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Abstract Background Disorder in bile acid (BA) metabolism is known to be an important factor contributing to diarrhea. However, the pathogenesis of BA disorder-induced diarrhea remains unclear. Methods The colonic BA pool and microbiota between health piglets and BA disorder-induced diarrheal piglets were compared. Fecal microbiota transplantation and various cell experiments further indicated that chenodeoxycholic acid (CDCA) metabolic disorder produced CDCA-3β-glucuronide, which is the main cause of BA disorder diarrhea. Non-targeted metabolomics uncovered the inhibition of the BA glucuronidation by Lactobacillus reuteri (L. reuteri) is through deriving indole-3-carbinol (I3C). In vitro, important gene involved in the reduction of BA disorder induced-diarrhea were screened by RNA transcriptomics sequencing, and activation pathway of FXR-SIRT1-LKB1 to alleviate BA disorder diarrhea and P53-mediated apoptosis were proposed in vitro by multifarious siRNA interference, CO-IP, immunofluorescence, and so on, which mechanism was also verified in a variety of mouse models. Results Here, we reveal for the first time that core microbiota derived I3C represses gut epithelium glucuronidation, particularly 3β-glucuronic CDCA production, which reaction is mediated by host UDP glucuronosyltransferase family 1 member A4 (UGT1A4) and necessary of BA disorder induced diarrhea. Mechanistically, L. reuteri derived I3C activates aryl hydrocarbon receptor to decrease UGT1A4 transcription and CDCA-3β-glucuronide content, thereby upregulating FXR-SIRT1-LKB1 signal. LKB1 binds with P53 based on protein interaction, ultimately resists to apoptosis and diarrhea. Moreover, I3C assists CDCA to attain the ameliorative effects of FXR activation in BA disorder diarrhea, through reversion of abnormal metabolism pathway, improving the outcomes of CDCA supplement. Conclusion These findings uncover the crucial interplay between gut epithelial cells and microbes, highlighting UGT1A4-mediated conversion of CDCA-3β-glucuronide as a key target for ameliorating BA disorder-induced diarrhea. Video Abstract

Abstract Background CD74 is ectopically expressed in many tumors and can regulate tumor immunity. However, there are many gaps in the study of the prognostic value of CD74 expression and immune infiltration in hepatocellular carcinoma (HCC). Methods An online tumor database was searched to obtain data on gene/protein expression. Immune infiltration analysis was performed using the Tumor Immune Estimation Resource and Comprehensive Analysis on Multi-Omics of Immunotherapy in Pan-cancer databases. Single-cell data were obtained from the Tissue-specific Gene Expression and Regulation, Single-cell Transcriptomes of Tumor Immune Microenvironment and Tumor Immune Single-cell Hub 2 databases. Results CD74 was highly expressed in HCC patients. HCC patients with high CD74 expression who consumed alcohol or were negative for hepatitis virus had a better prognosis than patients with low CD74 expression. CD74 was mainly enriched in immune response regulation pathways. Both copy number variations in CD74 and CD74 expression patterns affected the infiltration levels of immune cells. Interestingly, CD74 regulated the differentiation of myeloid cells. CD74 in macrophages and dendritic cells (DCs) forms complex networks with malignant cells and hepatic progenitor cell (HPC)-like cells, respectively. High CD74 expression in HPC-like cells and malignant cells significantly decreased the fraction of C-type lectin domain family 9 A (CLEC9A)-cDC1+ DCs and IL-1B+ macrophages, respectively. Their crosstalk subsequently shaped the tumor microenvironment of HCC, possibly through the CD74-MIF axis. Importantly, patients with high CD74 expression presented higher immune scores and achieved good outcomes after receiving immunotherapy. Conclusion High CD74 expression is associated with the abundance of a variety of immune cell types, mediating interactions among tumor and immune cells and shaping the malignant behavior of HCC. In summary, CD74 may be a hallmark for determining the prognosis and immune cell infiltration levels of HCC patients.

Abstract Broad‐spectrum antibacterial drugs often lack specificity, leading to indiscriminate bactericidal activity, which can disrupt the normal microbial balance of the host flora and cause unnecessary cytotoxicity during systemic administration. In this study, we constructed a specifically targeted antimicrobial peptide against Staphylococcus aureus by introducing a phage‐displayed peptide onto a broad‐spectrum antimicrobial peptide and explored its structure–function relationship through one‐factor modification. SFK2 obtained by screening based on the selectivity index and the targeting index showed specific killing ability against S. aureus. Moreover, SFK2 showed excellent biocompatibility in mice and piglet, and demonstrated significant therapeutic efficacy against S. aureus infection. In conclusion, our screening of phage‐derived heptapeptides effectively enhances the specific bactericidal ability of the antimicrobial peptides against S. aureus, providing a theoretical basis for developing targeted antimicrobial peptides.

Abstract Deoxynivalenol (DON) is a prevalent toxin causing severe liver damage through hepatocellular oxidative stress. However, the underlying mechanisms and effective therapeutic approaches remain unknown. Here, the unique role of the xenobiotic metabolism factor pregnane X receptor (PXR) in mediating DON‐induced hepatocellular oxidative stress is investigated. Treatment with the PXR agonist 3‐indole‐propionic acid (IPA) alleviates DON‐induced oxidative stress and liver injury both in vitro and in vivo. Mechanistically, it is discovered for the first time that PXR agonist IPA directly transactivates the m6A demethylase FTO expression, leading to site‐specific demethylation and decreased abundance of YTHDC1‐bound Malat1 lncRNA at single‐nucleotide resolution. The diminished m6A modification of Malat1 lncRNA reduces its stability and augments antioxidant pathways governed by NRF2, consequently mitigating DON‐induced liver injury. Furthermore, Malat1 knockout mice exhibit decreased DON‐induced liver injury, emphasizing the role of Malat1 lncRNA in oxidative stress. Collectively, the findings establish that PXR‐mediated m6A‐dependent Malat1 lncRNA expression determines hepatocyte oxidative stress via m6A demethylase FTO, providing valuable insights into the potential mechanisms underlying DON‐induced liver injury and offers potential therapeutic strategies for its treatment.

Abstract Staphylococcus aureus (S. aureus) is a common pathogenic bacterium in animal husbandry that can cause diseases such as mastitis, skin infections, arthritis, and other ailments. The formation of biofilms threatens and exacerbates S. aureus infection by allowing the bacteria to adhere to pathological areas and livestock product surfaces, thus triggering animal health crises and safety issues with livestock products. To solve this problem, in this review, we provide a brief overview of the harm caused by S. aureus and its biofilms on livestock and animal byproducts (meat and dairy products). We also describe the ways in which S. aureus spreads in animals and the threats it poses to the livestock industry. The processes and molecular mechanisms involved in biofilm formation are then explained. Finally, we discuss strategies for the removal and eradication of S. aureus and biofilms in animal husbandry, including the use of antimicrobial peptides, plant extracts, nanoparticles, phages, and antibodies. These strategies to reduce the spread of S. aureus in animal husbandry help maintain livestock health and improve productivity to ensure the ecologically sustainable development of animal husbandry and the safety of livestock products.

