Bacillus amyloliquefaciens attenuates the intestinal permeability, oxidative stress and endoplasmic reticulum stress: transcriptome and microbiome analyses in weaned piglets.

Endoplasmic reticulum (ER) stress is related to oxidative stress (OS) and leads to intestinal injury. Bacillus amyloliquefaciens SC06 (SC06) can regulate OS, but its roles in intestinal ER stress remains unclear. Using a 2 × 2 factorial design, 32 weaned piglets were treated by two SC06 levels (0 or 1 × 108 CFU/g), either with or without diquat (DQ) injection. We found that SC06 increased growth performance, decreased ileal permeability, OS and ER stress in DQ-treated piglets. Transcriptome showed that differentially expressed genes (DEGs) induced by DQ were enriched in NF-κB signaling pathway. DEGs between DQ- and SC06 + DQ-treated piglets were enriched in glutathione metabolism pathway. Ileal microbiome revealed that the SC06 + DQ treatment decreased Clostridium and increased Actinobacillus. Correlations were found between microbiota and ER stress genes. In conclusion, dietary SC06 supplementation increased the performance, decreased the permeability, OS and ER stress in weaned piglets by regulating ileal genes and microbiota.

Bacillus siamensis Improves the Immune Status and Intestinal Health of Weaned Piglets by Improving Their Intestinal Microbiota.

Previous studies on the early interference of gut microbiota by Bacillus siamensis (B. siamensis) in weaned piglets are rarely reported, and the present trial is a preliminary study. This experiment was conducted to investigate the effects of B. siamensis supplementation on the growth performance, serum biochemistry, immune response, fecal short-chain fatty acids and microbiota of weaned piglets. Sixty weaned piglets were randomly divided into a control group (CON) and a B. siamensis group (BS), which were fed a basal diet and the basal diet supplemented with 5 × 1010 CFU B. siamensis per kg, respectively. Each group had 3 replicates and 10 piglets per replicate. The trial lasted for 28 days. The results showed that B. siamensis significantly increased the serum growth hormone (GH) and insulin-like growth factor (IGF) in piglets. Compared with the CON group, the levels of serum immunoglobulin and inflammatory factors in the BS group were significantly improved. In addition, the serum concentrations of zonulin and endotoxin (ET) in the BS group were lower. The dietary addition of B. siamensis significantly increased fecal short-chain fatty acid (SCFA) levels in piglets. Notably, B. siamensis improved the microbial composition by increasing beneficial genera, including Weissella, Lachnospiraceae_NK4A136_group and Bifidobacterium, and decreasing pathogenic genera, including Pantoea, Fusobacterium and Gemella, in piglet feces. Correlation analysis showed that the benefits of dietary B. siamensis supplementation were closely related to its improved microbial composition. In summary, the addition of B. siamensis can improve the immunity function, inflammatory response, gut permeability and SCFA levels of weaned piglets, which may be achieved through the improvement of their microbiota.

Comparison of knee joint and temporomandibular joint development in pig embryos.

Although the knee joint (KNJ) and temporomandibular joint (TMJ) all belong to the synovial joint, there are many differences in developmental origin, joint structure and articular cartilage type. Studies of joint development in embryos have been performed, mainly using poultry and rodents. However, KNJ and TMJ in poultry and rodents differ from those in humans in several ways. Very little work has been done on the embryonic development of KNJ and TMJ in large mammals. Several studies have shown that pigs are ideal animals for embryonic development research. Embryonic day 30 (E30), E35, E45, E55, E75, E90, Postnatal day 0 (P0) and Postnatal day 30 (P30) embryos/fetuses from the pigs were used for this study. The results showed that KNJ develops earlier than TMJ. Only one mesenchymal condensate of KNJ is formed on E30, while two mesenchymal condensates of TMJ are present on E35. All structures of KNJ and TMJ were formed on E45. The growth plate of KNJ begins to develop on E45 and becomes more pronounced from E55 to P30. From E75 to E90, more and more vascular-rich cartilage canals form in the cartilage regions of both joints. The cartilaginous canal of the TMJ divides the condyle into sections along the longitudinal axis of the condyle. This arrangement of cartilaginous canal was not found in the KNJ. The chondrification of KNJ precedes that of TMJ. Ossification of the knee condyle occurs gradually from the middle to the periphery, while that of the TMJ occurs gradually from the base of the mandibular condyle. In the KNJ, the ossification of the articular condyle is evident from P0 to P30, and the growth plate is completely formed on P30. In the TMJ, the cartilage layer of condyle becomes thinner from P0 to P30. There is no growth plate formation in TMJ during its entire development. There is no growth plate formation in the TMJ throughout its development. The condyle may be the developmental center of the TMJ. The chondrocytes and hypertrophic chondrocytes of the growth plate are densely arranged. The condylar chondrocytes of TMJ are scattered, while the hypertrophic chondrocytes are arranged. Embryonic development of KNJ and TMJ in pigs is an important bridge for translating the results of rodent studies to medical applications.

