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Simple Summary: Low-protein (LPRO) diets provide benefits such as reduced feed costs and improved utilization. However, the necessary nutritional data for optimizing these diets are incomplete, and formulation techniques are still developing. Moreover, there is no consensus on the impact of low-protein diets with balanced amino acids on production performance. This study examined the impact of protease and Bacillus coagulans on broilers fed LPRO diets, finding that these additives can counteract the negative effects by increasing serum amino acids, upregulating transporter genes, enhancing intestinal barriers, and improving cecal microbiota, offering a basis for promoting LPRO feeds in broiler production. Low-protein (LPRO) diets can effectively reduce feed costs and decrease environmental pollution, making them an important pathway to enhance the sustainability of livestock production. However, they may have adverse effects on the growth performance of broiler chickens, which has limited their widespread application. This study aims to explore the impact of adding protease (PRO) to LPRO diets on the growth performance of broiler chickens, especially under conditions with or without the presence of Bacillus coagulans (BC), in order to provide theoretical support for the scientific application and promotion of LPRO feeds. We selected 432 one-day-old broiler chickens and divided them into four treatment groups, which were fed with the control (CON) diet, the LPRO diet, the PRO diet (LPRO diet with added protease), and the PAB diet (PRO diet with added BC). The LPRO group demonstrated decreased growth performance while both PRO and PAB diets resulted in a significant increase (p < 0.05). Both PRO and PAB diets significantly enhanced the expression of amino acid transport genes and tight junction genes (p < 0.05) and optimized the composition of the intestinal microbiota. Overall, LPRO diets have a detrimental effect on the growth of broiler chickens, while the PRO and PAB diets effectively counteract these negative effects by improving protein digestion, amino acid absorption, and intestinal health. [ABSTRACT FROM AUTHOR]

Faba bean (Vicia faba L.) is a valuable ingredient in plant-based foods such as meat and dairy analogues. However, its typical taste and aroma are considered off-flavours in these food applications, representing a bottleneck during processing. Breeding is needed to develop varieties with minimal off-flavours and high protein content. The genetic regulation of these traits is underexplored. To dissect their genetic architecture, we performed a genome-wide association study (GWAS). A total of 245 faba bean accessions (the CGN population) were genotyped using the 90K-SPET targeted assay. These accessions were phenotyped in 2021 and 2022 in the Netherlands for protein, oil, fatty acids, lipid-derived products, phenolic acids, flavonoids, and tannins. The CGN population showed large phenotypic variation and moderate-to-high narrow-sense heritability for most traits. The growing environment significantly affected all traits, with trait-specific genotype-by-year (GxY) interactions. Condensed tannins and fatty acids were the most stable across the two years and had the highest heritability estimates (h2 > 0.6). GWAS identified a total of 148 single nucleotide polymorphisms (SNPs) loci in 2021 and 167 in 2022. Key candidate regulators included genes involved in lipid biosynthesis (ATS2, KAS, LPP), amino acid transport (CAT4) for protein storage, zero tannins locus-1 (zt-1), and regulators of the phenylpropanoid pathway, such as a shikimate kinase gene and transcription factors bHLH137-like and MYB. These results pave the way for validation studies and biotechnological applications to improve the quality of faba bean-based foods. [ABSTRACT FROM AUTHOR]

Amino acids in wine grapes function as precursors for various secondary metabolites and play a vital role in plant growth, development, and stress resistance. The amino acid/auxin permease (AAAP) genes encode a large family of transporters; however, the identification and function of the AAAP gene family in grapes remain limited. Consequently, we conducted a comprehensive bioinformatics analysis of all AAAP genes in grapes, encompassing genome sequence analysis, conserved protein domain identification, chromosomal localization, phylogenetic relationship analysis, and gene expression profiling. This study identified 60 VvAAAP genes, distributed on 14 chromosomes and classified into eight subfamilies. Microarray and transcriptome data revealed that most VvAAAP genes decrease during development, but VvAAAP7 and VvAAAP33 gradually increase. VvAAAP23 and VvAAAP46 exhibited significantly higher expression levels, while VvAAAP30 demonstrated lower expression when subjected to salt and drought stress. VvAAAP genes exhibited diverse expression patterns, suggesting that the AAAP gene family possesses both diversity and specific functions in grapes. Furthermore, the expression patterns of VvAAAP genes analyzed by RT-qPCR facilitate further investigation into the biological functions of individual genes in different tissues. These findings provide valuable insights into the continued analysis of the AAAP gene family's functions in grapes. [ABSTRACT FROM AUTHOR]

Background: Soil microbes play a vital role in the ecosystem as they are able to carry out a number of vital tasks. Additionally, metagenomic studies offer valuable insights into the composition and functional potential of soil microbial communities. Furthermore, analyzing the obtained data can improve agricultural restoration practices and aid in developing more effective environmental management strategies. Methodology: In November 2023, sandy soil samples were collected from ten sites of different geographical areas surrounding natural lakes and artificial water points in the Tubaiq conservation area of King Salman Bin Abdulaziz Royal Natural Reserve (KSRNR), Saudi Arabia. In addition, genomic DNA was extracted from the collected soil samples, and 16S rRNA sequencing was conducted using high-throughput Illumina technology. Several computational analysis tools were used for gene prediction and taxonomic classification of the microbial groups. Results: In this study, sandy soil samples from the surroundings of natural and artificial water resources of two distinct natures were used. Based on 16S rRNA sequencing, a total of 24,563 OTUs were detected. The metagenomic information was then categorized into 446 orders, 1036 families, 4102 genera, 213 classes, and 181 phyla. Moreover, the phylum Pseudomonadota was the most dominant microbial community across all samples, representing an average relative abundance of 34%. In addition, Actinomycetes was the most abundant class (26%). The analysis of clustered proteins assigned to COG categories provides a detailed understanding of the functional capabilities and adaptation of microbial communities in soil samples. Amino acid metabolism and transport were the most abundant categories in the soil environment. Conclusions: Metagenome analysis of sandy soils surrounding natural lakes and artificial water points in the Tubaiq conservation area of KSRNR (Saudi Arabia) has unveils rich microbial activity, highlighting the complex interactions and ecological roles of microbial communities in these environments. [ABSTRACT FROM AUTHOR]

Brassica napus is an important oil crop in China and has a great demand for nitrogen nutrients. Cationic amino acid transporters (CAT) play a key role in amino acid absorption and transport in plants. However, the CATs family has not been reported in B. napus so far. In this study, genome-wide analysis identified 22 CAT members in the B. napus genome. Based on phylogenetic and synteny analysis, BnaCATs were classified into four groups (Group I–Group IV). The members in the same subgroups showed similar physiochemical characteristics and intron/exon and motif patterns. By evaluating cis-elements in the promoter regions, we identified some cis-elements related to hormones, stress and plant development. Darwin's evolutionary analysis indicated that BnaCATs might have experienced strong purifying selection pressure. The BnaCAT family may have undergone gene expansion; the chromosomal location of BnaCATs indicated that whole-genome replication or segmental replication may play a major driving role. Differential expression patterns of BnaCATs under nitrate limitation, phosphate shortage, potassium shortage, cadmium toxicity, ammonium excess and salt stress conditions indicated that they were responsive to different nutrient stresses. In summary, these findings provide a comprehensive survey of the BnaCAT family and lay a foundation for the further functional analysis of family members. [ABSTRACT FROM AUTHOR]

Amino acids are the main form of nitrogen in plants, and their transport across cell membranes relies on amino acid transporters (AATs). Among the plant AATs, the TaATLa subfamily comprises 18 members, yet the bioinformatics characteristics and functions of TaATLa genes in common wheat remain poorly understood due to their complex genomes. This study performed genomic analyses of TaATLas. These analyses included chromosome distributions, evolutionary relationships, collinearity, gene structures, and expression patterns. An analysis of cis-acting elements and predicted miRNA-TaATLas regulatory networks suggests that TaATLas are regulated by light, hormones, and stress signals. Functional assays revealed that TaATLa6 transports glutamine (Gln), glutamate (Glu), and aspartate (Asp) in yeast. In contrast, TaATLa4 specifically transports Gln and Asp. Furthermore, TaATLas exhibits diverse gene expression patterns, with TaATLa4-7D enhancing yeast heat tolerance in a heterologous expression system, indicating its potential role in adapting to environmental stress by regulating amino acid transport and distribution. This study sheds light on the functional roles of TaATLa genes, with implications for improving nitrogen use in wheat and other crop species. [ABSTRACT FROM AUTHOR]