Abstract In recent years, the important role of gut microbiota in promoting animal health and regulating immune function in livestock and poultry has been widely reported. The issue of animal health problems causes significant economic losses each year. Probiotics and postbiotics have been widely developed as additives due to their beneficial effects in balancing host gut microbiota, enhancing intestinal epithelial barrier, regulating immunity, and whole‐body metabolism. Probiotics and postbiotics are composed of complex ingredients, with different components and compositions having different effects, requiring classification for discussing their mechanisms of action. Probiotics and postbiotics have considerable prospects in preventing various diseases in the livestock industry and animal feed and medical applications. This review highlights the application value of probiotics and postbiotics as potential probiotic products, emphasizing their concept, mechanism of action, and application, to improve the productivity of livestock and poultry.

The endoparasitoids Chouioa cunea Yang and Tetrastichus septentrionalis Yang (Hymenoptera: Eulophidae) are both gregarious pupal parasitoids of the fall webworm, Hyphantria cunea (Drury) (Lepidoptera: Erebidae). In order to analyze the competitive interactions between both parasitoids exploiting H. cunea, we assessed both extrinsic and intrinsic competition. The search time, oviposition duration, and oviposition frequency were used as evaluation criteria for extrinsic competition. The number of survival days, female ratio, and number of parasitoids emerging from the host were used as evaluation criteria for intrinsic competition. The results indicated that both parasitoid species were able to parasitize hosts that were already parasitized by competitors. The first released species consistently emerged as the superior competitor in multiparasitized hosts. Both parasitoid release orders and time intervals between oviposition affect the competition of parasitoids and the parasitic efficiency. The results emphasize the parasitic abilities of both parasitoid species and provide a basis for future research on competition mechanisms and biological control of H. cunea.

Weaned stress may damage the tissue development, barrier function, and balance of microbiota of gut, resulting in the diarrhea and reduced growth performance of piglets. Probiotics with excellent characteristics can enhance the resistance of piglets to weaned stress. Under a poor sanitary condition, the Limosilactobacillus reuteri (L. reuteri) SLZX19-12 was supplemented to check its effects for piglets. Results showed that supplementation of L. reuteri significantly decreased the diarrhea incident, improved the growth performance, and enhanced the barrier integrity of gut. In ileum, L. reuteri decreased inflammation by NFκB p65 pathway, increased propionate, TCDCA, and THDCA contents, and regulated microbiota. In colon, L. reuteri decreased the inflammation by NFκB p65 pathway, reduced DCA content, and regulated microbiota. Therefore, the supplementation of L. reuteri may alleviate weaned stress by improving immune function and regulating the gut microbiota in piglets.

The invasion of pathogens derived from diet or the environment triggers intestinal inflammation, which is a result of the host intestinal barrier damage and immune dysfunction, such as the decrease of host defense peptides (HDPs) and inhibition of cell proliferation. Herein, the siRNA interference demonstrated that a critical lysozyme, which was mainly induced by dietary supplementations of sodium butyrate and forskolin, improved cell proliferation by inhibiting p38 MAPK and JNK signaling pathways and reinforced the intestinal barrier. Moreover, we established a mouse model of intestinal inflammation with Citrobacter rodentium (C. rodentium). It was found that NaBu and FSK stimulated intestinal epithelial proliferation to repair barrier damage, and performed stronger disease resistance to C. rodentium infection on account of the lysozyme upregulation in colon. Therefore, this study revealed that NaBu and FSK prevented or alleviated the development of foodborne infections by promoting lysozyme expression, which may be mediated by the effect of lysozyme on promoting cell proliferation and improving barrier function.

ABSTRACTSuccinate is a circulating metabolite, and the relationship between abnormal changes in the physiological concentration of succinate and inflammatory diseases caused by the overreaction of certain immune cells has become a research focus. Recent investigations have shown that succinate produced by the gut microbiota has the potential to regulate host homeostasis and treat diseases such as inflammation. Gut microbes are important for maintaining intestinal homeostasis. Microbial metabolites serve as nutrients in energy metabolism, and act as signal molecules that stimulate host cell and organ function and affect the structural balance between symbiotic gut microorganisms. This review focuses on succinate as a metabolite of both host cells and gut microbes and its involvement in regulating the gut – immune tissue axis by activating intestinal mucosal cells, including macrophages, dendritic cells, and intestinal epithelial cells. We also examined its role as the mediator of microbiota – host crosstalk and its potential function in regulating intestinal microbiota homeostasis. This review explores feasible ways to moderate succinate levels and provides new insights into succinate as a potential target for microbial therapeutics for humans.

The offspring of super-multiparous sows face problems such as decreased growth performance, poor meat quality and even diseases in animal husbandry. Gama-aminobutyric acid (GABA) has long been known to promote growth and suppress inflammation, but little is known about the mechanisms. A total of 72 growing-finishing pigs from the 8th generation were randomly allotted to 2 groups with 6 replicates per treatment to receive a corn–soybean basal diet or the basal diet supplemented 20 mg/kg GABA for 60 d. After the animal-trial period, samples of serum and liver were collected for further analysis. Additionally, a lipopolysaccharide (LPS)-induced inflammatory model using HepG2 cells was established to explore the role of GABA on regulating hepatic inflammation. The results indicated that inflammatory cell infiltration occurs in the liver of progeny of super-multiparous sows, and dietary supplementation with GABA influenced liver morphology, increased activities of antioxidant enzymes and decreased the expression abundance of pro-inflammatory cytokines, including tumor necrosis factor-α (TNFα) and interleukin (IL)-1β, in the liver of growing-finishing pigs (P

Cells are the most basic structural and functional units of living organisms. Studies of cell growth, differentiation, apoptosis, and cell-cell interactions can help scientists understand the mysteries of living systems. However, there is considerable heterogeneity among cells. Great differences between individuals can be found even within the same cell cluster. Cell heterogeneity can only be clearly expressed and distinguished at the level of single cells. The development of droplet microfluidics technology opens up a new chapter for single-cell analysis. Microfluidic chips can produce many nanoscale monodisperse droplets, which can be used as small isolated micro-laboratories for various high-throughput, precise single-cell analyses. Moreover, gel droplets with good biocompatibility can be used in single-cell cultures and coupled with biomolecules for various downstream analyses of cellular metabolites. The droplets are also maneuverable; through physical and chemical forces, droplets can be divided, fused, and sorted to realize single-cell screening and other related studies. This review describes the channel design, droplet generation, and control technology of droplet microfluidics and gives a detailed overview of the application of droplet microfluidics in single-cell culture, single-cell screening, single-cell detection, and other aspects. Moreover, we provide a recent review of the application of droplet microfluidics in tumor single-cell immunoassays, describe in detail the advantages of microfluidics in tumor research, and predict the development of droplet microfluidics at the single-cell level.