Chlorogenic acid ameliorates intestinal inflammation by inhibiting NF-κB and endoplasmic reticulum stress in lipopolysaccharide-challenged broilers.

Intestinal inflammation is a primary contributor to poor growth performance during poultry production. Chlorogenic acid (CGA) is a natural phenolic acid that exhibits superior anti-inflammatory activity and improved intestinal health. To investigate the protective effects and molecular mechanisms of CGA during intestinal inflammation in lipopolysaccharide (LPS)-challenged broilers, we randomly divided 288 one-day-old male Cobb broilers into 4 groups: a control group fed a basal diet (CON group), a basal diet + LPS group (LPS group), and 2 basal diet groups fed 500 or 750 mg/kg CGA + LPS (CGA_500 or CGA_750 groups). Broilers were injected with LPS or saline at 15, 17, 19, and 21 d old. Chlorogenic acid supplementation improved the growth performance of LPS-challenged broilers by increasing average daily gain (ADG) and reducing feed/gain (F/G) ratios (P < 0.05). CGA also improved intestinal barrier function in LPS-challenged boilers by enhancing jejunum morphology and integrity, decreasing intestinal permeability, and increasing occludin 3, zonula occludens-1, and mucin 2 expression (P < 0.05). CGA supplementation also improved systemic and jejunum antioxidant capacity by significantly enhancing glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) activities (P < 0.05), and reducing malonaldehyde (MDA) and protein carbonyl (PCO) levels (P < 0.05). Chlorogenic acid supplementation reduced systemic and jejunum pro-inflammatory cytokines (interleukin (IL)-1ß, IL-6, and IL-12) and increased anti-inflammatory cytokines (IL-10) in LPS-challenged broilers (P < 0.05) by inhibiting the toll like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling pathway (P < 0.05). In addition, the protective effects of CGA toward intestinal inflammation and apoptosis appeared to be correlated with inhibited endoplasmic reticulum (ER) stress (P < 0.05). In summary, CGA supplementation improved intestinal morphology and integrity by inhibiting TLR4/NF-κB and ER stress pathways, which potentially reduced oxidative stress and inflammation, and ultimately improved the growth performance of LPS-challenged broilers.

Bacillus subtilis HW2 enhances growth performance and alleviates gut injury via attenuation of endoplasmic reticulum stress and regulation of gut microbiota in broilers under necrotic enteritis challenge.