For the first time, we used an in vitro vs. in vivo experimental design to reveal core pathways under nitrogen deficiency (ND) in an evergreen tree crop. These pathways were related to lignin biosynthesis, cell redox homeostasis, the defense response to fungus, the response to Karrikin, amino acid transmembrane transport, the extracellular region, the cellular protein catabolic process, and aspartic-type endopeptidase activity. In addition, the mitogen-activated protein kinase pathway and ATP synthase (ATP)-binding cassette transporters were significantly upregulated under nitrogen deficiency in vitro and in vivo. Most of the MAPK downstream genes were related to calcium signaling (818 genes) rather than hormone signaling (157 genes). Moreover, the hormone signaling pathway predominantly contained auxin- and abscisic acid-related genes, indicating the crucial role of these hormones in ND response. Overall, 45 transcription factors were upregulated in both experiments, 5 WRKYs, 3 NACs, 2 MYBs, 2 ERFs, HD-Zip, RLP12, bHLH25, RADIALIS-like, and others, suggesting their ND regulation is independent from the presence of a root system. Gene network reconstruction displayed that these transcription factors participate in response to fungus/chitin, suggesting that nitrogen response and pathogen response have common regulation. The upregulation of lignin biosynthesis genes, cytochrome genes, and strigalactone response genes was much more pronounced under in vitro ND as compared to in vivo ND. Several cell wall-related genes were closely associated with cytochromes, indicating their important role in flavanols biosynthesis in tea plant. These results clarify the signaling mechanisms and regulation of the response to nitrogen deficiency in evergreen tree crops. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) is a debilitating central nervous system (CNS) disorder that leads to significant motor and sensory impairments. Given the limited regenerative capacity of adult mammalian neurons, this study presents an innovative strategy to enhance axonal regeneration and functional recovery by identifying a novel factor that markedly promotes axonal regeneration. Employing a zebrafish model with targeted single axon injury in Mauthner cells (M-cells) and utilizing the Tg (Tol056: EGFP) transgenic line for in vivo monitoring, we investigate the intrinsic mechanisms underlying axonal regeneration. This research specifically examines the role of amino acid transport, emphasizing the role of the solute carrier 1A4 amino acid transporter in axonal regeneration. Our findings demonstrate that Slc1a4 overexpression significantly enhances axonal regeneration in M-cells, whereas Slc1a4 deficiency impedes this process, which is concomitant with the downregulation of the P53/Gap43 signaling pathway. By elucidating the fundamental role of Slc1a4 in axonal regeneration and uncovering its underlying mechanisms, this study thus provides novel insights into therapeutic strategies for SCI. [ABSTRACT FROM AUTHOR]

Exogenous brassinolide (BR) and strigolactones (SLs) play an important role in alleviating salt stress in maize. We studied the morphological and physiological responses of the salt-sensitive genotype PH4CV and salt-tolerant genotype Zheng58 to BR (1.65 nM), SL (1 µM), and BS (1.65 nM BR + 1 µM SL) under salt stress. Phenotypic analysis showed that salt stress significantly inhibited the growth of maize seedlings and significantly increased the content of Na+ in the roots. Exogenous hormones increased oxidase activity and decreased Na+ content in the roots and mitigated salt stress. Transcriptome analysis showed that the interaction of BR and SL is involved in photosynthesis–antenna proteins, the TCA cycle, and plant hormone signal transduction pathways. This interaction influences the expression of chlorophyll a/b-binding protein and glucose-6-phosphate isomerase 1 chloroplastic, and aconitase genes are affected. Furthermore, the application of exogenous hormones regulates the expression of genes associated with the signaling pathways of cytokinin (CK), gibberellins (GA), auxin (IAA), brassinosteroid (BR), abscisic acid (ABA), and jasmonic acid (JA). Additionally, exogenous hormones inhibit the expression of the AKT2/3 genes, which are responsible for regulating ion transduction and potassium ion influx. Four candidate genes that may regulate the seedling length of maize were screened out through WGCNA. Respective KOG notes concerned inorganic ion transport and metabolism, signal transduction mechanisms, energy production and conversion, and amino acid transport and metabolism. The findings of this study provide a foundation for the proposition that BR and SL can be employed to regulate salt stress alleviation in maize. [ABSTRACT FROM AUTHOR]

Retinopathy of prematurity (ROP) is a primary cause of visual impairment and blindness in premature newborns, characterized by vascular abnormalities in the developing retina, with microvascular alteration, neovascularization, and in the most severe cases retinal detachment. To elucidate the pathophysiology and develop therapeutics for ROP, several pre-clinical experimental models of ROP were developed in different species. Among them, the oxygen-induced retinopathy (OIR) mouse model has gained the most popularity and critically contributed to our current understanding of pathological retinal angiogenesis and the discovery of potential anti-angiogenic therapies. A deeper comprehension of molecular regulators of OIR such as hypoxia-inducible growth factors including vascular endothelial growth factors as primary perpetrators and other new metabolic modulators such as lipids and amino acids influencing pathological retinal angiogenesis is also emerging, indicating possible targets for treatment strategies. This review delves into the historical progressions that gave rise to the modern OIR models with a focus on the mouse model. It also reviews the fundamental principles of OIR, recent advances in its automated assessment, and a selected summary of metabolic investigation enabled by OIR models including amino acid transport and metabolism. [ABSTRACT FROM AUTHOR]

Amino acid transporters mediate amino acid transport within and between cells and are the main mediators of nitrogen distribution in plants, which is crucial for maintaining plant growth and development. Many amino acid transporters have been identified in different plant species. In this review, we discuss the functions of amino acid transporters in plant absorption and amino acid transportation from root to shoot, which results in crop yield and quality improvement. Moreover, we summarize the role of amino acid transporters in response to environmental stimuli and the influence of N and C metabolic processes. We also elaborate on potential future research directions. [ABSTRACT FROM AUTHOR]

The role of amino acid transporter (AAT) genes in facilitating the transmembrane movement of amino acids between cells and various cellular components has been characterized in several plant species. Quinoa (Chenopodium quinoa Willd.), a renowned nutritious crop known for its amino acid composition, has not yet had its AAT genes characterized. Therefore, the identification and characterization of AAT genes in quinoa will help bridge this knowledge gap and offer valuable insights into the genetic mechanisms underlying amino acid transport and metabolism. This study focuses on gene expression, gene structure, duplication events, and a comparison of functions studied to establish the role of AAT genes. A total of 160 non-redundant AAT genes were identified in quinoa and classified into 12 subfamilies, with 8 subfamilies belonging to the amino acid/auxin permease (AAAP) family and 4 to the amino acid-polyamine-organocation (APC) superfamily family. The chromosomal localization, gene structures, and conserved motifs of these genes were systematically analyzed. Expression profiling revealed diverse expression patterns across various tissues and in response to drought and salt stresses. Segmental and tandem duplications were found to contribute to the gene duplication and expansion of the CqAAT gene family. Additionally, CqCAT6 and CqAAP1 were predicted to regulate the long-distance transportation and distribution of amino acids, making them potential candidate genes for further research. Overall, this information could serve as a foundation for the identification and utilization of CqAATs in Quinoa, enhancing our understanding of amino acid transport mechanisms in this important crop. [ABSTRACT FROM AUTHOR]

Simple Summary: Red pandas have evolved to become specialized bamboo eaters within Carnivora. Probably due to the difficulty in obtaining materials, reports on genes related to digestion and metabolism at expression and regulation levels in red pandas are rare. Red pandas and carnivorous mammal ferrets have a close phylogenetic relationship. They both consume highly nutritious milk during the suckling period, but consume low-energy bamboo and high-energy meat during the adult period, respectively. In order to explore the molecular mechanisms of dietary changes and nutrient utilization in red pandas, we discussed (1) the differences in expression changes of some genes related to digestion and metabolism in the stomach of these two species after food changes, as well as the expression adaptation of genes related to digestion and metabolism in both species during different feeding periods, and (2) the regulatory effects of lncRNAs and miRNAs on adaptive expressions of genes related to digestion and metabolism in both species from suckling to adult. Red pandas evolved from carnivores to herbivores and are unique within Carnivora. Red pandas and carnivorous mammals consume milk during the suckling period, while they consume bamboo and meat during the adult period, respectively. Red pandas and carnivorous mammal ferrets have a close phylogenetic relationship. To further investigate the molecular mechanisms of dietary changes and nutrient utilization in red pandas from suckling to adult, comparative analysis of the whole transcriptome was performed on stomach tissues from red pandas and ferrets during the suckling and adult periods. The main results are as follows: (1) we identified ncRNAs for the first time in stomach tissues of both species, and found significant expression changes of 109 lncRNAs and 106 miRNAs in red pandas and 756 lncRNAs and 109 miRNAs in ferrets between the two periods; (2) up-regulated genes related to amino acid transport regulated by lncRNA-miRNA-mRNA networks may efficiently utilize limited bamboo amino acids in adult red pandas, while up-regulated genes related to amino acid degradation regulated by lncRNAs may maintain the balance of amino acid metabolism due to larger daily intakes in adult ferrets; and (3) some up-regulated genes related to lipid digestion may contribute to the utilization of rich nutrients in milk for the rapid growth and development of suckling red pandas, while up-regulated genes associated with linoleic acid metabolism regulated by lncRNA-miRNA-mRNA networks may promote cholesterol decomposition to reduce health risks for carnivorous adult ferrets. Collectively, our study offers evidence of gene expression adaptation and ncRNA regulation in response to specific dietary changes and nutrient utilization in red pandas during suckling and adult periods. [ABSTRACT FROM AUTHOR]

Amino acid permeases (AAPs) transporters are crucial for the long-distance transport of amino acids in plants, from source to sink. While Arabidopsis and rice have been extensively studied, research on foxtail millet is limited. This study identified two transcripts of SiAAP9, both of which were induced by NO3− and showed similar expression patterns. The overexpression of SiAAP9L and SiAAP9S in Arabidopsis inhibited plant growth and seed size, although SiAAP9 was found to transport more amino acids into seeds. Furthermore, SiAAP9-OX transgenic Arabidopsis showed increased tolerance to high concentrations of glutamate (Glu) and histidine (His). The high overexpression level of SiAAP9 suggested its protein was not only located on the plasma membrane but potentially on other organelles, as well. Interestingly, sequence deletion reduced SiAAP9's sensitivity to Brefeldin A (BFA), and SiAAP9 had ectopic localization on the endoplasmic reticulum (ER). Protoplast amino acid uptake experiments indicated that SiAAP9 enhanced Glu transport into foxtail millet cells. Overall, the two transcripts of SiAAP9 have similar functions, but SiAAP9L shows a higher colocalization with BFA compartments compared to SiAAP9S. Our research identifies a potential candidate gene for enhancing the nutritional quality of foxtail millet through breeding. [ABSTRACT FROM AUTHOR]

