Maternal or post-weaning dietary fructo-oligosaccharide supplementation reduces stillbirth rate of sows and diarrhea of weaned piglets.

Fructo-oligosaccharides (FOS) are well-known prebiotics that have the potential to improve sow reproductive performance and increase piglet growth. However, previous studies were observed in sole FOS-supplemented diets of sows or weaned piglets and did not consider the sow-to-piglet transfer effect on the performance and diarrhea rate of weaned piglets. This study explores the effects of dietary FOS supplementation on the reproductive performance of sows, and the effects of FOS supplementation at different stages on the growth performance and diarrhea rate of weaned piglets. A split-plot experimental design was used with sow diet effect in the whole plot and differing piglet diet effect in the subplot. Fifty-two multiparous sows (223.24 ± 14.77 kg) were randomly divided into 2 groups (0 or 0.2% FOS). The experiment lasted from day 85 of gestation to day 21 of lactation. Reproductive performance, glucose tolerance, placental angiogenesis, and intestinal flora of sows were assessed. At weaning, 192 weaned piglets were grouped in 2 × 2 factorial designs, with the main effects of FOS supplemental level of sow diet (0 and 0.2%), and FOS supplemental level of weaned piglet diet (0 and 0.2%), respectively. The growth performance and diarrhea rate of the weaned piglets were analyzed during a 28-d experiment. Maternal dietary supplementation of FOS was shown to reduce the stillbirth and invalid piglet rates (P < 0.05), improve the insulin sensitivity (P < 0.05) and fecal scores (P < 0.05) of sows, increase the abundance of Akkermansia muciniphila (P = 0.016), decrease the abundance of Escherichia coli (P = 0.035), and increase the isovalerate content in feces (P = 0.086). Meanwhile, the placental angiogenesis marker CD31 expression was increased in sows fed FOS diet (P < 0.05). Moreover, maternal and post-weaning dietary FOS supplementation reduced the diarrhea rate of weaned piglets (P < 0.05) and increased the content of short-chain fatty acids in feces (P < 0.05). Furthermore, only post-weaning dietary FOS supplementation could improve nutrient digestibility of weaned piglets (P < 0.05). Collectively, FOS supplementation in sows can reduce stillbirth rate, perinatal constipation, and insulin resistance, as well as improve placental vascularization barrier. Additionally, maternal and post-weaning dietary FOS supplementation reduced the diarrhea rate of weaned piglets, but only FOS supplementation in piglets alone at weaning stage could improve their nutrient digestibility.

Effects of dietary iron supplementation on reproductive performance of sows and growth performance of piglets.

This experiment aimed to investigate the effects of dietary iron supplementation from different sources on the reproductive performance of sows and the growth performance of piglets. A total of 87 sows with similar farrowing time were blocked by body weight at day 85 of gestation, and assigned to one of three dietary treatments (n = 29 per treatment): basal diet, basal diet supplemented with 0.2% ferrous sulfate (FeSO4), and basal diet supplemented with 0.2% iron sucrose, respectively, with 30% iron in both FeSO4 and iron sucrose. Compared with the control (CON) group, iron sucrose supplementation reduced the rate of stillbirth and invalid of neonatal piglets (P < 0.05), and the number of mummified fetuses was 0. Moreover, it also improved the coat color of newborn piglets (P < 0.05). At the same time, the iron sucrose could also achieve 100% estrus rate of sows. Compared with the CON group, FeSO4 and iron sucrose supplementation increased the serum iron content of weaned piglets (P < 0.05). In addition, iron sucrose increased serum transferrin level of weaned piglets (P < 0.05) and the survival rate of piglets (P < 0.05). In general, both iron sucrose and FeSO4 could affect the blood iron status of weaned piglets, while iron sucrose also had a positive effect on the healthy development of newborn and weaned piglets, and was more effective than FeSO4 in improving the performance of sows and piglets.

Sows need more iron to meet the requirements for their and offspring's growth during pregnancy and lactation. Exogenous iron supplementation may improve the reproductive performance of sows and the growth performance of piglets, but different sources of iron have different effects. This study facilitates the understanding of the effects of iron sucrose and ferrous sulfate on the reproductive performance of sows and the growth performance of piglets.

Structure and activation mechanism of the rice Salt Overly Sensitive 1 (SOS1) Na+/H+ antiporter.