This study investigated the effects of Bacillus subtilis HW2 on the growth performance, immune response, endoplasmic reticulum (ER) stress, and intestinal health in broilers with necrotic enteritis. Three hundred 1-day-old male Cobb 500 broilers (33.88 ± 2.34 g) were randomly allocated to 5 groups including non-infected control (NC group), basal diet + necrotic enteritis challenge (NE group), basal diet + 1 × 106 CFU/g B. subtilis HW2 + necrotic enteritis challenge (L-Pro group), basal diet + 5 × 106 CFU/g B. subtilis HW2 + necrotic enteritis challenge (M-Pro group), and basal diet + 1 × 107 CFU/g B. subtilis HW2 + necrotic enteritis challenge (H-Pro group), with 6 replicates per group. All broilers except NC group were orally given with sporulated coccidian oocysts at day 14 and Clostridium perfringens from days 19 to 21. Results showed that L-Pro and M-Pro groups improved growth performance and intestinal morphology in necrotic enteritis-challenged broilers, and L-Pro, M-Pro, and H-Pro groups improved intestinal barrier function and immune response and decreased ER stress in necrotic enteritis-challenged broilers. Analysis of the gut microbiota revealed that L-Pro group increased the abundances of Alistipes, Coprobacter, Barnesiella, and Limosilactobacillus, decreased Erysipelatoclostridium abundance on day 42 in necrotic enteritis-challenged broilers. M-Pro group increased Turicibacter abundance on day 28 and the abundances of Alistipes, Barnesiella, and Limosilactobacillus on day 42 in necrotic enteritis-challenged broilers. H-Pro group decreased Romboutsia abundance on day 28 and unidentified_Clostridia abundance on day 42 in necrotic enteritis-challenged broilers. Analysis of short-chain fatty acids (SCFAs) revealed higher isobutyric acid and isovaleric acid levels in L-Pro and M-Pro groups than NE group. Correlation analysis revealed the correlations between the biochemical parameters and gut microbiota as well as SCFAs, especially Romboutsia, Barnesiella, Coprobacter, isobutyric acid, and isovaleric acid. Overall, our results indicated that B. subtilis HW2 supplementation could ameliorate necrotic enteritis infection-induced gut injury. The optimal dietary supplementation dosage of Bacillus subtilis HW2 was 5 × 106 CFU/g.

Multi-omics dataset of bovine mammary epithelial cells stimulated by ten different essential amino acids.

Application of high-throughput sequencing and screening help to detect the transcriptional and metabolic discrepancies in organs provided with various levels of nutrients. The influences of individual essential amino acid (EAA) administration on transcriptomic and metabolomic profilings of bovine mammary epithelial cells (BMECs) were systematically investigated. A RNA sequencing and liquid chromatography-tandem mass spectrometry generated a comprehensive comparison of transcriptomics, non-targeted metabolomics and targeted amino acids profilings of BMECs with individual EAA stimulation by turn. The sequencing data and raw LC-MS/MS data of samples were presented in the databases of Gene Expression Omnibus, MetaboLights and Figshare for efficient reuse, including exploring the divergences in metabolisms between different EAAs and screening valuable genes and metabolites regulating casein synthesis.

Effects of ß-mannanase supplementation on productive performance, inflammation, energy metabolism, and cecum microbiota composition of laying hens fed with reduced-energy diets.

The objective of this study is to investigate the beneficial effects and underlying mechanism of dietary ß-mannanase supplementation on the productive performance of laying hens fed with metabolic energy (ME)-reduced diets. A total of 448 Hy-Line gray laying hens were randomly assigned to seven groups. Each group had 8 replicates with 8 hens. The groups included a control diet (CON) with a ME of 2750 kcal/Kg, diets reduced by 100 kcal/Kg or 200 kcal/Kg ME (ME_100 or ME_200), and diets with 0.15 g/Kg or 0.2 g/Kg ß-mannanase (ME_100+ß-M_0.15, ME_100+ß-M_0.2, ME_200+ß-M_0.15, and ME_200+ß-M_0.2). The productive performance, egg quality, intestinal morphology, inflammatory response, mRNA expression related to the Nuclear factor kappa B (NF-κB) and AMPK pathway, and cecum microbiome were evaluated in this study. ME-reduced diets negatively impacted the productive performance of laying hens. However, supplementation with ß-mannanase improved FCR, decreased ADFI, and restored average egg weight to the level of the CON group. ME-reduced diets increased the levels of interleukin-1ß (IL-1ß) and IL-6 while decreasing the levels of IL-4 and IL-10 in the jejunum of laying hens. However, dietary ß-mannanase supplementation improved jejunum morphology, reduced pro-inflammatory cytokine concentrations, and increased levels of anti-inflammatory factors in laying hens fed with ME-reduced diets. The mRNA levels of IL-6, IFN-γ, TLR4, MyD88, and NF-κB in the jejunum of ME-reduced diets were significantly higher than that in CON, dietary ß-mannanase supplementation decreased these genes expression in laying hens fed with ME-reduced diets. Moreover, dietary ß-mannanase supplementation also decreased the mRNA levels of AMPKα and AMPKγ, and increased the abundance of mTOR in the jejunum of laying hens fed with ME-reduced diets. Cecum microbiota analysis revealed that dietary ß-mannanase increased the abundance of various beneficial bacteria (e.g., g_Pseudoflavonifractor, g_Butyricicoccus, and f_Lactobacillaceae) in laying hens fed with ME-reduced diets. In conclusion, dietary ß-mannanase supplementation could improve the productive performance of laying hens fed with a ME-reduced diet by improving intestinal morphology, alleviating intestinal inflammation, changing energy metabolism-related signaling pathways, and increasing cecum-beneficial microbiota.