The membrane Fo factor of ATP synthase is highly sensitive to mutations in the proton half-channel leading to the functional blocking of the entire protein. To identify functionally important amino acids for the proton transport, we performed molecular dynamic simulations on the selected mutants of the membrane part of the bacterial FoF1-ATP synthase embedded in a native lipid bilayer: there were nine different mutations of a-subunit residues (aE219, aH245, aN214, aQ252) in the inlet half-channel. The structure proved to be stable to these mutations, although some of them (aH245Y and aQ252L) resulted in minor conformational changes. aH245 and aN214 were crucial for proton transport as they directly facilitated H+ transfer. The substitutions with nonpolar amino acids disrupted the transfer chain and water molecules or neighboring polar side chains could not replace them effectively. aE219 and aQ252 appeared not to be determinative for proton translocation, since an alternative pathway involving a chain of water molecules could compensate the ability of H+ transmembrane movement when they were substituted. Thus, mutations of conserved polar residues significantly affected hydration levels, leading to drastic changes in the occupancy and capacity of the structural water molecule clusters (W1–W3), up to their complete disappearance and consequently to the proton transfer chain disruption. [ABSTRACT FROM AUTHOR]

Simple Summary: The ovine placenta facilitates transport of oxygen and nutrients to the growing fetus. Placental morphology and placental function are affected by environmental factors, and the changes are not well understood. This study aimed to identify the effect of tissue type (caruncle vs. cotyledon), placentome morphological subtype, and maternal parenteral arginine supplementation in mid–late pregnancy on the placental nutrient transport capacity at 140 days of gestation, using a gene expression approach. Results highlighted that placentome morphology and tissue type are associated with differential expression of specific amino acid (AA) transporter genes, suggesting a potential adaptive response to increase the transport capacity of the placenta. Maternal arginine supplementation influenced expression of genes involved in AA transport, placental efficiency, and angiogenesis, which may affect the placental transport capacity. The results contribute to an increased understanding of placental function and provide new insights into the effects influencing the placental nutrient transport capacity to support fetal growth in sheep. Placental nutrient transport capacity influences fetal growth and development; however, it is affected by environmental factors, which are poorly understood. The objective of this study was to understand the impact of the ovine placentome morphological subtype, tissue type, and maternal parenteral supplementation of arginine mono-hydrochloride (Arg) on nutrient transport capacity using a gene expression approach. Placentomal tissues of types A, B, and C morphologic placentome subtypes were derived from 20 twin-bearing ewes, which were infused thrice daily with Arg (n = 9) or saline (Ctrl, n = 11) from 100 to 140 days of gestation. Samples were collected at day 140 of gestation. Expression of 31 genes involved in placental nutrient transport and function was investigated. Differential expression of specific amino acid transporter genes was found in the subtypes, suggesting a potential adaptive response to increase the transport capacity. Placentomal tissues differed in gene expression, highlighting differential transport capacity. Supplementation with Arg was associated with differential expressions of genes involved in amino acid transport and angiogenesis, suggesting a greater nutrient transport capacity. Collectively, these results indicate that the morphological subtype, tissue type, and maternal Arg supplementation can influence placental gene expression, which may be an adaptive response to alter the transport capacity to support fetal growth in sheep. [ABSTRACT FROM AUTHOR]

The type III secretion system (T3SS) is a key factor for the symbiosis between rhizobia and legumes. In this study, we investigated the effect of calcium on the expression and secretion of T3SS effectors (T3Es) in Sinorhizobium fredii NGR234, a broad host range rhizobial strain. We performed RNA-Seq analysis of NGR234 grown in the presence of apigenin, calcium, and apigenin plus calcium and compared it with NGR234 grown in the absence of calcium and apigenin. Calcium treatment resulted in a differential expression of 65 genes, most of which are involved in the transport or metabolism of amino acids and carbohydrates. Calcium had a pronounced effect on the transcription of a gene (NGR_b22780) that encodes a putative transmembrane protein, exhibiting a 17-fold change when compared to NGR234 cells grown in the absence of calcium. Calcium upregulated the expression of several sugar transporters, permeases, aminotransferases, and oxidoreductases. Interestingly, calcium downregulated the expression of nodABC, genes that are required for the synthesis of nod factors. A gene encoding a putative outer membrane protein (OmpW) implicated in antibiotic resistance and membrane integrity was also repressed by calcium. We also observed that calcium reduced the production of nodulation outer proteins (T3Es), especially NopA, the main subunit of the T3SS pilus. Additionally, calcium mediated the cleavage of NopA into two smaller isoforms, which might affect the secretion of other T3Es and the symbiotic establishment. Our findings suggest that calcium regulates the T3SS at a post-transcriptional level and provides new insights into the role of calcium in rhizobia–legume interactions. [ABSTRACT FROM AUTHOR]

Insulin is a polypeptide hormone synthesized and secreted by pancreatic β-cells. It plays an important role as a metabolic hormone. Insulin influences the metabolism of glucose, regulating plasma glucose levels and stimulating glucose storage in organs such as the liver, muscles and adipose tissue. It is involved in fat metabolism, increasing the storage of triglycerides and decreasing lipolysis. Ketone body metabolism also depends on insulin action, as insulin reduces ketone body concentrations and influences protein metabolism. It increases nitrogen retention, facilitates the transport of amino acids into cells and increases the synthesis of proteins. Insulin also inhibits protein breakdown and is involved in cellular growth and proliferation. On the other hand, defects in the intracellular signaling pathways of insulin may cause several disturbances in human metabolism, resulting in several chronic diseases. Insulin resistance, also known as impaired insulin sensitivity, is due to the decreased reaction of insulin signaling for glucose levels, seen when glucose use in response to an adequate concentration of insulin is impaired. Insulin resistance may cause, for example, increased plasma insulin levels. That state, called hyperinsulinemia, impairs metabolic processes and is observed in patients with type 2 diabetes mellitus and obesity. Hyperinsulinemia may increase the risk of initiation, progression and metastasis of several cancers and may cause poor cancer outcomes. Insulin resistance is a health problem worldwide; therefore, mechanisms of insulin resistance, causes and types of insulin resistance and strategies against insulin resistance are described in this review. Attention is also paid to factors that are associated with the development of insulin resistance, the main and characteristic symptoms of particular syndromes, plus other aspects of severe insulin resistance. This review mainly focuses on the description and analysis of changes in cells due to insulin resistance. [ABSTRACT FROM AUTHOR]

In order to investigate the effects of various nitrogen (ammonium) concentrations on the epibiotic bacterial community associated with Oocystis borgei, a metabarcoding sequencing method was employed. The 16S rDNA sequencing and bioinformatic analysis were conducted on cultures of O. borgei that were grown on four different nitrogen element concentrations (2.5, 10, 50, and 100 mg/L), and the differences in the epibiotic bacterial community and functions of O. borgei among different nitrogen concentrations were compared. The results showed that the chlorophyll a content of O. borgei increased with increasing nitrogen concentrations. A total of 43 operational taxonomic units (OTUs) were obtained from the four groups, which were categorized into 7 phyla, 9 classes, 18 orders, 21 families, and 26 genera. Winogradskyella was the dominant genus in the groups with 2.5 and 100 mg/L nitrogen, while Marinobacter and Winogradskyella were relatively abundant in the groups with 50 and 100 mg/L nitrogen. Functional analysis using PICRUST2 showed that the three most abundant gene functions were carbohydrate metabolism, amino acid transport and metabolism, ribosomal structure and biogenesis, and energy production and conversion. BugBase phenotypic analysis revealed that there were no significant differences in phenotypes between the groups with 2.5 and 10 mg/L nitrogen, while the group with 50 mg/L nitrogen exhibited higher abundance in aerobicity, biofilm formation, mobile genetic elements, and stress tolerance phenotypes. Most of the bacteria in this work belonged to the aerobic types. A redundancy analysis (RDA) of environmental factors demonstrated that nitrogen concentration showed a positive correlation with species changes in the groups with 10 and 50 mg/L nitrogen; chlorophyll a exhibited a positive correlation with species changes in the groups with 50 and 100 mg/L nitrogen. Nitrogen concentration significantly influenced the epibiotic bacterial community associated with O. borgei, leading to changes in dominant species and community structure. This study provides important references for understanding the functional characteristics of the epiphytic microbial community of O. borgei and the exploration of specific microorganisms. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the effects of a complex comprising formic acid, benzoic acid, and essential oils (AO3) on the growth performance of weaned piglets and explore the underlying mechanism. Dietary AO3 supplementation significantly enhanced the average daily gain (ADG) and average daily feed intake (ADFI), while decreasing the feed conversion rate (FCR) and diarrhea rate (p < 0.05). Additionally, AO3 addition altered the fecal microflora composition with increased abundance of f_Prevotellaceae. LPS challenges were further conducted to investigate the detailed mechanism underlying the benefits of AO3 supplementation. The piglets fed with AO3 exhibited a significant increase in villus height and decrease in crypt depth within the jejunum, along with upregulation of ZO-1, occludin, and claudin-1 (p < 0.05) compared with those piglets subjected to LPS. Furthermore, AO3 supplementation significantly ameliorated redox disturbances (T-AOC, SOD, and GSH) and inflammation (TNF-α, IL-1β, IL-6, and IL-12) in both the serum and jejunum of piglets induced by LPS, accompanied by suppressed activation of the MAPK signaling pathway (ERK, JNK, P38) and NF-κB. The LPS challenge downregulated the activation of the AMPK signaling pathway, mRNA levels of electron transport chain complexes, and key enzymes involved in ATP synthesis, which were significantly restored by the AO3 supplementation. Additionally, AO3 supplementation restored the reduced transport of amino acids, glucose, and fatty acids induced by LPS back to the levels observed in the control group. In conclusion, dietary AO3 supplementation positively affected growth performance and gut microbiota composition, also enhancing intestinal barrier integrity, nutrient uptake, and energy metabolism, as well as alleviating oxidative stress and inflammation under LPS stimulation. [ABSTRACT FROM AUTHOR]