Abstract Background Cognitive impairment, an increasing mental health issue, is a core feature of the aging brain and neurodegenerative diseases. Industrialized nations especially, have experienced a marked decrease in dietary fiber intake, but the potential mechanism linking low fiber intake and cognitive impairment is poorly understood. Emerging research reported that the diversity of gut microbiota in Western populations is significantly reduced. However, it is unknown whether a fiber-deficient diet (which alters gut microbiota) could impair cognition and brain functional elements through the gut-brain axis. Results In this study, a mouse model of long-term (15 weeks) dietary fiber deficiency (FD) was used to mimic a sustained low fiber intake in humans. We found that FD mice showed impaired cognition, including deficits in object location memory, temporal order memory, and the ability to perform daily living activities. The hippocampal synaptic ultrastructure was damaged in FD mice, characterized by widened synaptic clefts and thinned postsynaptic densities. A hippocampal proteomic analysis further identified a deficit of CaMKIId and its associated synaptic proteins (including GAP43 and SV2C) in the FD mice, along with neuroinflammation and microglial engulfment of synapses. The FD mice also exhibited gut microbiota dysbiosis (decreased Bacteroidetes and increased Proteobacteria), which was significantly associated with the cognitive deficits. Of note, a rapid differentiating microbiota change was observed in the mice with a short-term FD diet (7 days) before cognitive impairment, highlighting a possible causal impact of the gut microbiota profile on cognitive outcomes. Moreover, the FD diet compromised the intestinal barrier and reduced short-chain fatty acid (SCFA) production. We exploit these findings for SCFA receptor knockout mice and oral SCFA supplementation that verified SCFA playing a critical role linking the altered gut microbiota and cognitive impairment. Conclusions This study, for the first time, reports that a fiber-deprived diet leads to cognitive impairment through altering the gut microbiota-hippocampal axis, which is pathologically distinct from normal brain aging. These findings alert the adverse impact of dietary fiber deficiency on brain function, and highlight an increase in fiber intake as a nutritional strategy to reduce the risk of developing diet-associated cognitive decline and neurodegenerative diseases. Video Abstract

Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrhea in children and travelers in developing countries. ETEC is characterized by the ability to produce major virulence factors including colonization factors (CFs) and enterotoxins, that bind to specific receptors on epithelial cells and induce diarrhea. The gut microbiota is a stable and sophisticated ecosystem that performs a range of beneficial functions for the host, including protection against pathogen colonization. Understanding the pathogenic mechanisms of ETEC and the interaction between the gut microbiota and ETEC represents not only a research need but also an opportunity and challenge to develop precautions for ETEC infection. Herein, this review focuses on recent discoveries about ETEC etiology, pathogenesis and clinical manifestation, and discusses the colonization resistances mediated by gut microbiota, as well as preventative strategies against ETEC with an aim to provide novel insights that can reduce the adverse effect on human health.

Abstract Intestinal epithelium undergoes rapid cellular turnover, relying on the local niche, to support intestinal stem cells (ISCs) function and self‐renewal. Research into the association between ISCs and disease continues to expand at a rapid rate. However, the detailed interaction of ISCs and gut microbes remains to be elucidated. Thus, this review witnessed major advances in the crosstalk between ISCs and gut microbes, delivering key insights into (1) construction of ISC niche and molecular mechanism of how to jointly govern epithelial homeostasis and protect against intestinal diseases with the participation of Wnt, bone morphogenetic protein, and Notch; (2) differentiation fate of ISCs affect the gut microbiota. Meanwhile, the presence of intestinal microbes also regulates ISC function; (3) microbiota regulation on ISCs by Wnt and Notch signals through pattern recognition receptors; (4) how do specific microbiota‐related postbiotics influence ISCs to maintain intestinal epithelial regeneration and homeostasis that provide insights into a promising alternative therapeutic method for intestinal diseases. Considering the detailed interaction is still unclear, it is necessary to further explore the regulatory role of gut microbiota on ISCs to utilize microbes to alleviate gut disorders. Furthermore, these major advances collectively drive us ever closer to breakthroughs in regenerative medicine and cancer treatment by microbial transplantation in the clinic.

Abstract Background Oxidative stress is a main cause of piglet gut damage and diarrhea. Pyrroloquinoline quinone (PQQ), is a novel redox cofactor with antioxidant properties. However, the effect and mechanism that PQQ supplementation decreases oxidative injury in weaned pigs is not understood. Therefore, the aim of this study is to confirm the effect of PQQ on regulating redox status in weaned pigs and the mechanism for antioxidant function by porcine intestinal epithelial cell line (IPEC-J2) challenged with H2O2. Results Experiment 1, 144 Duroc × Landrace × Yorkshire pigs (weaned at 28 d) were allocated to four groups: received a basal diet (control) and diets supplemented with 0.15%, 0.30% and 0.45% PQQ, respectively. On d 28, growth performance, diarrhea incidence and redox factors were measured. Experiment 2, IPEC-J2 were treated with or without PQQ in the presence or absence of H2O2 for indicated time points. Experiment 3, IPEC-J2 were transfected with or without Nrf2 siRNA, then treated according to Experiment 2. The cell viability, redox factors, protein of tight junctions and Nrf2 pathway were determined. In vivo, PQQ supplementation demonstrated dose-related improvements in average daily gain, and gain to feed ratio (Linear P

Bacillus subtilis can secret a variety of substances to improve human and animal gut health via inhibiting the proliferation of pathogenic bacteria. In this study, a fast-growing and stress-resistant strain of Bacillus subtilis M6 (B. subtilis M6) were isolated, which showed a strong antibacterial activity to E. coli K88, S. typhimurium ATCC14028, and S. aureus ATCC25923 in vitro. In vivo studies showed that B. subtilis M6 can significantly improve the average daily gain (ADG) using an AA broiler model. Dietary B. subtilis M6 improved the intestinal morphology. The villus height of jejunum and ileum were significantly increased. The concentration of malondialdehyde (MDA) in the ileal mucosa was significantly reduced in B. subtilis M6 treatment group, which suggested the oxidative stress of the ileum was significantly relieved. Though the β diversity of treatments was not significantly, B. subtilis M6 improved the composition of intestinal microbes, especially at the level of caecum genus, the dominant genus was changed from Ruminococcus to Akkermansia, which indicated the change of intestinal carbohydrate nutrition. In conclusion, these data indicate that the B. subtilis M6 shows a probiotic potential to improve intestinal health via altering gut microbiota.

ObjectiveTo explore the feasibility of a deep learning three-dimensional (3D) V-Net convolutional neural network to construct high-resolution computed tomography (HRCT)-based auditory ossicle structure recognition and segmentation models.MethodsThe temporal bone HRCT images of 158 patients were collected retrospectively, and the malleus, incus, and stapes were manually segmented. The 3D V-Net and U-Net convolutional neural networks were selected as the deep learning methods for segmenting the auditory ossicles. The temporal bone images were randomized into a training set (126 cases), a test set (16 cases), and a validation set (16 cases). Taking the results of manual segmentation as a control, the segmentation results of each model were compared.ResultsThe Dice similarity coefficients (DSCs) of the malleus, incus, and stapes, which were automatically segmented with a 3D V-Net convolutional neural network and manually segmented from the HRCT images, were 0.920 ± 0.014, 0.925 ± 0.014, and 0.835 ± 0.035, respectively. The average surface distance (ASD) was 0.257 ± 0.054, 0.236 ± 0.047, and 0.258 ± 0.077, respectively. The Hausdorff distance (HD) 95 was 1.016 ± 0.080, 1.000 ± 0.000, and 1.027 ± 0.102, respectively. The DSCs of the malleus, incus, and stapes, which were automatically segmented using the 3D U-Net convolutional neural network and manually segmented from the HRCT images, were 0.876 ± 0.025, 0.889 ± 0.023, and 0.758 ± 0.044, respectively. The ASD was 0.439 ± 0.208, 0.361 ± 0.077, and 0.433 ± 0.108, respectively. The HD 95 was 1.361 ± 0.872, 1.174 ± 0.350, and 1.455 ± 0.618, respectively. As these results demonstrated, there was a statistically significant difference between the two groups (P < 0.001).ConclusionThe 3D V-Net convolutional neural network yielded automatic recognition and segmentation of the auditory ossicles and produced similar accuracy to manual segmentation results.