Quantitative Phosphoproteomics Analysis Reveals the Protective Mechanism of Chlorogenic Acid on Immunologically Stressed Broiler Meat Quality.

Modern poultry production is stressful for the birds, and this stress is recognized as a major cause of inferior meat quality. Chlorogenic acid (CGA), a plant phenolic acid, has excellent antioxidant and anti-inflammatory properties. The antioxidant capacity and phosphoproteomics of immunologically stressed broiler breast muscle were assessed to elucidate the mechanism of the beneficial effects of CGA on meat quality. Dietary CGA decreased drip and cooking loss, postmortem pH and antioxidant capacity of breast muscle from stressed broilers, and increased MyHC-I mRNA levels. Quantitative phosphoproteomics revealed that CGA supplementation downregulated the phosphorylation of myofibrillar proteins, glycolytic enzymes, and endoplasmic reticulum proteins involved in homeostasis, which contributed to improving the meat quality of broilers. Moreover, 14 phosphorylation sites (e.g., P13538-Ser1236 and F1NN63-Ser117) in 13 phosphoproteins were identified as key regulators of processes related to broiler meat quality. Together, these findings provide novel regulatory targets and nutritional strategies for improving the stressed broiler meat quality.

BmSLC7A5 is essential for silk protein synthesis and larval development in Bombyx mori.

Insects produce silk to form cocoons, nests, and webs, which are important for their survival and reproduction. However, little is known about the molecular mechanism of silk protein synthesis at the translation level. The solute carrier family 7 (SLC7) genes are involved in activating the target of rapamycin complex 1 (TORC1) signaling pathway and protein translation process, but the physiological roles of SLC7 genes in silk-producing insects have not been reported. Here, we found that amino acid signaling regulates silk protein synthesis and larval development via the L-type amino acid transporter 1 (LAT1; also known as SLC7A5) in Bombyx mori. A total of 12 SLC7 homologs were identified in the silkworm genome, among which BmSLC7A5 was found to be a silk gland-enriched gene and may be involved in leucine transport. Bioinformatics analysis indicated that SLC7A5 displays high homology and a close phylogenetic relationship in silk-producing insects. Subsequently, we found that leucine treatment significantly increased silk protein synthesis by improving the transcription and protein levels of silk genes. Furthermore, systemic and silk gland-specific knockout of BmSLC7A5 led to decreased silk protein synthesis by inhibiting TORC1 signaling, and somatic mutation also resulted in arrested development from the 5th instar to the early pupal stage. Altogether, our study reveals that BmSLC7A5 is involved in regulating silk protein synthesis and larval development by affecting the TORC1 signaling pathway, which provides a new strategy and target for improving silk yield.

Chlorogenic acid protects against intestinal inflammation and injury by inactivating the mtDNA-cGAS-STING signaling pathway in broilers under necrotic enteritis challenge.