Membrane transporters are proteins that mediate the entry and exit of substances through the plasma membrane and organellar membranes and are capable of recognizing and binding to specific substances, thereby facilitating substance transport. Membrane transporters are divided into different types, e.g., ion transporters, sugar transporters, amino acid transporters, and aquaporins, based on the substances they transport. These membrane transporters inhibit reactive oxygen species (ROS) generation through ion regulation, sugar and amino acid transport, hormone induction, and other mechanisms. They can also promote enzymatic and nonenzymatic reactions in plants, activate antioxidant enzyme activity, and promote ROS scavenging. Moreover, membrane transporters can transport plant growth regulators, solute proteins, redox potential regulators, and other substances involved in ROS metabolism through corresponding metabolic pathways, ultimately achieving ROS homeostasis in plants. In turn, ROS, as signaling molecules, can affect the activity of membrane transporters under abiotic stress through collaboration with ions and involvement in hormone metabolic pathways. The research described in this review provides a theoretical basis for improving plant stress resistance, promoting plant growth and development, and breeding high-quality plant varieties. [ABSTRACT FROM AUTHOR]

Amino acid permeases (AAPs) play important roles in transporting amino acids in plant species, leading to increased low-nitrogen tolerance, grain yield, or protein content. However, very few AAPs have been characterized in soybean (Glycine max). In this study, we scanned the soybean reference genome and identified a total of 36 AAP genes (named GmAAP). The GmAAPs were phylogenetically divided into three evolutionary clades, with the genes in the same clades sharing similar gene structures and domain organization. We also showed that seventeen GmAAP genes on ten chromosomes were in collinearity, likely due to whole-genome duplication. Further analysis revealed a variety of cis-acting regulatory elements (such as hormone response elements (ABRE, ERE, GARE, P-box, and TGA-element), stress response elements (LTR, MBS, MYB-related components, TC-rich repeats, TCA-element, and WUN-motif), the tissue expression element (GCN4-motif), and the circadian regulatory element (circadian) present in the 2 kb region of the GmAAP promoter region, demonstrating functional diversity and expression specificity. RNA-Seq data and quantitative real-time PCR identified five GmAAPs showing differential expression under nitrogen limitation, including GmAAP3, GmAAP5, and GmAAP8 showing downregulation while GmAAP14, GmAAP29 showed upregulation, suggesting their involvement in low-nitrogen stress response. These results provide comprehensive information on soybean AAP genes in nitrogen stress, and provide putative candidates with possible roles in enhancing amino acid delivery to seeds for yield improvement. [ABSTRACT FROM AUTHOR]

ENA transporters are a group of P-type ATPases that are characterized by actively moving Na+ or K+ out of the cell against their concentration gradient. The existence of these transporters was initially attributed to some fungi, although more recently they have also been identified in mosses, liverworts, and some protozoa. Given the current increase in the number of organisms whose genomes are completely sequenced, we set out to expand our knowledge about the existence of ENA in organisms belonging to other phylogenetic groups. For that, a hidden Markov model profile was constructed to identify homologous sequences to ENA proteins in protein databases. This analysis allowed us to identify the existence of ENA-type ATPases in the most primitive groups of fungi, as well as in other eukaryotic organisms not described so far. In addition, this study has allowed the identification of a possible new group of P-ATPases, initially proposed as ENA but which maintain phylogenetic distances with these proteins. Finally, this work has also addressed this study of the structure of ENA proteins, which remained unknown due to the lack of crystallographic data. For this purpose, a 3D structure prediction of the NcENA1 protein of the fungus Neurospora crassa was performed using AlphaFold2 software v2.3.1. From this structure, the electrostatic potential of the protein was analyzed. With all these data, the protein regions and the amino acids involved in the transport of Na+ or K+ ions across the membrane were proposed for the first time. Targeted mutagenesis of some of these residues has confirmed their relevant participation in the transport function of ENA proteins. [ABSTRACT FROM AUTHOR]

Nitrogen (N), the most important macro-nutrient for plant growth and development, is a key factor that determines crop yield. Yet its excessive applications pollute the environment and are expensive. Hence, studying nitrogen use efficiency (NUE) in crops is fundamental for sustainable agriculture. Here, an association panel consisting of 123 flax accessions was evaluated for 21 NUE-related traits at the seedling stage under optimum N (N+) and N deficiency (N−) treatments to dissect the genetic architecture of NUE-related traits using a multi-omics approach integrating genome-wide association studies (GWAS), transcriptome analysis and genomic selection (GS). Root traits exhibited significant and positive correlations with NUE under N− conditions (r = 0.33 to 0.43, p < 0.05). A total of 359 QTLs were identified, accounting for 0.11% to 23.1% of the phenotypic variation in NUE-related traits. Transcriptomic analysis identified 1034 differentially expressed genes (DEGs) under contrasting N conditions. DEGs involved in N metabolism, root development, amino acid transport and catabolism and others, were found near the QTLs. GS models to predict NUE stress tolerance index (NUE_STI) trait were tested using a random genome-wide SNP dataset and a GWAS-derived QTLs dataset. The latter produced superior prediction accuracy (r = 0.62 to 0.79) compared to the genome-wide SNP marker dataset (r = 0.11) for NUE_STI. Our results provide insights into the QTL architecture of NUE-related traits, identify candidate genes for further studies, and propose genomic breeding tools to achieve superior NUE in flax under low N input. [ABSTRACT FROM AUTHOR]

Flower bud formation in the apple tree life cycle is associated with multiple biological processes. To explore the physiological and molecular mechanisms underlying the protein and metabolite changes in buds with different flowering capabilities, axillary buds with no flowering (Ab), long-shoot buds with a low flowering rate (Lb), and spur buds with a higher flowering rate than the Lb (Sb) were analyzed using a Tandem Mass Tag™ proteomic technique in combination with nLC–MS/MS analyses. We identified 471 (88 up- and 383 down-regulated), 459 (176 up- and 283 down-regulated), and 548 (387 up- and 161 down-regulated) differentially expressed proteins in Sb vs. Lb, Sb vs. Ab, and Lb vs. Ab, respectively, that were involved in carbohydrate, amino acid and lipid transport, and metabolism. Additionally, 110 (91 increased and 19 decreased), 89 (71 increased and 18 decreased), and 99 (37 increased and 62 decreased) metabolites having significantly different levels were identified in Sb vs. Lb, Sb vs. Ab, and Lb vs. Ab, respectively. The identified metabolites were related to amino acids and their isoforms, sugars and polyols, and organic acids, and occurred at significantly greater levels in the Sbs than the other buds. Thus, flower bud formation is a complex process that involves various biochemical materials and signals, such as carbohydrates, amino acids and their isoforms, and organic acids. [ABSTRACT FROM AUTHOR]

Bacillus subtilis is an important part of the gut microbiota and a commonly used probiotic. In the present study, to assess the biological characteristics and probiotic properties of B. subtilis derived from mink, we isolated B. subtilis MG-1 isolate from mink fecal samples, characterized its biological characteristics, optimized the hydrolysis of casein by its crude extract, and comprehensively analyzed its potential as a probiotic in combination with whole-genome sequencing. Biological characteristics indicate that, under low-pH conditions (pH 2), B. subtilis MG-1 can still maintain a survival rate of 64.75%; under the conditions of intestinal fluid, gastric acid, and a temperature of 70 °C, the survival rate was increased by 3, 1.15 and 1.17 times compared with the control group, respectively. This shows that it can tolerate severe environments. The results of hydrolyzed casein in vitro showed that the crude bacterial extract of isolate MG-1 exhibited casein hydrolyzing activity (21.56 U/mL); the enzyme activity increased to 32.04 U/mL under optimized reaction conditions. The complete genome sequencing of B. subtilis MG-1 was performed using the PacBio third-generation sequencing platform. Gene annotation analysis results revealed that B. subtilis MG-1 was enriched in several Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways, and most genes were related to Brite hierarchy pathways (1485–35.31%) and metabolism pathways (1395–33.17%). The egg-NOG annotation revealed that most genes were related to energy production and conversion (185–4.10%), amino acid transport and metabolism (288–6.38%), carbohydrate transport and metabolism (269–5.96%), transcription (294–6.52%), and cell wall/membrane/envelope biogenesis (231–5.12%). Gene Ontology (GO) annotation elucidated that most genes were related to biological processes (8230–45.62%), cellular processes (3582–19.86%), and molecular processes (6228–34.52%). Moreover, the genome of B. subtilis MG-1 was predicted to possess 77 transporter-related genes. This study demonstrates that B. subtilis MG-1 has potential for use as a probiotic, and further studies should be performed to develop it as a probiotic additive in animal feed to promote animal health. [ABSTRACT FROM AUTHOR]