Though the energy requirement for maintenance is an important part of net energy system, little is known of the metabolic characteristics of maintenance energy expenditure. This study was investigated the effect of feeding level at metabolizable energy requirement for maintenance (FLM) on plasma metabolites in growing pigs. Ten barrows (22.5 ± 0.5 kg BW) were kept in metabolism crates and catheterized in the precaval vein during adaptation period. Pigs were fed a corn-soybean meal diet at 782 kJ ME/kg BW0.6·d−1 during d 1 to 8 and then were refeeding at 2,400 kJ ME/kg BW0.6·d−1 on d 9. Plasma samples of each pig were collected by catheter on the morning of d 1, 3, 5, 7, 9, and 10, respectively, for metabolomics testing. Results showed that the concentration of plasma urea nitrogen decreased under FLM (p < 0.01) and increased significantly after refeeding (p < 0.01). The concentration of total cholesterol, high-density lipoprotein, low-density lipoprotein, and albumin in plasma were decreased significantly after refeeding (p < 0.01). Eleven identified compounds were up-regulated and six ones were down-regulated under FLM. In conclusion, the energy metabolism of growing pigs was relatively stable after 4 days of feeding at FLM.

Abstract Background Weaning stress of piglets causes a huge economic loss to the pig industry. Balance and stability of the intestinal microenvironment is an effective way to reduce the occurance of stress during the weaning process. Clostridium butyricum, as a new microecological preparation, is resistant to high temperature, acid, bile salts and some antibiotics. The aim of present study is to investigate the effects of C. butyricum on the intestinal microbiota and their metabolites in weaned piglets. Results There was no statistical significance in the growth performance and the incidence of diarrhoea among the weaned piglets treated with C. butyricum during 0–21 days experimental period. Analysis of 16S rRNA gene sequencing results showed that the operational taxonomic units (OTUs), abundance-based coverage estimator (ACE) and Chao index of the CB group were found to be significantly increased compared with the NC group (P

To explore the influence of the isolation ball in a crude oil pipeline running over complex terrain, a “U” undulating crude oil pipeline with a large drop was taken as a practical case (the maximum elevation difference was 1490 m). Based on the OLGA multiphase flow transient simulation method, this paper conducts a simulation study on the process of pushing water in a large drop crude oil pipe section. The effect of oil–water interface pig (isolation ball) in the process of pushing water from crude oil and the influence of key parameters such as isolation ball diameter were analyzed. the movement characteristics of the pig in the large-drop sections under the conditions of various throughputs and fluid volumes were studied and determined the maximum velocity, pressure, fluid-holding rate, travel distance, and slug behavior of the pig at various low points. The results show that in the selected pipe section, when the throughput was 900 m3/h to 2500 m3/h, the presence of the isolation ball reduced the mixture of oil and water by 84.2% to 93.7%, reduced the volume of gas generated by the vaporization of the light oil components during transport, and reduced the slug flow in the pipe, providing an effective basis for designing optimal conditions for crude oil pipeline transport.

Tryptophan (Trp) is not only a nutrient enhancer but also has systemic effects. Trp metabolites signaling through the well-known aryl hydrocarbon receptor (AhR) constitute the interface of microbiome-gut-brain axis. However, the pathway through which Trp metabolites affect central nervous system (CNS) function have not been fully elucidated. AhR participates in a broad variety of physiological and pathological processes that also highly relevant to intestinal homeostasis and CNS diseases. Via the AhR-dependent mechanism, Trp metabolites connect bidirectional signaling between the gut microbiome and the brain, mediated via immune, metabolic, and neural (vagal) signaling mechanisms, with downstream effects on behavior and CNS function. These findings shed light on the complex Trp regulation of microbiome-gut-brain axis and add another facet to our understanding that dietary Trp is expected to be a promising noninvasive approach for alleviating systemic diseases.

Abstract To explore the problem of the slack flow and waterhead having a huge impact on the low point of a pipeline during the water‐filling process of a large‐drop pipeline, the crossing section of the Nujiang China‐Myanmar crude oil pipeline (for which the maximum height difference is 1480 m) is taken as an actual case, and water filling of an oil pipe segment with a large drop is simulated based on an OLGA multiphase flow transient simulation. The maximum velocity, pressure, and corresponding liquid holdup at different low points of the pipeline are studied, and the variations of water flow velocity, pressure, and liquid holdup with time at different low points under different load conditions are obtained. A stress analysis of the pipeline is performed through CAESAR II. The results showed that, when the volume flow rate was 900‐2000 m3/h, the probability of slug flow in pipe could be reduced by 57%. Meanwhile, the tube pressure fluctuation and damage to the pipeline and equipment are reduced and pipeline transportation efficiency is improved, thereby providing an effective basis for engineering practice.

Transient creep during an earthquake cycle is very important to understand the rheology of fault and deformation mechanisms in the brittle–plastic transition zone. In this paper, we analyzed the microstructures of samples for mylonites, pseudotachylyte, and cataclasite under optical microscope, SEM, and EBSD, which were collected from the Red River fault in southwest of China, where we uncovered a series of ductile to brittle deformed rocks which recorded transient creep related to earthquakes. The results show that mylonites formed at the inter-seismic creep were overprinted by pseudotachylyte and cataclasite which were produced during co-seismic rupture, and cracks in cataclasite were healed during the post-seismic relaxation. Based on the analysis of the microstructures and deformation mechanism of fault rocks, we propose the oscillation deformation model to explain transient creep of the brittle–plastic transition zone during the seismic cycle in the Red River fault.

ABSTRACT Limosilactobacillus reuteri plays an important role in regulating intestinal functions and maintaining barrier integrity in animals. In this study, Limosilactobacillus reuteri strain SLZX19-12 was isolated from the fecal microbiota of Tibetan pigs, and it was found that this strain is sensitive to common antibiotics and has strong resistance to stress. Upon being administered by gavage at different doses, including low, medium, and high doses, for 14 days, Limosilactobacillus reuteri SLZX19-12 may enhance the intestinal barrier. After administration of a high dose of SLZX19-12, mice were challenged with Salmonella enterica serovar Typhimurium SL1344. Infection with Salmonella Typhimurium SL1344 led to disordered colonic microbiotas, colonic inflammation through the S100A8/S100A9–NF-κB pathway and potential apoptosis, and translocation of pathogens to parenteral visceral organs in mice. However, the mice pretreated with Limosilactobacillus reuteri SLZX19-12 showed lower loads of Salmonella in visceral organs, less colonic inflammation, and higher barrier integrity. More importantly, the administration of strain SLZX19-12 resulted in a more stable microbiota structure of the colon, in which the abundance of Alloprevotella was greatly enhanced. Therefore, this study suggests that Limosilactobacillus reuteri SLZX19-12 can protect the colon from infection by enhancing the stability of gut microbiota and barrier integrity and reducing inflammation. IMPORTANCE The use of antibiotics to treat bacterial infections leads to a series of side effects. As an alternative method, the biocontrol strategy, which uses probiotics to suppress pathogens, is considered a potential way to deal with bacterial infections in gut. However, there are few probiotics that are currently safe and can protect against infection. In this study, Limosilactobacillus reuteri strain SLZX19-12 was obtained from Tibetan pigs, which have higher resistance to infection. This strain is sensitive to conventional antibiotics, secretes a wide spectrum of enzymes, and also promotes the intestinal barrier function in mice. In addition, Limosilactobacillus reuteri SLZX19-12 can promote the stability of the gut microbiota to avoid or alleviate the occurrence or development of foodborne infections.

