and average daily gain (ADG) from day 0 to 42 compared to the control piglets, which is mainly attributed to the specific improvement on BW and ADG of LW piglets by the supplementation of GA. The decreased values of diarrhea incidence were seen in piglets fed GA, more particularly in LW piglets. In addition, dietary GA numerically reduced malondialdehyde (MDA) content in plasma of LW piglets. In conclusion, our study suggests that dietary GA may especially improve the growth and health in LW weaned piglets.

A nano resonator is designed consisting of the metal-insulator-metal (MIM) waveguide coupled with the concentric annulus cavity. The optical transmission characteristics and sensing characteristics of the designed sensor are studied by using finite element method. Experimental results show that the combination of the MIM waveguide and the concentric annulus cavity can produce bright mode and dark mode around the central wavelength of 565 nm. Due to the interaction between these modes, the Fano resonance phenomenon will be produced with a transitional dip around the wavelength of 585 nm. Compared with the impacts of the width of the metal baffle and the coupling gap, the Fano resonance effect is very sensitive to the variation of the radii of the concentric annulus cavity, which is helpful to design the tunable optical devices based on Fano resonance in the future. However the modulation depth is obviously influenced by the width of the metal baffle and the coupling gap. The research also demonstrates the sharp asymmetric Fano transmission spectrum is also sensitive to the surrounding medium. By calculating the shift of the resonant wavelength with the change of the refractive index of the medium in the resonator, the device can achieve the sensitivity of 550 nm/RIU and the figure of merit of 70. [ABSTRACT FROM AUTHOR]

Abstract Background Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are now recommended for patients with heart failure, but the mechanisms that underlie the protective role of SGLT2i in cardiac remodeling remain unclear. Aldehyde dehydrogenase 2 (ALDH2) effectively prevents cardiac remodeling. Here, the key role of ALDH2 in the efficacy of SGLT2i on cardiac remodeling was studied. Methods Analysis of multiple transcriptomic datasets and two-sample Mendelian randomization were performed to find out the differentially expressed genes between pathological cardiac hypertrophy models (patients) and controls. A pathological cardiac hypertrophy mouse model was established via transverse aortic constriction (TAC) or isoproterenol (ISO). Cardiomyocyte-specific ALDH2 knockout mice (ALDH2CMKO) and littermate control mice (ALDH2flox/flox) were generated to determine the critical role of ALDH2 in the preventive effects of dapagliflozin (DAPA) on cardiac remodeling. RNA sequencing, gene knockdown or overexpression, bisulfite sequencing PCR, and luciferase reporter assays were performed to explore the underlying molecular mechanisms involved. Results Only ALDH2 was differentially expressed when the differentially expressed genes obtained via Mendelian analysis and the differentially expressed genes obtained from the multiple transcriptome datasets were combined. Mendelian analysis revealed that ALDH2 was negatively related to the severity of myocardial hypertrophy in patients. DAPA alleviated cardiac remodeling in mouse hearts subjected to TAC or ISO. ALDH2 expression was reduced, whereas ALDH2 expression was restored by DAPA in hypertrophic hearts. Cardiomyocyte specific ALDH2 knockout abolished the protective role of DAPA in preventing cardiac remodeling. ALDH2 expression and activity were increased in DAPA-treated neonatal rat primary cardiomyocytes (NRCMs), H9C2 cells and AC16 cells. Moreover, DAPA upregulated ALDH2 in peripheral blood mononuclear cells (PBMCs) from patients with type 2 diabetes. Sodium/proton exchanger 1 (NHE1) inhibition contributed to the regulation of ALDH2 by DAPA. DAPA suppressed the production of reactive oxygen species (ROS), downregulated DNA methyltransferase 1 (DNMT1) and subsequently reduced the ALDH2 promoter methylation level. Further studies revealed that DAPA enhanced the binding of nuclear transcription factor Y, subunit A (NFYA) to the promoter region of ALDH2, which was due to the decreased promoter methylation level of ALDH2. Conclusions The upregulation of ALDH2 plays a critical role in the protection of DAPA against cardiac remodeling. DAPA enhances the binding of NFYA to the ALDH2 promoter by reducing the ALDH2 promoter methylation level through NHE1/ROS/DNMT1 pathway. Graphical abstract