This study aimed to determine the effects of chlorogenic acid (CGA) on the growth performance, intestinal health, immune response, and mitochondrial DNA (mtDNA)-cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway in broilers under necrotic enteritis (NE) challenge. The 180 one-day-old male Cobb 500 broilers with similar body weight of 44.59 ± 1.39 g were randomly allocated into 3 groups. The groups were control diet (Control group), control diet + NE challenge (NE group), and control diet + 500 mg/kg CGA + NE challenge (NE + CGA group), with 6 replicates per treatment. All broilers except the Control group were given sporulated coccidian oocysts (d 14) and Clostridium perfringens (d 19-21) by oral gavage. Our findings showed that CGA improved the growth performance and intestinal morphology in broilers under NE challenge. CGA supplementation elevated the barrier function in broilers under NE challenge, which reflected in the decreased serum concentrations of D-lactate and diamine oxidase, and upregulated jejunal protein expression of occludin. CGA supplementation also improved the immune function, which reflected in the increased concentrations and gene expressions of anti-inflammatory factors, and decreased concentrations and gene expressions of proinflammatory factors. CGA supplementation further enhanced intestinal cell proliferation and differentiation, which manifested in the increased number of goblet cells and positive cells of proliferating cell nuclear antigen on d 28 and 42. Furthermore, CGA supplementation decreased the mtDNA (d 42) and mitochondrial reactive oxygen species levels (d 28 and 42), and increased the mitochondrial membrane potential (d 42) and mitochondrial complex I (d 28 and 42) or III (d 28) activity. Broilers challenged with NE had upregulated jejunal protein expressions of cGAS, phospho-TANK-binding kinase 1, and phospho-interferon regulatory factor 7 compared with the Control group, which were downregulated after CGA supplementation. In conclusion, dietary supplementation CGA could protect against intestinal inflammation and injury by reducing the leakage of mtDNA and inactivating the cGAS-STING signaling pathway in broilers under NE challenge.

Defect Engineering of 2D Semiconductors for Dual Control of Emission and Carrier Polarity.

2D transition metal dichalcogenides (TMDCs) are considered as promising materials in post-Moore technology. However, the low photoluminescence quantum yields (PLQY) and single carrier polarity due to the inevitable defects during material preparation are great obstacles to their practical applications. Here, an extraordinary defect engineering strategy is reported based on first-principles calculations and realize it experimentally on WS2 monolayers by doping with IIIA atoms. The doped samples with large sizes possess both giant PLQY enhancement and effective carrier polarity modulation. Surprisingly, the high PL emission maintained even after one year under ambient environment. Moreover, the constructed p-n homojunctions shows high rectification ratio (≈2200), ultrafast response times and excellent stability. Meanwhile, the doping strategy is universally applicable to other TMDCs and dopants. This smart defect engineering strategy not only provides a general scheme to eliminate the negative influence of defects, but also utilize them to achieve desired optoelectronic properties for multifunctional applications.

Hierarchical processing enabled by 2D ferroelectric semiconductor transistor for low-power and high-efficiency AI vision system.

The growth of data and Internet of Things challenges traditional hardware, which encounters efficiency and power issues owing to separate functional units for sensors, memory, and computation. In this study, we designed an α-phase indium selenide (α-In2Se3) transistor, which is a two-dimensional ferroelectric semiconductor as the channel material, to create artificial optic-neural and electro-neural synapses, enabling cutting-edge processing-in-sensor (PIS) and computing-in-memory (CIM) functionalities. As an optic-neural synapse for low-level sensory processing, the α-In2Se3 transistor exhibits a high photoresponsivity (2855 A/W) and detectivity (2.91 × 1014 Jones), facilitating efficient feature extraction. For high-level processing tasks as an electro-neural synapse, it offers a fast program/erase speed of 40 ns/50 µs and ultralow energy consumption of 0.37 aJ/spike. An AI vision system using α-In2Se3 transistors has been demonstrated. It achieved an impressive recognition accuracy of 92.63% within 12 epochs owing to the synergistic combination of the PIS and CIM functionalities. This study demonstrates the potential of the α-In2Se3 transistor in future vision hardware, enhancing processing, power efficiency, and AI applications.