ObjectiveTo investigate the value of diffusion-weighted imaging (DWI) combined with the hepatobiliary phase (HBP) Gd-BOPTA enhancement in differentiating intrahepatic mass-forming cholangiocarcinoma (IMCC) from atypical liver abscess.Materials and MethodsA retrospective analysis was performed on 43 patients with IMCCs (IMCC group) and 25 patients with atypical liver abscesses (liver abscess group). The DWI signal, the absolute value of the contrast noise ratio (│CNR│) at the HBP, and visibility were analyzed.ResultsA relatively high DWI signal and a relatively high peripheral signal were presented in 29 patients (67.5%) in the IMCC group, and a relatively high DWI signal was displayed in 15 patients (60.0%) in the atypical abscess group with a relatively high peripheral signal in only one (6.7%) patient and a relatively high central signal in 14 (93.3%, 14/15). A significant (P

Abstract As a novel type of antibiotic alternative, peptide‐based antibacterial drug shows potential application prospects attributable to their unique mechanism for lysing the membrane of pathogenic bacteria. However, peptide‐based antibacterial drugs suffer from a series of problems, most notably their immature stability, which seriously hinders their application. In this study, self‐assembling chimeric peptide nanoparticles (which offer excellent stability in the presence of proteases and salts) are constructed and applied to the treatment of bacterial infections. In vitro studies are used to demonstrate that peptide nanoparticles NPs1 and NPs2 offer broad‐spectrum antibacterial activity and desirable biocompatibility, and they retain their antibacterial ability in physiological salt environments. Peptide nanoparticles NPs1 and NPs2 can resist degradation under high concentrations of proteases. In vivo studies illustrate that the toxicity caused by peptide nanoparticles NPs1 and NPs2 is negligible, and these nanoparticles can alleviate systemic bacterial infections in mice and piglets. The membrane permeation mechanism and interference with the cell cycle differ from that of antibiotics and mean that the nanoparticles are at a lower risk of inducing drug resistance. Collectively, these advances may accelerate the development of peptide‐based antibacterial nanomaterials and can be applied to the construction of supramolecular nanomaterials.

The interaction between exogenous microorganisms and the host has received great attention, and finding new probiotics is always the way to improve the health of humans and animals. Lactobacillus amylovorus (L. amylovorus) is a kind of Lactobacillus that can efficiently utilize starch, as a food and feed additive, it has been widely used for mildew prevention and antibacterial, bacteriostasis, and enzyme production. Herein, a strain of L. amylovorus was isolated from the feces of Tibetan weaned piglets, named L. amylovorus SLZX20-1. Physiological and biochemical experiments in vitro confirmed that it had a fast growth rate and could produce a variety of enzymes, including α-galactosidase, β-galactosidase, α-glucosidase, β-glucosidase, and ferulic acid esterase. In addition, L. amylovorus SLZX20-1 exerted antibiotic effects on the growth of Salmonella typhimurium (S. typhimurium) SL1344, Citrobacter rodentium (C. rodentium) DBS100, Salmonella pullorum (S. pullorum) CVCC1791, Staphylococcus aureus (S. aureus) CVCC1882, Escherichia coli (E. coli) O157, E. coli K88, E. coli K99, and E. coli 987P, which are closely related to acid productivity, such as lactic acid and acetic acid. In vitro co-culture, L. amylovorus SLZX20-1 has shown the strong adhesion ability to intestinal porcine epithelial cells (IPEC-J2 cells) and activated IPEC-J2 cells with high expression of host defense peptides (HDPs), such as NK-Lysin, PEP2C, and PBD-1. In vivo experiment, via intragastric administration, L. amylovorus SLZX20-1 significantly improved the feed intake of mice, declined the crypt depth of jejunum and ileum, L. amylovorus SLZX20-1 changed the composition of intestinal microbes, especially at the level of colonic genus, the dominant genus was changed from Lactobacillus to S24-7, which indicated the change of intestinal carbohydrate nutrition. In conclusion, L. amylovorus SLZX20-1 showed strong probiotic characteristics, which met with the standard of probiotics and is worth further exploring its impacts on host health and its potential as a candidate strain of probiotics.

Based on the characteristic of low diarrhea in native Chinese breeds, we introduce the enterotype model for piglets, which is a new perspective to decipher the colonization and the transition of the gut microbiota among various pig breeds. After eliminating environmental influences represented by diet, the microbiota, mainly shaped by host genetics, is focused. Three representative enterotype clusters were identified, which were represented by Bacteroides, Streptococcus, and Lactobacillus. Chinese native breeds were distributed in enterotype 1 (E1) and E3, which collectively drove the diversification and functionality of the microbial community of various Chinese pig breeds. Next, the Lactobacillus reuteri (L. reuteri), which is the representative strain of E3, was specifically isolated in all three enterotypes. The excellent stress-resistance of L. reuteri-E3 not only highlighted the stronger disease resistance of Chinese breeds but also had a great potential to intervene in weaned piglet diseases. Enterotype classification based on host genetics is much more deterministic and predictable, clarifying the driver of the host-microbiome dynamics and constructing the picture of the micro-coevolution of human host genetics with the gut microbiome.

The P-wave velocities of typical rocks in the Anninghe fault zone under pressures of 50–600 MPa were systematically measured. The P-wave velocities of the felsic, intermediate, and mafic rock types under atmospheric pressure were 5.86, 6.06, and 6.50 km/s, respectively, with pressure coefficients of 2.19 × 10–, 3.80 × 10–4, and 4.03 × 10–4 km/s/MPa, respectively. The results were combined with deep-imaging seismic data to establish crustal rock composition models at different depths in the study area. The composition of the Anninghe crust is very different in the horizontal and vertical directions. The most notable feature in the vertical direction is that the lithologic compositional change is gradual rather than abrupt with increasing depth. In the middle and upper crust, shallower than 25 km, the lithologic difference between the southern and northern sections of the Anninghe fault zone is primarily that the rocks in the southern section (Xichang) are more felsic than those in the northern section (Shimian).

Weaned piglets stayed in transitional stages of internal organ development and external environment change. The dual stresses commonly caused intestinal disorders followed by damaged growth performance and severe diarrhea. High dose of zinc oxide could improve production efficiency and alleviate disease status whereas caused serious environmental pollution. This research investigated if coated ZnO (C_ZnO) in low dose could replace the traditional dose of ZnO to improve the growth performance, intestinal function, and gut microbiota structures in the weaned piglets. A total of 126 cross-bred piglets (7.0 ± 0.5 kg body weight) were randomly allocated into three groups and fed a basal diet or a basal diet supplemented with ZnO (2,000 mg Zn/kg) or C_ZnO (500 mg Zn/kg), respectively. The test lasted for 6 weeks. C_ZnO improved average daily gain (ADG) and feed efficiency, alleviated diarrhea, decreased the lactulose/mannitol ratio (L/M) in the urine, increased the ileal villus height, and upregulated the expression of Occludin in the ileal tissue and the effect was even better than a high concentration of ZnO. Importantly, C_ZnO also regulated the intestinal flora, enriching Streptococcus and Lactobacillus and removing Bacillus and intestinal disease-associated pathogens, including Clostridium_sensu_stricto_1 and Cronobacter in the ileal lumen. Although, colonic microbiota remained relatively stable, the marked rise of Blautia, a potential probiotic related to body health, could still be found. In addition, C_ZnO also led to a significant increase of acetate and propionate in both foregut and hindgut. Collectively, a low concentration of C_ZnO could effectively promote growth performance and reduce diarrhea through improving small intestinal morphology and permeability, enhancing the barrier function, adjusting the structure of gut microbiota, and raising the concentration of short-chain fatty acids (SCFAs) in the weaned piglets.