Approximately one-third of agricultural land worldwide is affected by salinity, which limits the productivity and sustainability of crop ecosystems. Plant-growth-promoting rhizobacteria (PGPR) are a potential solution to this problem, as PGPR increases crop yield through improving soil fertility and stress resistance. Previous studies have shown that Priestia megaterium ZS-3(ZS-3) can effectively help plants tolerate salinity stress. However, how ZS-3 regulates its metabolic adaptations in saline environments remains unclear. In this study, we monitored the metabolic rearrangement of compatibilisers in ZS-3 and combined the findings with genomic data to reveal how ZS-3 survives in stressful environments, induces plant growth, and tolerates stress. The results showed that ZS-3 tolerated salinity levels up to 9%. In addition, glutamate and trehalose help ZS-3 adapt to osmotic stress under low NaCl stress, whereas proline, K+, and extracellular polysaccharides regulate the osmotic responses of ZS-3 exposed to high salt stress. Potting experiments showed that applying the ZS-3 strain in saline and neutral soils could effectively increase the activities of soil acid phosphatase, urease, and invertase in both soils, thus improving soil fertility and promoting plant growth. In addition, strain ZS-3-GFP colonised the rhizosphere and leaves of Cinnamomum camphora well, as confirmed by confocal microscopy and resistance plate count analysis. Genomic studies and in vitro experiments have shown that ZS-3 exhibits a variety of beneficial traits, including plant-promoting, antagonistic, and other related traits (such as resistance to saline and heavy metal stress/tolerance, amino acid synthesis and transport, volatile compound synthesis, micronutrient utilisation, and phytohormone biosynthesis/regulatory potential). The results support that ZS-3 can induce plant tolerance to abiotic stresses. These data provide important clues to further reveal the interactions between plants and microbiomes, as well as the mechanisms by which micro-organisms control plant health. [ABSTRACT FROM AUTHOR]

Our previous study demonstrated that L-tryptophan (Trp)-depleted cells display a marked enhancement in Trp uptake facilitated by extracellular tryptophanyl-tRNA synthetase (TrpRS). Here, we show that Trp uptake into TrpRS-overexpressing cells is also markedly elevated upon Trp starvation. These findings indicate that a Trp-deficient condition is critical for Trp uptake, not only into cells to which TrpRS protein has been added but also into TrpRS-overexpressing cells. We also show that overexpression of TrpRS mutants, which cannot synthesize tryptophanyl-AMP, does not promote Trp uptake, and that inhibition of tryptophanyl-AMP synthesis suppresses this uptake. Overall, these data suggest that tryptophanyl-AMP production by TrpRS is critical for high-affinity Trp uptake. [ABSTRACT FROM AUTHOR]

Simple Summary: NCG is a structural analogue of NAG, and can activate the rate-limiting enzyme of arginine synthesis and promote the synthesis of endogenous arginine in the intestine. Recent studies have found that NCG plays an important role in improving growth performance and maintaining intestinal health. However, there are few reports on the effects of NCG on the intestinal development and antioxidant capacity of piglets. The aim of this study was to investigate the effects of dietary NCG supplementation on the growth performance, apparent nutrient digestibility, jejunal morphology, amino acid transporters, and antioxidant capacity of weanling piglets. Studies have shown that dietary NCG supplementation can improve the growth performance and intestinal antioxidant capacity of weaned piglets. Weaning is an important period that affects the performance of piglets. However, the regulation of dietary amino acid levels is considered to be an effective way to alleviate the weaning stress of piglets. N-carbamylglutamate (NCG) plays an important role in improving the growth performance and antioxidant capacity of animals. A total of 36 weaned piglets were randomly assigned to two treatment groups, a control group (CON) and a 500 mg/kg NCG group (NCG), and the experiment lasted for 28 days. The results show that the NCG treatment group showed an increased 0–28 days average weight gain and average daily feed intake, and also increased contents of GLU and HDL, and lower SUN in serum, and an upregulation of the expression of the amino acid transporters SNAT2, EAAC1, SLC3A1, and SLC3A2 mRNA in the jejunum (p < 0.05), as well as an increased villus length and VH:CD ratio, and claudin-1, occludin, and ZO-1 mRNA expression in the jejunum (p < 0.05). The NCG treatment group showed an increased content of GSH-Px in serum and T-AOC and SOD in the jejunum, and a lower content of MDA (p < 0.05); and the upregulation of the mRNA expression related to antioxidant enzymes (CAT, SOD1, Gpx4, GCLC, GCLM and Nrf2, AhR, CYP1A1) in the jejunal mucosa (p < 0.05). In addition, compared with the control group, the NCG treatment group saw an upregulation in the mRNA expression of IL-10 and a decrease in the expression of IL-1β and IL-4 in the jejunal mucosa (p < 0.05). In summary, the results of this study suggest that NCG improved growth performance and jejunal morphology, improved the jejunal transport of amino acids related to the ornithine cycle, and improved the antioxidant capacity in weaned pigs. [ABSTRACT FROM AUTHOR]

Lysinuric protein intolerance (LPI) is a rare inborn error of metabolism (IEM), classified as an inherited aminoaciduria, caused by mutations in the SLC7A7 gene, leading to a defective cationic amino acid transport. The metabolic adaptations to the demands of pregnancy and delivery cause significant physiological stress, so those patients affected by IEM are at greater risk of decompensation. A 28-year-old woman with LPI had experienced 3 early miscarriages. While pregnancy was finally achieved, diverse nutritional and medical challenges emerged (food aversion, intrauterine growth restriction, bleeding risk, and preeclampsia suspicion), which put both the mother and the fetus at risk. Moreover, the patient requested a natural childbirth (epidural-free, delayed cord clamping). Although the existence of multiple safety concerns rejected this approach at first, the application of novel strategies made a successful delivery possible. This case reinforces that the woman's wish for a non-medicated, low-intervention natural birth should not be automatically discouraged because of an underlying complex metabolic condition. Achieving a successful pregnancy is conceivable thanks to the cooperation of interdisciplinary teams, but it is still important to consider the risks beforehand in order to be prepared for possible additional complications. [ABSTRACT FROM AUTHOR]

The integrated stress response is a signaling network comprising four branches, each sensing different cellular stressors, converging on the phosphorylation of eIF2α to downregulate global translation and initiate recovery. One of these branches includes GCN2, which senses cellular amino acid insufficiency and participates in maintaining amino acid homeostasis. Previous studies have shown that GCN2 is a viable cancer target when amino acid stress is induced by inhibiting an additional target. In this light, we screened numerous drugs for their potential to synergize with the GCN2 inhibitor TAP20. The drug sensitivity of six cancer cell lines to a panel of 25 compounds was assessed. Each compound was then combined with TAP20 at concentrations below their IC50, and the impact on cell growth was evaluated. The strongly synergistic combinations were further characterized using synergy analyses and matrix-dependent invasion assays. Inhibitors of proteostasis and the MEK–ERK pathway, as well as the pan-CDK inhibitors, flavopiridol, and seliciclib, were potently synergistic with TAP20 in two cell lines. Among their common CDK targets was CDK7, which was more selectively targeted by THZ-1 and synergized with TAP20. Moreover, these combinations were partially synergistic when assessed using matrix-dependent invasion assays. However, TAP20 alone was sufficient to restrict invasion at concentrations well below its growth-inhibitory IC50. We conclude that GCN2 inhibition can be further explored in vivo as a cancer target. [ABSTRACT FROM AUTHOR]

Glutamine (Gln), glutamate (Glu), and γ-amino butyric acid (GABA) are essential amino acids for brain metabolism and function. Astrocyte-derived Gln is the precursor for the two most important neurotransmitters in the central nervous system (CNS), which are the excitatory neurotransmitter Glu and the inhibitory neurotransmitter GABA. In addition to their roles in neurotransmission, these amino acids can be used as alternative substrates in brain metabolism that enable metabolic coupling between astrocytes and neurons in the glutamate–glutamine cycle (GGC). The disturbed homeostasis of these amino acids within the tripartite synapse may be involved in the pathogenesis of various neurological diseases. Interactions between astrocytes and neurons in terms of Gln, Glu, and GABA homeostasis were studied in different phases of experimental allergic encephalomyelitis (EAE) in Lewis rats. The results of the study showed a decrease in the transport (uptake and release) of Gln and GABA in both neuronal and astrocyte-derived fractions. These effects were fully or partially reversed when the EAE rats were treated with memantine, a NMDA receptor antagonist. Changes in the expression and activity of selected glutamine/glutamate metabolizing enzymes, such as glutamine synthase (GS) and phosphate-activated glutaminase (PAG), which were affected by memantine, were observed in different phases of EAE. The results suggested perturbed homeostasis of Gln, Glu, and GABA during EAE, which may indicate alterations in neuron–astrocyte coupling and dysfunction of the tripartite synapse. Memantine appears to partially regulate the disturbed relationships between Gln, Glu, and GABA. [ABSTRACT FROM AUTHOR]