Salinity is one of the most severe abiotic stresses that adversely affect plant growth and agricultural productivity. The plant Na+/H+ antiporter Salt Overly Sensitive 1 (SOS1) located in the plasma membrane extrudes excess Na+ out of cells in response to salt stress and confers salt tolerance. However, the molecular mechanism underlying SOS1 activation remains largely elusive. Here we elucidate two cryo-electron microscopy structures of rice (Oryza sativa) SOS1, a full-length protein in an auto-inhibited state and a truncated version in an active state. The SOS1 forms a dimeric architecture, with an NhaA-folded transmembrane domain portion in the membrane and an elongated cytosolic portion of multiple regulatory domains in the cytoplasm. The structural comparison shows that SOS1 adopts an elevator transport mechanism accompanied by a conformational transition of the highly conserved Pro148 in the unwound transmembrane helix 5 (TM5), switching from an occluded conformation in the auto-inhibited state to a conducting conformation in the active state. These findings allow us to propose an inhibition-release mechanism for SOS1 activation and elucidate how SOS1 controls Na+ homeostasis in response to salt stress.

ASCL1-mediated ferroptosis resistance enhances the progress of castration-resistant prostate cancer to neurosecretory prostate cancer.

Neuroendocrine prostate cancer (NEPC) is a multi-resistant variant of prostate cancer (PCa) that frequently emerges in castration-resistant prostate cancer (CRPC). NEPC is usually associated with tumor aggression, hormone therapy resistance, and poor clinical outcome. However, the mechanisms underlying the trans-differentiation from CRPC to NEPC have not been elucidated. Achaete-scute complex-like 1 (ASCL1) plays a role in neuronal commitment and differentiation and olfactory and autonomic neuron generation. This study revealed that ASCL1 was regulated by the SRY-box transcription factor 2 (SOX2) and highly expressed in NEPC cells, which was closely related to poor prognosis. Moreover, ASCL1 overexpression significantly enhanced CRPC progression to NEPC by resisting ferroptosis. Mechanically, ferroptosis resistance was mediated by CAMP-responsive element binding protein 1 (CREB1) phosphorylation, promoted by substantially upregulated ASCL1 in NEPC cells. In addition, upregulated SOX2 induced PCa cell differentiation into neuroendocrine tumors by mediating their lineage changes. In conclusion, inhibiting the ferroptosis resistance mediated by ASCL1 could provide a new NEPC therapeutic target and increase patient survival.

Rice pest identification based on multi-scale double-branch GAN-ResNet.

Rice production is crucial to the food security of all human beings, and how rice pests and diseases can be effectively prevented in and timely detected is a hotspot issue in the field of smart agriculture. Deep learning has become the preferred method for rice pest identification due to its excellent performance, especially in the aspect of autonomous learning of image features. However, in the natural environment, the dataset is too small and vulnerable to the complex background, which easily leads to problems such as overfitting, and too difficult to extract the fine features during the process of training. To solve the above problems, a Multi-Scale Dual-branch structural rice pest identification model based on a generative adversarial network and improved ResNet was proposed. Based on the ResNet model, the ConvNeXt residual block was introduced to optimize the calculation ratio of the residual blocks, and the double-branch structure was constructed to extract disease features of different sizes in the input disease images, which it adjusts the size of the convolution kernel of each branch. In the complex natural environment, data pre-processing methods such as random brightness and motion blur, and data enhancement methods such as mirroring, cropping, and scaling were used to allow the dataset of 5,932 rice disease images captured from the natural environment to be expanded to 20,000 by the dataset in this paper. The new model was trained on the new dataset to identify four common rice diseases. The experimental results showed that the recognition accuracy of the new rice pest recognition model, which was proposed for the first time, improved by 2.66% compared with the original ResNet model. Under the same experimental conditions, the new model had the best performance when compared with classical networks such as AlexNet, VGG, DenseNet, ResNet, and Transformer, and its recognition accuracy could be as high as 99.34%. The model has good generalization ability and excellent robustness, which solves the current problems in rice pest identification, such as the data set is too small and easy to lead to overfitting, and the picture background is difficult to extract disease features, and greatly improves the recognition accuracy of the model by using a multi-scale double branch structure. It provides a superior solution for crop pest and disease identification.

Dietary adenosine supplementation improves placental angiogenesis in IUGR piglets by up-regulating adenosine A2a receptor.

Abnormal placental angiogenesis is associated with the occurrence of intrauterine growth restriction (IUGR) in piglets, and effective treatment strategies against this occurrence remain to be explored. Adenosine has been reported to play an important role in angiogenesis, but its role in placental angiogenesis is still unknown. Here, we investigated the effect of dietary adenosine supplementation on IUGR occurrence in piglets by analyzing the role of adenosine in placental angiogenesis for Normal and IUGR piglets. Specifically, 88 sows were allotted to 2 treatments (n = 44) and fed a basal diet supplemented with 0% or 0.1% of adenosine from day 65 of gestation until farrowing, followed by collecting the placental samples of Normal and IUGR piglets, and recording their characteristics. The results showed that adenosine supplementation increased the mean birth weight of piglets (P < 0.05) and placental efficiency (P < 0.05), while decreasing the IUGR piglet rate (P < 0.05). Expectedly, the placenta for IUGR neonates showed a down-regulated vascular density (P < 0.05) and angiogenesis as evidenced by the expression level of vascular cell adhesion molecule-1 (VCAM1) (P < 0.05). Notably, dietary adenosine supplementation promoted angiogenesis (P < 0.05) both in the Normal and IUGR placenta. More importantly, the expression level of adenosine A2a receptor (ADORA2A) was lower (P < 0.05) in the IUGR placenta than in Normal placenta, whereas adenosine treatment could significantly increase ADORA2A expression, and also had an interaction effect between factors IUGR and Ado. Collectively, placentae for IUGR piglets showed impaired angiogenesis and down-regulated expression level of ADORA2A, while dietary adenosine supplementation could activate ADORA2A expression, improve the placental angiogenesis, and ultimately decrease the occurrence of IUGR in piglets.