Effects of Lactobacillus plantarum HW1 on Growth Performance, Intestinal Immune Response, Barrier Function, and Cecal Microflora of Broilers with Necrotic Enteritis.

The purpose of the study was to investigate the effects of Lactobacillus plantarum HW1 on growth performance, intestinal immune response, barrier function, and cecal microflora of broilers with necrotic enteritis. In total, 180 one-day-old male Cobb 500 broilers were randomly allocated into three groups comprising a non-infected control (NC) group, basal diet + necrotic enteritis challenge (NE) group, and basal diet + 4 × 106 CFU/g Lactobacillus plantarum HW1 + necrotic enteritis challenge (HW1) group. Broilers in the NE and HW1 groups were orally given sporulated coccidian oocysts at day 14 and Clostridium perfringens from days 19 to 21. The results showed that the HW1 treatment increased (p < 0.05) the average daily gain of broilers from days 15 to 28 and from days 0 to 28 compared with the NE group. Moreover, the HW1 treatment decreased (p < 0.05) the oocysts per gram of excreta, intestinal lesion scores, ileal interleukin (IL) 1ß and tumor necrosis factor α levels, and serum D-lactic acid and diamine oxidase levels, while increasing (p < 0.05) the ileal IL-10 level, thymus index, and protein expressions of ileal occludin and ZO-1. Additionally, the HW1 treatment decreased (p < 0.05) the jejunal and ileal villus height, jejunal villus height/crypt depth value, and cecal harmful bacterial counts (Clostridium perfringens, Salmonella, Escherichia coli, and Staphylococcus aureus), and increased (p < 0.05) the cecal Lactobacillus count. In conclusion, dietary supplementation with 4 × 106 CFU/g Lactobacillus plantarum HW1 could relieve necrotic enteritis infection-induced intestinal injury and improve growth performance in broilers by improving intestinal barrier function and regulating intestinal microbiology.

Gut microbiota metabolites, redox status, and the related regulatory effects of probiotics.

Oxidative stress is a state of imbalance between oxidation and antioxidation. It is caused by excess levels of free radicals and leads to the damage of DNA, proteins, and lipids. The crucial role of gut microbiota in regulating oxidative stress has been widely demonstrated. Studies have suggested that the redox regulatory effects of gut microbiota are related to gut microbiota metabolites, including fatty acids, lipopolysaccharides, tryptophan metabolites, trimethylamine-N-oxide and polyphenolic metabolites. In recent years, the potential benefits of probiotics have been gaining increasing scientific interest owing to their ability to modulate gut microbiota and oxidative stress. In this review, we summarise the adverse health effects of oxidative stress and discuss the role of the gut microbiota and its metabolites in redox regulation. Based on the influence of gut microbiota metabolites, the roles of probiotics in preventing oxidative stress are highlighted.

A combination of selenium and Bacillus subtilis improves the quality and flavor of meat and slaughter performance of broilers.

This study aimed to investigate the effects of the combination of selenium and Bacillus subtilis (Se-BS) on the quality and flavor of meat and slaughter performance of broilers. A total of 240 one-day-old Arbor Acres broilers were randomly allotted to four treatments of a basal diet supplemented with no selenium (control), sodium selenite (SS), BS, or Se-BS and raised for 42 days. Compared with the control group, Se-BS significantly increased the carcass weight, the half-eviscerated weight, the completely eviscerated weight, the carcass rate, and redness in broiler muscles; improved the antioxidant state by increasing glutathione peroxidase (GPx) and glutathione S-transferase activities, the total antioxidant capacity, and GPx-1 and thioredoxin reductase 1 messenger RNA (mRNA) levels; promoted biological activity by increasing the contents of glutamate, phenylalanine, lysine, and tyrosine; and increased Se and five types of nitrogenous volatile substances in muscles. On the other hand, Se-BS treatment decreased the shear force, drip loss, and the malondialdehyde, glutathione, and lead contents in muscles. Se-BS exerted a better effect on slaughter performance, the physicochemical quality of meat, the redox status, the amino acid contents, the trace element contents, and volatile substances compared with SS and BS. In conclusion, Se-BS had a positive effect on the quality and flavor of meat and slaughter performance of broilers, suggesting that Se-BS may be a beneficial feed additive.