The presence of foodborne pathogens in meat is linked to several contamination sources, and the slaughterhouse environment represents a relevant reservoir of contamination. Aureimonas altamirensis is a Gram-negative bacteria associated with different isolation sources, including human clinical cases. This study aims to identify and characterize an A. altamirensis isolate from chicken guts collected in an Italian slaughterhouse. The study approach includes whole-genome analysis jointly with phenotypical tests. Whole-genome sequencing (WGS) confirms the initial MALDI-TOF MS identification, finding putative virulence and biofilm-related genes. Moreover, the gene class evaluation reveals that the numerically largest gene category in the A. altamirensis genome is related to amino acid metabolism and transport. The analyses performed on a human gut mucus-producing cell line (HT29-MTX-E12) demonstrated the ability of A. altamirensis to colonize the host cell layer. Moreover, the antibiotic resistance test showed a high resistance of A. altamirensis to gentamicin (MIC 0.5 mg/L). The detection of a potential pathogenic and antibiotic-resistant A. altamirensis strain isolated from a slaughterhouse underlines the necessity of active surveillance studies focused on this species and the need for further studies about A. altamirensis in foods. [ABSTRACT FROM AUTHOR]

Plutella xylostella (Linnaeus) is one of the notorious pests causing substantial loses to numerous cruciferous vegetables across many nations. The sterile insect technique (SIT) is a safe and effective pest control method, which does not pollute the environment and does not produce drug resistance. We used proteomics technology and bioinformatics analysis to investigate the molecular mechanisms responsible for the effects of different doses of radiation treatment on the reproductive ability of male P. xylostella. A total of 606 differentially expressed proteins (DEPs) were identified in the 200 Gy/CK group, 1843 DEPs were identified in the 400 Gy/CK group, and 2057 DEPs were identified in the 400 Gy/200 Gy group. The results showed that after 200 Gy irradiation, the testes resisted radiation damage by increasing energy supply, amino acid metabolism and transport, and protein synthesis, while transcription-related pathways were inhibited. After 400 Gy irradiation, the mitochondria and DNA in the testis tissue of P. xylostella were damaged, which caused cell autophagy and apoptosis, affected the normal life activities of sperm cells, and greatly weakened sperm motility and insemination ability. Meanwhile, Western blotting showed that irradiation affects tyrosine phosphorylation levels, which gradually decrease with increasing irradiation dose. [ABSTRACT FROM AUTHOR]

Simple Summary: Climate change plays a major role in livestock production. Hence the utilization of crossbreeding strategies allows for the improvement of animal production during harsh environmental conditions. The aim of this study was to identify the genetic differences in the F1 Nguni × Bonsmara and its reciprocal cross (Bonsmara × Nguni). This was achieved by studying the changes in structural variation, such as copy number variants in these two crosses. The major findings from this study have revealed several genes relating to adaption in these crossbred cattle. Crossbreeding forms part of Climate-Smart beef production and is one of the strategies to mitigate the effects of climate change. Two Nguni-sired and three Bonsmara-sired crossbred animals underwent whole genome sequencing. Following quality control and file preparation, the sequence data were investigated for genome-wide copy number variation (CNV) using the panelcn.MOPS tool. A total of 355 CNVs were identified in the crossbreds, of which 274 were unique in Bonsmara-sired crossbreds and 81 unique in the Nguni-sired crossbreds. Genes that differed in copy number in both crossbreds included genes related to growth (SCRN2, LOC109572916) and fertility-related factors (RPS28, LOC1098562432, LOC109570037). Genes that were present only in the Bonsmara-sired crossbreds included genes relating to lipid metabolism (MAF1), olfaction (LOC109569114), body size (HES7), immunity (LOC10957335, LOC109877039) and disease (DMBT1). Genes that were present only in the Nguni-sired crossbreds included genes relating to ketosis (HMBOX1) and amino acid transport (LOC109572916). Results of this study indicate that Nguni and Bonsmara cattle can be utilized in crossbreeding programs as they may enhance the presence of economically important traits associated with both breeds. This will produce crossbred animals that are good meat producers, grow faster, have high fertility, strong immunity and a better chance of producing in South Africa's harsh climate conditions. Ultimately, this study provides new genetic insights into the adaptability of Nguni and Bonsmara crossbred cattle. [ABSTRACT FROM AUTHOR]

Huanglongbing (HLB), caused by the Candidatus Liberibacter spp., is the most devastating disease in the citrus industry. HLB significantly affects and alters the microbial community structure or potential function of the microbial community of leaves and roots. However, it is unknown how the microbial community structure of the pericarp with different pigments is affected by Candidatus Liberibacter asiaticus (CLas). This study identified the enriched taxa of the microbial community in the citrus pericarp with normal or abnormal pigment and determine the effects of HLB on the pericarp microbial community using 16S rRNA-seq. The alpha and beta diversity and composition of microbial communities were significantly different between normal and abnormal pigment pericarp tissues of ripe fruits infected by CLas. Firmicutes, Actinobacteriota, Bacteroidota, Acidobacteriota, and Desulfobacterota dominated the pericarp microbiota composition in WDYFs (whole dark yellow fruits) samples. The relative abundance of most genera in WDYFs was higher than 1%, such as Burkholderia, and Pelomonas. However, with the exception of the HLB pathogen, the relative abundance of most genera in the abnormal-colored pericarp samples was less than 1%. CLas decreased the relative abundance of pericarp taxonomic. The predicted function of microbial was more plentiful and functional properties in the WDYF sample, such as translation, ribosomal structure and biogenesis, amino acid transport and metabolism, energy production and conversion, and some other clusters of orthologous groups (COG) except for cell motility. The results of this study offer novel insights into understanding the composition of microbial communities of the CLas-affected citrus pericarps and contribute to the development of biological control strategies for citrus against Huanglongbing. [ABSTRACT FROM AUTHOR]

Spikelet number per panicle (SNP) is one of the most important yield components in rice. Rice ENHANCING BIOMASS AND SPIKELET NUMBER (OsEBS), a gene involved in improved SNP and yield, has been cloned from an accession of Dongxiang wild rice. However, the mechanism of OsEBS increasing rice SNP is poorly understood. In this study, the RNA-Seq technology was used to analyze the transcriptome of wildtype Guichao 2 and OsEBS over-expression line B102 at the heading stage, and analysis of the evolution of OsEBS was also conducted. A total of 5369 differentially expressed genes (DEGs) were identified between Guichao2 and B102, most of which were down-regulated in B102. Analysis of the expression of endogenous hormone-related genes revealed that 63 auxin-related genes were significantly down-regulated in B102. Gene Ontogeny (GO) enrichment analysis showed that the 63 DEGs were mainly enriched in eight GO terms, including auxin-activated signaling pathway, auxin polar transport, auxin transport, basipetal auxin transport, and amino acid transmembrane transport, most of which were directly or indirectly related to polar auxin transport. Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway analysis further verified that the down-regulated genes related to polar auxin transport had important effects on increased SNP. Analysis of the evolution of OsEBS found that OsEBS was involved in the differentiation of indica and japonica, and the differentiation of OsEBS supported the multi-origin model of rice domestication. Indica (XI) subspecies harbored higher nucleotide diversity than japonica (GJ) subspecies in the OsEBS region, and XI experienced strong balancing selection during evolution, while selection in GJ was neutral. The degree of genetic differentiation between GJ and Bas subspecies was the smallest, while it was the highest between GJ and Aus. Phylogenetic analysis of the Hsp70 family in O. sativa, Brachypodium distachyon, and Arabidopsis thaliana indicated that changes in the sequences of OsEBS were accelerated during evolution. Accelerated evolution and domain loss in OsEBS resulted in neofunctionalization. The results obtained from this study provide an important theoretical basis for high-yield rice breeding. [ABSTRACT FROM AUTHOR]

Ectothermic animals, such as teleosts, have increasingly been exposed to stressful high-temperature events due to global warming. Currently, the effects of thermal stress on skeletal muscle, a key tissue for fish growth, are unknown. This study examined the impact of high-temperature stress on the skeletal muscle transcriptome of rainbow trout (Oncorhynchus mykiss) in control (15 °C) and high-temperature (20 °C) conditions. Additionally, we examined the plasmatic levels of cortisol, glucose, and creatine kinase activity, and examined oxidative damage and autophagy activation in skeletal muscle. High-temperature stress induced significant increases in cortisol and glucose plasmatic levels. Nevertheless, no changes were observed in creatine kinase activity in plasma and skeletal muscle oxidation. Skeletal muscle RNA was isolated and sequenced using the HiSeq Illumina platform. A total of 383,796,290 reads were mapped onto the reference rainbow trout genome. The transcriptomic analysis showed that 293 genes were upregulated in the high-temperature group, mainly associated with autophagosome assembly, amino acid transport, and the glutamine metabolic process. On the other hand, 119 genes were downregulated in the high-temperature group, mainly associated with digestion, proteolysis, and the muscle contraction process. In addition, RT-qPCR of differentially expressed representative genes and Western blot analysis of LC3-II/LC3-I levels confirmed skeletal muscle autophagy induced by high temperature. This study sheds light on intriguing facets of the adaptive response of rainbow trout skeletal muscle to high-temperature stress and provides significant insights into the physiology of autophagy in teleosts. [ABSTRACT FROM AUTHOR]

Through a comprehensive analysis of the gene expression and dependency in HCC patients and cell lines, LAT1 was identified as the top amino acid transporter candidate supporting HCC tumorigenesis. To assess the suitability of LAT1 as a HCC therapeutic target, we used CRISPR/Cas9 to knockout (KO) LAT1 in the epithelial HCC cell line, Huh7. Knockout of LAT1 diminished its branched chain amino acid (BCAA) transport activity and significantly reduced cell proliferation in Huh7. Consistent with in vitro studies, LAT1 ablation led to suppression of tumor growth in a xenograft model. To elucidate the mechanism underlying the observed inhibition of cell proliferation upon LAT1 KO, we performed RNA-sequencing analysis and investigated the changes in the mTORC1 signaling pathway. LAT1 ablation resulted in a notable reduction in phosphorylation of p70S6K, a downstream target of mTORC1, as well as its substrate S6RP. This reduced cell proliferation and mTORC1 activity were rescued when LAT1 was overexpressed. These findings imply an essential role of LAT1 for maintenance of tumor cell growth and additional therapeutic angles against liver cancer. [ABSTRACT FROM AUTHOR]