Objectives. The clinical and imaging features of asymptomatic carriers of severe acute respiratory syndrome coronavirus 2 and symptomatic COVID-19 patients. Methods. The clinical and chest computed tomography imaging data of 47 asymptomatic carriers and 36 symptomatic COVID-19 patients were derived. All patients underwent 4–6 CT scans over a period of 2–5 days. Results. The bulk of asymptomatic carriers who developed symptoms and most of the COVID-19 patients were older than 18 years of age with a decreased lymphocyte count, abnormal hepatic and renal function, and increased D-dimer and C-reactive protein. In the early stage, the pulmonary lesion involved mostly 1–2 lobes at the peripheral area in asymptomatic carriers but more than three lobes at both the central and peripheral areas in COVID-19 patients. In the progression stage, the lesion of asymptomatic carriers extended from the peripheral to the central area, and no significant difference was found in the lesion range compared with the symptomatic control group. In early improvement stage, the lesion was rapidly absorbed, and lesions were located primarily at the peripheral area in asymptomatic carriers; contrastingly, lesions were primarily located at both the central and peripheral areas in symptomatic patients. Asymptomatic carriers reflected a significantly shorter duration from disease onset to peak progression stage compared with the symptomatic. Conclusions. Asymptomatic carriers are a potential source of transmission and may become symptomatic COVID-19 patients despite indicating less severe pulmonary damage, earlier improvement, and better prognosis. Early isolation and intervention can eliminate such carriers as potential sources of transmission and improve their prognosis.

In this study, Co, Cu, Pd, and Pd/Cu composite metal ions were used to synthesize metal nanoparticles with high efficiency in purifying hydrogen cyanide gas. The pure liquid phase catalytic purification of hydrogen cyanide gas was studied. According to the removal rate, the Pd/Cu composite metal ions had the best purification efficiency among the nanoparticles of different metal types. The removal rate order was Pd/Cu>Pd>Cu>Co. The gas after reaction were analyzed by gas chromatography, and it was found that HCN was converted into CO2, N2 and NH3 by nanoparticles. Then, Pd/Cu composite metal ions with the highest purification efficiency were used to study the electrochemical synergistic liquid-phase catalytic purification of HCN gas. The effects of electrochemical conditions and current on the electro-hydraulic synergistic purification were studied. The removal efficiency of HCN by electrochemical synergistic liquid phase catalysis was better than that by pure liquid phase catalysis. The different nanoparticles before and after HCN absorption were characterized and analyzed to explore the purification process of HCN. The purification mechanism of hydrogen cyanide by Pd-Cu catalyst under applied voltage was studied under certain conditions. During the catalytic reaction, the nano-catalyst was partially dissolved in liquid phase and partially HCN reacts with metal ions on the free or nanoparticles to form complex [Mc(CN)n]2−n. Homogeneous and quasi-homogeneous reactions in liquid phase interweave together to form a more complex reaction system.

Abstract Clostridium species, as a predominant cluster of commensal bacteria in our gut, exert lots of salutary effects on our intestinal homeostasis. Up to now, Clostridium species have been reported to attenuate inflammation and allergic diseases effectively owing to their distinctive biological activities. Their cellular components and metabolites, like butyrate, secondary bile acids and indolepropionic acid, play a probiotic role primarily through energizing intestinal epithelial cells, strengthening intestinal barrier and interacting with immune system. In turn, our diets and physical state of body can shape unique pattern of Clostridium species in gut. In view of their salutary performances, Clostridium species have a huge potential as probiotics. However, there are still some nonnegligible risks and challenges in approaching application of them. Given this, this review summarized the researches involved in benefits and potential risks of Clostridium species to our health, in order to develop Clostridium species as novel probiotics for human health and animal production.

During the commissioning process of ”first injection of crude oil after water injection”, due to the density difference between crude oil and water, the oil pressure on the left side of the ”U” section is less than the right hydraulic pressure, and the running process of the oil head is stagnated in a hilly oil pipeline with high elevation difference. Concerning this problem, solution of discharging pressure by using relief valve in valve station nearby oil–water interfacial point is proposed in this paper. According to the actual data, gas–liquid flow in a gas-cap empty process of a big drop and hilly oil pipeline was numerically investigated by dynamic multiphase simulation software OLGA. Simulation data in terms of flow rate, pressure and leakage were compared under different leaking apertures. The simulation results show that the general pressure variation tendencies at the vent, bottom point or top and low elbows show no connection with vent diameters but its final fluctuation that the smaller the diameter is, the more intensive the fluctuation gets.. And as for the emptying of a big drop and hilly pipeline, appropriate increase of leaking aperture can improve the drainage ratio (leakage/general capacity of the pipeline) and drainage rate, but excessive aperture will cause severe negative pressure and breakage cavity which foster the likelihood of close water-surge and damage to the pipe safety. Keywords: Big drop, Oil pipeline, U-type, Water discharge, Leaking aperture

Abstract Gossypol is a toxic polyphenolic product that is derived from cotton plants. The toxicity of gossypol has limited the utilization of cottonseed meal (CSM) in the feed industry. The gene, Helicoverpa armigera CYP9A12, is a gossypol-inducible cytochrome P450 gene. The objective of our study was to obtain the functional recombinant H. armigera CYP9A12 enzyme in Pichia pastoris and to verify whether this candidate enzyme could decrease gossypol in vitro. Free and total gossypol contents were detected in the enzyme solution and in CSM. The H. armigera CYP9A12 enzyme degraded free concentration of gossypol. After optimization of the single-test and response surface method, free gossypol content could be decreased to 40.91 mg/kg in CSM by the H. armigera CYP9A12 enzyme when the initial temperature was 35 °C, the enzymatic hydrolysis time lasted 2.5 h, the enzyme addition was 2.5 mL, and the substrate moisture was 39%.