Effects of Lactiplantibacillus plantarum on oxidative stress, mitophagy, and NLRP3 inflammasome activation in broiler breast meat.

Poultry meat has a high polyunsaturated fatty acids content, making it vulnerable to oxidative stress. Mitophagy participates in the regulation of oxidative stress and the nucleotide-binding and oligomerization domain (NOD)-like receptor family as well as pyrin domain-containing protein 3 (NLRP3) inflammasome activation. Lactiplantibacillus plantarum P8 (P8) is a probiotic strain with an antioxidant capacity. In the present study, we investigated the effects of P8 on oxidative stress, mitochondrial function, mitophagy, and NLRP3 inflammasome in the breast meat of oxidatively stressed broilers. Four hundred 1-day-old male broilers were assigned to a 2 × 2 factorial design with 2 P8 levels (0 or 1 × 108 cfu/g), either with or without dexamethasone (DEX) injection, for a 21-day experimental period. DEX was injected intraperitoneally once daily from d 16 to 21. The breast meat was collected on d 21. The results showed that P8 supplementation decreased malondialdehyde (MDA) levels, increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and activated the Keap1-Nrf2 pathway in DEX-injected broilers. Moreover, P8 supplementation downregulated mitochondrial DNA (mtDNA) copy number and increased the expressions of peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α), silent information regulator 1 (SIRT1), mitochondrial fusion protein 1 (Mfn1), and optic atrophy protein 1 (OPA1) in DEX-treated broilers. In addition, the decreased mitophagy level in DEX-treated broilers was elevated with P8 supplementation, as reflected by the increased gene expression of autophagy-related gene 5 (ATG5), Bcl-2-interacting protein (Becline-1), Parkin, PTEN-induced kinase 1 (PINK1), light chain 3 II (LC3II)/LC31, and the protein expression of Parkin as well as decreased p62 expression. In addition, P8 supplementation inhibited NLRP3 inflammasome activation by decreasing the transcription of NLRP3, IL-18, cysteinyl aspartate-specific proteinase-1 (Caspase-1), and the expression of NLRP3 and IL-18 in DEX-treated broilers. In conclusion, dietary P8 supplementation alleviates oxidative stress, improves mitophagy, and inhibits NLRP3 inflammasome activation in the breast meat of oxidatively stressed broilers.

Serpin-1a and serpin-6 regulate the Toll pathway immune homeostasis by synergistically inhibiting the Spätzle-processing enzyme CLIP2 in silkworm, Bombyx mori.

The Toll receptor signaling pathway is an important innate immune response of insects to pathogen infection; its extracellular signal transduction involves serine protease cascade activation. However, excessive or constitutive activation of the Toll pathway can be detrimental. Hence, the balance between activation and inhibition of the extracellular protease cascade must be tightly regulated to achieve favorable outcomes. Previous studies have shown that serpins-serine protease inhibitors-negatively regulate insect innate immunity by inhibiting extracellular protease cascade signaling. Although the roles of serpins in insect innate immunity are well described, the physiological mechanisms underlying their synergistic effects remain poorly understand. Here, we characterize the molecular mechanism by which serpin-1a and serpin-6 synergistically maintain immune homeostasis of the silkworm Toll pathway under physiological and pathological conditions. Through in vitro biochemical assays and in vivo bioassays, we demonstrate that clip-domain serine protease 2 (CLIP2), as the Toll cascade-activating terminal protease, is responsible for processing proSpätzle1 to induce the expression of antimicrobial peptides. Further biochemical and genetic analyses indicate that constitutively expressed serpin-1a and inducible serpin-6 synergistically target CLIP2 to maintain homeostasis of the silkworm Toll pathway under physiological and pathological conditions. Taken together, this study provides new insights into the precise regulation of Toll cascade activation signals in insect innate immune responses and highlights the importance and complexity of insect immune homeostasis regulation.