Biomarkers of aging.

Aging biomarkers are a combination of biological parameters to (i) assess age-related changes, (ii) track the physiological aging process, and (iii) predict the transition into a pathological status. Although a broad spectrum of aging biomarkers has been developed, their potential uses and limitations remain poorly characterized. An immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research: How old are we? Why do we get old? And how can we age slower? This review aims to address this need. Here, we summarize our current knowledge of biomarkers developed for cellular, organ, and organismal levels of aging, comprising six pillars: physiological characteristics, medical imaging, histological features, cellular alterations, molecular changes, and secretory factors. To fulfill all these requisites, we propose that aging biomarkers should qualify for being specific, systemic, and clinically relevant.

Dietary fiber supplementation during the last 50 days of gestation improves the farrowing performance of gilts by modulating insulin sensitivity, gut microbiota, and placental function.

Our previous study found dietary konjac flour (KF) supplementation could improve insulin sensitivity and reproductive performance of sows, but its high price limits its application in actual production. This study aimed to investigate the effects of supplementation of a cheaper combined dietary fiber (CDF, using bamboo shoots fiber and alginate fiber to partially replace KF) from the last 50 days of gestation to parturition on farrowing performance, insulin sensitivity, gut microbiota, and placental function of gilts. Specifically, a total of 135 pregnant gilts with a similar farrowing time were blocked by backfat thickness and body weight on day 65 of gestation (G65d) and assigned to 1 of the 3 dietary treatment groups (n = 45 per group): basal diet (CON), basal diet supplemented with 2% KF or 2% CDF (CDF containing 15% KF, 60% bamboo shoots fiber, and 25% alginate fiber), respectively. The litter performance, insulin sensitivity and glucose tolerance parameters, placental vessel density, and short-chain fatty acids (SCFAs) levels in feces were assessed. The gut microbiota population in gilts during gestation was also assessed by 16S rDNA gene sequencing. Compared with CON, both KF and CDF treatments not only increased the piglet birth weight (P < 0.05) and piglet vitality (P < 0.01) but also decreased the proportion of piglets with birth weight ≤ 1.2 kg (P < 0.01) and increased the proportion of piglets with birth weight ≥ 1.5 kg (P < 0.01). In addition, KF or CDF supplementation reduced fasting blood insulin level (P < 0.05), homeostasis model assessment-insulin resistance (P < 0.05), serum hemoglobin A1c (P < 0.05), and the level of advanced glycation end products (P < 0.05) at G110d, and increased the placental vascular density (P < 0.05) at farrowing. Meanwhile, KF or CDF supplementation increased microbial diversity (P < 0.05) and SCFAs levels (P < 0.05) in feces at G110d. Notably, the production cost per live-born piglet was lower in CDF group (¥ 36.1) than KF group (¥ 41.3). Overall, KF or CDF supplementation from G65d to farrowing could improve the farrowing performance of gilts possibly by improving insulin sensitivity, regulating gut microbiota and metabolites, and increasing placental vascular density, with higher economic benefits and a similar effect for CDF vs. KF, suggesting the potential of CDF as a cheaper alternative to KF in actual production.

Dietary konjac flour (KF) supplementation could improve insulin sensitivity and reproductive performance of sows, but its high price limits its application in actual production. This study investigated the impact of 2% konjac flour (KF) and 2% combined dietary fiber (CDF, containing 15% KF, 60% bamboo shoots fiber, and 25% alginate fiber) supplementation from the last 50 days of gestation to farrowing on farrowing performance, placental function, insulin sensitivity, and gut microbiota of gilts. Results indicated that KF or CDF supplementation during this time could improve the farrowing performance of gilts possibly by improving insulin sensitivity and gut microbiota, and increasing placental vascular density. Meanwhile, CDF could lower the production cost per live-born piglet and have a similar effect to KF, thus a cheaper alternative to KF in actual production. This study facilitates understanding the beneficial effects of KF and non-conventional dietary fiber sources on the reproductive performance of gilts.

Immunization with recombinant Erns-LTB fusion protein elicits protective immune responses against bovine viral diarrhea virus.