Abstract Background The aim of this study was to investigate the intergeneric transfer of vancomycin resistance gene vanA between probiotic enterococci in the fermentation progress of soybean meal and in the digestive tract of growing pigs. One vanA genotype vancomycin resistant E. faecium strain, Efm4, and one chloramphenicol-resistant E. faecalis strain, Efs2, were isolated from twenty-nine probiotic basis feed material / additive samples. For in vitro conjugation, Efm4 and Efs2 were used as starter to ferment soybean meal. For in vivo conjugation, thirty growing pigs were randomly assigned to five groups (n = 6), treated with a basic diet, or supplemented with 10% fermented soybean meal, 1% Efm4, 5% Efs2 or a combination of 1% Efm4 + 5% Efs2 for 7 d, respectively. Fecal samples of pigs in each group were collected daily for the isolation and dynamic analysis of Efm4, Efs2 and transconjugants. The sequence types (STs) of Efm4, Efs2 and transconjugants were analyzed by multilocus sequence typing (MLST). The vanA harboring plasmid in Efm4 and transconjugants was analyzed by S1-pulsed field gel electrophoresis (PFGE) and further verified by multiple alignments. Results The results showed that, in FSBM, transconjugants were detected 1 h after the fermentation, with a conjugation frequency of ~ 10− 3 transconjugants / recipient. Transconjugants proliferated with Efm4 and Efs2 in the first 8 h and maintained steadily for 10 d till the end of the experiment. Additionally, in vivo experiment showed that transcojugants were recovered in one of six pigs in both FSBM and Efm4 + Efs2 groups, with conjugation frequency of ~ 10− 5 and ~ 10− 4, respectively. MLST revealed the ST of Efm4, Efs2 and transconjugants was ST1014, ST69 and ST69, respectively. S1-PFGE confirmed the existence of the vanA-harboring, 142,988-bp plasmid, which was also a multi-drug resistant plasmid containing Tn1546-like transposon. Conclusions The findings revealed the potential safety hazard existing in the commercial probiotic enterococci in China, because the horizontal transfer from farm to fork could potentially pose a safety risk to the public.

PurposeThis study was to investigate the role of different radiomics models with enhanced computed tomography (CT) scan in differentiating low from high grade renal clear cell carcinomas.Materials and MethodsCT data of 190 cases with pathologically confirmed renal cell carcinomas were collected and divided into the training set and testing set according to different time periods, with 122 cases in the training set and 68 cases in the testing set. The region of interest (ROI) was delineated layer by layer.ResultsA total of 402 radiomics features were extracted for analysis. Six of the radiomic parameters were deemed very valuable by univariate analysis, rank sum test, LASSO cross validation and correlation analysis. From these six features, multivariate logistic regression model, support vector machine (SVM), and decision tree model were established for analysis. The performance of each model was evaluated by AUC value on the ROC curve and decision curve analysis (DCA). Among the three prediction models, the SVM model showed a high predictive efficiency. The AUC values of the training set and the testing set were 0.84 and 0.83, respectively, which were significantly higher than those of the decision tree model and the multivariate logistic regression model. The DCA revealed a better predictive performance in the SVM model that possessed the highest degree of coincidence.ConclusionRadiomics analysis using the SVM radiomics model has highly efficiency in discriminating high- and low-grade clear cell renal cell carcinomas.

The study investigated the impact of dietary montmorillonite on the growth performance, intestinal mucosal barrier, and microbial community in weaned piglets with control group (CON) and dietary supplementation of 0.2% montmorillonite (0.2% M). Compared with the CON group, 0.2% M feed in the diet increased the average daily gain (ADG) on days 15–35 and day 1–35 and the average daily feed intake on days 1–35 (ADFI) (0.05 < P < 0.1). Besides, higher villus height of the duodenum and jejunum and lower crypt depth of duodenum and colon were revealed in the 0.2% M group than in the CON group (P < 0.05). Moreover, the V/C (ratio of the villus height and crypt depth) in the 0.2% M group was increased compared to that in the CON group both from the duodenum and ileum (P < 0.05). The relative mRNA expression of mucin-1, ITGB1 (β1-integrins), and PKC (protein kinase C) of ileum in the 0.2% M group were upregulated (P < 0.05) compared to that in the CON group. The digesta sample of ileum from piglets in the 0.2% M group contained greater (P < 0.05) intestinal bacterial diversity and abundances of probiotics, such as Streptococcus, Eubacterium_rectale_group, and Lactobacillus, which could promote the synthesis of carbon-containing biomolecules. Overall, dietary supplementation of 0.2% M was shown to have a tendency to improve the growth performance of weaned piglets and may enhance their intestinal mucosal barrier function via altering the gut microbiota.

This study aimed to evaluate the effect of dietary supplementation with pyrroloquinoline quinone (PQQ) on gut inflammation and microbiota dysbiosis induced by enterotoxigenic Escherichia coli (ETEC). Twenty Duroc × Landrace × Yorkshire crossbred barrows were assigned to four groups: two E. coli K88 challenge groups and two non-challenge groups, each provided a basal diet supplemented with 0 or 3 mg/kg PQQ. On day 14, piglets were challenged with 10 mL 1 × 109 CFU/mL of E. coli K88 or PBS for 48 h. The villus height (VH) and villus height/crypt depth (VCR) ratio of the E. coli K88-challenged group supplemented with PQQ was significantly reduced than in the non-supplemented challenge group (P < 0.05), while levels of jejunal zonula occludens-3 (ZO-3), diamine oxidase, secretory immunoglobulin A (SIgA), interleukin-10 (IL-10), and IL-22 proteins were higher (P < 0.05), as were the activities of glutathione peroxidase, total superoxide dismutase, and total antioxidant capability (P < 0.05). Moreover, PQQ supplementation alleviated an increase in levels of mucosal inflammatory cytokines and reduced the activity of nuclear factor-kappa B (NF-κB) pathway by E. coli K88 (P < 0.05). Gene sequencing of 16S rRNA showed dietary supplementation with PQQ in E. coli K88-challenged piglets attenuated a decrease in Lactobacillus count and butyrate, isobutyrate level, and an increase in Ruminococcus and Intestinibacter counts, all of which were observed in non-supplemented, challenge-group piglets. These results suggest that dietary supplementation with PQQ can effectively alleviate jejunal mucosal inflammatory injury by inhibiting NF-κB pathways and regulating the imbalance of colonic microbiota in piglets challenged with E. coli K88.

Abstract Background Squalene is currently used widely in the food, cosmetics, and medicine industries. It could also replace petroleum as a raw material for fuels. Microbial fermentation processes for squalene production have been emerging over recent years. In this study, to study the squalene-producing potential of Escherichia coli (E. coli), we employed several increasing strategies for systematic metabolic engineering. These include the expression of human truncated squalene synthase, the overexpression of rate-limiting enzymes in isoprenoid pathway, the modification of isoprenoid-feeding module and the blocking of menaquinone pathway. Results Herein, human truncated squalene synthase was engineered in Escherichia coli to create a squalene-producing bacterial strain. To increase squalene yield, we employed several metabolic engineering strategies. A fivefold squalene titer increase was achieved by expressing rate-limiting enzymes (IDI, DXS, and FPS) involved in the isoprenoid pathway. Pyridine nucleotide transhydrogenase (UdhA) was then expressed to improve the cellular NADPH/NADP+ ratio, resulting in a 59% increase in squalene titer. The Embden–Meyerhof pathway (EMP) was replaced with the Entner–Doudoroff pathway (EDP) and pentose phosphate pathway (PPP) to feed the isoprenoid pathway, along with the overexpression of zwf and pgl genes which encode rate-limiting enzymes in the EDP and PPP, leading to a 104% squalene content increase. Based on the blocking of menaquinone pathway, a further 17.7% increase in squalene content was achieved. Squalene content reached a final 28.5 mg/g DCW and 52.1 mg/L. Conclusions This study provided novel strategies for improving squalene yield and demonstrated the potential of producing squalene by E. coli.