Evaluation of deep learning models for quality control of MR spectra.

Purpose: While 3D MR spectroscopic imaging (MRSI) provides valuable spatial metabolic information, one of the hurdles for clinical translation is its interpretation, with voxel-wise quality control (QC) as an essential and the most time-consuming step. This work evaluates the accuracy of machine learning (ML) models for automated QC filtering of individual spectra from 3D healthy control and patient datasets. Methods: A total of 53 3D MRSI datasets from prior studies (30 neurological diseases, 13 brain tumors, and 10 healthy controls) were included in the study. Three ML models were evaluated: a random forest classifier (RF), a convolutional neural network (CNN), and an inception CNN (ICNN) along with two hybrid models: CNN + RF, ICNN + RF. QC labels used for training were determined manually through consensus of two MRSI experts. Normalized and cropped real-valued spectra was used as input. A cross-validation approach was used to separate datasets into training/validation/testing sets of aggregated voxels. Results: All models achieved a minimum AUC of 0.964 and accuracy of 0.910. In datasets from neurological disease and controls, the CNN model produced the highest AUC (0.982), while the RF model achieved the highest AUC in patients with brain tumors (0.976). Within tumor lesions, which typically exhibit abnormal metabolism, the CNN AUC was 0.973 while that of the RF was 0.969. Data quality inference times were on the order of seconds for an entire 3D dataset, offering drastic time reduction compared to manual labeling. Conclusion: ML methods accurately and rapidly performed automated QC. Results in tumors highlights the applicability to a variety of metabolic conditions.

Catalyst-Oriented Design Based on Elementary Reactions (CODER) for Triarylamine Synthesis.

Recently, the application of computational tools to the rational design of catalysts has received considerable attention, but progress has been limited by the reliance on databases and because mechanistic data have been almost neglected. Herein, we report a new strategy for catalyst design, designated catalyst-oriented design based on elementary reactions (CODER), which fully utilizes mechanistic data, combines the strengths of computational tools and researcher experience. CODER enabled the development of extremely efficient Pd catalysts for C-N coupling, which markedly improved the efficiency of the synthesis of widely used triarylamine optoelectronic materials by enhancing the turnover numbers (up to 340000) to 1-3 orders of magnitude towards literature values.

Atlas-Based Adaptive Hadamard-Encoded MR Spectroscopic Imaging at 3T.

BACKGROUND: This study aimed to develop a time-efficient method of acquiring simultaneous, dual-slice MR spectroscopic imaging (MRSI) for the evaluation of brain metabolism. METHODS: Adaptive Hadamard-encoded pulses were developed and integrated with atlas-based automatic prescription. The excitation profiles were evaluated via simulation, phantom and volunteer experiments. The feasibility of γ-aminobutyric acid (GABA)-edited dual-slice MRSI was also assessed. RESULTS: The signal between slices in the dual-band MRSI was less than 1% of the slice profiles. Data from a homemade phantom containing separate, interfacing compartments of creatine and acetate solutions demonstrated ~0.4% acetate signal contamination relative to the amplitude in the excited creatine compartment. The normalized signal-to-noise ratios from atlas-based acquisitions in volunteers were found to be comparable between dual-slice, Hadamard-encoded MRSI and 3D acquisitions. The mean and standard deviation of the coefficients of variation for NAA/Cho from the repeated volunteer scans were 8.2% ± 0.8% and 10.1% ± 3.7% in the top and bottom slices, respectively. GABA-edited, dual-slice MRSI demonstrated simultaneous detection of signals from GABA and coedited macromolecules (GABA+) from both superior grey and deep grey regions of volunteers. CONCLUSION: This study demonstrated a fully automated dual-slice MRSI acquisition using atlas-based automatic prescription and adaptive Hadamard-encoded pulses.