The metabolism and intercellular transfer of glutathione or its precursors may play an important role in cellular defense against oxidative stress, a common hallmark of neurodegeneration. In the 1990s, several studies in the Neurobiology field led to the widely accepted notion that astrocytes produce large amounts of glutathione that serve to feed neurons with precursors for glutathione synthesis. This assumption has important implications for health and disease since a reduction in this supply from astrocytes could compromise the capacity of neurons to cope with oxidative stress. However, at first glance, this shuttling would imply a large energy expenditure to get to the same point in a nearby cell. Thus, are there additional underlying reasons for this expensive mechanism? Are neurons unable to import and/or synthesize the three non-essential amino acids that are the glutathione building blocks? The rather oxidizing extracellular environment favors the presence of cysteine (Cys) as cystine (Cis), less favorable for neuronal import. Therefore, it has also been proposed that astrocytic GSH efflux could induce a change in the redox status of the extracellular space nearby the neurons, locally lowering the Cis/Cys ratio. This astrocytic glutathione release would also increase their demand for precursors, stimulating Cis uptake, which these cells can import, further impacting the local decline of the Cis/Cys ratio, in turn, contributing to a more reduced extracellular environment and subsequently favoring neuronal Cys import. Here, we revisit the experimental evidence that led to the accepted hypothesis of astrocytes acting as suppliers of neuronal glutathione precursors, considering recent data from the Human Protein Atlas. In addition, we highlight some potential drawbacks of this hypothesis, mainly supported by heterogeneous cellular models. Finally, we outline additional and more cost-efficient possibilities by which astrocytes could support neuronal glutathione levels, including its shuttling in extracellular vesicles. [ABSTRACT FROM AUTHOR]

36611813 6 Morris M.B., Ozsoy S., Zada M., Zada M., Zamfirescu R.C., Todorova M.G., Day M.L. Selected amino acids promote mouse pre-implantation embryo development in a growth factor-like manner. Similarly, glycine fosters the preimplantation development of mouse embryos in a hypertonic oviductal fluid-like medium, but it also antagonizes the positive effects of proline, possibly by inhibiting proline transport [[1]]. The articles in this Special Issue address a wide variety of topics concerning molecular and clinical advances in understanding early embryo development. In both early human and early mouse embryos, the ectoderm cell lineages show the weakest domain segregation, whereas the endoderm cell lineages display the strongest domain segregation in germ layers [[13]]. [Extracted from the article]

The stringent response is a rapid response system that is ubiquitous in bacteria, allowing them to sense changes in the external environment and undergo extensive physiological transformations. However, the regulators (p)ppGpp and DksA have extensive and complex regulatory patterns. Our previous studies demonstrated that (p)ppGpp and DksA in Yersinia enterocolitica positively co-regulated motility, antibiotic resistance, and environmental tolerance but had opposite roles in biofilm formation. To reveal the cellular functions regulated by (p)ppGpp and DksA comprehensively, the gene expression profiles of wild-type, ΔrelA, ΔrelAΔspoT, and ΔdksAΔrelAΔspoT strains were compared using RNA-Seq. Results showed that (p)ppGpp and DksA repressed the expression of ribosomal synthesis genes and enhanced the expression of genes involved in intracellular energy and material metabolism, amino acid transport and synthesis, flagella formation, and the phosphate transfer system. Additionally, (p)ppGpp and DksA inhibited amino acid utilization (such as arginine and cystine) and chemotaxis in Y. enterocolitica. Overall, the results of this study unraveled the link between (p)ppGpp and DksA in the metabolic networks, amino acid utilization, and chemotaxis in Y. enterocolitica and enhanced the understanding of stringent responses in Enterobacteriaceae. [ABSTRACT FROM AUTHOR]

Simple Summary: Aphis gossypii Glover is an important agricultural pest distributed worldwide, which can reduce the yield of cotton crops and cause huge economic losses. Binodoxys communis Gahan is the main parasitoid wasp of A. gossypii. Previous studies have shown that parasitization causes reduced egg production in A. gossypii, but the effects on the symbiotic bacteria of the host ovaries are unknown. In this study, we analyzed the microbial communities in cotton aphid ovaries by 16S rDNA sequencing and their changes before and after parasitization, performed a functional prediction analysis of the microbial communities in cotton aphid ovaries, and finally performed RT-qPCR on some core symbiotic bacteria. In summary, our results provide a framework for investigating shifts in the microbial communities in host ovaries and broaden our understanding of the interactions among aphids, parasitoid wasps, and endosymbionts. Background: Aphis gossypii Glover is an important agricultural pest distributed worldwide. Binodoxys communis Gahan is the main parasitoid wasp of A. gossypii. Previous studies have shown that parasitization causes reduced egg production in A. gossypii, but the effects of parasitism on the symbiotic bacteria in the host ovaries are unknown. Results: In this study, we analyzed the microbial communities in the ovaries of A. gossypii without and after parasitization. Whether parasitized or not, Buchnera was the dominant genus of symbiotic bacteria in the ovaries, followed by facultative symbionts including Arsenophonus, Pseudomonas, and Acinetobacter. The relative abundance of Buchnera in the aphid ovary increased after parasitization for 1 d in both third-instar nymph and adult stages, but decreased after parasitization for 3 d. The shifts in the relative abundance of Arsenophonus in both stages were the same as those observed for Buchnera. In addition, the relative abundance of Serratia remarkably decreased after parasitization for 1 d and increased after parasitization for 3 d. A functional predictive analysis of the control and parasitized ovary microbiomes revealed that pathways primarily enriched in parasitization were "amino acid transport and metabolism" and "energy production and conversion." Finally, RT-qPCR analysis was performed on Buchnera, Arsenophonus, and Serratia. The results of RT-qPCR were the same as the results of 16S rDNA sequencing. Conclusions: These results provide a framework for investigating shifts in the microbial communities in host ovaries, which may be responsible for reduced egg production in aphids. These findings also broaden our understanding of the interactions among aphids, parasitoid wasps, and endosymbionts. [ABSTRACT FROM AUTHOR]

The L-type amino acid transporter (LAT) family contains four members, LAT1~4, which are important amino acid transporters. They mainly transport specific amino acids through cell membranes, provide nutrients to cells, and are involved in a variety of metabolic pathways. They regulate the mTOR signaling pathway which has been found to be strongly linked to cancer in recent years. However, in the field of prostate cancer (PCa), the LAT family is still in the nascent stage of research, and the importance of LATs in the diagnosis and treatment of prostate cancer is still unknown. Therefore, this article aims to report the role of LATs in prostate cancer and their clinical significance and application. LATs promote the progression of prostate cancer by increasing amino acid uptake, activating the mammalian target of rapamycin (mTOR) pathway and downstream signals, mediating castration-resistance, promoting tumor angiogenesis, and enhancing chemotherapy resistance. The importance of LATs as diagnostic and therapeutic targets for prostate cancer was emphasized and the latest research results were introduced. In addition, we introduced selective LAT1 inhibitors, including JPH203 and OKY034, which showed excellent inhibitory effects on the proliferation of various tumor cells. This is the future direction of amino acid transporter targeting therapy drugs. [ABSTRACT FROM AUTHOR]

Maize (Zea mays L.) is the largest grain crop in Heilongjiang Province. Carbon-based fertilizer is a mixed fertilizer produced by adding a certain proportion of chemical fertilizer with biochar as the loading substrate. In this study, the effects of carbon-based fertilizer on the rhizosphere soil microenvironment and maize root system were discussed. Two maize varieties, Xianyu 335 and Jingke 968, were selected and six treatments were set as follows, including no fertilization (CK1), conventional fertilizer (CK2) and the amount of carbon-based fertilizer, which were 3 t/hm2, 3.75 t/hm2, 4.5 t/hm2 and 5.25 t/hm2, respectively. The results showed that carbon-based fertilizer increased the total root length, root volume, root area and root tip number of maize, and the root length, root volume, root area and root tip number of 4.5 t treatment performed better at all stages, which was significantly higher than that of chemical fertilizer. On 16 August (early filling stage), most of the root color changed from milky white to dark brown, the root clarity decreased, the number of roots decreased, the root volume significantly decreased and the root began to age, while the number and volume of roots treated with the carbon-based fertilizer remained stable, the root color was milky white, the morphological structure was clear and there was basically no aging. The carbon-based fertilizer treatment significantly increased the root biomass of 0–15 cm above the plant, 15–30 cm and 30–45 cm between the plants and 0–15 cm between the ridges, forming a wide and deep high-yield root system. The carbon-based fertilizer significantly increased the bleeding rate. On 8 July (jointing stage), Xianyu 335 and Jingke 968 reached the maximum value at the 3 t and 3.75 t treatments, respectively. The carbon-based fertilizer treatment had no significant effect on the amino acid content, but significantly increased the amino acid transport rate on 8 July (jointing stage) and 16 August (early filling stage). The transport rate of inorganic phosphorus gradually decreased with the advancement of the growth process. On 8 July (jointing stage), the ammonium nitrogen content and transport rate of the two varieties reached the maximum value at the treatment of 4.5 t and 3.75 t, which was significantly higher than the treatment of chemical fertilizer and no fertilizer, and showed a gradual downward trend with the advancement of the growth process. The soluble sugar content was relatively low in the early stage and increased rapidly on 4 September (waxy ripening stage). Both varieties reached the maximum value at 4.5 t treatment, and the transport rate reached the maximum value at 3.75 t treatment, which was significantly higher than that of the chemical fertilizer treatment. In conclusion, the carbon-based fertilizer significantly increased the yield of maize, and the yield of maize under the 4.5 t treatment reached the maximum, which was 15.02% and 18.24% higher than that of the chemical fertilizer treatment, respectively. [ABSTRACT FROM AUTHOR]