Bovine viral diarrhea virus (BVDV), a major infectious pathogen and is associated with major economic losses and significant impact on animal welfare worldwide. Here, recombinant Erns-LTB protein vaccine containing MF59 adjuvant was prepared and assessed using a mouse model. The recombinant plasmid (pET32a-Erns-LTB) was constructed and transformed into BL21 (DE3) cells to produce Erns-LTB protein. The Erns-LTB protein was formulated with MF59 adjuvant, when delivered intraperitoneally in mice, exhibited higher immunogenic and induced superior levels of anti-BVDV IgG compared with the MF59 adjuvanted Erns protein. Importantly, after challenged with different BVDV BJ175170 and BJ1305 isolate strains, mice inoculated with Erns-LTB protein displayed alleviated pathological damage and decreased plasma virus shedding compared with mice inoculated with Erns protein. The enhanced protection from Erns-LTB protein is mediated by T cell immunity and primarily based on CD4+ T helper (Th) and CD8+ cytotoxic T lymphocyte (CTL), these results suggest that Erns-LTB protein has potential to protect against a broad range of BVDV strains thereby providing a novel direction for developing broadly protective vaccines.

Butyrate-mediated autophagy inhibition limits cytosolic Salmonella Infantis replication in the colon of pigs treated with a mixture of Lactobacillus and Bacillus.

Probiotics as an effective and safe strategy for controlling Salmonella infection are much sought after, while autophagy is a central issue in eliminating intracellular pathogens of intestinal epithelial cells. In this study, an animal model of colitis has been developed by infecting weaned pigs orally with a strain of Salmonella Infantis in order to illuminate the potential efficacy of a mixture of Lactobacillus and Bacillus (CBB-MIX) in the resistance to Salmonella infection by regulating butyrate-mediated autophagy. We found that CBB-MIX alleviated S. Infantis-induced colitis and tissue damage. Autophagy markers ATG5, Beclin-1, and the LC3-II/I ratio were significantly enhanced by S. Infantis infection, while treatment with CBB-MIX suppressed S. Infantis-induced autophagy. Additionally, S. Infantis-induced colonic microbial dysbiosis was restored by this treatment, which also preserved the abundance of the butyrate-producing bacteria and the butyrate concentration in the colon. A Caco-2 cell model of S. Infantis infection showed that butyrate had the same effect as the CBB-MIX in restraining S. Infantis-induced autophagy activation. Further, the intracellular S. Infantis load assay indicated that butyrate restricted the replication of cytosolic S. Infantis rather than that in Salmonella-containing vacuoles. Suppression of autophagy by knockdown of ATG5 also attenuated S. Infantis-induced cell injury. Moreover, hyper-replication of cytosolic S. Infantis in Caco-2 cells was significantly decreased when autophagy was inhibited. Our data demonstrated that Salmonella may benefit from autophagy for cytosolic replication and butyrate-mediated autophagy inhibition reduced the intracellular Salmonella load in pigs treated with a probiotic mixture of Lactobacillus and Bacillus.

Recombinant Erns-E2 protein vaccine formulated with MF59 and CPG-ODN promotes T cell immunity against bovine viral diarrhea virus infection.

To obtain an effective vaccine candidate against bovine viral diarrhea virus (BVDV) disease which causes great economical loss in cattle industries, recombinant Erns-E2 protein vaccine containing MF59 and CPG-ODN adjuvants was prepared and assessed in this study. The recombinant plasmid (pET32a-Erns-E2) was constructed and transformed into BL21 (DE3) cells to produce Erns-E2 protein. We immunized mice with the MF59-and CPG-ODN-adjuvanted recombinant Erns-E2 protein, E2 protein, or Erns protein, respectively. To evaluate immunogenicity and efficacy of a vaccine-adjuvant combination, mice were challenged with BVDV BJ175170 strain after immunization. All adjuvanted vaccines elicited detectable humoral and cellular immune responses, the BVDV-specific antibody titers as well as interleukin 4 (IL-4) levels in sera of mice immunized with the recombinant Erns-E2 protein were higher than in those of mice immunized with either the recombinant Erns or E2 protein. Besides, immunization with the Erns-E2 vaccines induced higher percentage of CD4+IFN-γ+, CD8+IFN-γ+ T cells and CD3+TNF-α+ T cells compared with the other vaccines. More protective efficacy against BVDV infection was acquired in the mice treated with the recombinant Erns-E2 protein, as shown by a reduction of viremia and slight pathological changes compared with both the control mice and the other vaccinated mice. Our findings suggest that the use of the recombinant Erns-E2 protein vaccine formulated with MF59 and CPG-ODN adjuvants enhances T cell responses and viral control, which warrants the Erns-E2 protein vaccine-adjuvant combination could be as a vaccine strategy to against BVDV.