Abstract Background Lysine is used widely in livestock production due to the shortage of feed protein resources. L-lysine·H2SO4 contains L-lysine sulphate as well as fermentation co-products which contain other amino acids and phosphorus. However, there are few articles about L-lysine·H2SO4 product regarding intestinal morphology and liver pathology of broiler chickens. In this article, we focus on the absorption and metabolism of L-lysine·H2SO4 revealed in the variation of intestinal morphology and liver pathology to determine the tolerance of chicks for L-lysine·H2SO4. Methods To evaluate the tolerance of broilers for L-lysine·H2SO4, 240 one day old broilers were allocated randomly to one of five dietary treatments which included corn-soybean diets containing 0, 1%, 4%, 7% or 10% L-lysine·H2SO4 (L-lysine content = 55%). Results Supplementation of 1% L-lysine·H2SO4 in the diet had no negative effects. However, 4%, 7% or 10% L-lysine·H2SO4 supplementation produced negative responses on broiler performance, carcass characteristics, blood biochemistry, and particularly on intestinal morphology and liver pathology compared with broilers fed the control diet. Conclusion Our results show that supplementation with 1% L-lysine·H2SO4 had no negative effects on performance, carcass characteristics, blood biochemistry, intestinal morphology and liver pathology in broilers, but supplementation with 4%, 7% or 10% L-lysine·H2SO4 produced a negative response, particularly with respect to intestinal morphology and liver pathology.

Background Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. However, the molecular mechanisms involved in HCC remain unclear and are in urgent need of elucidation. Therefore, we sought to identify biomarkers in the prognosis of HCC through an integrated bioinformatics analysis. Methods Messenger RNA (mRNA) expression profiles were obtained from the Gene Expression Omnibus database and The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) for the screening of common differentially expressed genes (DEGs). Function and pathway enrichment analysis, protein-protein interaction network construction and key gene identification were performed. The significance of key genes in HCC was validated by overall survival analysis and immunohistochemistry. Meanwhile, based on TCGA data, prognostic microRNAs (miRNAs) were decoded using univariable and multivariable Cox regression analysis, and their target genes were predicted by miRWalk. Results Eleven hub genes (upregulated ASPM, AURKA, CCNB2, CDC20, PRC1 and TOP2A and downregulated AOX1, CAT, CYP2E1, CYP3A4 and HP) with the most interactions were considered as potential biomarkers in HCC and confirmed by overall survival analysis. Moreover, AURKA, PRC1, TOP2A, AOX1, CYP2E1, and CYP3A4 were considered candidate liver-biopsy markers for high risk of developing HCC and poor prognosis in HCC. Upregulation of hsa-mir-1269b, hsa-mir-518d, hsa-mir-548aq, hsa-mir-548f-1, and hsa-mir-6728, and downregulation of hsa-mir-139 and hsa-mir-4800 were determined to be risk factors of poor prognosis, and most of these miRNAs have strong potential to help regulate the expression of key genes. Conclusions This study undertook the first large-scale integrated bioinformatics analysis of the data from Illumina BeadArray platforms and the TCGA database. With a comprehensive analysis of transcriptional alterations, including mRNAs and miRNAs, in HCC, our study presented candidate biomarkers for the surveillance and prognosis of the disease, and also identified novel therapeutic targets at the molecular and pathway levels.

Abstract Background The high mortality of pre-weanling piglets is a dominant challenge which severely restricts the development of pig industry. A number of factors including nutrients imbalance and temperature variation during postnatal period of piglets have been reported to closely associated with the high mortality of postnatal piglets. This study aims to find out the relationship between fat deposition and survival of newborn piglets. Results There were no differences in organ coefficient and bone density between the surviving and dead piglets (P > 0.05). The body weight and the fat deposition in the dead piglets were lower than the live individuals (P

Traditionally, antibiotics are included in animal feed at subtherapeutic levels for growth promotion and disease prevention. However, recent links between in-feed antibiotics and a rise in antibiotic-resistant pathogens have led to a ban of all antibiotics in livestock production by the European Union in January 2006 and a removal of medically important antibiotics in animal feeds in the United States in January 2017. An urgent need arises for antibiotic alternatives capable of maintaining animal health and productivity without triggering antimicrobial resistance. Host defense peptides (HDP) are a critical component of the animal innate immune system with direct antimicrobial and immunomodulatory activities. While in-feed supplementation of recombinant or synthetic HDP appears to be effective in maintaining animal performance and alleviating clinical symptoms in the context of disease, dietary modulation of the synthesis of endogenous host defense peptides has emerged as a cost-effective, antibiotic-alternative approach to disease control and prevention. Several different classes of small-molecule compounds have been found capable of promoting HDP synthesis. Among the most efficacious compounds are butyrate and vitamin D. Moreover, butyrate and vitamin D synergize with each other in enhancing HDP synthesis. This review will focus on the regulation of HDP synthesis by butyrate and vitamin D in humans, chickens, pigs, and cattle and argue for potential application of HDP-inducing compounds in antibiotic-free livestock production. Keywords: Host defense peptides, Antibiotic alternatives, Butyrate, Vitamin D, Antibiotics

Abstract Background Fasting is a simple metabolic strategy that is used to estimate the maintenance energy requirement where the energy supply for basic physiological functions is provided by the mobilization of body reserves. However, the underlying metabolic components of maintenance energy expenditure are not clear. This study investigated the differences in heat production (HP), respiratory quotient (RQ) and plasma metabolites in pigs in the fed and fasted state, using the techniques of indirect calorimetry and metabolomics. Methods Nine barrows (45.2 ± 1.7 kg BW) were fed corn-soybean based meal diets and were kept in metabolism crates for a period of 14 d. After 7 d adaptation, pigs were transferred to respiratory chambers to determine HP and RQ based on indirect calorimetry. Pigs were fed the diet at 2,400 kJ ME/(kg BW0.6·d) during d 8 to 12. The last 2 d were divided into 24 h fasting and 48 h fasting treatment, respectively. Plasma samples of each pig were collected from the anterior vena cava during the last 3 d (1 d while pigs were fed and 2 d during which they were fasted). The metabolites of plasma were determined by high-resolution mass spectrometry using a metabolomics approach. Results Indirect calorimetry analysis revealed that HP and RQ were no significant difference between 24 h fasting and 48 h fasting, which were lower than those of fed state (P

Reactive oxygen species (ROS) are produced by living cells as normal cellular metabolic byproduct. Under excessive stress conditions, cells will produce numerous ROS, and the living organisms eventually evolve series of response mechanisms to adapt to the ROS exposure as well as utilize it as the signaling molecules. ROS molecules would trigger oxidative stress in a feedback mechanism involving many biological processes, such as apoptosis, necrosis and autophagy. Growing evidences have suggested that ROS play a critical role as the signaling molecules throughout the entire cell death pathway. Overwhelming production of ROS can destroy organelles structure and bio-molecules, which lead to inflammatory response that is a known underpinning mechanism for the development of diabetes and cancer. Cytochrome P450 enzymes (CYP) are regarded as the markers of oxidative stress, can transform toxic metabolites into ROS, such as superoxide anion, hydrogen peroxide and hydroxyl radical which might cause injury of cells. Accordingly, cells have evolved a balanced system to neutralize the extra ROS, namely antioxidant systems that consist of enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidases (GPxs), thioredoxin (Trx) as well as the non-enzymatic antioxidants which collectively reduce oxidative state. Herein, we review the recent novel findings of cellular processes induced by ROS, and summarize the roles of cellular endogenous antioxidant systems as well as natural anti-oxidative compounds in several human diseases caused by ROS in order to illustrate the vital role of antioxidants in prevention against oxidative stress.