The World Health Organization has cautioned that antimicrobial resistance (AMR) will be responsible for an estimated 10 million deaths annually by 2050. To facilitate prompt and accurate diagnosis and treatment of infectious disease, we investigated the potential of amino acids for use as indicators of bacterial growth activity by clarifying which amino acids are taken up by bacteria during the various growth phases. In addition, we examined the amino acid transport mechanisms that are employed by bacteria based on the accumulation of labeled amino acids, Na+ dependence, and inhibitory effects using a specific inhibitor of system A. We found that 3H-L-Ala accurately reflects the proliferative activity of Escherichia coli K-12 and pathogenic EC-14 in vitro. This accumulation in E. coli could be attributed to the amino acid transport systems being different from those found in human tumor cells. Moreover, biological distribution assessed in infection model mice with EC-14 using 3H-L-Ala showed that the ratio of 3H-L-Ala accumulated in infected muscle to that in control muscle was 1.20. By detecting the growth activity of bacteria in the body that occurs during the early stages of infection by nuclear imaging, such detection methods may result in expeditious diagnostic treatments for infectious diseases. [ABSTRACT FROM AUTHOR]

Pseudothermotoga elfii strain DSM9442 and P. elfii subsp. lettingae strain DSM14385 are hyperthermophilic bacteria. P. elfii DSM9442 is a piezophile and was isolated from a depth of over 1600 m in an oil-producing well in Africa. P. elfii subsp. lettingae is piezotolerant and was isolated from a thermophilic bioreactor fed with methanol as the sole carbon and energy source. In this study, we analyzed both strains at the genomic and transcriptomic levels, paying particular attention to changes in response to pressure increases. Transcriptomic analyses revealed common traits of adaptation to increasing hydrostatic pressure in both strains, namely, variations in transport membrane or carbohydrate metabolism, as well as species-specific adaptations such as variations in amino acid metabolism and transport for the deep P. elfii DSM9442 strain. Notably, this work highlights the central role played by the amino acid aspartate as a key intermediate of the pressure adaptation mechanisms in the deep strain P. elfii DSM9442. Our comparative genomic and transcriptomic analysis revealed a gene cluster involved in lipid metabolism that is specific to the deep strain and that was differentially expressed at high hydrostatic pressures and might, thus, be a good candidate for a piezophilic gene marker in Pseudothermotogales. [ABSTRACT FROM AUTHOR]

Short-chain fatty acids (SCFAs) play a pivotal role in regulating the proliferation and development of bovine rumen epithelial cells (BRECs). G protein-coupled receptor 41 (GPR41) is involved in the signal transduction in BRECs as a receptor for SCFAs. Nevertheless, the impact of GPR41 on the proliferation of BRECs has not been reported. The results of this research showed that the knockdown of GPR41 (GRP41KD) decreased BRECs proliferation compared with the wild-type BRECs (WT) (p < 0.001). The RNA sequencing (RNA-seq) analysis showed that the gene expression profiles differed between WT and GPR41KD BRECs, with the major differential genes enriched in phosphatidylinositol 3-kinase (PIK3) signaling, cell cycle, and amino acid transport pathways (p < 0.05). The transcriptome data were further validated by Western blot and qRT-PCR. It was evident that the GPR41KD BRECs downregulated the level of the PIK3-Protein kinase B (AKT)-mammalian target of the rapamycin (mTOR) signaling pathway core genes, such as PIK3, AKT, eukaryotic translation initiation factor 4E binding protein 1 (4EBP1) and mTOR contrasted with the WT cells (p < 0.01). Furthermore, the GPR41KD BRECs downregulated the level of Cyclin D2 p < 0.001) and Cyclin E2 (p < 0.05) compared with the WT cells. Therefore, it was proposed that GPR41 may affect the proliferation of BRECs by mediating the PIK3-AKT-mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

Simple Summary: A. fabalis are the main migratory waterfowl during the winter. The main habitats of A. fabalis are Caizi lake and Shengjin Lake in the Middle and Lower Yangtze River Floodplain. We utilized high-throughput sequencing and bioinformatics to analyze the composition and structural characteristics of the intestinal microbiota of Caizi Lake (CL) and Shengjin Lake (SL) A. fabalis during overwintering. Lactobacillus is the main genus of A. fabalis, of which Lactobacillus aviaries is the highest. There was only a positive correlation between Bacteroidetes and Proteobacteria in the intestinal microbiota of SL A. fabalis, and the species were closely related. However, CL is mainly associated with a positive correlation between Firmicutes and Actinomycetes. The functions of intestinal microbiota of A. fabalis involve energy production and transformation, amino acid transport and metabolism, carbohydrate transport and metabolism, and transcription. This study provides basic data for the study of intestinal microbiota of A. fabalis. The intestinal microbiota of migratory birds participate in the life activities of the host and are affected by external environmental factors. The difference in habitat environment provides diversity in external environmental selection pressure for the same overwintering waterfowl, which may be reflected in their intestinal microbiota. Caizi lake and Shengjin Lake in the Middle and Lower Yangtze River Floodplain are the main habitats for migratory waterfowl in winter, especially the Anser fabalis (A. fabalis). It is important to explore the changes in intestinal microbiota composition and function of A. fabalis in the early overwintering period to clarify the effect of habitat size and protection status on intestinal microbiota. In this study, the composition and structural characteristics of the intestinal microbiota of A. fabalis in Shengjin Lake (SL) and Caizi Lake (CL) were preliminarily explored in order to obtain data for the migratory birds. In both SL and CL groups, 16S rRNA amplicon sequencing analysis showed that Firmicutes was the dominant bacterial phylum, but the relative abundance showed significant differences. Lactobacillus was the most abundant genus in both SL and CL groups. At the species level, the abundance of L. aviaries was the highest, with a relative abundance in both SL and CL groups of more than 34%. When comparing the average relative abundance of the 15 most abundant genera, it was found that Subdoligranulum, Exiguobacterium, and Terrisporobacter had higher abundances in the intestinal microbiota of CL A. fabalis, while Streptococcus and Rothia had higher abundances in the intestinal microbiota of SL A. fabalis. There was only a positive correlation between Bacteroidota and Proteobacteria in the intestinal microbiota flora of SL A. fabalis, and the species were closely related. At the same time, there were positive and negative correlations between Firmicutes and Actinomycetes. However, CL is mainly associated with a positive correlation between Firmicutes and Actinomycetes, and there are also a small number of connections between Firmicutes. PICRUSt1 prediction analysis revealed that the Clusters of Orthologous Groups (COG) functions of SL and CL involve energy production and transformation, amino acid transport and metabolism, carbohydrate transport and metabolism, and transcription. Understanding the changes in intestinal microbiota in Aves during the overwintering period is of great importance to explore the adaptation mechanism of migratory Aves to the overwintering environment. This work provides basic data for an A. fabalis intestinal microbiota study. [ABSTRACT FROM AUTHOR]

Simple Summary: Maternal nutrient supply during the periconceptual period has long-term effects on fetal development and tissue function. During pregnancy, the fetus relies on the dam for its nutrient supply. Our objective was to ascertain whether the periconceptual and early life plan of nutrition could affect fetal liver development and gene expression profiles. To this end, we investigated the impacts of maternal vitamin and mineral supplementation (from pre-breeding to day 83) and two rates of body-weight gain during the first 83 days of pregnancy in female fetuses of crossbred Angus beef heifers. We identified 591 unique differentially expressed genes across all six vitamin-gain contrasts. Over-represented pathways were related to energy metabolism, lipid metabolism, and mineral and amino acid transport. Our findings suggest that periconceptual maternal nutrition affects fetal hepatic function through altered expression of energy- and lipid-related genes. During pregnancy, the fetus relies on the dam for its nutrient supply. Nutritional stimuli during fetal organ development can program hepatic metabolism and function. Herein, we investigated the role of vitamin and mineral supplementation (VTM or NoVTM—at least 71 days pre-breeding to day 83 of gestation) and rate of weight gain (low (LG) or moderate (MG)—from breeding to day 83) on the fetal liver transcriptome and the underlying biological pathways. Crossbred Angus beef heifers (n = 35) were randomly assigned to one of four treatments in a 2 × 2 factorial design (VTM_LG, VTM_MG, NoVTM_LG, and NoVTM_MG). Gene expression was measured with RNA-Seq in fetal livers collected on day 83 ± 0.27 of gestation. Our results show that vitamin and mineral supplementation and rate of weight gain led to the differential expression of hepatic genes in all treatments. We identified 591 unique differentially expressed genes across all six VTM-gain contrasts (FDR ≤ 0.1). Over-represented pathways were related to energy metabolism, including PPAR and PI3K-Akt signaling pathways, as well as lipid metabolism, mineral transport, and amino acid transport. Our findings suggest that periconceptual maternal nutrition affects fetal hepatic function through altered expression of energy- and lipid-related genes. [ABSTRACT FROM AUTHOR]